IMMUNOLOGIC AND ALLERGIC DISEASES

IMMUNE SYSTEM Mission: to seek and kill

“invaders” or foreign bodies (microorganisms, parasites, cancer cells, etc.)

Must be able to distinguish between what is self and non-self

Any substance identified as non-self, stimulate an immune response in the body

INTRODUCTION

Antigen – maybe contained within or on bacteria, viruses, other microorganisms or cancer cells- They may exist on their owne.g. food molecules, pollen

A normal immune responseAg (antigen) – activates / mobilizes forces to defend by attacking it.

Mistake self for non-self – attack own tissues (autoimmune disorder)

Immune System is made up of lymphoid tissues in the body which includes:- bone marrow - parts of spleen – GIT

- Thymus - tonsils- proteins and cells in

the blood are also part of the immune system

TERMINOLOGIES: Antibody (immunoglobulin) – a protein produced by

B cells – interacts with antigen

Antigen – any substance that the immune system recognizes and can stimulate an immune response

B Cell (B Lymphocyte / Bursa Cells / Humoral Immunity) – bone marrow derived or bursa equivalent lymphocyte in a WBC that produces antibodies specific to the Ag that stimulated their production

UNDERSTANDING THE IMMUNE SYSTEM

T Cell (T Lymphocyte / Thymus / Cellular Immunity)- thymus derived, WBC that is involved in specific immunity and that maybe one of 3 types:

• Helper T-Cell• Killer (Cytotoxic) T-Cell• Regulatory T-Cell

Basophil – WBC that releases histamine- produces substances to attract other WBC to a troubled spot

Cytokines – proteins secreted by cells that act as the immune systems messengers and that help regulate an immune response

Eosinophils – WBC that kills bacteria- Kills other foreign cells too big to ingest- Help immobilize and kill parasites- Participates in allergic reactions- Help destroy cancer cells

Macrophage – large cell that develops from a WBC called monocyte- ingests bacteria and other foreign cells

Neutrophil – WBC that ingests and kills bacteria and other foreign cells

Phagocyte – A cell that ingests / kills / destroys invading microorganisms, other cells and cell fragments

B CELL or HUMORAL IMMUNITY

T CELL or CELLULAR IMMUNITY

1. The body generates an immune response against itself (autoimmune disorder)

2. The body cannot generate appropriate immune responses against invading microorganisms (immunodeficiency disorder)

3. An excessive immune response to often harmless foreign antigens damages normal tissues (an allergic reaction)

DISORDERS OF THE IMMUNE SYSTEM OCCUR WHEN:

- immune system mistakenly attacks and destroys healthy body tissue response is a hypersensitivity reaction similar to the response in allergic reaction.ALLERGY – reaction to an outside substance that it would normally ignoreAUTOIMMUNE DISORDER – reaction to normal body tissue that it would normally ignore

I. AUTOIMMUNE DISORDERS

CAUSE: UNKNOWNTHEORY: some microorganisms

(bacteria & virus) or drugs may trigger some of these changes, especially in people who have genes that make them more likely to get autoimmune disorders.

1. An autoimmune disorder may result in:• destruction of one or more types of body tissues• abnormal growth of an organ• changes in organ function

CHARACTERISTICS:

2. An autoimmune disorder may affect one or more organ or tissue types.a. It can be organ specific:

• ENDOCRINE SYSTEMthyroid gland – Hashimoto’s

thyroiditis – Grave’s disease – Type I & II

autoimmune polyglandular syndrome

– Insulin dependent DM

• SKIN- pemphigus vulgaris- dermatitis herpetiformis- epidermolysis bullosa- autoimmune alopecia- contact dermatitis

• HEMOTOLOGIC- autoimmune hemolytic anemia- autoimmune thrombocytopenic purpura- autoimmune neutropenia

• NEURO-MUSCULAR SYSTEM- myasthenia gravis- multiple sclerosis- Guillain – Barre’ Syndrome

