Chapter 8: Alterations in Immunity

Hypersensitivity reactions represent pathologic immune responses categorized by four distinct mechanisms. Type I hypersensitivity involves immunoglobulin E-mediated reactions to environmental triggers such as foods, medications, pollen, fungi, and arthropod venoms, manifesting as localized responses like allergic rhinitis and asthma or systemic anaphylaxis with potentially fatal cardiovascular and respiratory collapse. Type II hypersensitivity encompasses antibody-directed damage to specific tissues, exemplified by autoimmune hemolytic anemia and Graves disease affecting thyroid function. Type III hypersensitivity results from deposition of circulating immune complexes in tissue spaces, triggering inflammatory cascades characteristic of systemic lupus erythematosus, serum sickness, and Arthus-type reactions. Type IV hypersensitivity operates through T-cell and macrophage-mediated mechanisms with delayed kinetics, driving graft rejection, contact dermatitis, and certain autoimmune diseases including rheumatoid arthritis and type 1 diabetes mellitus. The chapter then addresses autoimmunity, wherein breakdown of self-tolerance permits immune attack against autoantigens through mechanisms including molecular mimicry, genetic predisposition, and loss of regulatory control. Systemic lupus erythematosus exemplifies this process, involving both antibody-mediated and immune complex-driven pathology. Alloimmunity describes immune responses to non-self antigens from genetically different individuals, including transfusion reactions involving ABO and Rh incompatibility, hemolytic disease in newborns, and organ transplant rejection occurring through hyperacute, acute, and chronic phases with human leukocyte antigen mismatch as a critical determinant. The latter section examines immune deficiencies arising from congenital genetic disorders or acquired conditions. Primary immunodeficiencies include severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, and complement component defects, predisposing to recurrent infections and malignancy. Secondary deficiencies develop from malnutrition, aging, pregnancy, malignancy, trauma, and medical interventions including chemotherapy and immunosuppressive medications. Human immunodeficiency virus infection represents a critical secondary immunodeficiency; its pathogenesis involves viral attachment via surface glycoproteins to CD4-positive T-helper lymphocytes, genomic integration, progressive viral replication, and systematic CD4 depletion. Clinical progression follows distinct stages from acute infection through latency to advanced immunosuppression, characterized by opportunistic infections, neoplastic transformations, and cachexia. Antiretroviral therapy combining reverse transcriptase, protease, integrase, and entry inhibitor classes has transformed HIV from uniformly fatal to chronic manageable disease, though lifelong adherence remains mandatory.