CHAPTER 1

INTRODUCTION

1.1 Background

Infectious disease are disorders caused by organisms — such as bacteria,

viruses, fungi or parasites. Many microorganisms colonize in and on our bodies.

They're normally harmless or even helpful, but under certain conditions may cause

disease. Some infectious disease can be passed from person to person. Some,

however, are transmitted via bites from insects or animals. Others are acquired by

ingesting contaminated food or water or other exposures in the environment. Signs

and symptomps of infectious diseases vary, but often include fever and chills. Mild

complaints may respond to home remedies, while some life-threatening infections

may require hospitalization and intravenous antibiotics.

Infection refers to the ability of microorganism to invade tissue and find

condition that are suitable for growth and replication. It should be noted that it is, in

general, not in the interests of the organism to destroy the host; rather it is preferable

to find an ecological niche that will allow tissue colonization with perhaps some

replication, but without the risks of invasion. It is the exception for microorganisms

to cause infection rather than the rule. Alterations in the site of colonization, the

bacterial density or level of host immune competence will alter the likelihood of

infection. Infection is also sometimes a function of the host’s response to

microorganisms. Infections may cause either clinical or subclinical illness i.e.

apparent versus inapparent illness. Many individuals develop an immune response to

a pathogen without manifesting any signs of illness.

Periodontal disease, is the most common disease in the world and the leading

cause of tooth loss in adults is a chronic infection that slowly attacks and destroys the

gums and bone that support the teeth. Symptoms associated with periodontal disease

are sore, inflamed gums that have a tendency to bleed. Estimations have shown that at

least 75 percent of the adult population in America has some form of periodontal

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disease. Adults are not the only group susceptible to the disease; one-third of children

ages 6-11 and two-thirds of adolescents have some form of periodontal disease

Periodontal disease is caused by more than 200 species of bacteria. These

bacteria form masses of sticky film called plaque, which is able to adhere to the

surface of teeth and gums. The bacteria are then nourished by the consumption of

foods, especially sweets. The sugars are metabolized by the bacteria which causes the

secretion of acids, enzymes, and other soft tissue irritants and bone destroyers. When

left untreated, the bacteria begin to spread to areas that are hard to reach with normal

brushing and flossing; for instance, areas below the gum line, thus causing

periodontal disease (periodontal).

1.2 Problems

In this case, a man with 50 years old was being treated in hospital, reffered to

dental clinic for dental treatment especially molar treatment that had cavity and

continous pain and also bleeding.The patient had shortness breathing for the last 2

weeks with continous chest pain and chronic cough for more than 1 month. Patient

had fever for the last 2 weeks especially in the evening, sweat in the night, loss of

appetite and loss of weight.

1.3 Purpose

The purpose for making this paper :

• To know about basic concept of infection and spread of infection itself

• To know the importance of maintaining healthy teeth

• Understand the symptoms caused by infectious disease so as to choose the

appropriate treatment for patients.

1.4 Benefit

The benefit is we can figure out how the mechanism of occurrence infectious

disease so as to provide the best treatment to the patient and dentist himself/herself

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CHAPTER 2

THEORITICAL REVIEW

2.1 CARIES

Caries is the process of deterioration of enamel, dentine and pulpa weefsel.

The lesion as a result of this damage occurs, a carious lesion is characterized by

demineralization of the inorganic component of tooth structure and disintegration of

the organic component. The development of a lesion is an intermittent process of

demineralization and remineralization, which is an important component of the

microbial cariogenic plaque.2

Tooth decay, or dental caries, is one of the two most prevalent forms of dental

disease, periodontal disease being the other. For major factors are necessary for caries

to occur: a susceptible tooth, presence of acid-producing bacteria, access to

fermentable carbohydrates (predominantly sugar) and time. Dental caries is the

dissolution of both enamel and dentin by the acid by-products of certain bacteria

living on the tooth surfaces.3

Dental caries starts slowly because the process must first works its way

through the highly mineralized enamel surface of the tooth. Once the process reaches

the less mineralized dentin, the speed of destruction increases. Left alone, the decay

may eventually close in on the pulp, causing pain, possible pulpal death, and abscess

formation.4

Dental caries is a proceed that may take place on any tooth surface in the oral

cavity where dental plaque is allowed to develop over a period of time. Plaque

formaton is a natural. Plaque is an example of a biofilm, which means it is not a

haphazard collection of bacteria but a community of microorganisms attached to a

surface. This community works together, having a collective physiology. The bacteria

in the biofilm are always metabolically active. Some of the bacteria are capable of

fermenting a suitable dietary carbohydrate substrate (such as the sugars sucrose and

glucose), to produce acid, causing the plaque pH to fall to below 5 within 1-3

minutes. Repeated falls in pH may in time result in demineralization of the tooth

3

surface. However, the acid produced is neutralized by saliva, so the pH increases and

mineral may be regained. This is called remineralization. The cumulative results of

the deand remineralization processes may be a net loss of mineral and a carious lesion

that can be seen. Alternatively, the changes may be so slight that a carious lesion

never becomes apparent.5

The metabolism of this plaque is influenced by several factors including diet,

oral hygiene, saliva composition and presence of fluoride. The dynamic nature of the

caries process is the balance between these factors. The caries process is not time-

called a halt - by preventive or restorative measures - will extend to the lesion there is

a 'deep' carious lesion or caries profunda.

At an early stage, reactions to the caries process observed in the pulp dentine

complex. Whether these reactions occur with the initial (enamel) lesion or only at the

dentinelaesie in the literature is still disputed.6

Caries can be subdivided according to the extent of the damage it has already

caused. Caries initialis or caries superficialis occurs if the caries is located within the

enamel. A caries affliction of the dentin is caries media or caries profunda, depending

on the depth of the dentin caries.

1. Caries initialis

Initial caries is still reversible. The loss of minerals in the enamel is displayed

as a whitish spot. It can be repaired through the redeposition of mineral substances.

The affected areas are treated with a fluoride gel or a fluoride solution. This serves to

4

Figure 2.1. Initial caries (white spot lesions)

promote the redeposition of mineral substances (remineralisation).1

2. Caries superficialis

Superficial (surface) caries is irreversible. A first cavity is created by the

mineral loss occurring under an intact tooth surface. Defects such as these represent

ideal hiding places for bacteria. Plaque is permanently present in these defects. The

acid formed by the bacteria cannot be neutralised by saliva and leads to a further loss

in minerals. The expansion of caries superficialis is as yet still limited to the enamel

and does not cause pain.7

Tooth destruction through caries

If the carious process reaches the dentin, we speak of caries media. The

bacteria can now advance more rapidly through the little dentin canals within the

dentin. Caries can thus also advance more rapidly. Dentin caries can expand

considerably, even under an almost intact dental enamel surface. In the case of

extensive caries media, the probe remains stuck in the softened dentin. The larger the

defect, the more frequently decay processes (bacterial decay of food residues) take

place.

3. Caries profunda

If the dentin caries reaches the proximity of the pulpa.. The carious defect

with softened dentin has encompassed large areas of the tooth. Without therapy, the

tooth will be destroyed by the caries and as a consequence of bacterial damage caused

to the pulpa a pulpitis (inflammation of the dental pulp) would develop.7

A carious lesion has several distinctive areas : zone of bacterial invasion and

destruction, demineralized zone, sclerotic or transparent / translucent zone and a

reactive zone. At the histological level in these zones a number of responses to the

caries process which can not be removed. Destruction takes place in an area of dental

tissue caused by the action of acid and pro-teolytische enzymes produced by

anaerobic micro-organisms are formed in the microbial biomass present. Axially of

5

this zone there is bacterial invasion. The demineralized zone is generally not infected,

but is subject to the microorganisms diffusing acid. Due to the active, defensive

reaction of the mug-pa-dentine complex forms the transparent zone (zone 3).

Demineralization has increased porosity results. Now to increase diffusion of acid

and enzymes to combat turn until the odontoblasten tubular sclerosis. Intratubular

formation of hydroxylapatite and witlockietkristallen (ß-tricalcium phosphate)

significantly reduces the patency of the tubules. The reactive zone (zone 4) is named

after the deposition of reactionary or reparatief tertiary dentin on the pulpal side of

the pulp-Dentine complex. This dentin is less mineralized and composed of

irregularly shaped tubules. These local deposition of dentin is often accompanied by a

reduction in the number odontoblasten. Demineralization takes place at a distance of

0.5 to 1 millimeter to the mug-pa, then the inflammatory reactions observed in sub

odontoblastenlaag (zone of Weil). These often chronic inflammation with the

presence of lymphocytes, macrophages and plasma cells are probably due to the

presence of bacterial products.7

2.2 DIABETES MELITUS

Diabetes mellitus (DM) is a chronic, non-communicable disease and also one

of the major global public health issues. It produces many complex changes in the

lives of those affected. Diabetes mellitus is defined as a clinical syndrome

characterized by hyperglycemia due to absolute or relative deficiency of insulin.

Diabetes mellitus is an etiologically and clinically heterogeneous group of metabolic

disorders that share the commonality of hyperglycemia. It is chronic disorder

characterized by :

• Hyperglycemia

• Major abnormalities in carbohydrate, fat and protein metabolism.

• Marked propensity to develop relatively specific forms of vascular, renal, ocular,

neurologic and periodontal complications. It is a common disease with concomitant

oral manifestations that impact on dental care. Virtually every practicing dentist

encounters patients with known or undiagnosed diabetes. (Azodo, 2009)

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There are four etiologic types of diabetes, although the most frequent are type

1 (90%) and 2 (5- 10%). Prevalence of diabetes in adults worldwide was estimated to

be 4% in 1995, and is predicted to rise to 5’4% by the year 2025. The countries with

the largest number of people with diabetes are India, China and the U.S. In

developing countries, the majority are in the age range of 45–64 years. In the

developed countries, the majority of people with diabetes are aged 65 years. There are

more women than men with diabetes. Poorly controlled diabetes could lead to

complications that may even be life- threatening. Long- term complications include:

retinopathy, nephropathy, autonomic neuropathy, peripheral neuropathy and

cardiovascular disease. The dentist plays a major role with other members of the

health team in helping a patient maintain glycemic control by achieving optimal oral

health; and by referring undiagnosed patients with complications suggestive of

diabetes to physicians for further evaluation. (Alamo et al, 2011)

Tabel 2.1 Criteria for the diagnosis of diabetes (American Diabetes Association,

2010)

2.2.1 Classification of diabetes mellitus

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The criteria for diagnosis of diabetes include symptoms of hyperglycaemia

(polyuria, polydipsia, unexplained weight loss, visual blurring, genital thrush,

lethargy) associated with a raised random venous plasma glucose (≥11.1mmol/l)

level, or a raised fasting plasma glucose level (≥7.0mmol/l) in the presence or

absence of symptoms, with the test being performed on two separate occasions.

(Wilson et al, 2010)

There are three main categories of diabetes :

1. Type 1 (insulin-dependent diabetes mellitus), which results from an absolute

insulin deficiency.

2. Type 2 (non-insulin-dependent diabetes mellitus), which is the result of insulin

resistance and an insulin secretory defect.

3. Gestational diabetes presenting for the first time during pregnancy, which occurs in

2-5% of all pregnancies. Impaired glucose tolerance (IGT) and impaired fasting

glycaemia (IFG) are intermediate conditions in the transition between normality and

diabetes. Patients with these conditions are now referred to as having ‘pre diabetes’

and are at high risk of progressing to type 2 diabetes mellitus, although this is not

inevitable. IGT and IFG are associated with metabolic syndrome, which includes

obesity (especially abdominal or visceral obesity), dyslipidaemia of the high

triglyceride and/or low high-density lipoprotein (HDL) type, and hypertension.

