Disorders Associated with the Immune System

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• Disorders Associated with the Immune System

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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

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Hypersensitivity Reactions

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

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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
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Type I (Anaphylactic) Reactions

• Skin testing
• Desensitization

Figure 19.3
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Type II (Cytotoxic) Reactions

• Involve IgG or IgM antibodies and complement
• Complement activation causes cell lysis or damage
  by macrophages

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ABO Blood Group System
Table 19.2
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Hemolytic Disease of the Newborn
Figure 19.4
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Drug-induced Thrombocytopenic Purpura
Figure 19.5
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Type III (Immune Complex) Reactions

• IgG antibodies and antigens form complexes that
  lodge in basement membranes.

Figure 19.6
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Type IV (Cell-Mediated) Reactions

• Delayed-type hypersensitivities due to TD cells
• Cytokines attract macrophages and initiate tissue
  damage

Figure 19.8
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Comparison of Different Types of hypersensitivity Comparison of Different Types of hypersensitivity Comparison of Different Types of hypersensitivity Comparison of Different Types of hypersensitivity 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 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
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Comparison of Different Types of hypersensitivity Comparison of Different Types of hypersensitivity Comparison of Different Types of hypersensitivity Comparison of Different Types of hypersensitivity 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 antibody antibody T-cells
examples allergic asthma, hay fever Erythroblastosis fetalis, Goodpasture's nephritis SLE, farmer's lung disease   tuberculin test, poison ivy, granuloma
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Hypothesis of Autoimmune Diseases

• Molecular Mimicry Due to antibodies against
  pathogens 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

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Autoimmune Diseases

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

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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

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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

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Diseases Related to Specific HLAs
Table 19.3
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HLA Typing
Figure 19.1
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Spectrum of autoimmune diseases, target organs
and diagnostic tests
Disease Organ Antibody to Diagnostic Test
Hashimoto's thyroiditis Thyroid Thyroglobulin, thyroid peroxidase (microsomal) RIA, Passive, CF, hemagglutination
Primary Myxedema Thyroid Cytoplasmic TSH receptor Immunofluorescence (IF)
Graves' disease Thyroid   Bioassay, Competition for TSH receptor
Pernicious anemia Red cells Intrinsic factor (IF), Gastric parietal cell B-12 binding to IF  immunofluorescence
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Disease Organ Antibody to Diagnostic Test
Addison's disease Adrenal Adrenal cells Immunofluorescence
Premature onset menopause Ovary Steroid producing cells Immunofluorescence
Male infertility Sperm Spermatozoa Agglutination, Immunofluorescence
Insulin dependent juvenile diabetes Pancreas Pancreatic islet beta cells  
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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
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Rheumatoid arthritis Skin, kidney, joints etc IgG IgG-latex agglutination
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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

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Treatment

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

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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.

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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

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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

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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)

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I. Disorders of T cells

• C) Bare leukocyte syndrome
• MHC deficiency
• these patients have fewer CD4 cells and are
  infection prone

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II. Disorders of B lymphocytes

• x-linked infantile hypogammaglobulinemia
• Transient hypogammaglobulinemia
• IgA deficiency
• Selective IgG deficiency
• These patients are susceptible to pyogenic
  infections. 

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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

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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.

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Acquired Immunodeficiency Syndrome (AIDS)
Figure 19.12a
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HIV Infection
Figure 19.12b