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Host Defense

Host Defense. Outlines. The Innate Immune Response The Adaptive Immune Response Failures of the Immune Response Diseases Associated with the Immune Response Practical Application of Immunity. Objectives. At the end of this lecture the students will be able to:

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Host Defense

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  1. Host Defense

  2. Outlines • The Innate Immune Response • The Adaptive Immune Response • Failures of the Immune Response • Diseases Associated with the Immune Response • Practical Application of Immunity

  3. Objectives • At the end of this lecture the students will be able to: • Understand Innate Immune Response. • Describe Adaptive Immune Response. • Define Diseases Associated with the Immune Response Enumerate the elements of infection cycle. • Predict & practice Application of Immunity.

  4. Introduction From our discussion to this point, you can see that pathogenic microorganisms are endowed with special properties that enable them to cause disease if given the right opportunity. If microorganisms never encountered resistance from the host, we would constantly be ill and would eventually die of various diseases.

  5. Innate Immunity: Nonspecific Defenses of the Host Susceptibility = lack of resistance Resistance = ability of host to ward off disease. 1. Nonspecific resistance (Innate Immunity) -defenses that protect against any pathogen, immediate, no memory response, present at birth, always available to provide rapid response, early-warning system 2. Specific resistance (Adaptive Immunity) -defense against a particular pathogen, requires time to develop, involves specialized cells, has memory

  6. Nonspecific Defenses / Innate Immunity First line of defense: keep microbes out 1). Skin & Mucous Membranes. A. Physical factors: barriers or removal • Skin: -dry, unfavorable, constantly shed. -impermeable ( cannot be penetrated by microbes) unless damaged or moist.

  7. Mucous membranes: -thick, moist epithelium. -less protective than keratinized. -has goblet cells for mucus production. • Lacrimal apparatus: (lacrimal gland &lacrimal canals). -constant tears over eye. -washes microbes off.

  8. Salivary glands: • Saliva acts as cleansing action, helps dilute the numbers of microorganisms and prevent colonization by microbes • Vomiting & diarrhea: • rapid contractions of gastrointestinal tract to rapidly flush out microbes and toxins

  9. B. Chemical factors: • Mucus: -glycoproteins + water -thick, inhibits colonization • Sebum: -oily, from sebaceous glands -fatty acids & lactic acids make skin pH 3-5 -acid pH inhibits microbe growth • Perspiration: -water + salts -water flushes microbes off skin -salt accumulates inhibiting microbe growth

  10. Gastric juice: -HCl + enzymes + mucus -pH 1-3 destroys most bacteria and toxins 2). Normal Micro biota -alter environment (pH, oxygen) -produce toxins (e.g. bacteriocins) 3). Leukocytes = White Blood Cells -usually low #s in blood, increase during infection leukocytosis = increase in WBC % in blood (leukopenia = decrease in WBCs due to damage by some pathogens

  11. 4). Inflammation: -process triggered by damage to body -results in: redness (erythema), pain, heat, swelling (edema), and sometimes loss of Function. 5.) Fever (elevated body temp) -triggered by microbial substance or cytokines from activated phagocytes which reset thermostat in hypothalamus -accelerates defense mechanisms & repair

  12. Adaptive Immunity:Specific Defenses of the Host Immunity: resistance: defense against foreign material. Adaptive immunity: is the ability of the body to specifically react to a microbial infection.

  13. Types of Adaptive Immunity: 1. Naturally Acquired Active Immunity -everyday exposure to antigens & disease -development of B and T cell responses & memory, immunity may be life long 2. Naturally Acquired Passive Immunity -transfer of antibodies from mother to fetus or infant across placenta or in milk -immunity lasts as long as antibodies, weeks to months 3. Artificially Acquired Active Immunity -vaccination / immunization: forced introduction of non virulent antigens -development of B and/or T cell responses & memory, immunity may be life long 4. Artificially Acquired Passive Immunity -injection of preformed antibodies from people or animals, called antiserum -immunity lasts as long as antibodies, weeks to months

  14. Antigens and antibodies The nature of antigen: • Antigen is a chemical substance that causes the body to produce specific antibodies. • Antigens are proteins or large polysaccharide.

  15. The nature of antibodies: 1. It is a protein produced by B cell in response to an antigen and is capable of combining specifically with that antigen. 2. Antibodies recognize and bind to specific shape of antigen’s epitope. 3. Antibodies have great specificity. 4. Affinity means, strength of bond between antigen and antibody.

  16. Disorders of the Immune System • Hypersensitivity. • Acquired immunodeficiency syndrome

  17. 1. Hypersensitivity What is Hypersensitivity? • Hypersensitivity reaction represent immunological responses to an antigen(allergen) that leads to tissue damage rather than immunity. • It occurs when a person has been sensitized to an antigen.

  18. Types of Hypersensitivity Hypersensitivity following secondary exposure to antigen comes in 4 basic forms: *Type I: allergic reactions – anaphylactic (“immediate” hypersensitivity) • very rapid (2-30 minutes) Most allergic reactions are local: • itching, redness, hives in the skin, mucus, sneezing. • usually due to inhaled or ingested antigens. Systemic allergic reactions can be lethal: • severe loss of blood pressure, breathing difficulty(anaphylactic shock)

  19. Some common Allergens • Grains of pollen. • Foods: • e.g., corn, eggs, nuts, peanuts, onions. • Dust mites: • the allergen is actually dust mite feces (yuck!).