(Wilson et al, 2010)

2.2.2 Factors that contribute in DM

Diabetes involves chronic levels of abnormally high glucose

(hyperglycemia). Many patients, especially those with type 2 diabetes, also have

elevated blood pressure (hypertension), chronic high levels of insulin

(hyperinsulinemia) and unhealthy levels of cholesterol and other blood fats

(hyperlipidemia). All of these factors contribute to the long-term complications of

diabetes, which include:

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Vascular disease (diabetic angiopathy), atherosclerosis, heart conditions and

stroke: These cardiovascular disorders are the leading cause of death in people with

diabetes.

Kidney disease (diabetic nephropathy): Diabetes is the chief cause of end-

stage renal disease, which requires treatment with dialysis or a kidney transplant.

Eye diseases: These include diabetic retinopathy, glaucoma and cataracts.

Diabetes is a leading cause of visual impairment and blindness.

Nerve damage (diabetic neuropathy): This includes peripheral neuropathy,

which often causes pain or numbness in the limbs, and autonomic neuropathy, which

can impede digestion (gastroparesis) and contribute to sexual dysfunction and

incontinence. Neuropathy may also impair hearing and other senses.

Impaired thinking: Many studies have linked diabetes to increased risk of

memory loss, dementia, Alzheimer’s disease and other cognitive deficits. Recently

some researchers have suggested that Alzheimer’s disease might be “type 3 diabetes,”

involving insulin resistance in the brain.

Infections and wounds: Foot conditions and skin disorders, such as ulcers,

make diabetes the leading cause of nontraumatic foot and leg amputations. People

with diabetes are also prone to infections including periodontal disease, thrush,

urinary tract infections and yeast infections.

Cancer: Diabetes increases the risk of malignant tumors in the colon,

pancreas, liver and several other organs.

Musculoskeletal disorders: Conditions ranging from gout to osteoporosis to

restless legs syndrome to myofascial pain syndrome are more common in diabetic

patients than nondiabetics.

Pregnancy complications: Diabetes increases the risk of preeclampsia,

miscarriage, stillbirth and birth defects.

Emotional difficulties: Many but not all of the studies exploring connections

between diabetes and mental illness have found increased rates of depression, anxiety

and other psychological disorders in diabetic patients. In addition to chronic

hyperglycemia, diabetic patients can experience acute episodes of hyperglycemia as

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well as hypoglycemia (low glucose). Severe cases can cause seizures, brain damage

and a potentially fatal diabetic coma. Acute glucose emergencies include:

Insulin shock: This advanced stage of hypoglycemia is typically due to

excessive amounts of insulin medication or certain antidiabetic agents.

Diabetic ketoacidosis: A lack of insulin can force the body to burn fats instead

of glucose for energy. The result is a toxic byproduct called ketones, along with

severe hyperglycemia.

Hyperosmolar hyperglycemic nonketotic state: This involves severe

hyperglycemia and dehydration.

2.2.3 Risk factors and causes of diabetes

The causes of diabetes are complex and only partly understood. This disease

is generally considered multifactorial, involving several predisposing conditions and

risk factors. In many cases genetics, habits and environment may all contribute to a

person’s diabetes.

Genetics and family history: Certain genes are known to cause maturity-onset

diabetes of the young (MODY) and Wolfram syndrome. Genes also contribute to

other forms of diabetes, including types 1 and 2.

Family medical history is also influential to varying degrees: For example, a

person whose parents both have type 1 diabetes has a 10 to 25% chance of developing

that disease, according to the American Diabetes Association, and someone whose

parents both have type 2 diabetes has a 50% chance of developing that disease.

Weight and body type: Overweight and obesity are leading factors in type 2

diabetes and gestational diabetes. Excess fat, especially around the abdomen (central

obesity), promotes insulin resistance and metabolic syndrome.

Sex : The prevalence of diabetes in American men and women was similar

until 1999, when a growing disparity began, according to an analysis of statistics

published by the U.S. Centers for Disease Control and Prevention (CDC). Little or no

research has been conducted to explain this trend. One factor may be the documented

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increase in recent years of low testosterone levels (male hypogonadism), which

scientists have linked to insulin resistance.

Level of physical activity: Lack of regular exercise is blamed for much of the

twin global epidemics of obesity and diabetes.

Diet: The effect of diet in the development of diabetes is controversial. Some

studies have linked heavy consumption of soft drinks and other simple carbohydrates

to risk of metabolic diabetes, and foods low in the glycemic index, such as whole

grains, to reduced risk. Yet the ADA states that eating foods containing sugar does

not cause the disease. The culprit, rather, is the weight gain due to sedentary habits

and excess intake of calories, according to the ADA.

2.2.4 Treatment Of Diabetes Mellitus

Medical nutrition therapy (also known as dietary therapy) and lifestyle

modification form the centerpiece of the management of DM, irrespective of

modality of therapy chosen. The goals of therapy are to prevent complications of DM.

Tight blood glucose control prevents microvascular complications in both type 1 and

type 2 DM.11,34 Although glycemic control may not be as effective in reducing

macrovascular complications, aggressive therapies aimed at blood pressure levels,

lipid levels and smoking cessation are effective in preventing macrovascular

complications.

Insulin therapy

Insulin therapy is the mainstay for patients with type 1 DM, and, in most

patients, frequent multiple dosing (basal and bolus) plans are common. Continuous

insulin delivery via pumps also is a fairly common practice. All of these methods

typically involve subcutaneous injection, and a variety of insulin preparations can be

used that allow the physician and patient to select the best method on the basis of cost

and flexibility. Insulin therapy should mimic the physiological release of insulin,

which is characterized by a continuous basal secretion, to prevent fasting

hyperglycemia, as well as prandial insulin release to prevent postprandial

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hyperglycemia. During fasting, long-acting basal insulin, which has a flat profile

without a peak, is used, and at mealtime, a bolus injection of fast-acting insulin is

administered to produce a peak coinciding with absorption of ingested carbohydrates.

In the past, insulin was derived from porcine and bovine sources. These sources have

been replaced by recombinant human insulin. Many types of insulin have been

developed to produce varying levels of onset of action, ranging from rapid-acting (for

example, analog insulins such as aspart, lispro and glulisine) to intermediateacting

(for example, neutral protamine Hagedorn, commonly referred to as NPH) to long-

acting (for example, glargine and detemir). Insulin pump therapy, also known as

continuous subcutaneous insulin infusion, is portable and provides flexibility and the

convenience of fewer injections, especially for patients with type 1 DM. The insulin

pump consists of an external pump and a needle inserted into the skin that are

connected by tubing. The pump has a reservoir, which is filled with rapid- or short-

acting insulin for continuous infusion. The pump can be programmed to deliver

different basal and bolus rates and allows delivery of sophisticated regimens of

insulin that can be customized to each patient’s lifestyle. The basis for any successful

insulin therapy is the ability of patients to monitor their own blood glucose levels by

using glucometers, education that allows patients to adjust their insulin doses, diet

and exercise to produce normoglycemia and prevent hypoglycemia. Insulin therapy is

associated with the risk of experiencing significant weight gain and developing

hypoglycemia.

Pramlintide

Since the secretion of amylin from islets in patients with type 1 DM also is

defective, amylin injections may help with glucose control. Amylin decreases

postprandial glucagon release and delays gastric emptying (similar to

actions of incretins), which may help prevent large excursions in glucose after meals.

The commercial preparation of amylin is pramlintide, which is approved by the U.S.

Food and Drug Administration for treatment of patients with both type 1 and type 2

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DM. However, it has to be injected before each meal. For glucose control in patients

with type 1 DM, there are no orally active agents.

OHAs

These are the first-line agents used to treat patients with type 2 DM, and they

either increase pancreatic insulin secretion or improve insulin action (the term

“sensitizer” is used to describe them). Although debate continues about the merits of

one kind over another, each class of OHA generally is as effective as the other. At

first approximation, most OHAs lead to an average 1.0 to 1.2 percent decrease in

glycosylated hemoglobin (HbA1c). Insulin secretagogues are those that stimulate

insulin secretion from pancreatic beta cells. They are of value only in patients in

whom there is some residual pancreatic function. Their advantage is that they mimic

physiological insulin secretion. This class of agents includes sulfonylureas and

meglitinides, both of which work through sulfonylurea receptors on beta cells to

release insulin. Insulin sensitizers improve the action of insulin in target tissues

(hepatic, skeletal muscle and adipose tissues) in people with insulin resistance. This

class of agents includes biguanides (for example, metformin), which principally

reduces hepatic gluconeogenesis and improves muscles’ uptake of glucose, and

thiazolidinediones (for example, pioglitazone and rosiglitazone) that act primarily on

adipose and skeletal muscle to improve insulin action. α-Glucosidase inhibitors

(acarbose and miglitol) decrease glucose absorption in the gut.

Incretins

The newest group of oral agents used to treat patients with type 2 DM target

the incretin pathway. This group includes dipeptidyl peptidase IV inhibitors. These

agents prevent the rapid breakdown of two intestinally secreted hormones (glucagon-

like peptide-1 and gastricinhibitory peptide) that are released in response to meals.

These hormones increase insulin secretion, decrease glucagon secretion and delay

gastric emptying. 37-39 The incretin pathway is attenuated in patients with type 2

DM,40 and oral agents that specifically target the enzyme dipeptidyl peptidase IV

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increase their half-lives in the bloodstream. Naturally occurring incretins in humans

have a short half-life and are not useful therapeutically. Exenatide is a synthetic

analog of Gila monster incretin (exendin-4), and it targets the glucagon-like peptide-1

receptor. It is an injectable drug, however, and leads to weight loss, unlike insulin,

which causes weight gain.41-44 Of all the approved agents used to treat DM, only

two (metformin and exenatide) consistently reduce weight, as well as improve

glycemic con trol. All other agents tend to lead to weight gain. These OHAs can be

used alone or in combination with one another and with insulin. Regimens should

complement each other and not produce the same effects; for example, combining a

sulfonylurea with a meglitinide may not be effective because both act on the

sulfonylurea receptors to release insulin. On the other hand, either of these can be

combined with any of the insulin sensitizers or the incretin therapies. Use of

combination therapies is commonplace for the control of DM.

Transplantation

Transplantation of the whole pancreas or isolated islet cells is one of the

treatment options for patients with type 1 DM. Islet cell transplantation is

experimental, whereas whole pancreas transplantation usually is performed in

conjunction with renal transplantation. If successful, both forms of transplantation

eliminate or reduce the need for intensive insulin therapy, which has been associated

with severe hypoglycemia, to attain nearly normal glycemic control. Whole pancreas

transplantation can be performed alone, in combination with kidney transplantation or

after kidney transplantation, and its success can be limited by organ availability, graft

failure and morbidity associated with immunosuppressive therapy and surgical

complications.46 Improvements in surgical techniques and immunosuppressive

therapy regimens have helped reduce morbidity and mortality, making this a viable

therapeutic alternative for the treatment of DM. The greatest promise of islet cell

transplantation is the possibility of immunosuppression-free transplantation,

obviating the high rates of adverse effects resulting from the use of

immunosuppressive agents. (Kidambi, 2008)

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2.3 SMOKING

Smokers have greater susceptibility to periodontitis but paradoxically less

gingivitis. The reasons for this are not understood but smoking is known to interfere

with inflammatory and immune reactions probably by activating endothelial and

inflammatory cells inappropriately in the lungs and circulation, and by inducing them

to secrete cytokines and other compounds. Also, nicotine is a vasoconstrictor, though

its effects on the gingiva have proved difficult to measure. Overall, smokers have

greater loss of attachment, early tooth loss and respond less well to treatment.

(Slootweg PJ. 2007).

Smoking is known a risk factor for many diseases, and increasing evidence

suggests that smoking adversely affects periodontal health. The concept that smoking

tobacco may be detrimental to periodontal health is not new. In fact, Pindborg

observed an association between acute necrotizing ulcerative gingivitis and smoking

nearly 60 years ago. Since then, various investigators have attempted to identify the

role of tobacco smoking in the etiology of periodontal diseases. Earlier investigators

had attributed the increased prevalence and severity of periodontal disease seen in

smokers to the greater presence of plaque and calculus than compared to nonsmokers.

