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. Allergies and transplant rejection are harmful immune reactions

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

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

Type I (Anaphylactic) Reactions Skin testing Desensitization Figure 19.3

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

ABO Blood Group System Table 19.2

Hemolytic Disease of the Newborn Figure 19.4

Drug-induced Thrombocytopenic Purpura Figure 19.5

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

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

Comparison of Different Types of hypersensitivity characteristics type-I (anaphylactic) type-II (cytotoxic) type-III (immune complex) type-IV (delayed type) antibody IgE IgG, IgM None antigen exogenous cell surface soluble tissues & organs response time 15-30 minutes minutes-hours 3-8 hours 48-72 hours appearance weal & flare lysis and necrosis erythema and edema, necrosis erythema and induration histology basophils and eosinophil antibody and complement complement and neutrophils monocytes and lymphocytes

Comparison of Different Types of hypersensitivity characteristics type-I (anaphylactic) type-II (cytotoxic) type-III (immune complex) type-IV (delayed type) histology basophils and eosinophil antibody and complement complement and neutrophils monocytes and lymphocytes transferred with antibody T-cells examples allergic asthma, hay fever Erythroblastosis fetalis, Goodpasture's nephritis SLE, farmer's lung disease   tuberculin test, poison ivy, granuloma

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 emberyonic Ags are not recognized as self present in very low concn. to induce autoimmune dis. Some cases as in thyroid and testes

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

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

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

Diseases Related to Specific HLAs Table 19.3

HLA Typing Figure 19.1

Spectrum of autoimmune diseases, target organs and diagnostic tests Antibody to Diagnostic Test Hashimoto's thyroiditis Thyroid Thyroglobulin, thyroid peroxidase (microsomal) RIA, Passive, CF, hemagglutination Primary Myxedema Cytoplasmic TSH receptor Immunofluorescence (IF) Graves' disease   Bioassay, Competition for TSH receptor Pernicious anemia Red cells Intrinsic factor (IF), Gastric parietal cell B-12 binding to IF  immunofluorescence

Organ Antibody to Diagnostic Test Disease Organ Antibody to Diagnostic Test Addison's disease Adrenal Adrenal cells Immunofluorescence Premature onset menopause Ovary Steroid producing cells Male infertility Sperm Spermatozoa Agglutination, Immunofluorescence Insulin dependent juvenile diabetes Pancreas Pancreatic islet beta cells  

Insulin resistant diabetic  Systemic Insulin receptor Competition for receptor Myasthenia graves Muscle Muscle, acetyl choline receptor  Immunofluorescence, competition for receptor   Rheumatoid arthritis Skin, kidney, joints etc IgG IgG-latex agglutination

Rheumatoid arthritis Skin, kidney, joints etc IgG IgG-latex agglutination

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

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

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.

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

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

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)

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

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

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

Acquired Immunodeficiency Syndrome (AIDS) SCONDRY IMMUNODEFICIENCIES  Acquired Immunodeficiency Syndrome (AIDS) 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.

Acquired Immunodeficiency Syndrome (AIDS) Figure 19.12a

HIV Infection Figure 19.12b