  20. Managing Allergic Reactions Avoidance: • avoiding contact with allergen is by far the safest and most effective way of managing allergies Medications: Antihistamines: • drugs that block histamine receptors on target cells. • histamine is still released but has little effect. Epinephrine: (adrenalin) necessary to halt systemic anaphylaxis Desensitization: antigen injection protocol to induce tolerance.

  21. *Type II: cytotoxic reactions: • Cell damage due to complement activation via IgM or IgG • Symptoms take several hours to appear • Most commonly observed with blood transfusions • reaction to ABO blood antigens • reaction to Rh antigen • Can occur via the Rh antigen in newborns • requires Rh- mother and Rh+ child • Rh- mother produces anti-Rh+ IgG following birth • subsequent Rh+ children are vulnerable

  22. *Type III: immune complex reactions cell damage due to excess antibody/antigen complexes, that are not cleared efficiently by phagocytes and tend to deposit in certain tissues: • blood vessel endothelium in kidneys, lungs • joints This can result in local cell damage via: • complement activation • attraction of phagocytes, other cells involved in inflammation (e.g., neutrophils)

  23. *Type IV: Delayed Cell-Mediated Reactions • Delayed cell-mediated hypersensitivity reactions are due to primarily to T cell proliferation. • Sensitized T cell secrete cytokines in response to the appropriate antigen. • Cytokines attract and activate macrophages and initiate tissue damage. • The tuberculin skin test and allergic contact dermatitis are example of delayed hypersensitivity. * Types I-III are all antibody-mediated, Type IV is not!

  24. Acquired Immunodeficiency Syndrome(AIDS) The origin of AIDS: HIV is though to have original in central Africa and was brought to other countries by modern transportation and unsafe sexual practice.

  25. HIV infection • AIDS is the final stage of HIV infection. • HIV is a retrovirus with single-stander RNA, reserve transcriptase. • HIV evades the immune system in latency by using cell-cell fusion and by antigenic change. • The progression from HIV infection to AIDS takes about 10 years. • The life of an AIDS patient can be prolonged by the proper treatment of opportunistic infections.

  26. Diagnostic methods • HIV antibodies are detected. • plasma viral load tests detect viral nucleic acid and are used to quantify HIV in blood.

  27. HIV transmission • HIV I transmitted by sexual contact, breast milk, contaminated needles, transplacental infection, and blood transfusion. • In developed countries, blood transfusion are not a likely source of infection because blood is tested for HIV antibodies. AIDS worldwide: Heterosexual intercourse is the primary method of HIV transmission.

  28. Preventing and treating AIDS • The use of condoms and sterile needles prevent the transmission of HIV. • Vaccine development is difficult because the virus remains inside host cells. • Current chemotherapeutic agents the virus enzymes, including reverse transcriptase , integrase, and protease.

  29. Practical Applications of Immunology Applications of Immunology: • Vaccines • Diagnostic tests

  30. Vaccines: Chinese were first to “vaccinate”: variolation • ground up small pox scabs, rub into wound or inhale. • some people got mildly ill and then were immune to small pox. • some died. Jenner developed first Western vaccine: • observed that milk maids that got cow pox never got small pox. • he inoculated people with cow pox to prevent small pox infection. • set stage for vaccine development (vacca = cow: name given by Pasteur later) vaccine = suspension of organisms or fraction of organisms usedtoinduce immunity.

  31. Only way to deal with deadly viral diseases (bacterial diseases can be treated after with antibiotics) • Mechanism of action: Exposure (injection) induces primary immune response: • antibodies and long term memory cells are formed -slow, takes 1-2 weeks. Natural exposure later induces secondary immune response: • memory cells stimulated to act. • rapid and intense response. • pathogen destroyed before it causes disease. Herd immunity = having enough of the population vaccinated to prevent spread of disease

  32. Diagnostic Immunology Use purified antibody solutions (antiserum) to diagnose disease Diagnostic antibodies can be produced to detect particular microbes: • A. In animals (mixed antiserum) • inject animal with microbe or antigenic fragments. 2. allow immune response (1-2 weeks). 3. harvest blood. 4. purify antibodies from serum to make antiserum = purified antibody solution to one particular antigen. These preparations will produce multiple antibody types that recognize different epitopes on the antigen

  33. B. Monoclonal antibodies: • isolate one immortalized B cell • clone in culture • produce cheap, pure, antiserum with one type of antibody that recognizes only one epitope on the antigen • requires cell culture, but no need for animal husbandry and blood • diagnostic immunology is the future of medical diagnosis for infectious disease: no more biochemical tests

  34. Types of Diagnostic Immunology • Agglutination Reactions -to detect particulate antigens in solution. -antibodies cause clumping (agglutination) of their specific antigens. (e.g. Hemagglutination for blood typing: detects surface antigens on RBCs)

  35. 2. Fluorescent Antibody Labeling: -use antibody chemically linked to florescent dye that is visible with UV light 3. ELISA (Enzyme Linked ImmunoSorbant Assay): -used to detect either antibodies or antigens in patient sample -performed in microtiter plate -positive reaction produces color change

  36. 4. Western Blot / Immunoblotting: -often used to confirm ELISA positive result -blot assays both size of protein antigen and specific reaction with antibody

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