Hansen’s Disease (Leprosy) Mycobacterium leprae Bubonic Plague January 1900 Yersinia pestis.

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Transcript of Hansen’s Disease (Leprosy) Mycobacterium leprae Bubonic Plague January 1900 Yersinia pestis.

Page 4: Hansen’s Disease (Leprosy) Mycobacterium leprae Bubonic Plague January 1900 Yersinia pestis.

Antibiotic Resistance• Antibiotics- drugs that fight infection

caused by bacteria• Antibiotic resistance- when bacteria

change eliminating the effectiveness of the drug designed to cure or prevent infection.

How does it happen?• Bacteria survive antibiotic control

and continue to multiply into resistant strains.

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Timeline of Antibiotic Resistance

• 1929- Alexander Fleming discovers the 1st antibiotic (penicillin)

• 1942- penicillin available through mass production

• 1954- 2 million lbs of antibiotics produced in the U.S. annually

• 1960’s- various resistant strains emerging due to abused antibiotic use

• Today- 50 million lbs of antibiotics produced in the U.S. annually

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Diseases that have Exhibited Antibiotic Resistance

• Gonorrhea• Head lice• Malaria• Methicillin- resistant

Staphylococcus aureus (MRSA)

• Streptococcus pneumoniae

• Typhoid fever• Vancomysin/Glyco

peptide intermediate Stapylococcus aureus (VISA/GISA)

• Vancomycin-resistant Enterococci

• Tuberculosis

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The Nature of DiseaseThe Nature of Disease

• Pathogenic Organisms• Genetic Disorders• Toxic Chemicals• Other Environmental Factors• Physical Damage to Organs• Nutritional Disorders

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Types of Pathogenic Types of Pathogenic OrganismsOrganisms

• VirusesViruses• BacteriaBacteria• ProtozoanProtozoan• FungiFungi• AnimalAnimal• ParasitesParasites

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Mechanisms of Mechanisms of Disease by PathogensDisease by Pathogens

• Utilization of host nutritional Utilization of host nutritional resourcesresources

• Physical damage to host tissuesPhysical damage to host tissues• Production of toxic substancesProduction of toxic substances• Chromosomal and gene damageChromosomal and gene damage• Body cells behave abnormallyBody cells behave abnormally

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VirusesViruses

nucleic acid

capsid

envelope

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BacteriaBacteria

cell wall

plasma membrane

cytoplasm

circular DNA

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Defense Mechanisms

1. External defense2. Internal Defense3. Immune Defense

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• Skin acts as barrier to microbes and viruses- sweat has a low pH

• Mucus traps foreign particles• Saliva cleanses oral cavity• Tears

- Lysozyme has antimicrobial action• Gastric stomach acid

1st Line of Defense

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Body Coverings: The Body Coverings: The SkinSkin

sebaceous glands

sweat gland

epidermis

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Body Coverings: Body Coverings: Mucous MembranesMucous Membranes

mucus

cilia

columnar epithelium

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• Phagocytic cells (WBCs)- N L M E B- Natural Killer (NK) Cells: attack virus

infected cells• Inflammatory Response• Antimicrobial proteins

- Lysozyme- Interferon- Antibodies

2nd Line of Defense

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Nonspecific PhagocytosisNonspecific Phagocytosis

NeutrophilsMonocytesEosinophils

NeutrophilsMonocytesEosinophils

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Mechanism of Mechanism of PhagocytosisPhagocytosis

Mechanism of PhagocytosisMechanism of Phagocytosis

MacrophageMacrophage

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Natural Killer Cells

• Innate immunity• Cytoxic • Activated by presence of

interferon• Kills cancer and virus-infected cells

before the adaptive immune system is activated.

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Inflammatory Response

Histamine & prostaglandins released

Capillaries dilateClotting begins

Chemotactic factors attract phagocytic cells

Phagocytes consume pathogens & cell debris

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Antimicrobial Protein

• INF- Secreted by infected cells

• Complement System- 20 plasma proteins- MAC

http://www.youtube.com/watch?v=IWMJIMzsEMg

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Characteristics of Characteristics of ImmunityImmunity

• Recognition of self versus non-self• Response is specific• Retains a “memory” allowing an

accelerated second response• Can respond to many different

materials• Involves lymphocytes and

antibodies

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Types of Acquired ImmunityTypes of Acquired Immunity

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The production of antibodies against a The production of antibodies against a specific disease by the immune system. specific disease by the immune system.

Naturally acquired through disease Naturally acquired through disease Artificially acquired through vaccination Artificially acquired through vaccination

• Vaccines include inactivated toxins, killed Vaccines include inactivated toxins, killed microbes, parts of microbes, and viable but microbes, parts of microbes, and viable but weakened microbes.weakened microbes.

Active immunity is usually permanentActive immunity is usually permanent

Active ImmunityActive Immunity

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A vaccinated person has a secondary A vaccinated person has a secondary response based on memory cells response based on memory cells when encountering the specific when encountering the specific pathogen.pathogen.• Routine immunization against infectious Routine immunization against infectious

diseases such as measles and whooping diseases such as measles and whooping cough, and has led to the eradication of cough, and has led to the eradication of smallpox, a viral disease.smallpox, a viral disease.

