sensitization phase

The sensitization phase of Type II hypersensitivity reactions is marked by the production of IgG and IgM antibodies specific for a cell surface antigen (Fig. 13.4). The eliciting antigens are either constitutive components of the cell, or exogenous antigens (e.g., drugs or drug metabolites) that have bound to cell surface molecules. Consequently, any cell may be a target.

Effector phase

Unlike Type I hypersensitivity reactions, Type 2 hypersensitivity reactions need not "await" re-exposure to antigen because the antigen is not eliminated during primary exposure to the immune system. Destruction of cells expressing antigen/ antibody (IgM or IgG) complexes occurs when the classical pathway of complement is activated, leading either to osmotic lysis of cells by the membrane attack complex, or opsonin-mediated phagocytosis when C3b is deposited on the target cell. Cell bound IgG can also serve as an opsonin for phagocytosis.

Cell destruction may also occur by antibody dependent cell mediated cytotoxicity (ADCC). ADCC occurs when natural killer cells expressing the FcyR bind IgG, initiating secretion of the cytotoxic molecule, perforin, that induces osmotic cell lysis (Fig. 13.4). Continued exposure to antigen induces higher titers of high avidity antibody (Chapter 8). Re-exposure to antigen (e.g., to a drug bound to a cell) results in more exaggerated effector responses. When the antigen is a constitutive component of the cell, ongoing cell destruction occurs.

Clinical manifestations

Clinical manifestations of Type II hypersensitivity responses include (i) transfusion reactions; (ii) hemolytic disease of the newborn, primarily due to Rh incompatibility; (iii) autoimmune reactions to cellular antigens or tissues; and (iv) hyperacute rejection of transplanted tissue. Note that in each case the antibody is directed to a cell surface, not soluble, antigen.

Transfusion reactions

Individuals receiving blood transfusions are "matched" to ensure that the recipient does not have antibodies recognizing the glycoproteins, predominantly of the ABO system, on the donor's red blood cells. Naturally occurring IgM antibodies, isohemagglutinins, bind to these glycoproteins on red cells, and activate complement leading to either cell lysis or opsonin-mediated (C3b) phagocytosis. Isohemagglutinins develop as a result of immunization by gut commensal organisms that have surface antigens identical to the AB antigens present on human red blood cells. Individuals inherit genes leading to the expression of the glycoproteins designated A and/or B. Some individuals do not express either A or B and are classified as the "O" blood phenotype.

Hypersensitivity Type II: Sensitization Phase

Hypersensitivity Type II: Effector Phase

Circulating antibodies bind cell surface antigens

Hypersensitivity Type II: Effector Phase

Circulating antibodies bind cell surface antigens

Complement activation

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