However, with the better understanding of the host response, evidence suggests that

the effect of smoking on periodontal status is independent from the plaque index and

oral hygiene of individual. So, this clearly suggests that smoking has a direct

influence on periodontal tissues. (Cawson, 2002)

Smokers have been associated with deeper pockets and greater attachment

loss, more pronounced radiographic evidence of furcation involvement, and increased

alveolar bone loss. There is an established biologic rationale for the negative effect of

smoking on periodontal tissues. It has an immunosuppressive effect on the host,

adversely affecting. host-bacterial interactions, and this alteration may be due to

changes in the composition of subgingival plaque. Smoking may also provide a

conducive environment for some of the periodontopathic species in the plaque and

may be one reason why smoking is a risk factor in periodontal disease development.

(Cawson, 2002)

15

Smoking exerts a strong, chronic, and dose-dependent suppressive effect on

gingival bleeding on probing. Bleeding on probing was less evident in smokers than

nonsmokers, indicating its effect on gingival blood vessels. The mechanism by which

smoking suppresses gingival bleeding is not understood exactly. On the basis of the

observation that smokers may present with a lower level of gingival inflammation, it

has been speculated that the gingival blood flow in smokers may be less in

comparison to non smokers. This would also induce a decreased local host response.

So, smoking is thought mainly to affect the periodontal tissues by way of the vascular

and immunological response of the body. (Slootweg PJ. 2007)

2.3.1 Toxicity of Tobaco Smoking

Tobacco smoking is an addictive habit first introduced into Europe. Smoking

is now recognized as the most important cause of preventable death and disease.

Currently, the most of adult population smoke cigarettes. The number of cigarette

smokers is slowly declining, but those who do smoke are smoking more. However,

nowadays, the smokers are changing to lower-tar brands. Consumption is rising in

developing countries, particularly where tobacco production bring great economic

benefits, and it will probably continue to rise for the foreseable future. (Slootweg PJ.

2007)

Hundreds of different compounds have been identified in tobacco smoke and

some occur in concentrations judged to be harmful to health. Some of these

substances are indisputably carcinogenic, and smoking has been implicated in the

aetiology of oral neoplasia . Tobacco smoke also contains such noxious substances as

benzanthracene and hydrogene cyanide, which undoubtedly have anti-bacterial

properties. Among the substances found in tobacco smoke is the alkaloid nicotine,

which appears to be responsible for the dependence that characterizes the smoking

habit . During smoking, nicotine is rapidly absorbed into the bloodstream, where 30%

remains in its free form. It is highly lipid-soluble and readily penetrates cell

membranes. Nicotine has actions on almost all the organs of the body. (Calsina 2002)

16

Nicotine is considered the most pharmacologically active compound in

tobacco smoke. Most is absorbed through the lung alveoli, but nicotine can also be

absorbed, though more slowly, through the oral mucosa insufficient quantities to have

a pharmacological effect. Nicotine has pronounced effects on the cardiovascular

system. During smoking it increases the heart rate, cardiac output, and blood pressure

by autonomic stimulation, which also effects peripheral vasoconstriction . There is

also evidence that nicotine acts directly on blood vessels and capillaries to produce

vasoconstriction.(Calsina 2002)

For the last few decades, dentists and dental researches have become more

aware of the critical role of smoking on the incidence and severity of periodontal

disease and smoking is now considered a risk factor in periodontal disease. There is a

long history of association between tobacco smoking and periodontal disease. In

1983, Ismail et al. analyzed smoking and periodontal disease and found that after

adjusting for potential confounding variables such as age, oral hygiene, gender and

socioeconomic status, smoking remained a major risk indicator for periodontal

diseases. Locker and Leake found that among Canadians, smoking was one of the

most consistent predictors of periodontal disease experience. (Calsina 2002)

2.3.2 Plaque Formation

The early studies that examined the relation between smoking and oral

cleanlines consistently found that smokers had poorer oral hygiene than non-

smokers . Macgregor measured the area of stained plaque, and the proportion of

gingival margin in contact with plaque in 64 smokers and 64 non-smokers, matched

for age and sex. In both sexes, smokers had significantly more plaque than non-

smokers, and there was a trend towards increased plaque deposits with increasing

cigarette consumption. However, others have reported contrary findings.

Feldman , in the study of periodontal measures, found significantly less plaque in

smokers than in nonsmokers.(Haber 2000)

Bergstrom and Eliasson similarly found no difference in mean Pl index scores

amongst 285 musicians (31% smokers and 69% non-smokers). Bergstrom and Preber

17

studied the rate of plaque growth in 20 dental students, 10 of whom were smokers,

and 10 non-smokers. Again, there was no quantitative difference between the growth

rates of plaque in smokers and non-smokers.(Haber 2000)

Smokers had more calculus than non-smokers, but the effect of smoking was

independent of the amount of calculus present. There have been consistent reports of

more calculus in smokers than in non-smokers from the earliest epidemiological

studies . Some authors reported that significantly more pipe smokers than cigarette

smokers had supragingival calculus. This might be because the pH of pipe smoke is

higher than that of cigarette smoke, and because pipe smokers circulate the smoke

around the mouth, whereas cigarette smoke tends to be inhaled. Moreover, the

smoking cycle is much longer in pipe smokers than in cigarette smokers, causing pipe

smokers to salivate more.(Luzzi 2004)

Reports that calculus formation is more abundant in smokers may be due to

the increased salivary flow rates. There is an increased calcium concentration in fresh

saliva in smokers following smoking . Nicotine affects the exocrine glands by an

initial increase in salivary and bronchial secretions that are followed by inhibition of

the secretions. The calcium phosphates found in supragingival calculus are in the

main derived from the saliva. The organic components may also arise from this

source, the proteins and polypeptides constituting the major fraction. The increased

amount of calculus found in smokers might therefore be due to an effect of tobacco

smoke upon properties of saliva.(Haber 2000)

2.3.3 Smoking and Gingival Inflammation

Gingival inflammation which develops through several phases, so that it

further affects the other parts of parodont, and finally turns into periodontitis. The

changes at the level of blood vessels appear as the first manifestations of gingival

inflammation (initial lesion). There is dilatation of capillaries and increase of blood

flow. In the early lesion, the initial lesion are becoming more marked, inflammatory

infiltrate also increases, which clinically brings about the enlargement of gingiva.

This is followed by changes in the cell population, with increasing in the number of

18

lymphocytes and macrophages. Developed lesion occurs as the consequence of dental

plaque persistence, when some of the bacteria may penetrate into the host tissue.

Perivascular accumulation of chronic inflammatory cells is evident in this stage. The

increasing number of cells in the chronic inflammatory content is followed by the loss

of collagen in the affected connective tissue. However, in this stage, there is still no

loss of the bone or connective tissue

attachment. (Slootweg PJ. 2007)

Smoking does not normally lead to striking gingival changes. A reduction in

clinical signs of gingivitis has been reported in smokers and this effect has been

shown to be independent of plaque levels. Heavy smokers may have greyish

discoloration and hyperkeratosis of the gingiva: an increased number of keratinized

cells has been found in the gingiva of smokers. Changes in the epithelium were

described as keratotic, hyperkeratotic and hyperplastic. Smoking has long been

considered an etiologic factor in acute necrotizing ulcerative gingivitis (ANUG).

Rowland in a series of studies determined that tobacco smoking was a factor in

ANUG and that with the increase in the use of tobacco there was an increase in

frequency of ANUG. The tar in the smoke exerted a direct irritating effect on the

gingiva giving rise to gingivitis, and that nicotine could caused contraction of the

capillaries. (Slootweg PJ. 2007)

Bleeding from the gum margin is an important early symptom of gingivitis,

and gingival bleeding on probing is now widely used in clinical examination as a

means of identifying active lesions in periodontal disease. Although smoking is

known to produce peripheral vasoconstriction, in some subjects this is preceded by

vasodilatation. In any particular instance, the effect produced is probably related to

the degree of inhalation of the tobacco smoke and the rate of nicotine absorption .

Nicotine from cigarette stimulates the sympathetic ganglia to produce

neurotransmitters including catecholamines. These affect the alpha-receptors on

blood vessels which in turn causes vasoconstriction. The vasoconstriction of

peripheral blood vessels caused by smoking can also effect the periodontal tissue as

smokers have less overt signs of gingivitis than nonsmokers and clinical signs of

19

gingival inflammation such as redness, bleeding and exudation are not as evident in

smokers. The vasoconstrictive actions of nicotine may be responsible for the

decreased gingival blood flow, have found less gingival bleeding in smokers than in

non-smokers, due to vasoconstriction of gingival vessels, but may also be attributable

to the heavier keratinization of the gingivae in smokers.(Cawson 2002)

More recently Palmer and colleagues measured gingival blood flow, using a

laser Doppler technique, and their data did not support the view that smoking

compromised blood flow in the periodontal tissues. Tobacco use has also been

associated with reduced permeability of peripheral blood vessels (34). While there

might be some controversy regarding the effect of tobacco consumption on the

gingival vasculature, the clinical relevance is clear. Prolonged and heavy smoking can

reduce gingival bleeding and therefore mask the clinical marker of bleeding on

probing often used by dentists to monitor periodontal health. (Cawson 2002)

2.3.4 Smoking and Periodontal Disease

Periodontitis is defined as "inflammatory disease of supportive tissue of teeth

caused by specific microorganisms which lead to progressive destruction of

periodontal membrane and alveolar bone, with formation of periodontal pockets and

gingival recession. Opinions have been divided about the effect of smoking on

chronic inflammatory periodontal disease. Earlier reviews of the epidemiology of

periodontal disease concluded that smoking was a possible causative factor. (Calsina,

2002)

Few studies have conclusively demonstrated any relevant microbiological

changes in the periodontal tissues attributable to smoking. Some authors using self-

reported smoking data, investigated the relationship between periodontal pathogens

and cigarette consumption. They reported an increased risk for smokers to have

subgingival infection with Porphyromonas gingivalis although this was not found to

be statistically significant. In this same study the investigators found smokers were 3

times more likely to harbor A. actinomycetemcomitans.

20

Many authors investigated the relationship between cigarette smoking and the

prevalence of periodontal pathogens using polymerase chain reaction techniques. In

this study, which included equal numbers of smoking and non-smoking subjects with

generalized aggressive periodontitis, the investigators could find no significant

differences in the occurrence of any of the pathogenic species which included

Porphyromonas gingivalis, Prevotella intermedia, Tanarella forsythensis,

Actinobacillus actinomycetemcomitans and Tanarella denticola. (Calsina, 2002)

Young smokers diagnosed with aggressive forms of periodontitis were shown

to have more affected teeth and a higher mean loss of periodontal attachment than

non-smokers with these conditions. Cigarette smokers had significantly greater

probing depths and bone loss than non-smokers although no difference was found in

relation to tooth mobility. Bergstrom et al. found smokers not only to have

significantly increased probing depths and alveolar bone loss, but also increased tooth

mobility. Some studies have also highlighted the dose relationship between the effect

of cigarette consumption and periodontal attachment loss. Relationship between

alveolar bone loss and tobacco consumption. The findings when they investigated the

relationship between cigarette smoking and bone loss in a group of dental hygienists

were suggestive of an effect on alveolar bone that was independent of plaque levels.

They also reported that this relationship was age-related, suggesting that progression

was more significant in younger smokers.(Feldman, 2008)

Nicotine metabolites can concentrate in the periodontium and their effects

include the promotion of vasoconstriction, and the impairment of the functional

activity of polymorphs and macrophages. The numbers of neutrophils in peripheral

blood are also increased by tobacco use and their migration through capillary walls.

