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Disorders Associated with the Immune System. Disorders Associated with the Immune System. Infection and immunosuppression are failures of the immune system. Superantigens cause release of cytokines that cause adverse host responses.

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Disorders Associated with the Immune System

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    1. Disorders Associated with the Immune System

    2. Disorders Associated with the Immune System • Infection and immunosuppression are failures of the immune system. • Superantigens cause release of cytokines that cause adverse host responses. • Allergies and transplant rejection are harmful immune reactions

    3. Hypersensitivity Reactions • Response to antigens (allergens) leading to damage • Require sensitizing dose(s)

    4. Type I (Anaphylactic) Reactions • Involve IgE antibodies • Localized: Hives or asthma from contact or inhaled antigens • Systemic: Shock from ingested or injected antigens Figure 19.1a

    5. Type I (Anaphylactic) Reactions • Skin testing • Desensitization Figure 19.3

    6. Type II (Cytotoxic) Reactions • Involve IgG or IgM antibodies and complement • Complement activation causes cell lysis or damage by macrophages

    7. ABO Blood Group System Table 19.2

    8. Hemolytic Disease of the Newborn Figure 19.4

    9. Drug-induced Thrombocytopenic Purpura Figure 19.5

    10. Type III (Immune Complex) Reactions • IgG antibodies and antigens form complexes that lodge in basement membranes. Figure 19.6

    11. Type IV (Cell-Mediated) Reactions • Delayed-type hypersensitivities due to TD cells • Cytokines attract macrophages and initiate tissue damage Figure 19.8

    12. Hypothesis of Autoimmune Diseases • Molecular Mimicry: Due to antibodies against pathogen’s epitope that is identical to a self antigen e.g Streptococcus gp A and rheumatic fever. • Modification of cell-surface antigens : eg. Thermbocytopenia (low level of platelets) and anemia (low level of RBC) due to sulfa drugs. • Availability of normally sequestered self-Ag: The emberyonicAgs are not recognized as self present in very low concn. to induce autoimmune dis. Some cases as in thyroid and testes

    13. Autoimmune Diseases • Clonal deletion during fetal development ensures self-tolerance • Autoimmunity is loss of self-tolerance

    14. Autoimmune Diseases • Type I — Due to antibodies against pathogens • Type II — Antibodies react with cell-surface antigens • Type III (Immune Complex) — IgM, IgG, complement immune complexes deposit in tissues • Type IV — Mediated by T cells

    15. Reactions Related to the Human Leukocyte Antigen (HLA) Complex • Histocompatibility antigens: Self antigens on cell surfaces • Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens • Human leukocyte antigen (HLA) complex: MHC genes in humans

    16. Diseases Related to Specific HLAs Table 19.3

    17. HLA Typing Figure 19.1

    18. Spectrum of autoimmune diseases, target organs and diagnostic tests

    19. Immune Deficiencies • 1ry =Congenital: Due to defective or missing genes • Selective IgA immunodeficiency • Severe combined immunodeficiency • 2ry= Acquired: Develop during an individual's life, due to drugs, cancers, infections • Artificial: Immunosuppression drugs • Natural: HIV infections

    20. Treatment • Anti-inflammatory (corticosteroid) and immunosuppressive (cyclosporin) drug therapy is the present method of treating autoimmune diseases.

    21. PRIMARY IMMUNODEFICIENCIES  Primary immunodeficiencies are inherited defects of the immune system. These defects may be in the specific or nonspecific immune mechanisms. They are classified on the basis of the site of lesion in the developmental or differentiation pathway of the immune system.

    22. Disorders of lymphoid stem cells Severe combined Immunodeficiency: (SCID). Patients with SCID are susceptible to a variety of bacterial, viral, mycotic and protozoan + TB infections. Diagnosis is based on enumeration of T and B cells and immunoglobulin measurement Severe combined immunodeficiency can be treated with bone marrow transplant

    23. I. Disorders of T cells • A) DiGeorge's syndrome: This the most clearly defined T-cell immunodeficiency • Recurrent intercellular bacterial (eg. TB) and fungal infection infections

    24. I. Disorders of T cells • B) Wiskott-Aldrich syndrome • This syndrome is associated with normal T cell numbers with reduced functions • Boys with this syndrome develop severe eczema, petechia (Fungal Infection)

    25. I. Disorders of T cells • C) Bare leukocyte syndrome • MHC deficiency • these patients have fewer CD4 cells and are infection prone

    26. II. Disorders of B lymphocytes • x-linked infantile hypogammaglobulinemia • Transient hypogammaglobulinemia • IgA deficiency • Selective IgG deficiency • These patients are susceptible to pyogenic infections. 

    27. III. Defects of the phagocytic system • A) Chronic granulomatous disease (CGD) • Leukocytes have poor intracellular killing and low respiratory burst. • B) Chediak-Higashi syndrome • inability of phagosome and lysosome fusion and proteinase deficiency

    28. Acquired Immunodeficiency Syndrome (AIDS) SCONDRY IMMUNODEFICIENCIES  • 1981 In U.S., cluster of Pneumocystis and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function. • 1983 Discovery of virus causing loss of immune function.

    29. Acquired Immunodeficiency Syndrome (AIDS) Figure 19.12a

    30. HIV Infection Figure 19.12b