• Unfortunately, not all infectious agents Unfortunately, not all infectious agents are easily managed by vaccination.are easily managed by vaccination.–HIV vaccine in the worksHIV vaccine in the works

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Passive ImmunityPassive Immunity- Protection - Protection against disease through antibodies against disease through antibodies produced by another human being produced by another human being or animal. or animal.

Effective, but temporaryEffective, but temporary Ex. Maternal antibodiesEx. Maternal antibodies Colostrum.Colostrum.

Passive ImmunityPassive Immunity

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Passive immunity can be Passive immunity can be transferred artificially by transferred artificially by injecting antibodies from an injecting antibodies from an animal that is already animal that is already immune to a disease into immune to a disease into another animal.another animal.• Rabies treatment: injection Rabies treatment: injection

with antibodies against with antibodies against rabies virus that are both rabies virus that are both passive immunizationspassive immunizations (the (the immediate fight) and immediate fight) and active active immunizationsimmunizations (longer term (longer term defense).defense).

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Immune System Response Immune System Response to Antigensto Antigens

Humoral Immunity• Involves antibodies (secreted from B

cells) dissolved in the blood plasma.• Demonstrated as a immune response

using only the blood serum.• Defense against bacteria, bacterial

toxins, & viruses.

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Cell-Mediated Immunity• Involves the activities of specific

white blood cells (T cells).• Defense against cancer cells, virus-

infected cells, fungi, animal parasites, & foreign cells from transplants.

Immune System Response Immune System Response to Antigensto Antigens

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Lymphocyte Formation

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B CellsB Cells• Mature in bone marrow• Involved in humoral immunity• Once activated by antigen,

proliferate into two clones of cells: plasma cells that secrete antibodies and memory cells that may be converted into plasma cells at a later time

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B CellsB Cells

antibodies

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B CellsB Cells B Cells

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Activation of B Cells by Activation of B Cells by AntigenAntigen

antigen

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Clonal SelectionClonal Selection

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Clonal SelectionClonal Selection

plasma cells memory cells

antibodies

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Overview of Immune System Responses

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Humoral Immune ResponseHumoral Immune Response

time (days)

antib

ody

conc

entr

atio

n

first exposure to antigen A

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Humoral Immune ResponseHumoral Immune Response

time (days)

antib

ody

conc

entr

atio

n

first exposure to antigen A

primary response: concentration of anti-A antibodysecond exposure

to antigen A

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Humoral Immune ResponseHumoral Immune Response

time (days)

antib

ody

conc

entr

atio

n

secondary response: concentration of anti-A antibody

second exposure to antigen A

first exposure to antigen B

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Humoral Immune ResponseHumoral Immune Response

time (days)

antib

ody

conc

entr

atio

n

primary response: concentration of anti-B antibody

first exposure to antigen B

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Antibodies constitute a group of Antibodies constitute a group of globular serum proteins called globular serum proteins called immunoglobinsimmunoglobins ( (IgsIgs).).• A typical antibody molecule has two A typical antibody molecule has two

identical antigen-binding sites identical antigen-binding sites specific for the epitope that provokes specific for the epitope that provokes its production.its production.

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Antibody Antibody MoleculeMolecule

antigen binding sites

antigen

light chains heavy chains

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Mechanisms on Antibody Mechanisms on Antibody ActionAction

• Precipitation of soluble antigens• Agglutination of foreign cells• Neutralization• Enhanced phagocytosis• Complement activation leading to

cell lysis• Stimulates inflammation

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The binding of antibodies to antigens to form The binding of antibodies to antigens to form antigen-antibody complexes is the basis of antigen-antibody complexes is the basis of several antigen disposal mechanisms.several antigen disposal mechanisms.

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The classical complimentary pathway, resulting in lysis of a target cell

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Immunoglobin ClassesImmunoglobin Classes

IgM• 1st response to antigen• Effective in agglutination• Can’t cross placenta

IgG• Most common form• Crosses blood vessels• Crosses placenta

(passive immunity to fetus)

IgA• Secreted from mucus

membranes• Prevents attachment of

bacteria to epithelial surface• In colostrum

IgD• B cell activation• Can’t cross placenta

IgE• Histamine

reactions and allergies

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T CellsT Cells

• Mature in thymus• Involved in cell-mediated immunity• Activated when another cell

presents antigen to them• Several types of T cells: cytoxic T

cells, helper T cells, suppressor T cells, and memory T cells

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• There are two main types of T cells, and each responds to one class of MHC molecule.– Cytotoxic T cells (TC) have antigen receptors

that bind to protein fragments displayed by the body’s class I MHC molecules.

– Helper T cells (TH) have receptors that bind to peptides displayed by the body’s class II MHC molecules.