The polymorphonuclear leukocyte (PMN) is the most abundant phagocyte found at

the site of acute inflammation, and probably has an important role in the defence of

the marginal periodontal tissues against bacterial invasion. Corberand found PMN

morbility to be severely depressed by a solution of tobacco-cmoke concentrate,

although phagocytosis and bactericidal activity were not affected. Smokers have

21

higher blood PMN counts than do non-smokers and chemotaxis of PMN s from

smokers was suppressed relative to nonsmokers. (Feldman, 2008)

Alani et al. reported lower levels of both salivary elastase and neutrophils in

the oral cavity in smokers with periodontitis. Their study demonstrated that oral

elastase and neutrophil counts are lower in smokers compared with nonsmokers with

similar levels of periodontal disease. Their results also suggest that these values

return to non-smoking levels after smoking cessation. The passage of fluid through

the junctional epithelium into the gingival crevice is markedly increased in gingival

inflammation and resembles an inflammatory exudate. It contains leukocytes and

plasma proteins, and probably plays an important role in the deffence of the

gingival tissues against bacterial attack. (Cawson, 2002)

Smoking appears to reduce the flow of this gingival fluid exudate. Bergstrom

and Preber studied 10 smokers and 10 non-smokers over a 4-week period during

which the subjects absained from all oral hygiene measures. They found that the

degree of gingival redness,the occurrence of bleeding from gingival margin, and the

gingival fluid exudate all increased during the experimental period. It should also be

noted that a significant genetic component has been identified in relation to

aggressive periodontitis and the combined interaction of cigarette smoking and

various genetic polymorphisms might also contribute to disease status in young

adults.(Cawson, 2002)

2.4 RELATION OF IMMUNE WITH CARIES

2.4.1 Dentinal Fluid and the Deposition of Intratubular Immunoglobulins

Diffusion of noxious stimuli through the dentinal tubules. The finding that

nonvital teeth have a significantly higher bacterial invasion rate than vital human

teeth further supports the protective role of dentinal fluid pressure18

The composition of dentinal fluid is not fully determined, but it is considered

to be serum-derived tissue fluid containing serum proteins and immunoglobulins

(Igs)19. There is a dynamic change of localization and intensity of Igs deposited in

uninfected dentin beneath caries that seems to follow the changes in vascular

22

permeability during inflammation. In the normal pulp, IgG is detected in the

interstitial fluid20,21 and is localized in the dentinal tubules near the predentin22,23.

Beneath shallow caries, IgG1, IgA1, and IgM, but not IgA2, were detected in

uninfected dentinal tubules. In teeth with deep caries, IgG1, IgA1, IgA2, and IgM

were localized in the uninfected dentinal tubules with high intensity23. The possible

protective functions of antibodies in dentinal fluids can be antigen specific or

nonspecific. For example, natural antibodies against Streptococcus mutans in serum 24,25 may diffuse extravascularly into dentinal tubules via the dentinal fluid to react

with bacterial antigens in carious lesions. IgG along with serum-derived proteins such

as albumin or fibrinogen can adhere to dentinal tubules and nonspecifically decrease

the inward diffusion of antigens. On the other hand, products of the degradation of

Igs in dentinal tubules might serve as a nutrient source for the caries pathogens.

Future study of the role of intratubular Igs in the growth of caries bacteria is clearly

needed. The role of complement-mediated bacterial lysis in the initial pulpal response

to caries appears to be limited. Although complement in the dentinal fluid may be

activated by immune complexing of antibodies to bacterial antigens, Gram-positive

bacteria, the predominant flora in shallow caries, are resistant to complement lysis 26,27In fact, the strongest association of caries bacteria and complement is found in

plaque, and is much weaker in the hard portion of carious dentin28 . However,

complement by-products such as C3a and C5a could participate ain the initial

response by recruiting and activating leucocytes.

2.5 INNATE EFFECTOR IMMUNE CELLS IN THE DENTAL PULP

The principal innate effector cells in most tissues are neutrophils,

mononuclear phagocytes (monocytes and macrophages), and innate lymphocytes

including NK cells. In the dental pulp, both T cells and immature DCs are considered

important in immunosurveillance as part of the innate response to caries. Possible

interactions between innate immune cells, cytokines, odontoblasts, and neuropeptides

in normal and reversible pulpitis pulps beneath shallow caries are proposed .

Neutrophils and macrophages are professional phagocytes in innate immune

23

responses. Neutrophils may not be important in reversible pulpitis; only a few

neutrophils were observed in pulpal tissues under shallow caries29,30,31, and the

physical barrier of the dentin prevents close contact between neutrophils and bacteria.

Instead, an intriguing phagocytic role for odontoblasts has been suggested 33,34,35.

Tissue macrophages are generally derived from circulating monocytes and show a

high degree of heterogeneity, which is influenced by their microenvironment. For

instance, alveolar macrophages express high titers of pattern recognition receptors

with high cytokine induction, whereas macrophages from the lamina propria of the

gut exhibit high phagocytic and bactericidal activity but weak production of

proinflammatory cytokines36. Activated macrophages are effective killers that

eliminate pathogens in both innate and adaptive immune responses 32, and are also

important in tissue homeostasis, through the clearance of senescent cells, and in

remodeling and repair of tissue after inflammation. Although the characteristics of

macrophages in the healthy dental pulp have not been examined, VEGF, a potent

inducer of angiogenesis and vascular permeability, is secreted when mouse

macrophages are challenged with LTA. Furthermore, the number of macrophages

increases with the progression of caries and is always higher than that of DCs at all

stages of the caries invasion . Therefore, these monocyte-derived macrophages may

be activated in

2.6. CYTOKINES IN INNATE IMMUNITY

The cytokines secreted by innate immune cells include TNF-_, IL-1, IL-12,

interleukin-18 (IL-18), IFN-_, IL-6, and interleukin-10 (IL- 10) (1). TNF-_ and IL-1

act on vascular endothelial cells at the site of infection to induce the expression of

adhesion molecules that promote extravasation of phagocytes during inflammation.

Rapid induction of IFN-_ production from NK cells and resting T cells by IL-12 and

IL-18 directs the subsequent adaptive cellular immune response toward type 137,38(.

IFN-_ activates not only phagocytes and APCs, but also potentiates many of the

actions of TNF-alpha on endothelial cells, which include T-cell adhesion and

24

extravasation to sites of infection . IFN-_ is also secreted by activated T cells and is

important in the adaptive immune response39 .

IL-10, mainly produced by activated macrophages, inhibits functions of

macrophages and DCs that control innate immune reactions and cell-mediated

immunity. IL-6 is secreted by various cell types in response to microbes or cytokines,

particularly IL-1 and TNF-_. IL-6 stimulates the synthesis of acute-phase proteins

and neutrophils from bone marrow progenitors. Small amounts of mRNA expression

of IL- 1_, IL-1_, IL-4, IL-6, IL-10, IL-18, and IFN-_ were detected in normal or

asymptomatic pulps40,41.Future studies of comprehensive cytokine gene expression in

pulps from normal and enamel caries teeth are warranted to understand their role in

the initial immune response.

2.6.1. Neuropeptides, Neurogenic Inflammation, and Caries

Sensory neuropeptides such as calcitonin gene-related peptide (CGRP),

substance P (SP), and neurokinin A (NKA) are detected in normal human pulps, with

a higher concentration of CGRP than SP.

Figure 2.2 Caries and Immune system

25

NKA. Arterioles in the dental pulp are heavily innervated by CGRPand SP-

containing fibers42. Significant increases in innervation (nerve sprouting) and

neuropeptide concentration were observed following pulpal injury. Increased

concentrations of neuropeptides were detected in painful pulpitis samples43,44. In fact,

SP expression was significantly greater in painful pulpitis specimens45 than in grossly

carious asymptomatic specimens. Neuropeptides from sensory nerves participate in

neurogenic inflammation46,47

These vasoactive neuropeptides, released upon stimulation via an axon reflex

mechanism, cause increased pulpal blood flow and vascular permeability. For

example, CGRP is the prime mediator of neurogenic vasodilatation of arterioles. SP

and NKA are the main messengers of postcapillary venular permeability. Although

CGRP per se does not cause protein leakage, it is able to enhance the exudative

response to SP and NKA. The end result of neurogenic inflammation is a transient

increase of interstitial tissue pressure and outward flow of dentinal fluid, which is

considered protective as discussed above. If the pulp is healthy, excess interstitial

fluid resulting from transient neurogenic inflammation will be absorbed into the

circulatory or lymphatic system via edema-preventing mechanisms. If pulp is not

capable of resolving the increased tissue pressure, increased levels of neuropeptides

and persistent edema could contribute to pain and local necrosis. The unique

intratubular localization of nerve fibers and their involvement in the outward flow of

dentinal fluid from neurogenic inflammation make the neural component an

importantpart of the initial vascular response to caries.

2.6.2. T Cells in Innate Immunity in the Dental Pulp

The predominant T-cell type in the normal pulp is the memory CD8_ T cell,

but its functions in the normal pulp remain undefined. The well-known functions of

CD8_T cells are to kill virusinfected or transformed host cells via induction of

apoptosis or perforin production, and to produce IFN-_ to augment phagocytosis. The

mech-anism that preferentially attracts CD8_ T cells in normal healthy pulp was not

understood until recently. Studies demonstrated that CD8_ T-cells exhibited higher

26

migratory capacity across endothelial cells than CD4_T cells49,50, and memory CD8_T

cells can migrate into tissue sites distant from the site of their initial antigen

challenge51,52

Therefore, an immune surveillance role of CD8_ T cells was proposed 53,54.

The recruitment of T cells to non inflammed human skin is partially from a basal

expression of E-selectin, chemokine CCL17, and intercellular adhesion molecule-1

(ICAM-1) in dermal vessels55. Interestingly, endothelium in the healthy dental pulp

exhibits low levels of E-selectin and P selectin56. Whether CD8_T cells in normal

pulp tissue are part of the immune surveillance system remains to be determined.

Figure 2.3 Immune surveillance system

2.7 TUBERCULOSIS

Tuberculosis, or TB, is an infection caused by a bacteria that usually involves

the lungs (pulmonary TB) but could affect other parts of the body (extra-pulmonary

TB); for example, brain, lymph nodes, kidneys, bones, joints, larynx, intestines or

eyes. TB infection may result after close contact with a person who has TB disease.

TB infection is determined by a significant reaction to the Mantoux skin test with no

27

symptoms of TB and no TB bacteria found in the sputum. Sputum is mucous or

phlegm coughed up from the lungs. TB disease is characterized by the appearance of

symptoms, a significant reaction to the Mantoux skin test and identification of TB

bacteria. TB may last for a lifetime as an infection, never developing into disease.

However, individuals with TB infection are at considerable risk of developing TB

disease, particularly during the first year after acquiring the infection. Additionally,

individuals with weakened immune systems, such as people with HIV, are at high

risk of developing TB disease if TB infection is untreated.

2.7.1 Spread Of Tb

M. Tuberculosis is carried in airborne particles, called droplet nuclei, of 1–5

microns in diameter. Infectious droplet nuclei are generated when persons who have

pulmonary or laryngeal TB disease cough, sneeze, shout, or sing. Depending on the

environment, these tiny particles can remain suspended in the air for several hours.

M. Tuberculosis is transmitted through the air, not by surface contact, clothes, dishes,

floors or furniture. Transmission occurs when a person inhales droplet nuclei

containing M. Tuberculosis, and the droplet nuclei traverse the mouth or nasal

passages, upper respiratory tract, and bronchi to reach the alveoli of the lungs.