• HEPATOBILIARY SYSTEM- autoimmune chronic active hepatitis- primary biliary sclerosis- sclerosing cholangitis

• GIT- pernicious anemia- inflammatory bowel disease

b) It can be organ nonspecific• CONNECTIVE TISSUE DISEASES

- systemic lupus erythematosus- rheumatoid arthritis- scleroderma- sjogren’s syndrome- ankylosing spondylitis- psoriasis

• VASCULITIC SYNDROMES- hypersensitivity vasculitis- Wegener’s Granulomatosis- Takayasu’s Arteritis- Kawasaki’s Disease- Sarcoidosis- Graft versus host disease

symptoms of an autoimmune disease vary based on the disease and location of the abnormal immune response

symptoms that often occur with autoimmune diseases include- fatigue- fever- body malaise

SYMPTOMS:

depends on the type of disease which will generally include:- ANA (antinuclear antibody tests)- autoantibody test- CBC- C-Reactive Protein (CRP)- erythrocyte sedimentation rate (ESR)

DIAGNOSIS:

GOALS:• reduce the symptoms• control the autoimmune process• maintain the body’s ability to fight disease

1. SUPPLEMENTS- hormonal replacement- vitamins e.g. B12

- insulin injections- thyroid supplements

TREATMENT:

2. BLOOD TRANSFUSION3. PHYSICAL THERAPY4. MEDICINE

- to control or reduce immune system’s response (immunosuppressive drugs)- corticosteroids- non-steroidal drugs - azathioprine- cyclophosphamide- sirolimus- tacrolimus

- Depends on the disease- Can be controlled by treatment- Symptoms can come and go- Flare-up when symptoms worsen

PROGNOSIS:

- Occurs when the body’s immune response is reduced or absent

- Occurs when T or B lymphocytes do not work as well as they should or when the body does not produce enough antibodies.

- Can be congenital, spontaneously acquired or iatrogenic

- Unusual susceptibility to infection and frequently to autoimmune diseases and lymphoreticular malignancies.

II. IMMUNODEFICIENCY DISORDER

- Ataxia telangiectasia- Chediak-Higashi Syndrome- Combined immunodeficiency disease- Complement deficiencies- Di George Syndrome- Hypogammaglobulinemia- Panhypogammaglobulinemia- Selective deficiency of IgA- Wiscott-Aldrich Syndrome

A. PRIMARY IMMUNODEFICIENCIES

- Acquired Immuno Deficiency Syndrome (AIDS)

- Iatrogenic- Idiopathic CD4 and T lymphocytopenia

B. ACQUIRED IMMUNODEFICIENCY

depend on the disorderTELL-TALE SIGNS:

• chronic infection• severe infection from bacteria or other forms that do not usually cause severe infection• poor response to treatment• delayed or incomplete recovery from illness• certain types of cancers (Kaposi’s sarcoma or non-Hodgkin’s lymphoma• certain infections

SYMPTOMS:

Complement levels in blood HIV Test Blood immunoglobulin levels CHON electrophoresis T lymphocyte count WBC Count

DIAGNOSIS:

GOAL – to prevent infections and treat any disease and infections that do develop.

1. Avoid contact with persons who have infections or contagious disorders

2. Avoid people who have been vaccinated with live virus vaccine within the past 2 weeks

3. Aggressive Treatment – long term use of Abtx. or antifungal- Prophylactic Tx

TREATMENT:

4. Interferon – tx viral infection and some types of cancer- immunostimulant drug

5. Bone Marrow Transplant6. Passive Immunity7. Immunoglobulin Infusions

4 Types of Hypersensitivity Reactions:TYPE I: immediate Ig-E mediated which causes rapid degranulation of

mast cells IgE binds to the mast cells via a high

affinity Fc receptor. Early Phase: within minutes Late Phase: hours after initial response

e.g. allergic rhinitis, food allergy, allergic or atopic asthma.

