Causes of immune deficiency The primary pathogenic mechanism in HIV infection is the damage caused to the CD4+ T lymphocytes- The T4 cells decrease in numbers and the T4:T8 cell ratio is reversed. The infected cells do not release cytokines. This has a marked damping effect in the cell mediated immune response. Though the major damage is to cellular immunity, the humoral mechanisms are also affected. AIDS patients are unable to respond to new antigens. There is polyclonal activation of B lymphocytes leading to hypergammaglobulinemia. These are non specific antibodies and are irrelevant to antigens. Monocyte, macrophage system is also affected apparently due to the lack of the activating factors by the T4 lymphocytes. The activity of NK cells and Tc (T Cytotoxic) cells are also affected. The clinical manifestations are due to failure of the immune responses. This renders the patient susceptible to life threatening opportunistic infections and malignancies. The exceptions to this may be the neurological lesions seen in AIDS. Dementia and other degenerative neurological lesions seen in AIDS are due to direct toxic effects of HIV on the central nervous system. Clinical Manifestations AIDS is only the last stage in the wide spectrum of clinical features in HIV infection. The center for disease control (USA) has classified the clinical course of HIV infection under various groups. 1. Acute HIV infection 2. Asymptomatic or Latent infection 3. Persistent generalized lymphadenopathy (PGL) 4. AIDS related complex 5. Full blown AIDS (Last stage) 1. Acute HIV infection Many people do not develop symptoms after they first get infected with HIV. Others have a flu-like illness with fever, sore throat, headache, tiredness, skin rashes and enlarged lymph nodes in the neck within several days to weeks after exposure to virus. These symptoms usually disappear of their own within a few weeks. The test for HIV antibodies appears negative while HIV antigenemia (p24 antigen) and viral nucleic acids can be demonstrated at the beginning of the phase. This phase is also called window period or phase of Sero conversion. 2. Asymptomatic or Latent infection All persons infected with HIV, pass through a phase of symptomless infection (Clinical latency), which may last up to several years. The progression of disease varies widely among individuals. This state may last from a few months to more than 10 years. During this period, the virus continues to multiply actively and infects and kills the cells of the immune system. The virus destroys the CD4 cells that are the primary infection fighters. Even though the person has no symptoms, he or she is contagious and can pass HIV to others through the routes listed above. The patients show positive antibody tests during this phase. The infection progresses in course of time through various stages, CD4 lymphocytopenia, minor opportunistic infections, persistent generalized lymphadenopathy, AIDS related complex, ultimately terminating in full blown AIDS.(Figure-5) The median time between primary HIV infection and development of AIDS has been stated as approximately 10 years. About 5-10 % percent of the infected appear to escape clinical AIDS for 15 years or more. They have been ‘long term survivors” or “long term non progressors”. The mechanism for such long time survivors is not exactly known, though many viral and host determinants are responsible. During this period the host mounts an immune response against the virus, both humoral and cellular, which can only limit the viral load but can not clear it completely. A chronic persistent infection with varying degree of multiplication is the result. 3. Persistent generalized lymphadenopathy (PGL) This has been defined by presence of enlarged lymph nodes, at least I cm in diameter, in two or more non contiguous extra inguinal sites, that persist for at least three months, in the absence of any current illness or medication that may cause lymphadenopathy. These are diagnostic of HIV when blood tests are positive for antibodies. 4. AIDS related complex This group includes patients with considerable Immuno deficiency suffering from various constitutional symptoms of minor opportunistic infections. The patients present with weight loss – of more than 10% of body weight, persistent fever, diarrhea, generalized fatigue and signs of other opportunistic infections may be apparent. The opportunistic infections are oral candidiasis, herpes zoster, salmonellosis or Tuberculosis and hairy cell leucoplakia. The patients are usually severely ill and many of them progress to AIDS in few months. The CD4 cell count decreases steadily when the count falls to 200, or less, clinical AIDS usually sets in. For this reason the case definition by CDC includes all HIV infected cases with CD4 + T cell counts of 200 or less, irrespective of clinical condition. 5. Full blown AIDS This is the end stage disease representing the irreversible break down of immune defense mechanisms. In addition to the opportunistic infections the patient may develop primary CNS lymphomas and progressive multifocal leukoencephalopathy, dementia and other neurological abnormalities. Kaposi sarcoma (Figure-4) and Pneumocystis pneumonia are almost always observed in a majority of patients.
Posted on: Sun, 21 Jul 2013 11:51:50 +0000
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