28

Figure 2.4. Transmission of Tuberculosis in human

2.7.2 The Difference Between Tb Infection And Tb Disease

Latent TB infection (LTBI) does not cause a person to feel sick, and there are

no symptoms. Tuberculin skin tests (TSTs) or interferon gamma release assay

(IGRA) blood tests are used to diagnose LTBI. A positive result means that TB

infection is present. Treatment for LTBI is effective in preventing persons with LTBI

from developing TB disease. Nine in ten people with a normal immune system with

LTBI will never develop TB disease. However, one in ten of those infected will

develop TB disease at some time in their lives, though the risk is lower if they receive

preventive therapy. About half of these will develop TB disease within the fi rst 2

years after they become infected. There is no way to determine which people with

LTBI will later get sick with TB disease. The following persons are at high risk for

progressing from LTBI to TB disease:

• Persons infected with HIV and other diseases, such as diabetes and renal condi-tions

that require dialysis, that weaken the immune system

• Persons infected with M. tuberculosis within the previous 2 years

• Infants and children <4 years old

29

• Persons who receive medical treatments, such as certain cancer treatments or pro-

longed steroid use, that weaken the immune system

• Persons with a history of untreated or inadequately treated TB disease

2.7.3 TB Disease

Most TB disease occurs in the lungs, but about 15% occurs in other parts of

the body (e.g., bone, eye, and brain). General symptoms of pulmonary TB include:

• Cough

• Fever

• Night sweats

• Fatigue

• Unexplained weight loss

• Hemoptysis (bloody sputum)

Without treatment, a person with TB disease will get sicker. A person with

untreated pulmonary TB disease of the lungs or larynx will also become more

contagious. Untreated TB can become a life-threatening disease; however, with

effective and complete treat-ment,TB can be cured. A person with a cough lasting 3

or more weeks along with any other symptoms of TB disease (fever, night sweats,

fatigue, unexplained weight loss, hemoptysis [ bloody spu-tum]) should be evaluated

by a healthcare provider as soon as possible. If TB disease is diagnosed or suspected,

treatment will be prescribed.

2.7.4 When TB is Infectious

With rare exceptions, TB is infectious only when it occurs in the lungs or

larynx. TB that occurs elsewhere in the body is usually not infectious, unless the

person also has TB in the lungs or larynx at the same time. In general, a person with

suspected or confi rmed TB disease of the lungs or larynx should be considered

infectious until the person has :

30

1. Had three negative acid-fast bacilli (AFB) sputum smear results obtained 8-24

hours apart, with at least one being an early morning specimen (an AFB sputum

smear is a type of medical test used in the diagnosis of TB); and

2. Shown to have clinical improvement as a result of antituberculosis treatment (for a

minimum of 2 weeks) that is based on susceptibility results,

3. Been determined to be noninfectious by a physician knowledgeable and experi-

enced in managing TB disease. A person who has met all three of the above

conditions must continue to take TB medications as prescribed and continue to

receive medical care for TB.

2.7.5 Pathogenesis Of Tb

Route and site of infection : Mycobacterium tuberculosis is an obligatory

aerobic, intracellular pathogen, which has a predilection for the lung tissue rich in

oxygen supply. The tubercle bacilli enter the body via the respiratory route. The

bacilli spread from the site of initial infection in the lung through the lymphatics or

blood to other parts of the body, the apex of the lung and the regional lymphnode

being favoured sites. Extrapulmonary TB of the pleura, lymphatics, bone,

genitourinary system, meninges, peritoneum, or skin occurs in about 15 percent of

TB patients.

Events following entry of bacilli: Phagocytosis of M.tuberculosis by alveolar

macrophages is the first event in the host-pathogen relationship that decides outcome

of infection. Within 2 to 6 week of infection, cell-mediated immunity (CMI)

develops, and there is an influx of lymphocytes and activated macrophages into the

lesion resulting in granuloma formation. The exponential growth of the bacilli is

checked and dead macrophages form a caseum. The bacilli are contained in the

caseous centers of the granuloma. The bacilli may remain forever within the

granuloma, get reactivated later or may get discharged into the airways after

enormous increase in number, necrosis of bronchi and cavitation.

Fibrosis represents the last-ditch defense mechanism of the host, where it

occurs surrounding a central area of necrosis to wall off the infection when all other

31

mechanisms failed. In our laboratory, in guineapigs infected with M. tuberculosis,

collagen, elastin and hexosamines showed an initial decrease followed by an increase

in level. Collagen stainable by Van Gieson’s method was found to be increased in the

lung from the 4th week onwards.

2.7.6 Evasion of host immune response by M. Tuberculosis

M. Tuberculosis is equipped with numerous immune evasion strategies,

including modulation of antigen presentation to avoid elimination by T cells. Protein

secreted by M. Tuberculosis such as superoxide dismutase and catalase are

antagonistic to ROI. Mycobacterial components such as sulphatides, LAM and

phenolic glycolipid I (PGL-I) are potent oxygen radical scavengers. M. Tuberculosis

infected macrophages appear to be diminished in their ability to present antigens to

CD4+ T cells, which leads to persistent infection. Another mechanism by which

antigen presenting cells (APCs) contribute to defective T cell proliferation and

function is by the production of cytokines, including TGF-β, IL-10 or IL-6. In

addition, it has also been reported that virulent mycobacteria were able to escape

from fused phagosomes and multiply.

2.7.7 Host immune mechanisms in TB

Innate immune response: The phagocytosis and the subsequent secretion

of IL-12 are processes initiated in the absence of prior exposure to the antigen and

hence form a component of innate immunity. The other components of innate

immunity are natural resistance associated macrophage protein (Nramp),

neutrophils, natural killer cells (NK) etc. Our previous work showed that plasma

lysozyme and other enzymes may play an important role in the first line defense, of

innate immunity to M. tuberculosis.The role of CD-1 restricted CD8+ T cells and

non-MHC restricted T cells have been implicated but incompletely understood.

Nramp

32

Nramp is crucial in transporting nitrite from intracellular compartments such

as the cytosol to more acidic environments like phagolysosome, where it can be

converted to NO. Defects in Nramp production increase susceptibility to

mycobacteria. Newport et al 44 studied a group of children with susceptibility to

mycobacterial infection and found Nramp1 mutations as the cause for it. Our

laboratory study on pulmonary and spinal TB patients and control subjects

suggested that NRAMP1 gene might not be associated with the susceptibility to

pulmonary and spinal TB in the Indian population.

Neutrophil

Increased accumulation of neutrophil in the granuloma and increased

chemotaxis has suggested a role for neutrophils 46. At the site of multiplication

of bacilli, neutrophils are the first cells to arrive followed by NK cells, γ / δ cells and

α / β cells. There is evidence to show that granulocyte-macrophage colony

stimulating factor (GM-CSF) enhances phagocytosis of bacteria by neutrophils.

Human studies have demonstrated that neutrophils provide agents such as defensins,

which is lacking for macrophage-mediated killing. From our source have shown that

neutrophils can bring about killing of M. tuberculosis in the presence of calcium

under in vivo conditions.

Natural killer (NK) cell

NK cells are also the effector cells of innate immunity. These cells may

directly lyse the pathogens or can lyse infected monocytes. In vitro culture with

live M. tuberculosis brought about the expansion of NK cells implicating that they

may be important responders to M. Tuberculosis infection in vivo. During early

infection, NK cells are capable of activating phagocytic cells at the site of

infection. A significant reduction in NK activity is associated with multidrug-resistant

TB. NK activity in BAL has revealed that different types of pulmonary TB are

accompanied by varying degrees of depression. IL-2 activated NK cells can bring

about mycobactericidal activity in macrophages infected with M . avium complex

33

(MAC) as a non specific response. Apoptosis is a likely mechanism of NK

cytotoxicity. NK cells produce IFN-γ and can lyse mycobacterium pulsed target cells.

From the research demonstrate that lowered NK activity during TB infection is

probably the effect and not the cause’for the disease as demonstrated by the follow up

study. Augmentation of NK activity with cytokines implicates them as potential

adjuncts to TB chemotherapy.

The Toll-like receptors (TLR)

The recent discovery of the importance of the TLR protein family in immune

responses in insects, plants and vertebrates has provided new insight into the link

between innate and adaptive immunity. From the research Showed that a human

homologue of the Drosophila Toll protein signals activation of adaptive immunity.

The interactions between M. tuberculosis and TLRs are complex and it appears that

distinct mycobacterial components may interact with different members of the TLR

family. M. Tuberculosis can immunologically activate cells via either TLR2 or TLR4

in a CD 14-independent, ligand-specific manner.

2.7.8 Acquired immune response

Humoral immune response: Since M. tuberculosis is an intracellular pathogen,

the serum components may not get access and may not play any protective role.

Although many researchers have dismissed a role for B cells or antibody in protection

against TB, recent studies suggest that these may contribute to the response to

TB. Mycobacterial antigens inducing humoral response in humans have been studied,

mainly with a view to identify diagnostically relevant antigens. Several protein

antigens of M. Tuberculosis have been identified using murine monoclonal

antibodies. The immunodominant antigens for mice include 71, 65, 38, 23, 19, 14 and

12kDa proteins. The major protein antigens of M. leprae and M. Tuberculosis have

been cloned in vectors such as Escherichia coli. Not all the antigens identified based

on mouse immune response were useful to study human immune response. In our

laboratory a number of M. Tuberculosis antigens have been purified and used for

34

diagnosis of adult and childhood TB. Combination of antigens were also found to be

useful in the diagnosis of HIV-TB. Detection of circulating immune complex bound

antibody was found to be more sensitive as compared to serum antibodies. The

purified antigens were evaluated for their utility in diagnosing infection.

2.7.9 Cellular Immune Response

T cells

M. tuberculosis is a classic example of a pathogen for which the protective

response relies on CMI. In the mouse model, within 1 week of infection with virulent

M. tuberculosis, the number of activated CD4+ and CD8+ T cells in the lung draining

lymphnodes increases. Between 2 and 4 week post-infection, both CD4+ and CD8+ T

cells migrate to the lungs and demonstrate an effector/memory phenotype

(CD44hiCD45LoCD62L-); approximately 50 percent of these cells are CD69+. This

indicates that activated T cells migrate to the site of infection and are interacting

with APCs. The tuberculous granulomas contain both CD4+ and CD8+ T cells that

contains the infection within the granuloma and prevent reactivation.

CD4 T cells

M. tuberculosis resides primarily in a vacuole within the macrophage, and

thus, major histocompatibility complex (MHC) class II presentation of

mycobacterial antigens to CD4+ T cells is an obvious outcome of infection. These

cells are most important in the protective response against M. tuberculosis. Murine

studies with antibody depletion of CD4+ T cells, adoptive transfer, or the use of gene

disrupted mice have shown that the CD4+ T cell subset is required for control of

infection.

In humans, the pathogenesis of HIV infection has demonstrated that the loss

of CD4+ T cells greatly increases susceptibility to both acute and reactivation TB. The

primary effector function of CD4+ T cells is the production of IFN-γ and possibly

other cytokines, sufficient to activate macrophages. In MHC class II-/- or CD4-/-

mice, levels of IFN-γ were severely diminished very early in infection. NOS2

35

expression by macrophages was also delayed in the CD4+ T cell deficient mice, but

returned to wild type levels in conjunction with IFNγ expression. In a murine model

of chronic persistent M. tuberculosis infection77, CD4 T cell depletion caused rapid

re-activation of the infection. IFN-γ levels overall were similar in the lungs of CD4+

T cell-depleted and control mice, due to IFN γ production by CD8+ T cells.

Moreover, there was no apparent change in macrophage NOS2 production or activity

in the CD4+ T cell-depleted mice. This indicated that there are IFN-γ and NOS2-

independent, CD4+ T cell-dependent mechanisms for control of TB. Apoptosis or

lysis of infected cells by CD4+ T cells may also play a role in controlling infection.

Therefore, other functions of CD4+ T cells are likely to be important in the protective

response and must be understood as correlates of immunity and as targets for vaccine

design.

