Immune Hypersensitivity Reaction: immune responses which result in tissue damage
Type I Hypersensitivity = Immediate Hypersensitivity (Allergy)
Mechanism
Initial Encounter with Allergen (Pollen, Food, Insect Venom, Animal Dander, Drugs): leads to sensitization (which is often asymptomatic)
Repeat Encounter with Allergen in Allergic Person: leads to activation of TH2 Cells -> IL-4 and IL-13 secretion -> IgE antibody directed against environmental antigen -> IgE binds to mast cells -> mast cell release of vasoactive amines/lipid mediators/cytokines -> recruitment of leukocytes (eosinophils, neutrophils, and Th2 cells)
Early Phase (Within Minutes): increased vascular permeability and smooth muscle contraction
Late Phase (Within Hours): cytokine-mediated inflammation with eosinophils and neutrophils (cytokine-mediated inflammation) -> tissue injury
While Some Cases of Asthma are Not Associated with Elevated IgE, All Cases of Asthma are Associated with Mast Cell Activation (The mechanism of Mast Cell Activation in These Non-IgE Cases is Unclear)
IgM/IgG Antibodies Against Cell Surface or Extracellular Matrix Antigens: leads to complement + Fc receptor-mediated recruitment and activation of neutrophils/macrophages -> opsonization and phagocytosis of cells
Abnormalities in cellular function (hormone receptor signaling)
Pharmacology: decreases antibody and immune complex levels
Type III Hypersensitivity = Immune Complex-Mediated
Mechanism
Immune Complexes of Circulating Antigens + IgM/IgG Antibodies Deposited in Vascular Basement Membrane: leads to complement + Fc receptor-mediated recruitment and activation of neutrophils/macrophages
Pharmacology: decreases antibody and immune complex levels
Type IV Hypersensitivity = T Cell-Mediated
Mechanism
CD4 Cells (Delayed-Type Hypersensitivity) and CD8 Cells (T Cell-Mediated Cytolysis of Host Cells): leads to macrophage activation and cytokine-mediated inflammation -> direct target cell lysis and cytokine-mediated inflammation
Hypersensitivity Vasculitis (see Vasculitis): involves both type III and type IV mechanisms
Inflammatory Bowel Disease (IBD) (see Inflammatory Bowel Disease): T-cells target against uknown antigens (there is a possible role of intestinal microbial flora in this process)