There are several inherited and acquired immune deficiency disorders. In some individuals, T or B cells never form; in others, B cells lose the ability to give rise to plasma cells. In either case, the affected individual is unable to mount an adaptive immune response and thus lacks a major line of defense against pathogens. The T_H cell is perhaps the most central component of the immune system because of its essential roles in both the humoral and cellular immune responses (see Figure 41.6). This cell is the target of human immunodeficiency virus (HIV), the retrovirus that results in acquired immune deficiency syndrome (AIDS).

HIV can be transmitted from person to person in body fluids containing the virus (such as blood, semen, or vaginal fluid). The recipient tissue is either blood (by transfusion) or a mucous membrane lining an organ (the mucus contains a high concentration of lymphocytes). HIV initially infects macrophages, T_H cells, and antigen-presenting dendritic cells in the blood and tissues. At first there is an immune response to the viral infection, and T_H cells are activated. But because HIV infects the T_H cells, they are killed both by HIV itself and by T_C cells that lyse infected T_H cells. Consequently T_H cell numbers decline after the first month or so of infection. Meanwhile, the extensive production of HIV by infected cells activates the humoral immune system. Antibodies bind to HIV, and the complexes are removed by phagocytes. The HIV level in blood goes down. There is still a low level of infection, however, because of the depletion of T_H cells (Figure 41.16). This process reaches a low, steady-state level called the “set point.” This point varies among individuals and is a strong predictor of the rate of progression of the disease. For most people it takes 8–10 years without treatment for the more severe manifestations of AIDS to develop. In some it can take as little as a year; in others, 20 years.

During this dormant period, people carrying HIV generally feel fine, and their T_H cell levels are adequate for them to mount immune responses. Eventually, however, the virus destroys the T_H cells, and their numbers fall to the point where the infected person is susceptible to infections that the T_H cells would normally eliminate. These infections result in conditions such as Kaposi’s sarcoma, a skin tumor caused by a herpes virus; pneumonia caused by the fungus Pneumocystis jirovecii; and lymphoma tumors caused by the Epstein–Barr virus. These conditions result from opportunistic infections because the pathogens take advantage of the crippled immune system of the host. They lead to death within a year or two.

HIV has been intensively studied. This has resulted in the development of drugs targeted to HIV proteins, such as the reverse transcriptase that makes cDNA from the viral RNA, and the viral protease that cuts the large precursor viral protein into its final active proteins. Treatment with combinations of such drugs has had spectacular success. Getting AIDS before the 1990s was a death sentence, with few sufferers surviving beyond a year or two. Today the survival of a treated, infected person is decades longer. Unfortunately, like many medical treatments, HIV drugs are not available to all who need them—particularly in poor regions of the world where AIDS is prevalent. Since AIDS is caused by a viral infection, a vaccine would seem an appropriate preventive agent. Unfortunately, despite a huge international effort that is ongoing, a vaccine against HIV has not been developed, probably because the virus “hides out” inside cells and is prone to a high mutation rate. There are about 1.2 million deaths per year worldwide from AIDS.