III. ALLERGIC DISEASES:

TYPE II: Antibody mediated Ab binds to cells and causes

damage or impairment of functionse.g. transfusion reactions, hemolytic anemias, graft rejection, myasthenia gravis, good pastures syndrome

TYPE III: immune complex mediated

- Occurs when IgG or IgM binds with Ag and the complexes are deposited in tissuese.g. serum sickness, glomerulonephritis, arthritis

TYPE IV: T-Cell mediated (delayed hypersensitivity)

- First exposure: T-cell is sensitized subsequent exposure: allergen is recognized and detected, thereby these cells are lysed by T Cells.e.g. contact dermatitis, granulomatous diseases

ALLERGY – exaggerated immunologic response to an otherwise innocuous agent, which causes harm to the host

ALLERGEN – inciting agent

PATHOPHYSIOLOGY:• IgE binds to surface of mast cells and basophils• Cross linking of IgE by Ag causes cellular activation• release of mediators – histamines

– prostaglandins– leukotrienes– SRS-A (slow-

reacting substance of

anaphylaxis

TYPE I HYPERSENSITIVITY(Immediate Type)

- Anaphylaxis- Serum Sickness- Generalized Drug Reactions- Food Allergy- Insect Venom- Mastocytosis

ALLERGIC DISEASES

GENERALIZED

- Allergic rhinitis- Asthma- Hypersensitivity

pneumonitis

- Urticaria- Angioedema- Eczema- Atopic dermatitis

AIRWAYS SKIN

- Allergic conjunctivitis- Atopic keratoconjunctivitis- Giant papillary conjunctivitis- Contact allergy

OCULAR ALLERGY

DEFINITION: the life threatening anaphylactic response of a sensitized human appears within minutes after administration of specific Ag and is manifested by respiratory distress, often followed by vascular collapse or by shock without antecedent respiratory difficulty.

A. ANAPHYLAXIS

Hallmark of anaphylactic reaction: onset of S/S within seconds to minutes after introduction of the AgS/S: laryngeal edema – lump in throat, hoarseness or stridorbronchial obstruction – tightness in the chest or wheezing cutaneous wheals – erythematous, raised, serpiginous borders and blanched centers; pruritic

PATHOPHYSIOLOGY ANDMANIFESTATION

- Early recognition- Mild symptoms (pruritis and urticaria)

– 0.2 ml to 0.5 ml of 1:1000 epinephrine SQ

- Hypotension – volume expanders – vasopressor agents

(dopamine) O2

-

TREATMENT:

URTICARIA – involves the superficial portion of the dermiswell-circumscribed wheals

ANGIOEDEMA – well demarcated localized edema involving the deeper areas / layers of the skin, including the subQ tissues

ACUTE – recurrent episodes of less than 6 weeksCHRONIC – attacks persisting beyond 6 weeks

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B. URTICARIA and ANGIOEDEMA

- Urticarial eruptions are pruritic, appear in crops of 24 – 72o duration- Most common sites: extremities, external genitalia, face

- History- Skin testing- Laboratory exam: complement levels, ESR

PATHOPHYSIOLOGY ANDMANIFESTATION

DIAGNOSIS

- Avoidance of offending agents- H1 and H2 antihistamines

• ranitidine 150 mg p.o. BID• diphenhydramine 25-50 mg p.o. QID• hydroxyzine 25-50 mg p.o QID

-

TREATMENT

- Inflammatory condition of the nose characterized by sneezing, rhinorrhea and obstruction of nasal passages

PATHOPHYSIOLOGY:impingement of allergens on nasal mucosa Ig-Edependent triggering of mast cells release of mediators hyperemia, swelling, fluid transudation

C. ALLERGIC RHINITIS

- Accurate history- physical examination: boggy nasal mucosa- nasal smear – large # of eosinophils

- Antihistamines- Oral Sympathomimetics: pseudoephedrine 30-60mg p.o. QID- topical nasal steroids: beclomethasone 2 sprays in each nostril BID – TID- topical nasal cromolyn sodium 1-2 sprays in each nostril QID.

DIAGNOSIS:

TREATMENT: