Immunodeficiencies(AIDS)

Immunodeficiencies can be divided into the primary immunodeficiency disorders, which are almost always genetically determined, and secondary immunodeficiency states, which may arise as complications of cancers, infections, malnutrition, or side effects of immunosuppression, irradiation, or chemotherapy for cancer and other diseases. The primary immunodeficiency syndromes are accidents of nature that provide valuable insights into some of the critical molecules of the human immune system. Here we briefly discuss the more important primary immunodeficiencies, to be followed by a more detailed description of acquired immunodeficiency syndrome (AIDS), the most devastating example of secondary immunodeficiency.
Morphology. The anatomic changes in the tissues (with the exception of lesions in the brain) are neither specific nor diagnostic. In general, the pathologic features of AIDS include those of widespread opportunistic infections, KS, and lymphoid tumors. Most of these lesions are discussed elsewhere, because they also occur in individuals who do not have HIV infection. Lesions in the central nervous system are described in Chapter 28 .
Biopsy specimens from enlarged lymph nodes in the early stages of HIV infection reveal a marked follicular hyperplasia. The mantle zones that surround the follicles are attenuated, and hence the germinal centers seem to merge with the interfollicular area. These changes, affecting primarily the B-cell areas of the node, are the morphologic reflections of the polyclonal B-cell activation and hypergammaglobulinemia seen in patients with AIDS. Under the electron microscope and by in situ hybridization, HIV particles can be detected within the germinal centers. Here they seem to be concentrated on the processes of follicular dendritic cells, presumably trapped in the form of immune complexes. During the early phase of HIV infection, viral DNA can be found within the nuclei of CD4+ T cells located predominantly in the parafollicular regions. The B cell hyperplasia is also reflected in the bone marrow, which typically contains increased numbers of plasma cells, and in peripheral blood smears, which often demonstrate rouleaux, the abnormal stacking of red cells that results from hypergammaglobulinemia. With disease progression, the frenzy of B-cell proliferation subsides and gives way to a pattern of severe follicular involution. The follicles are depleted of cells, and the organized network of follicular dendritic cells is disrupted. The germinal centers may even become hyalinized. During this advanced stage viral burden in the nodes is reduced, in part because of the disruption of the follicular dendritic cells. These “burnt-out” lymph nodes are atrophic and small and may harbor numerous opportunistic pathogens. Because of profound immunosuppression, the inflammatory response to infections both in the lymph nodes and at extranodal sites may be sparse or atypical. For example, mycobacteria may not evoke granuloma formation because CD4+ cells are deficient. In the empty-looking lymph nodes and in other organs, the presence of infectious agents may not be readily apparent without special stains. As might be expected, lymphoid depletion is not confined to the nodes; in later stages of AIDS, the spleen and thymus also appear to be “wastelands.”