Hypersensitivity Reactions
Type II Cont...
(1) *transfusion reactions*, in which cells from an incompatible donor react with and are opsonized by preformed antibody in the host; (2) *erythroblastosis fetalis*, in which there is an antigenic difference between the mother and the fetus, and antibodies (of the IgG class) from the mother cross the placenta and cause destruction of fetal red cells; (3) *autoimmune hemolytic anemia, agranulocytosis, and thrombocytopenia*, in which individuals produce antibodies to their own blood cells, which are then destroyed; and (4) *certain drug reactions*, in which antibodies are produced that react with the drug, which may be attached to the surface of erythrocytes or other cells.
Summaries
- A type I hypersensitive reaction is mediated by IgE antibodies, whose Fc region binds to receptors on mast cells or blood basophils. Crosslinkage of the fixed IgE by allergen leads to mast cell or basophil degranulation with release of pharmacologically active mediators. The principal effects of these mediators are smooth-muscle contraction and vasodilation. Clinical manifestations of type I reactions include potentially life-threatening systemic anaphylaxis and localized responses such as hay fever and asthma. - A type II hypersensitive reaction occurs when antibody reacts with antigenic determinants present on the surface of cells, leading to cell damage or death through complement-mediated lysis or antibody-dependent cell-mediated cytotoxicity (ADCC). Transfusion reactions and hemolytic disease of the newborn are type II reactions. - A type III hypersensitive reaction is mediated by the formation of immune complexes and the ensuing activation of complement. Complement split products serve as immune effector molecules that elicit localized vasodilation and chemotactically attract neutrophils. Deposition of immune complexes near the site of antigen entry can induce an Arthus reaction, in which lytic enzymes released by the accumulated neutrophils and the complement membrane-attack complex cause localized tissue damage. - A type IV hypersensitive reaction involves the cell-mediated branch of the immune system. Antigen activation of sensitized TH1 cells induces release of various cytokines that cause macrophages to accumulate and become activated. The net effect of the activation of macrophages is to release lytic enzymes that cause localized tissue damage. (Marcus, David A. Immunology, 5th Edition. W.H. Freeman & Company, 012003. VitalBook file.)
Type 2
-*Cytotoxic hypersensitivity* or antibody-dependent cellular cytotoxicity (ADCC) -Reaction takes minutes to hours -IgM and *IgG mediated, opsonization via complement* and IgG -Examples are drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia -This type of reaction is caused by an antibody response to self via antibodies. The antigens that the antibodies are binding to can be endogenous or exogenous. In the case of exogenous antigens the foreign element is encorporated into cell membranes (melds can do this), then the antibodies bind to the antigen and tag the cell for death. -So in this type the antibody is always binding to an antigen on a cell surface
Type 4
-Delay type hypersensitivity -T-cell mediated. Helper T-cells recruit cytotoxic t-cells and monocytes that do the majority of the damage -Can take many hours to days to manifest -Classic examples are TB test and contact dermatitis, graft rejection
Type I Cont...
-Dendritic cell presents antigen to Naive T helper 2 cell - IL-4 production activates B cells (IL-5 activates Eosinophils, IL-13 mucous production) - Plasma cells make IgE which primes Mast cells. -Once antigen is encountered again, primed Mast cells degranulate - smooth muscle spasm, vasodilation (edema), leukocyte infiltration and mucous production (late phase)
Type I Cont...
Antigen and IgE crosslinking...
Type 3
-Immune complex hypersensitivity -Characterized by antibody complexes that form with soluble antigens only -Classic examples of the would be lupus erythematosus, reactive arthritis, and serum sickness -Mostly IgG class antibodies
Type 1
-immediate or anaphylactic hypersensitivity -*IgE mediated* -Primary involved cells types are basophils (in circulation - small numbers, *mast cells (normally present in tissues)*, and eosinophils -Reaction is immediate
Type III Cont...
Development of a localized Arthus reaction (type III hypersensitive reaction). Complement activation initiated by immune complexes (classical pathway) produces complement intermediates that (1) mediate mast-cell degranulation, (2) chemotactically attract neutrophils, and (3) stimulate release of lytic enzymes from neutrophils trying to phagocytose C3b-coated immune complexes.
Cont...
Development of delayed-type hypersensitivity reaction after a second exposure to poison oak. Cytokines such as IFN-γ, macrophage-chemotactic factor (MCF), and migration-inhibition factor (MIF) released from sensitized TH1 cells mediate this reaction. Tissue damage results from lytic enzymes released from activated macrophages.
Type IV Cont...
Overview of the DTH response. (a) In the sensitization phase after initial contact with antigen (e.g., peptides derived from intracellular bacteria), TH cells proliferate and differentiate into TH1 cells. Cytokines secreted by these T cells are indicated by the dark blue balls. (b) In the effector phase after subsequent exposure of sensitized TH1 cells to antigen, the TH1 cells secrete a variety of cytokines and chemokines. These factors attract and activate macrophages and other nonspecific inflammatory cells. Activated macrophages are more effective in presenting antigen, thus perpetuating the DTH response, and function as the primary effector cells in this reaction.