CD8 T cells

CD8+ cells are also capable of secreting cytokines such as IFN-γ and IL-4 and

thus may play a role in regulating the balance of Th1 and Th2 cells in the lungs of

patients with pulmonary TB. The mechanism by which mycobacterial proteins gain

access to the MHC class I molecules is not fully understood. Bacilli in

macrophages have been found outside the phagosome 4-5 days after infection, but

presentation of mycobacterial antigen by infected macrophages to CD8 T cells can

occur as early as 12 h after infection. Reports provide evidence for a

mycobacteria-induced pore or break in the vesicular membrane surrounding the

bacilli that might allow mycobacterial antigen to enter the cytoplasm of the infected

cell.

γ/δ T-cells in TB

The role of γ/δ T cells in the host response in TB has been incompletely

worked out. These cells are large granular lymphocytes that can develop a dendritic

morphology in lymphoid tissues; some γ/δ T cells may be CD8+. In general, γ/δ T

cells are felt to be non-MHC restricted and they function largely as cytotoxic T cells.

36

Animal data suggest that γ / δ cells play a significant role in the host

response to TB in mice and in other species, including humans. M. tuberculosis

reactive γ / δ T cells can be found in the peripheral blood of tuberculin positive

healthy subjects and these cells are cytotoxic for monocytes pulsed with

mycobacterial antigens and secrete cytokines that may be involved in granuloma

formation. Studies demonstrated that γ/δ cells were relatively more common (25 to

30% of the total) in patients with protective immunity as compared to patients with

ineffective immunity. Our study in childhood TB patients showed that the

proportion of T cells expressing the γ/δ T cell receptor was similar in TB patients and

controls. Thus γ/δ cells may indeed play a role in early immune response against TB

and is an important part of the protective immunity in patients with latent infection.

2.8 MALNUTRITION

The World Health Organization defines malnutrition as "the cellular

imbalance between the supply of nutrients and energy and the body's demand for

them to ensure growth, maintenance, and specific functions." Put otherwise,

malnutrition may be seen as the antithesis to good nutrition or ‘well-nutrition’.

2.8.1 Defining BMI

Except for extremely muscular individuals, BMI is a relatively accurate

measure of an individual’s body fat content. The higher a person’s BMI, the greater

the health risks. For example, conditions such as diabetes, hypertension,

cardiovascular disease, and increased cancer risk are directly related to the degree of

obesity as measured by BMI. Conversely, low BMI (less than 19 kilograms per

square meter [kg/m²]) is also associated with increased morbidity and mortality; the

lower the BMI, the greater the risk.

BMI is calculated using a person’s height and weight and the following

equation: BMI = (weight in pounds) ÷ 2.2 = kg/m [height in inches ÷ 39.6]².

37

Although BMI is a clean, precise mathematical calculation, the concept of

malnutrition is inexact and somewhat subjective. First, there are no authoritative

definitions of malnutrition or the severity of malnutrition, although some are expected

soon from the American Dietetic Association. Furthermore, the diagnosis of

malnutrition is a complicated, multi factorial clinical determination that requires more

than simply finding a low albumin or pre albumin.

Malnutrition includes such criteria as:

»»Physical findings like emaciation, cachexia or muscle/adipose wasting, or atrophy

(e.g., temporal wasting, thenar atrophy)

»»Presence of risk factors such as cancer, chemotherapy, AIDS, alcoholism, end-

stage disease, mal absorption syndromes, or other gastrointestinal and pancreatic

disorders

»»Biochemical markers including low albumin, pre albumin, cholesterol, transferin,

blood urea nitrogen/creatinine ratio, and/or anemia

»»Recent or progressive weight loss, low body weight, or low BMI

Table 2.2 Level condition of BMI for human

The ultimate diagnosis of malnutrition and its severity depends upon the

physician’s clinical judgment based on a constellation of the above findings in each

individual case. No particular finding is required or definitive. As summarized in the

38

“General classification of malnutrition” table, the severity of malnutrition should be

classified as mild, moderate, or severe. Therefore, “unspecified” malnutrition really

has no clinical meaning, but it is a coding convention used when the severity of

malnutrition has not been documented by a provider.

Table 2.3 General classification of malnutrition condition

2.8.2 Malnutrition Leads to a Vicious Cycle of Immune Dysfunction and

Diseases

Although infectious illnesses vary in severity and duration, they all put a

physiological and biochemical burden on the immune system. In order to withstand

this metabolic challenge, the function of cells building the immune system needs to

be supported by a continuous supply of nutrients.

Malnutrition, unhealthy diets deficient in micronutrients, and micronutrient

imbalances can disrupt the function of various immune system components. This

weakens immune defense, decreasing its effectiveness in the elimination of pathogens

and making us vulnerable to various diseases. In addition, the illness itself, whether

symptomatic or asymptomatic, is always accompanied by the loss of many nutrients

in the body, which further aggravates already existing nutrient deficiencies.

39

If these nutrient losses are not adequately and quickly addressed, the vulnerability to

other diseases increases, thereby triggering a spiral of diseases often impossible to

control.

Figure 2.5 The Leading Cause of Immune Deficiency Diseases; Malnutrition triggers

2.8.3 Nutrients Support All the Critical Steps of Our Immunity

Good nutrition and an optimum supply of micronutrients are important in

supporting various cellular functions critical for an effective immune response.

Among them, nutrients are needed to support:

• Non-specific defense components, which are needed to defend against any type of

infection. These include the synthesis of interferon and the optimum function of

phagocytic cells.

• Protective anti-microbial barriers created by the skin, mucus membranes, tears,

saliva, gastric juice, etc. An optimum supply of nutrients, in particular those

supporting protein synthesis, is also important for normalizing serum proteins, some

of which function as anti-microbial agents (e.g. lysozyme).

• Production of antibodies and optimization of cell-mediated immunity. Based on its

functions, the immune system is divided into the cellular system and humoral system.

40

The humoral system consists of B-lymphocytes, plasma cells, and specific immune

globulins that produce antibodies. The cellular system is the major defense

mechanism that the body uses to combat various viral and bacterial infections, as well

as fungal and parasitic diseases. This cell-mediate immunity is built and depends on

the function of T-lymphocytes – a subset of white blood cells produced in the bone

marrow – that requires the proper function of the thymus for their functional maturity.

Impaired T-lymphocyte response has been associated with general protein

malnutrition, which is usually accompanied by a deficiency of vitamins and other

micronutrients in the body.

2.8.4 Older people may be especially vulnerable to malnutrition

The prevalence of malnutrition rises with age. Many changes associated with

the process of ageing may exacerbate malnutrition – although malnutrition is by no

means an inevitable facet of ageing. Older patients may be at greater risk of not being

able to recover from malnutrition. Malnutrition may be secondary to certain

conditions (disease-related malnutrition), such as cancer, arthritis, diabetes, or

emphysema. It is also a condition in its own right. Common risk factors for

malnutrition are summarised below.

Calcium, vitamin D, vitamin B12 and folate are micronutrients frequently

under consumed in older people. These deficiencies induce a decreased immune

response that could negatively impact on quality of life and health status.

41

Table 2.4 Risk factors for malnutrition

2.8.5 Physical factors and malnutrition

Weight loss can result from physical factors such as dysphagia, poor dentition,

anorexia, altered taste and smell, and constipation (Table 1). Poor chewing and

swallowing ability can significantly impact the type and amount of food consumed.

Texture modified diets rarely have the same nutritional quality of a full diet, which

can send dysphagic patients on a continuous downward spiral leading to protein

energy malnutrition.

42

2.8.6 Social factors and malnutrition

Poor appetite, inappropriate food choices, food aversion, decreased energy

and inability to self feed can result from social factors and can place individuals at

risk of malnutrition. Malnutrition is more common for institutionalized elderly than

independently living elderly – with more than 50% of people living in hospitals or

nursing homes affected.15 Obtaining adequate vitamin D can be a challenge for

institutionalized and house bound older people who have limited sun exposure.

Living or eating alone causes older people to eat less and increases their risk

of compromised nutritional status, with men being particularly vulnerable. Many

older people living alone exist on a ‘tea and toast’ diet that is low in energy, protein

and micronutrients. Taste changes often result in a dislike and avoidance of nutrient

dense foods (eg. lean meat). These factors place the individual at a higher risk of

malnutrition and micronutrient deficiencies.

Restrictive diets due to personal preference, cultural or religious beliefs, or for

medical purposes (including low cholesterol, low salt, vegetarian, kosher and halal

diets) can increase the risk of protein malnutrition and micronutrient deficiency as

they remove or limit common high protein foods.

2.8.7 Screening for malnutrition

As often the first point of contact of patient care in the community, general

practitioners have the opportunity to identify and assess risk factors leading to

compromised nutritional status in elderly patients. No one standard test or

biochemical marker is used to indicate or diagnose malnutrition in the elderly. A

combination of medical, social, anthropometric, biochemical, clinical and dietary data

are required to thoroughly assess, monitor, evaluate and determine appropriate

nutritional therapy.

The Subjective Global Assessment (SGA) tool is the ‘gold standard’ for

assessing malnutrition in hospitalised elderly due to its simplicity, accuracy and

reliability. The Mini Nutritional Assessment Short Form (MNA-SF) is well validated

for early detection of malnutrition in community dwelling elderly people.

43

Weight alone is inadequate in measuring nutritional status in older people as a

stable weight may mask changes in body composition. Adipose tissue replaces

muscle mass in normal aging (Figure 1) with greater rates being likely in a sick,

elderly population. A body mass index (BMI) range of 22–27 kg/m2 can be used to

determine a healthy weight range in older people. Although age related changes in

body composition can make BMI an unreliable indicator of malnutrition, a BMI <20

kg/m2 is a reasonable threshold to define a high risk of malnutrition.

Figure 2.6 Body composition changes in healthy adult males

2.9 PERIODONTAL DISEASE

Periodontal disease, the most common disease in the world and the leading

cause of tooth loss in adults is a chronic infection that slowly attacks and destroys the

gums and bone that support the teeth (Hafernick, 2000). Symptoms associated with

periodontal disease are sore, inflamed gums that have a tendency to bleed.

Estimations have shown that at least 75 percent of the adult population in America

has some form of periodontal disease (Scheffler, 2000). Adults are not the only group

susceptible to the disease; one-third of children ages 6-11 and two-thirds of

adolescents have some form of periodontal disease (periodontal).

The term periodontal disease usually refers only to plaque related

inflammatory disease of the dental supporting tissues. A wide variety of diseases of

44

the oral mucosa can also affect the gingival occasionally, so that conditions as diverse

as tuberculosis or lichen planus can produce lesions in this area. Such conditions do

not play any significant part in the development of periodontal disease in its

commonly accepted sense. (Cawson, 2002)

Periodontal disease is caused by more than 200 species of bacteria. These

bacteria form masses of sticky film called plaque, which is able to adhere to the

surface of teeth and gums. The bacteria are then nourished by the consumption of

foods, especially sweets. The sugars are metabolized by the bacteria which causes the

secretion of acids, enzymes, and other soft tissue irritants and bone destroyers. When

left untreated, the bacteria begin to spread to areas that are hard to reach with normal

brushing and flossing; for instance, areas below the gum line, thus causing

periodontal disease (periodontal)(Bathesda,2001)

Chronic gingivitis is, with few exceptions, the preliminary stage to the

development of chronic periodontitis, but clinically no sharp dividing line can be

drawn between chronic gingivitis and the onset of periodontitis. Nevertheless, the

distinction is important in that chronic gingivitis can generally be cured by plaque

control. By contrast, loss of bone and tooth support due to chronic periodontitis is

largely irreversible. (Cawson, 2002)

The bone of the alveolar crest shows resorption as demonstrated by the

presence of Hownship’s lacunae sometimes still containing multinucleated

osteoclasts. The epithelial attachment that normally lies in contact with the tooth

enamel has moved downwards to be partly opposite the enamel and the root

cementum or even entirely opposite the root cementum. Resorption of bone and

downward displacement of the epithelial attachment may continue until there is

insufficient periodontal tissue left for adequate fixation of the tooth in the jaw. Caries

may add to the damage caused by periodontitis by attacking the cementum covering

the exposed root surface.( Slootweg PJ, 2007)

45

Figure 2.7 Type of periodontal Disease

46

SMOKING DECREASING IMMUNE SYSTEMDECREASING IMMUNE SYSTEM

ARB (+)

TBC

PLAQUE

BACTERIA

SIGH IN BLOOD VESSEL

TOKSIN OF BACTERIA

INTERRUPTED INSULIN SECRETION

DAMAGE OF PERODONTAL TISSUE

INFLAMMATION OF PERODONTAL TISSUE

DISEASE PERIODONTAL

SNACKINGDIABETESMELITUS (DM)

CARBOHYDRATE BACKWARD IN TEETH

CARIES

HOARD OF FOOD/ OVERFLOW

MALNUTRITION

WEIGHT LOSSDECREASING IMUN SYSTEM

CHAPTER 3

CONCEPTUAL MAPPING

47

CHAPTER 4

DISCUSSION

In this case, a man with 50 years old was being treated in hospital, reffered to

dental clinic for dental treatment especially molar treatment that had cavity and

continous pain and also bleeding. The patient had shortness of breathing for the last 2

weeks with continous chest pain and chronic cough for more than 1 month. Patient

had fever for the last 2 weeks especially in the evening, sweat in the night, loss of

appetite and loss of weight.

