Hypersensitivity Diseases
Terms
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- Four Classes of Hypersensitivity Diseases
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Immediate
Antibody Mediated
Immune Complex Mediated
T-Cell Mediated - Mechanism of Immediate Hypersensitivity
-
antigen induces IgE/Th2
IgE binds Fc on mast cells and is cross-linked by antigen, then mast cell degranulation - Mast Cell Mediators
- vasoactive amines, prostaglandins, leukotrienes, proteases, cytokines
- Three classes of immediate hypersensitivity therapy
-
1) Inhibit Mast cell degranulation
2) Antagonize effects of mast cell mediators (antihistamines)
3) Reduce inflammation (corticosteroids) - Mechanism Antibody Mediated Diseases
-
failure of self-tolerance
antibodies vs. self antigens
cross reactive antibodies against microbial antigens - Example of Antibody Mediated Disease
- Autoimmune Hemolytic Anemia
- Mechanism of Immune Complex Mediated Disease
- Antigen/Antibody complexes deposit in joints, vessels, kidney glomeruli
- Examples of Immune Complex Diseases
- Lupus, AGN
- Mechanism of T-Cell Mediated Disease
-
CD4 Mediated - Delayed Type Hypersensitivity
CD8 Mediated - Host Cell Lysis - Example of T-Cell Mediated Disease
- TB Granuloma formation
- Target Antigen in Autoimmune Hemolytic Anemia
- RBC membrane proteins (Rh, I Antigen), leads to opsonization and phagocytosis of RBC
- Target Antigen in Autoimmune Thrombocytopenic Purpura
- Platelet membrane proteins (gpIIb/IIIa); opsonization and phagocytosis of platelets, causes bleeding
- Target Antigen in Pemphigus Vulgaris
- Epidermal junction proteins: Ab mediated activation of proteases, causes bullae
- Target Antigen in Goodpasture's Syndrome
- Anti-GBM, basement membrane, in glomeruli and lung alveoli
- Target Antigen in Acute Rheumatic Fever
- Strep cell wall antigen, cross reacts with mycardial antigen, causes mycarditis/arthritis
- Target Antigen in Myasthenia Gravis
- acetycholine receptor, inhibits Ach binding, leads to muscle weakness/paralysis
- Target Antigen in Grave's Disease
- TSH Receptor, antibody mediated stimulation of TSH receptor, causes hyperthyroidism
- Target Antigen in Pernicious Anemia
- Ab neutralize intrinsic factor of gastric parietal cells, decreased B12 absorption, leads to abnl erythropoeiesis and anemia
- Primary Mediators of Type I reactions
- Histamine, proteases, chemokines, heparin
- Secondary mediators of Type I reactions
- PAF, leukotrienes, prostaglandins, bradykinins, other cytokines