1. Microbiology: A Systems Approach Chapter 16 Disorders in Immunity PowerPoint to accompany Cowan/Talaro Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. 2 Chapter 16 Topics - Allergies - Autoimmunity - Immunodeficiency

3. 3 Allergies Allergens (antigens) cause an exaggerated immune response or hypersensitivity –Type I –Type II –Type III –Type IV

4. 4 Type I Epidemiology Allergens Mechanisms Syndromes

5. 5 Epidemiology 10% - 30% of population suffer from allergies Hereditary – generalized susceptibility to allergies Allergic antibody (IgE) production Increased reactivity of mast cells Age, infection, and geographic locale can also determine risk for allergies

6. 6 Allergens Protein Hapten (must combine with a larger carrier molecule) Entry –Respiratory tract Inhalants (pollen, mold spores) –Gastrointestinal tract Ingestants (food, water) –Skin Injectants (bites)

7. 7 Example of dust mites and pollen, which are a source of allergies. Fig. 16.2 Monitoring airborne allergens

8. 8 Common allergens for the respiratory tract, gastrointestinal tract, and skin. Table 16.2 Common allergens, classified by portal of entry

9. 9 Mechanisms First exposure –Sensitizing dose - elicits no symptoms –Memory B cells are produced –Small amount of IgE antibodies are produced Mast cells and basophils Reexposure Second expoure

10. 10 Mast cells and basophils Contain receptors that bind IgE antibodies Ubiquitous location (connective tissue for most organs) Secrete chemical mediators from cytoplasmic granules Release contents of granules by degranulation

11. 11 Second exposure Allergens bind to memory B cells B cells produce large amounts of IgE antibodies (high titer) IgE bind to mast and basophil cells Release chemical mediators Degranulation

12. 12 Chemical mediators Responsible for allergic symptoms –Histamine –Serotonin –Leukotriene –Platelet-activating factor –Prostaglandins –Bradykinin

13. 13 Histamine Fast-acting allergic mediator Constricts smooth muscle layers – small bronchi, intestine Relaxes vascular smooth muscle, dilates arterioles and venules Stimulator of glands and eosinophils Wheal and flare reactions in the skin Pruritis (itching) Headache Anaphylaxis

14. 14 Serotonin Complements histamine Increases vascular permeability, capillary dilation, smooth muscle contraction, intestinal peristalsis, respiratory rate Diminishes central nervous system activity

15. 15 Leukotriene Different types Prolonged bronchospasm Vascular permeability Mucous secretions Stimulate polymorphonuclear leukocyte activity

16. 16 Platelet-activating factor Lipid Produced by basophils, neutraphils, monocytes, and macrophages Response similar to histamine

17. 17 Prostaglandins Vasodilation Increase vascular permeability Increase sensitivity to pain Bronchoconstriction

18. 18 Bradykinin Prolonged smooth muscle contractions of the bronchioles Dilatation of peripheral arterioles Increase capillary permeability Increase mucous secretion

19. 19 The mechanism of action of chemical mediators. Fig. 16.4 The spectrum of reactions to inflammatory cytokines

20. 20 Summary of the Type I allergic response. Fig. 16.3 A schematic view of cellular reactions during the Type I allergic response.

21. 21 Syndromes Atopic diseases Food allergy Drug allergy Anaphylaxis Treatment

22. 22 Atopic diseases Atopy – chronic local allergy –Hay fever (allergic rhinitis) –Asthma –Dermatitis

23. 23 Hay fever Reaction to pollen or molds Targets respiratory membranes Symptoms –Nasal congestion –Sneezing –Coughing –Mucous secretions –Itchy, red and teary eyes –Mild bronchoconstriction

24. 24 Asthma Severe bronchoconstriction Symptoms –Shortness of breath to suffocation –Wheezing –Cough –Inflamed respiratory tract

25. 25 Atopic dermatitis Intense itchy inflammatory condition of the skin (eczema) Can begin in infancy and progress to adulthood Symptoms –Dry, scaly, thickened skin –Face, scalp, neck, inner surface of limbs and trunk

26. 26 An example of atopic dermatitis in an infant. Fig. 16.5 Atopic dermititis

27. 27 Anaphylaxis Cutaneous –Wheal and flare inflammatory reaction to the local injection of an allergen Systemic –Rapid immune response that can disrupt respiratory and circulatory systems –Can result in death

28. 28 Treatment Diagnosis –Skin testing Drug –Antiallergy medications Desensitizing –IgG antibodies block IgE function

29. 29 An example of a typical skin test to determine sensitivity to certain allergens. Fig. 16.6 A method for conducting an allergy skin test.

30. 30 The method of desensitization. Fig. 16.8 The blocking antibody theory for allergic desensitization.

31. 31 Type II Interaction of antibodies, foreign cells, and complement, which then leads foreign cell lysis –ABO blood groups –Rh factor –Other RBC antigens

32. 32 ABO blood groups RBC markers (glycoproteins) Genetically determined Alleles – A, B, O Blood types

33. 33 Blood types Each individual will have antibodies against another antigenic type (environmental sensitization). –Type A will have anti-b antibodies –Type B will have anti-a antibodies –Type O will have anti-b and anti-a antibodies Universal donor –Type AB will has no anti-b or a antibodies Universal recipient

34. 34 Major characteristics of the four bloods types. Table 16.3 Characteristics of ABO blood groups

35. 35 Specific genes that encode for enzymes that add a unique sugar to the RBC receptor are the basis for the A and B antigens. Fig. 16.9 The genetic/molecular basis for the A and B antigens (receptors) on red blood cells.