T Cells

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Cytotoxic T CellCytotoxic T Cell

perforin

pores in target cell

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Helper T CellsHelper T Cells

interleukin 1macrophage

helper T cell

bacteriumbacterialantigens

T cell receptor

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The central role of helper T cells

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The central role in Cytotoxic T cells in an The central role in Cytotoxic T cells in an infected cellinfected cell

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• T-independentT-independent antigensantigens–T cells activated by binding to certain T cells activated by binding to certain

antigensantigens

–No memory cells generatedNo memory cells generated

–Weaker response than t-dependentWeaker response than t-dependent

• T-dependent antigensT-dependent antigens–Most antigens require co-stimulation to Most antigens require co-stimulation to

evoke a B-cell responseevoke a B-cell response

–Antibody production stimulated with help Antibody production stimulated with help from Tfrom THH

–Most antigens are t-dependentMost antigens are t-dependent

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T-dependent antigensT-dependent antigens- - can trigger a humoral can trigger a humoral immune response by immune response by B cells only with the B cells only with the participation of helper participation of helper T cells.T cells.

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ABO Blood TypesABO Blood Types

Blood TypeBlood Type AntigenAntigen AntibodyAntibody

O -O - antibody anti a & b antibody anti a & b A AA A antibody anti b antibody anti b B BB B antibody anti a antibody anti a AB ABAB AB -- RhRh++ + + - - RhRh-- - - antibody Rhantibody Rh--

Universal Donor ?Universal Recipient ?

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Malfunctions of the immune system can Malfunctions of the immune system can produce effects ranging from the minor produce effects ranging from the minor inconvenience of some allergies to the inconvenience of some allergies to the serious and often fatal consequences of serious and often fatal consequences of certain autoimmune and immunodeficiency certain autoimmune and immunodeficiency diseases.diseases.

Abnormal immune function can Abnormal immune function can lead to diseaselead to disease

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Abnormal Immune Abnormal Immune FunctionFunction

• Autoimmune Disease• Allergy• Immunodeficiency

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Autoimmune DiseaseAutoimmune Disease

• Rheumatoid arthritis• Type I Diabetes• MS• Lupis• Crohn’s disease• Grave’s disease

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Mast cells, IgE, Mast cells, IgE, and the allergic and the allergic response.response.

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AIDS

• Acquired Immunodeficiency Syndrome

• HIV (virus) attacks T-cells

• Weakens or eliminates immune system

• Susceptible to many fatal diseases

ProblemsProblems

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Transmission of HIV requires the transfer Transmission of HIV requires the transfer of body fluids containing infected cells, of body fluids containing infected cells, such as semen or blood, from person to such as semen or blood, from person to person.person.• Unprotected sex Unprotected sex • Nonsterile needles Nonsterile needles • HIV transmission among heterosexuals is HIV transmission among heterosexuals is

rapidly increasing as a result of rapidly increasing as a result of unprotected sex with infected partners.unprotected sex with infected partners.

• HIV in Africa and Asia- primarily by HIV in Africa and Asia- primarily by heterosexual sexheterosexual sex

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AIDSAIDSIn 1983, a retrovirus, now called human

immunodeficiency virus (HIV), had been identified as the causative agent of AIDS.

HIV budding

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HIV/AIDS in Hawaii

Hawaii State Department of Health

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HIV/AIDS in Hawaii

Hawaii State Department of Health

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With the AIDS mortality close to With the AIDS mortality close to 100%, HIV is the most lethal 100%, HIV is the most lethal pathogen ever encountered.pathogen ever encountered.

• Molecular studies reveal that the Molecular studies reveal that the virus probably evolved from virus probably evolved from another HIV-like virus in another HIV-like virus in chimpanzees in central Africa and chimpanzees in central Africa and appeared in humans sometimes appeared in humans sometimes between 1915 and 1940.between 1915 and 1940.

– These first rare cases of infection and These first rare cases of infection and AIDS went unrecognized.AIDS went unrecognized.

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AIDSAIDS

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AIDSAIDS

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HIV Testing:HIV Testing:• The HIV antibody test has be used to screen The HIV antibody test has be used to screen

all blood supplies in the U.S. since 1985.all blood supplies in the U.S. since 1985.– May take weeks or months before anti-HIV May take weeks or months before anti-HIV

antibodies become detectable.antibodies become detectable.

- Drug treatment availableDrug treatment available- Best prevention is education and protected sexBest prevention is education and protected sex

Scientists Report First Cure Of HIV In A Child, Say It's A Game-Changerhttp://www.npr.org/blogs/health/2013/03/04/173258954/scientists-report-first-cure-of-hiv-in-a-child-say-its-a-game-changer

HIV/AIDS patients “cured” by bone marrow transplantshttp://www.npr.org/blogs/health/2012/07/26/157444649/two-more-nearing-aids-cure-after-bone-marrow-transplants-doctors-say

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INQUIRY1. What are the proteins secreted by plasma cells called?2. Which cell terminates or decreases the immune

response?3. Which type of T cell lyses cells that have been infected

with a virus?4. Which cell provides an accelerated immune response

upon second exposure to a particular antigen?5. A disease in which a person’s immune system attacks

a persons own normal tissue is called _____?