Hypothesis : Tubeculosis, Periodontal Disease, Diabetes Mellitus

The Physical Examination Result :

The patient’s profile :

- Work as driver for urban transportation

- Love to eat snack

- A Smoker

- Age : 50 Years old ( Productive’s age level )

Medical’s History :

Was being treated in hospital

- Shortness of breathing for the last 2 weeks with continous chest pain and chronic

cough for more than 1 month.

- Had fever for the last 2 weeks especially in the evening, sweat in the night, loss of

appetite and loss of weight.

Extra Oral : Examination test result for Lymph Gland was normal

Body weight = 46 kg and 160 cm tall, the normal weight should 60 kg

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Intra Oral :

- Oral Hygiene : bad

- mucosal : looks pale

-Gingival : pain and bleed easily for long time

Status localist:

Blood Glucose = 370 mg/dl

Blood Pressure = 130/80 mmHg ( level Pre-Hipertensi )

Body Temperature = 37,6 0C

Acid Resistant Bacteria Test ( ARB ) = +

The Teeth 16 with deep cavity and feels so pain

Pocket with periodontal probe :

Buccal and lingual = 5 mm

mesial and distal = 5 mm

Panoramic x-ray picture :

Visible tooth 16 with crest alveolar bone resorption and widening of the periodontal

space

From this case, we have found one of the main reasons for this to happen is

smoking. A burning cigarette is a chemical plant that produces over 6700 chemical

components and 4000 have been identified. the component particles are generally

cigarette tar and nicotine. Pulmonary TB is the main entry of germs is by inhalation

of airborne droplets. Only 1-5 micron droplet size that can pass through or penetrate

the airway mucociliary system so as to achieve and lodged in the bronchioles and

alveoli. At this point, the TB bacilli multiply and spread through the lymph and

blood flow without resistance from the host because there is no early immune. Non-

specific inflammatory reaction occurs in the alveoli. Macrophages in the alveoli will

phagosites but most of the TB bacilli are able to kill him so that the bacilli in

49

macrophages can generally survive and breed. TB bacilli are spread through lymph

channels that reach the regional lymph nodes via the blood stream to reach the

various organs of the body as well as a transfer of antigen to lymphocytes. Before

imunity specific form of TB bacilli in the field on lung, kidney, bone and brain easier

to breed. Specific imunity formed is usually strong enough to inhibit further breeding

TB bacilli that TB lesions will heal and no clinical symptoms. TB bacilli during

primary infection takes place nested in the hilar lymph nodes and mediastenum and

can be nested in other lymph nodes. The infection in the gland may take into active

TB within a few years later or never becomes active.

Hipersensitivity some components of M. Tb can be seen in the tuberculin skin

test which usually occurs 2-10 weeks after infection, when it occurs in a cell-

mediated immune response. After the first infection of TB bacilli spread throughout

the body one day will grow and cause a disease. Immunologic response against TB

infection in the form of imunity cellular (cell-mediated immunity) and slow type

hypersensitivity (delayed-type hypersensitivity) an immune response is weak or fails

then there is active TB in individuals infected with M. Tb. Imunity cell causes T

lymphocyte proliferation-Cluster of Differentiation (CD4) and local cytokine

production in response to antigens released M. Tb helper1 T lymphocytes (Th1) T

lymphocytes activate macrophages whereas helper2 (Th2) adds humoral antibody

synthesis and then produce cytokines necrosing factor a (TNF-a) and interferon-g

(INFg). These cytokines will draw blood monocytes and activate TB lesions.

Activated monocytes or macrophages and lymphocytes TCD4 produce lysosomal

enzymes, oxygen radicals, nitrogen intermediate and interleukin-2 (IL-2). Imunity

activate macrophages thereby inhibiting cell replication slow type hipersensitivity

basil inhibit replication by destroying macrophages containing bacilli have not been

active and M. Tuberculosis, also isolate active lesions caused M. Tuberculosis

became dormant, tissue damage, fibrosis, and scarring. Macrophages are activated by

cellular imunity not able to prevent the proliferation of cells in cavity extra basil.

Antigen bacilli released in mass melt. Toxicity dinsing antigen to cause the nearby

airways become necrotic, broken, and it has spread formation cavity basil M.

50

Tuberculosis and mass the liquid to other parts of the lung. Then the mass melting

cause disease to take hold. tissue damage caused by the cellular response to bacillus

M. imunity Tuberculosis or toxin.

On the other side, the smoking effect has some another problems for his body.

Mutans streptococci participate in the formation of biofilms on tooth surfaces. These

biofilms are known as dental plaque(s). Sucrose is required for the accumulation of

mutans streptococci. Initial attachment of mutans streptococci to tooth surfaces, this

attachment is thought to be the first event in the formation of dental plaque. The

mutans streptococcal adhesin (known as antigen I / II) interacts with - galactosides in

the saliva - derived glycoprotein constituents of the tooth pellicle. Accumulation of

mutans streptococci on tooth surfaces in the presence of sucrose, glucosyltransferases

enzymes (GTFs) synthesize extracellular glucans from glucose (after the breakdown

of sucrose into glucose and fructose), and this is thought to be the second event in the

formation of dental plaque. The mutans streptococcal Glucan - binding protein (GBP)

is a receptor - like protein that is distinct from GTFs, and it specifically binds glucans.

GTFs themselves also have a glucan - binding domain and can therefore also function

as receptors for glucans. Mutans streptococci bind pre - formed glucans through GBP

and GTFs, and this gives rise to aggregates of mutans streptococci. Acid production

by mutans streptococci. The metabolism of various saccharides (including glucose

and fructose) by the accumulated bacterial biofilm results in the production and

secretion of considerable amounts of the metabolic end - product lactic acid, which

can cause demineralization of the tooth structure when present in sufficient amounts

in close proximity to the tooth surface. This is thought to be the third event in the

formation of dental plaque, and it eventually results in a carious lesion.

Smoking and its relation to dental caries is may be due to high proportion of

sugar in some type of smokeless tobacco. Smoking increases thiocyanate level in

saliva. Thiocyanate, a normal constituent of saliva, was found to have a possible

caries inhibiting effect. Smoking is associated with lower salivary cystatin activity

and output of cystatin C during gingival inflammation. Cystatins are thought to

contribute to maintaining oral heath by inhibiting certain proteolytic enzymes. In

51

addition, studies have confirmed from earlier results that there were no significant

differences in salivary flow rates between smokers and non-smokers. The decreased

buffering effect of smoker’s saliva and the higher number of lactobacilli and S.

mutans group may indicate an increased susceptibility to caries.

Saliva is a complex oral fluid consisting of a mixture of secretions from the

major salivary glands and the minor glands of the oral mucosa. The normal

stimulated secretion rate in adults is 1 - 2 ml per minute. However, it may be reduced

to less than 0.1 ml per minute in individuals with severe salivary gland malfunction.

Salivary sampling protocols are advantageous in that they make for frequent and easy

collection of samples by non - invasive, stress - free techniques. Patients find little

difficulty in salivating into disposable tubes and can provide an adequate volume in

~10 min. Saliva represents the first line of defense against foreign pathogens as well

as commensal residents when high population densities can also be pathogenic.

Secretory IgA (S - IgA) is the prominent immunoglobulin in whole saliva and

is considered to be the main specific defense mechanism in the oral cavity. In

conjunction with several antimicrobial substances, including lysozyme, lactoferrin,

salivary peroxidase, and mucins, S - IgA may help maintain the oral cavity disease

free by limiting microbial adherence to epithelial and tooth surfaces by neutralizing

virulence factors. S-IgA may also prevent the penetration of antigens into the oral

mucosa. Passive smoking was associated with a decrease in secretory IgA

concentration in young children.

People with diabetes are at an increased risk of developing oral conditions like

periodontal disease, which has been associated with persistent poor glycemic control.

Periodontal disease can lead to recession of the gingival margin, which can expose

more tooth surfaces to caries attack. People with diabetes can also experience

hyposalivation and they may suffer from salivary dysfunction. Hyperglycemia in

children, adolescents, and adults with insulin-dependent diabetes mellitus have also

been associated with decreased salivary secretion and high salivary glucose. Aside

from calcium and phosphates that help remineralize tooth enamel, saliva also contains

components that can directly attack cariogenic bacteria. The absence of copious

52

saliva may result in minimizing buffer activity which promotes remineralization of

tooth structures early in the caries process. The reduction in saliva thus decreases

resistance to caries-producing bacteria. In addition, high glucose levels in the saliva

can increase the amount of fermentable carbohydrates by oral bacteria, leading to

production of acidic byproducts that cause teeth demineralization in dental caries.

Abundant glucose in the saliva may also promote the growth of cariogenic bacteria

and facilitate the frequency and duration of acidic episodes.

This man is also like to snacking which can cause diabetes mellitus,

malnutrition, and caries. Limiting lunch or dinner can avoid obesity and diabetes. Due

to not full, the stomach is filled with a piece or two pieces of biscuits and snacks like

potato chips. In fact, cookies, potato chips, and other sweet pastries containing high

carbohydrate content and without adequate food which called "snacking". All the

food was classified into foods with a high glycemic index. Meanwhile, sugar and

starch contained in it have a role in raising blood sugar levels.

Foods that contain saturated fat, trans fat or cholesterol are foods that can lead

to narrowing of the arteries due to plaque formation on artery walls. Foods that

contain saturated fat include meats with a high fat content and whole milk products

such as cheese and ice cream, store-bought cookies, cakes, doughnuts, mayonnaise

and palm oil. Foods with trans fat are cakes, cookies, crackers, pies, potato chips and

other processed foods which usually are from snack. Liver, pork, sausage and some

whole milk foods contain cholesterol. Other unhealthy foods are salty foods that can

raise blood pressure and sugar foods that can result diabetes when consumed in

excess.

Sugar as a sweetener virtually inseparable in everyday consumption. A variety

of food and drink was not good when not using sugar as a sweetener. The cookies are

also biscuits is synonymous with the sweetness of sugar, as well as enjoy tea, coffee

and other beverages will taste more delicious when added sugar. Sugar is included in

carbohydrates but not the main source of energy, is the main energy source of

complex carbohydrates. The use of too much sugar is not recommended. Whatever

type of sugar, if consumed in excess it can lead to various problems such as diabetes

53

and obesity. Health experts even say, sugar is toxic if consumed can be called more

than 8 teaspoons per day. And 8 teaspoons of sugar per day is equivalent to 291.2

calories.