36. 36 Agglutination test will confirm the blood type of an individual. Fig. 16.10 Interpretation of blood typing.

37. 37 Incompatible blood will result in agglutination, complement activation, and cell lysis. Fig. 16.11 Microscopic view of a transfusion.

38. 38 Rh factor Another RBC antigen –At least one dominant allele = Rh + –Two recessive alleles = Rh - Placental sensitization Hemolytic disease Prevention

39. 39 Hemolysis Rh - mother and Rh + fetus First birth –Little anti-Rh antibody produced –Memory cells Second birth –Larger immune response –Hemolysis

40. 40 Prevention Passive immunity using anti-Rh factor immunoglobulin –28-38 weeks –Immediately after delivery Administer for each pregnancy that involves Rh + fetus Ineffective if mother is already sensitized

41. 41 Placental sensitization can cause hemolysis, but this can be prevented by immunoglobulin treatments. Fig. 16.12 Development and control of Rh incompatibility.

42. 42 Type III Mechanism Immune complex reactions Diseases

43. 43 Mechanisms Similar to Type II, except antibodies react with free- antigens, no fixed antigens Ab-Ag complexes deposit in tissue causing immune complex reactions

44. 44 Steps associated with the formation of immune complexes. Fig. 16.13 Pathogenesis of immune complex disease.

45. 45 Diseases Arthus reaction Serum sickness

46. 46 Arthus reaction Injected antigen (eg. Vaccine, drug) Localized dermal injury due to inflamed blood vessels Acute response to a second similar antigen injection Severe cases result in necrosis and loss of tissue

47. 47 Serum sickness Injection of serum, hormones, drugs Systemic injury Ag-Ab complexes circulate in the blood and eventually settle into membranes (kidney, heart, skin) Chronic – enlarged lymph nodes, rashes, painful joints, swelling, fever, and renal dysfunction

48. 48 Type IV Cell-mediated (delayed) reactions –Primary a T cell response Delayed-type hypersensitivity

49. 49 Delayed-type hypersensitivity Infectious allergy Contact dermatitis Tissue rejection

50. 50 An example of an infectious allergy would be an individual that is sensitized by a tuberculosis infection. Fig. 16.14 Positive tuberculin test.

51. 51 Contact dermatitis can result from poison oak. Fig. 16.15 Contact dermatitis

52. 52 Tissue rejection T cell mediated recognition of foreign MHC receptors –Cytotoxic T cells –Host rejection of graft –Graft rejection of host Classes of grafts Types of transplants

53. 53 Two possible reactions that can occur due to transplantation. Fig. 16.16 Potential reactions in transplantation.

54. 54 Classes Autograft Isograft Allograft

55. 55 Types of transplants Live donors – skin, liver, kidney, bone marrow Fetal donors – pancreas, brain tissue Cadaver donors – heart, kidney, cornea Stem cells – bone marrow, blood, umbilical cord

56. 56 Autoimmunity Antibodies, T cells or both, mount an immune response against self antigens –Systemic or organ-specific –Type II or III reactions Cause –Genetic –Gender Origins Diseases

57. 57 An example some major autoimmune diseases. Table 16.4 Selected autoimmune diseases.

58. 58 Origins Sequestered antigen theory Clonal selection theory Theory of immune deficiency Inappropriate expression of MHC II Molecular mimicry Viral infections

59. 59 Diseases Systemic autoimmunities –Systemic lupus erythematosus –Rheumatoid arthritis Endocrine –Graves disease –Hashimoto thyroiditis –Diabetes mellitus Neuromuscular –Myasthenia gravis –Multiple sclerosis

60. 60 An example of systemic lupus and rheumatoid arthritis. Fig. 16.17 Common autoimmune diseases.

61. 61 The autoimmune response in Type I diabetes mellitus. Fig. 16.18 The autoimmune component in diabetes mellitus.

62. 62 The autoimmune reaction of myasthenia gravis, in which antibodies block the attachment of acetylcholine. Fig. 16.19 Mechanism for involvement of autoantibodies in myasthenia gravis.

63. 63 Immunodeficiency A person can be born with or develop a weakened immune system –Primary –Secondary

64. 64 Primary Affects antibody production and phagocytosis Inherited abnormality –Deficiencies in B-cell or T-cell and development and expression –Combined B- and T-cell deficiency

65. 65 Deficiencies in B and T cell development can reduce the level of protection by the immune system. Fig. 16.20 The stages of development and the function

66. 66 Example of DeGeorge syndrome, which is a T cell development deficiency. Fig. 16.21 Facial characteristics of a child with DiGeorge syndrome

67. 67 Secondary Caused by –Infection –Organic disease –Chemotherapy –Radiation

68. 68 Summary of the primary and secondary immunodeficiency diseases. Table 16.5 General catagories of immunodeficiency diseases