Chapter 3 Immunopathology
• Close matches of HLA-A, -B, and -D loci in both the donor and graft recipient increase the chance of graft survival.
A. Type I (immediate) hypersensitivity
• IgE antibody–mediated activation of mast cells (effector cells) produces an inflammatory reaction.
• Positive response is a histamine-mediated wheal-and-flare reaction after introduction of an allergen into the skin.
(1) Antibody (IgM) directed against antigen on the cell membrane activates the complement system, leading to lysis of the cell by the membrane attack complex.
(3) Example—transfusion of group A blood (contains anti-B-IgM antibodies) into a group B individual (refer to Chapter 15)
(1) IgG attaches to basement membrane/matrix → activates complement system → C5a is produced (chemotactic factor) → recruitment of neutrophils/monocytes to the activation site → release of enzymes, reactive oxygen species → damage to tissue
(2) Example—Goodpasture’s syndrome with IgG antibodies directed against pulmonary and glomerular capillary basement membranes (refer to Chapter 19)
(3) Example—acute rheumatic fever with IgG antibodies directed against antigens in heart, skin, brain, subcutaneous tissue, joints (refer to Chapter 10)
(1) Fixed macrophages (e.g., in spleen) phagocytose hematopoietic cells (e.g., RBCs) coated by IgG antibodies or complement (C3b).
• Group O mother has anti-A,B-IgG antibodies that cross the placenta and attach to fetal blood group A or B red blood cells.
(1) Cells are coated by IgG → leukocytes (neutrophils, monocyte, NK cells) bind to IgG → activated cells release inflammatory mediators causing lysis of the cells
• Helminth in tissue is coated by IgE antibodies → eosinophil IgE receptors attach to the IgE → eosinophils release major basic protein, which kills the helminth
Myasthenia gravis, Graves’ disease: antibodies against receptors; type II HSR
c. IgG autoantibodies directed against cell surface receptors → impair function of the receptor (e.g., anti-acetylcholine receptor antibodies in myasthenia gravis) or stimulate function (e.g., anti-thyroid-stimulating hormone receptor antibodies in Graves’ disease)
• Activation of the complement system by circulating antigen-antibody complexes (e.g., DNA–anti-DNA complexes)
Type III hypersensitivity: complement activation by circulating antigen-antibody complexes
4. Test used to evaluate type III hypersensitivity
Antibody-mediated hypersensitivity reactions: types I, II, and III
a. Control of infections caused by viruses, fungi, helminths, mycobacteria, intracellular bacterial pathogens
• CD4 cells interact with macrophages (APCs with MHC class II antigens), resulting in cytokine injury to tissue (refer to Chapter 2).
(1) CD8 T cells interact with altered MHC class I antigens on neoplastic, virus-infected, or donor graft cells, causing cell lysis.
• Example—suspected allergen (e.g., nickel) placed on an adhesive patch is applied to the skin to see if a skin reaction occurs.
4. Chance of a sibling in a family having another sibling with a 0, 1, or 2 haplotype match is illustrated in Figure 3-1.
• Transplantation rejection involves a humoral or cell-mediated host response against MHC antigens in the donor graft.
(1) ABO incompatibility or action of preformed anti-HLA antibodies in the recipient directed against donor antigens in vascular endothelium
(a) Host CD4 T cells release cytokines, resulting in activation of host macrophages, proliferation of CD8 T cells, and destruction of donor graft cells.
(b) Extensive interstitial round cell lymphocytic infiltrate in the graft, edema, and endothelial cell injury
(2) Antibody-mediated type II hypersensitivity reaction
(a) Cytokines from CD4 T cells promote B-cell differentiation into plasma cells, producing anti-HLA antibodies that attack vessels in the donor graft.
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