Immunodeficiency disease syndromes

An effective immune system requires that any antigens that are not native to the body be quickly recognized and destroyed, and that none of the antigens native to the body be identified as foreign. Excesses in the latter constitute the autoimmune diseases. Deficiencies in the body's ability to recognize antigens as foreign or a diminished capacity to respond to recognized antigens constitute the immunodeficiency syndromes.

There are many causes associated with immunodeficiencies. Primary immunodeficiencies are inherited conditions in which specific genes or gene families are corrupted by mutations or chromosome deletions. These syndromes are discussed elsewhere in this volume. Secondary immunodeficiencies are acquired conditions that may result from infections, cancers, aging, exposure to drugs, chemicals or radiation, or a variety of other disease processes.

Bacteria , viral, fungi , protozoa , and even parasitic infections can result in specific deficiencies of B cells , T cells , macrophages, and granulocytes. The best characterized of the infectious diseases is the acquired immunodeficiency syndrome (AIDS ).

Infection by two viruses , HIV-1 and HIV-2, is associated with a wide range of responses in different people from essentially asymptomatic to a full-blown AIDS in which cell-mediated immunity is seriously compromised. HIV-1 and HIV-2 are retroviruses that attack humans and compromise cellular function. In contrast, the human T cell lymphotrophic viruses (HTLV ) tend to provoke lymphoid neoplasms and neurologic disease. AIDS is most often associated with HIV-1 infection. The chance of developing AIDS following infection with HIV-1 is approximately one to two percent per year initially, and increases to around five percent per year after the fifth year of infection. Roughly, half of those infected with the virus will develop AIDS within ten years. In between those who are asymptomatic, and those with AIDS who are symptomatic with conditions associated with AIDS.

In AIDS, cellular immunity mechanisms are disrupted. Some immunologic cells are reduced in number and others, such as natural killer cells, have reduced activity despite their normal numbers. HIV infects primarily T helper lymphocyte cells and a variety of cells outside of the lymphoid system such as macrophages, endothelial, and epithelial cells. Because the T helper cells normally express a surface glycoprotein called CD4, counts of CD4 cells are helpful in predicting immunologic depression in HIV-infected individuals. The amount of viral RNA in circulation is also a helpful predictor of immunologic compromise. In addition to cell-mediated immunity, antibody responses (humoral immunity) are also muted in individuals with AIDS.

Initially, there is a period of several weeks to months where the host remains HIV antibody negative and viral replication occurs rapidly. Some subjects develop an acute response that appears like the flu or mononucleosis . Symptoms typically include fever, malaise, joint pain, and swollen lymph nodes. As the initial symptoms dissipate, patients enter an antibody positive phase without symptoms associated with AIDS. A variety of relatively mild symptoms like thrush , diarrhea, fever, or other viral infections may manifest along with a wide array of partial anemias. Nerve function can become compromised resulting in weakness, pain, or sensory loss. Eventually, life threatening opportunistic infections resulting from decreased immunologic function occur and may be accompanied by wasting, dementia, meningitis , and encephalitis. Drug therapy in the form of antiretroviral agents is directed toward inhibition of proteases and reverse transcriptase enzymes which are critical for replication of the viruses.

Although not nearly as well known as AIDS, there are a variety of other acquired immunodeficiencies. Infections other than HIV can significantly alter the numbers and functions of other cells within the immune system. While individually these various infections may appear to be relatively uncommon, depression in the numbers of platelets, T cells, B cells, natural killer (NK) cells, and granulocytes can lead to immunologic dysfunction. The manifestations of these various conditions will depend on the specific cell population that is involved and its normal function within the immune system. B cell deficiencies tend to result in an increased susceptibility to bacterial infections. Decreased natural killer cell activity can result in the survival of tumor cells which would otherwise be destroyed by the immune system.

Chemical and physical agents (such as radiation) also can potentially depress various fractions of cells within the immune system, and like the immunodeficiencies caused by infectious agents, the manifestations of these agents will differ depending on the cells which are influenced. Cancer chemotherapeutic agents are often immunosuppressive. Likewise, immune function often declines with age. T cell populations (including the T helper cells) decline as the thymus gland activity decreases. Frequently, B cell populations proliferate at an accelerated rate in older people. Over production of cells within the immune system such as leukemias, lymphomas, and related disorders also may disturb immune function by radically altering the distribution of white cells. A number of other diverse disease processes can alter or compromise immune function. These include diabetes, liver disease, kidney disease, sickle cell anemia, Down syndrome, and many of the autoimmune diseases.

See also AIDS, recent advances in research and treatment; Autoimmunity and autoimmune diseases; Immunodeficiency diseases, genetic causes