Consuming excessive sugar, the pancreas has the ability to convert the sugar

limits to energy. If the pancreas is experiencing fatigue then one is the impact of

diabetes mellitus. Because of the sugar we consume will be converted into energy

used for various activities of cells and tissues, if the excessive amount of insulin will

take an important role. Insulin is a hormone produced by the pancreas Langerhans

cells will lower blood sugar. This mechanism made include increasing the rate of

glucose utilization through oxidation, glikogenesis (change glucose into glycogen)

and lipogenesis (change glucose into fat).

In patients with diabetes mellitus insulin production is inadequate result when

sugars and other carbohydrates as a result of the excessive glucose metabolism will

accumulate in the blood and an increase in blood sugar. which eventually can escape

from the process in the kidney so it would carry over into the urine. This can lead to

the emergence of symptoms of diabetes such as frequent urination and weight loss

because the body can not use the energy from food. If left untreated, diabetes can

cause blood sugar levels to be very high, which can lead to serious health conditions

or even death.

In both types of diabetes, the immune system plays a crucial role. Type 1

diabetes, or juvenile onset diabetes, is an autoimmune condition where the body’s

immune system overreacts and attacks the pancreas, effectively shutting off insulin

production, the important link to utilizing glucose within the body. There is also

increasing evidence that low-grade inflammation is involved in the progression of

Type 2 diabetes and associated complications. Elevated levels of some inflammatory

cytokines, such as tumor necrosis factor (TNF) - [ alpha ] and interleukin (IL) - 6,

may predict the development of Type 2 diabetes. Several drugs with anti -

inflammatory properties lower such markers, as well as blood sugar levels, while

possibly decreasing the risk of developing Type 2 diabetes. This mild state of

inflammation may be the common precedent of both Type 2 diabetes and

54

atherosclerosis (hardening of the arteries). Diabetics, both Type 1 and Type 2, are

often more susceptible to infections as a result of their bodies not being able to

properly utilize glucose. These diabetes - related complications include problems of

the heart, kidneys, eyes, feet and skin, nerves, teeth and gums.

Diabetes has a high glucosa level in the blood, which called hyperglycemia.

Hyperglycemia dangerous to the various cells and organ systems due to its effect on

the immune system, can act as a mediator of inflammation, resulting in vascular

response, and the response of brain cells. In a state of hyperglycemia easily occur due

to infection phagocyte dysfunction. Acute hyperglycemia can cause a variety of

adverse effects on the cardiovascular system, among others facilitate the occurrence

of heart failure. Incidence of thrombosis is often associated with hyperglycemia.

Hyperglycemia can lead to decreased plasma fibrinolytic activity and plasminogen

activator activity.

The most common problem that the patients suffering from diabetes face is

that as diabetes affects the immune system of the patients, the other organs of the

body start developing complications and abnormalities which hamper the regular

functioning of the organs effecting the body. Therefore it is relatively important for

diabetic patients to have mediation which will help in improving the immune system

of the body.

Snacking can also make an effect for dental. The one result effect of snacking

is dental caries. Dental caries occurs as a result of fluctuations in the pH of the dental

plaque in response to the availability of fermentable carbohydrates as a substrate for

the plaque bacteria. Frequent snacking on sugary foods, or even simply eating food

with low cariogenic potential, frequently will increase the development of the caries

lesion. Any fermentable carbohydrates can act as a food source for these bacteria.

Sucrose is the most potent of the extrinsic sugars, but lactose and fructose can also

produce significant reductions in plaque pH. The oral environment is in a constant

state of flux with changes in local pH occurring every time food is ingested.

All carbohydrate foods eventually break down into simple sugars: glucose,

fructose, maltose and lactose. Some foods, called fermentable carbohydrates, break

55

down in the mouth, whereas others don't break down until they move further down

the digestive tract. It's the fermentable carbohydrates that work with bacteria to begin

the decay process and eventually destroy teeth. They include the obvious sugary

foods, such as cookies, cakes, soft drinks and candy, but they also include less

obvious food, such as bread, crackers, bananas and breakfast cereals.

Certain bacteria on teeth use the sugars from these foods and produce acids.

These acids dissolve minerals inside the tooth enamel in a process called

demineralization. Teeth also regain minerals in a natural process called

remineralization. Saliva helps this process, as does fluoride and some foods. Dental

decay begins inside the tooth enamel when minerals are being lost faster than they are

being regained.

The longer food stays near the bacteria on the tooth, the more acids will be

produced. So sticky carbohydrates, such as raisins, can do more acid damage. But

other foods that pack into crevices can also cause decay. Potato chips are a terrific

example. Eat a handful of chips and see how long you have to work to get all the

stuck bits out from between your teeth. Teeth with a lot of nooks and crannies, such

as molars, are more likely to trap food and are more susceptible to decay. To make

matters worse, tooth-unhealthy foods don't create acids on teeth only while they are

being eaten. The acids stick around for the next half-hour. People who sip soft drinks

or sweetened coffee throughout the day or who eat many small sweet or carbohydrate

snacks provide a sugar source for the bacteria to produce acid almost constantly. And

because acid damage is cumulative, decay is more likely.

Poor oral hygiene in this diabetic man is a possible cause of an increase in

periodontal disease. A possible cause of increased plaque accumulation includes

increased glucose content of the saliva. This could provide nutrients for the

development of the plaque through production of extracellular polysaccharides such

as glucans and fructans. It has also been suggested that lack of compliance with

recommended diabetic therapy might in turn reflect on attitudes to maintenance of

oral health Oral hygiene varies according to socioeconomic status, age, sex and other

56

individual factors. Factors affecting oral hygiene must be reported in cross-sectional

studies in order to eliminate these as a confounding element in the analysis.

In periodontal disease, the materials that accumulates around the gingival

margin and contents of the pockets contain a large number of micro - organism, dead

and dying leucocytes and food debris. In addition, though protein content of food is

normally not altered during its usual brief sojourn in the mouth, it may be

decomposed by proteolytic bacteria if it is retained in these stagnation areas. Dental

caries is not usually considered to be responsible for alimentary disorders, yet if many

teeth are grossly affected, the bacterial flora of the mouth is considerably increased,

so that it is also a potential factor in spreading infection along the alimentary tract.

Dental plaque has been implicated as the prime etiologic factor in dental

caries, gingivitis, and periodontal disease. It is a complex bacterial biofilm

community for which the composition is governed by factors such as cell adherence,

coaggregation, and growth and survival in the environment. Plaque bacteria utilize

the readily fermentable carbohydrates on tooth surfaces to produce acids that promote

and prolong the cariogenic challenge to teeth, leading to enamel demineralization and

tooth decay. The development and progression of dental caries depends on the

amount of food particles that become trapped on the surfaces of teeth that may serve

as ready sources of fermentable carbohydrates, thereby promoting acid production by

plaque bacteria. This prolongs the cariogenic challenge to the teeth, leading to enamel

demineralization and tooth decay. To date, mechanical plaque elimination with

assorted devices remains the primary and most widely accepted means of maintaining

good oral hygiene and controling plaque-mediated diseases.

The development and progression of dental caries depends on both their

frequency of consumption of cariogenic carbohydrates and on the amount of food

particles that become trapped on the surfaces of teeth. Both of these serve as ready

sources of fermentable carbohydrates that promote acid production by plaque

bacteria. When plaque is not removed, the prolonged cariogenic challenge (pH below

the threshold of 5.5) leads to enamel demineralization and tooth decay. However, the

57

frequency of consumption of cariogenic carbohydrates plays a much larger role in

caries progression than the amount of food particles trapped on the surfaces of teeth.

Although bacteria are necessary for periodontal disease to take place, a

susceptible host is also needed. The immune-inflammatory response that develops in

the gingival and periodontal tissues in response to the chronic presence of plaque

bacteria results in destruction of structural components of the periodontium leading,

ultimately, to clinical signs of periodontitis The host response is essentially

protective, but both hyporesponsiveness and hyper-responsiveness of certain

pathways can result in enhanced tissue destruction. Both the host and bacteria in the

periodontal biofilm release proteolytic enzymes that damage tissue. They release

chemotactic factors that recruit poly morphonuclear leucocytes into the tissues; if

sustained, these cells release various enzymes that break down tissues. Hundreds or

even thousands of microbial antigens evoke both humoral antibody-mediated and

cell-mediated immune responses. These responses are usually protective, but a

sustained microbial challenge in the presence of the forementioned risk factors results

in the breakdown of both soft and hard tissues, mediated by cytokine and prostanoid

cascades.

Histologically, non-progressive inflammatory foci tend to be composed

predominantly of T lymphocytes and macrophages, suggesting that the cell-mediated

response can control disease. Destructive lesions are dominated by B lymphocytes

and plasma cells suggesting that humoral immunity is not always effective. Chronic

inflammation may result in central sensitization and wind-up pain. In cases of chronic

oral pain, neurons in the brain stem (nucleus caudalis) are chemically stimulated,

enhancing the frequency and intensity of the pain signal to the brain. Glutamate and

other chemicals bind to the NMDA receptor, sensitizing the postsynaptic neuron and

adding to the local pain response. Specific NMDA-receptor antagonists, such as

ketamine, can be used to counter this wind-up component of pain. Once a periodontal

pocket forms and becomes filled with bacteria, the situation becomes largely

irreversible. Gingival epithelium proliferates to line the pocket and even if treatment

resolves the inflammation and some bone and connective tissue are regenerated,

58

complete restoration of the lost tooth support is impossible. Without adequate

treatment, active periodontitis leads to tooth loss.

Related with the bad habits, snacking and smoking have a role in

memperparah periodontal disease. It can be complete with poor oral hygiene.

Smokers had more calculus than non-smokers, but the effect of smoking was

independent of the amount of calculus present. calculus formation is more abundant

in smokers may be due to the increased salivary flow rates. There is an increased

calcium concentration in fresh saliva in smokers following smoking. Nicotine affects

the exocrine glands by an initial increase in salivary and bronchial secretions that are

followed by inhibition of the secretions. The calcium phosphates found in

supragingival calculus are in the main derived from the saliva. The organic

components may also arise from this source, the proteins and polypeptides

constituting the major fraction. The increased amount of calculus found in smokers

might therefore be due to an effect of tobacco smoke upon properties of saliva.

Bleeding from the gum margin is an important early symptom of gingivitis,

and gingival bleeding on probing is now widely used in clinical examination as a

means of identifying active lesions in periodontal disease. Although smoking is

known to produce peripheral vasoconstriction, in some subjects this is preceded by

vasodilatation. In any particular instance, the effect produced is probably related to

the degree of inhalation of the tobacco smoke and the rate of nicotine absorption.

Nicotine from cigarette stimulates the sympathetic ganglia to produce

neurotransmitters including catecholamines. These affect the alpha-receptors on

blood vessels which in turn causes vasoconstriction. The vasoconstriction of

peripheral blood vessels caused by smoking can also effect the periodontal tissue as

smokers have less overt signs of gingivitis than nonsmokers and clinical signs of

gingival inflammation such as redness, bleeding and exudation are not as evident in

smokers. The vasoconstrictive actions of nicotine may be responsible for the

decreased gingival blood flow.

59

CHAPTER V

CLOSING

5.1 Conclusion

Infectious diseases are caused by a lot of microorganisms such as bacteria,

viruses, fungi, parasites. It could cause illness. Every particular individual creating an

immune response against the pathogen without eliciting any particular symptoms.

Caries is one of the ways the spread of infectious diseases namely acid bacteria that

could cause demineralisation and death pulpa and abscesses. This condition is getting

badly with the habit of smoking, smoking can trigger gingivitis, heavy smoker prone

to germs exposed to TB is aggravating the periodontal tissues. Diabetes mellitus as a

predisposition factor as well as create a network around the teeth or periodontal who

makes swollen.

5.2 Solution

Since we know that infectious disease and periodontal disease can cause by

any factors such as smoking, snacking etc. We have to decrease the number of those

bad habits or bad activity in our daily life so that the disease could not be more worse.

60

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