87. Acquired immunodeficiency syndrome: etiology, pathogenesis, pathological anatomy of the organs of immunogenesis.

The causative agent of AIDS is the human immunodeficiency virus, a retrovirus belonging to the lentivirus family. This virus has a number of features: a long incubation period, tropism to the hematopoietic and nervous systems, the ability to cause immunosuppression and cytopathic effects. There are two genetically different forms of the AIDS virus — human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2). HIV-1 is the most common type.

Pathogenesis: There are two main targets for the AIDS virus: the immune system and the central nervous system, the pathogenesis of AIDS is characterized by the development of deep immunosuppression, which is associated with a marked decrease in the number of CD4+T cells. Infection begins with the binding of the gp120 virus envelope glycoprotein to CD4 molecules. Then the virus merges with the cell membrane. The cell genome undergoes reverse transcription, which leads to the formation of proviral DNA.

In dividing T lymphocytes, proviral DNA enters the nucleus and then integrates into the host genome, leading to cell death.

Infection of monocytes and macrophages is an extremely important link in the pathogenesis of AIDS. Like T-lymphocytes, most macrophages infected with the immunodeficiency virus are formed in tissues, not in peripheral blood. Despite the fact that virus replication is possible in macrophages, unlike CD4+T cells, they are resistant to the cytoplasmic action of the virus.

Infection of macrophages leads to the fact that monocytes and macrophages turn into a real factory for the production of viruses and a reservoir for their storage. Macrophages are able to transport the virus throughout the body, especially to the nervous system. Dendritic cells in the lymph node reproduction centers are also an important reservoir of the virus.

CD4+T cells, macrophages and dendritic cells, rather than blood cells, are the main reservoirs of the virus. AIDS patients develop profound disorders of the functioning of B lymphocytes. Thus, these patients have hypergammaglobulinemia and circulating immune complexes associated with polyclonal activation of B lymphocytes.

Course: consists of three phases: early (acute) phase; middle (chronic) phase; final (crisis) phase. In the early phase, the initial response of an immunocompetent person to the virus develops. It is characterized by a high level of virus formation and widespread contamination of lymphoid tissue. During this period, the infection is controlled by an antiviral immune response. The chronic phase is a period of relative containment of the virus. The immune system is intact, there is weak replication of the virus, mainly in lymphoid tissue. This phase can last for several years. The final phase is characterized by a violation of the host's defense mechanisms and virus replication. The CD4+ content decreasesT cells. After an unstable period, serious opportunistic infections, secondary tumors, and signs of neurological disease appear.

It is known that the direct lesion consists in the infection and destruction of cells of the nervous system that have the CD4 receptor. These include: astrocytes, oligodendrocytes, microglia, monocytes, fibroblast-like brain cells, blood vessel endothelial cells, neurons. In addition, glial cells are affected not only due to infection, i.e. the penetration of HIV into the cell itself, but also due to their membrane lysis by the gp120 protein. The gp120 glycoprotein plays a key role in the pathogenesis of HIV-neuronal damage by blocking neuroleukin (lymphokine with neurotrophic action). Under the influence of gp120, astrocytes do not retain glutamate in synapses, which leads to an increased ion load of Ca2+ and cytotoxic action.

Pathological anatomy. The lymph nodes decrease sharply and are difficult to identify. The damage to the central nervous system is represented by HIV encephalomyelitis, with the main changes in the white matter and subcortical nodes of the brain. One of the most common and characteristic infections in AIDS is caused by pneumocysts. It leads to the development of severe pneumonia with the formation of a large number of foamy eosinophilic masses in the alveoli, in which pneumocysts are detected. Toxoplasma infection also occurs quite often. With cryptosporidiosis, the intestines are affected, enteritis and colitis develop, manifested by prolonged profuse diarrhea.

Malignant tumors in AIDS occur in 40% of cases. Kaposi's sarcoma (in 30% of patients) and malignant lymphomas are the most characteristic.

Kaposi's sarcoma (multiple idiopathic hemorrhagic sarcoma) is a rare disease that usually occurs in men over 60 years old, characterized by a slow, rather benign course. It is manifested by purplish-red spots, plaques and nodes, usually located on the skin of the distal parts of the lower extremities. Ulceration is characteristic. Microscopically, the tumor consists of a multitude of newly formed randomly arranged thin-walled vessels with well-defined endothelium and bundles of spindle-shaped cells (Fig. 254). Hemorrhages and accumulations of hemosiderin are often visible in the loose stroma. In AIDS patients, Kaposi's sarcoma has a malignant character and differs from the classical version by generalization of the process with damage to the lymph nodes, gastrointestinal tract, lungs and other internal organs.

Malignant lymphomas in AIDS are predominantly B-cell. Burkitt's lymphoma is common