Outline and chapter notes to accompany chapter 16 HIV AND AIDS Dec., 2003 A. AIDS IS AN IMMUNE SYSTEM DEFICIENCY AIDS stands for Acquired Immune Deficiency Syndrome THE IMMUNE SYSTEM protects the body by eliminating certain cells and molecules. The immune system recognizes that these cells and molecules should not normally be present under conditions of good health. Major cells of the immune system include: B lymphocytes, which protect the body by secreting proteins called antibodies; Cytotoxic T lymphocytes (also called CD8), which kill infected cells; Helper T lymphocytes (also called CD4 or T4), which secrete interleukin-2. Interleukin-2 is a chemical messenger (cytokine) which provides the stimulus for B lymphocytes to secrete their antibodies or for cytotoxic T lymphocytes to begin killing infected cells. IMMUNE DEFICIENCY Immune deficiency is the absence of one or more normal functions of the immune system. Deficiencies in the immune system lower resistance to infectious diseases and cancer. In particular, opportunistic infections are those which healthy individuals can easily fight off, but which spread through the bodies of people suffering from immunodeficiency. Immune deficiency can be inherited, as in SCIDS (see chapter 3). It can also be acquired (temporarily) when immune-suppressing drugs are given to transplant patients. It can also be acquired as a lasting infection, as in AIDS. B. AIDS IS CAUSED BY A VIRUS CALLED HIV DISCOVERY OF THE CONNECTION BETWEEN HIV AND AIDS Much of the early evidence came from epidemiology, the study of diseases in populations. First, a cluster of unusual pneumonia cases was noticed in San Francisco. (This pneumonia was caused by a parasite called Pneumocystis carinii instead of the usual bacteria.) Second, a cluster of Kaposi's sarcoma occurred in New York. This cancer is normally rare, normally slow-growing, and normally found in aged men. These patients were young, previously healthy men, and the cancer grew aggressively. One of the men proved to have a reduced number of CD4 T lymphocytes; subsequent tests showed reduced counts of these lymphocytes in the other Kaposi's patients and in the Pneumocystis pneumonia patients. The new disease was therefore characterized as an immunodeficiency in which the function of CD4 lymphocytes (helper T cells) was impaired. The disease was named Acquired Immune Deficiency Syndrome or AIDS. A few cases of AIDS showed up in hemophiliacs who had received blood products (clotting factors) to treat their disease. The blood had been filtered to remove all bacteria, but viruses were capable of passing through such filters. This led some researchers to suspect that a virus was responsible for AIDS. Since helper T cells were killed off among AIDS patients, researchers looked for viruses that grew inside human T cells. One research group, led by Robert Gallo, had been growing human T-cell leukemia viruses (HTLV). Two types, called HTLV-I and HTLV-II, proved not to be present in AIDS patients, but a third type, HTLV-III was present. Meanwhile, researchers in France had identified a virus that they called LAV. LAV and HTLV-III were later determined to be the same virus, which was renamed Human Immunodeficiency Virus, or HIV. Methods for identification of HIV or other specific viruses are outlined in Box 13.1. ESTABLISHING CAUSE AND EFFECT For most infectious diseases, identification of a causative organism follows Koch's postulates: 1. the suspect organism must be obtained from sick individuals with the disease; 2. the organism must not be present in individuals who do not have the disease; 3. the organism must be grown in pure culture containing no other microorganisms; 4. the organisms must be injected into healthy individuals and they must get the disease; 5. organisms of the same type must be re-isolated from the cases infected in step 3. These criteria are difficult to realize in the case of diseases like AIDS, because: a. viruses cannot be grown in pure culture, but only in host cells. b. it is not ethical to infect human volunteers, and there are no other animal species in which HIV will grow. However, a great deal of circumstantial evidence points to HIV as the cause of AIDS: a. HIV (or antibodies against HIV) is present in nearly all AIDS patients; b. most people who have HIV eventually get AIDS; c. HIV attacks the same type of cells that are depleted in AIDS patients; d. HIV can be recovered at autopsy from people who die from AIDS. VIRUSES AND HIV In general, viruses infect host cells by injecting their genetic material (DNA or RNA), using the host's genetic machinery to replicate the virus DNA, transcribe the DNA to make viral RNA, translate the RNA into a protein sequence, assemble new virus particles, and release thousands of new viruses ready to infect new cells. HIV belongs to a small group of viruses called retroviruses. In these viruses, the genetic material is RNA, and the RNA is first used to make DNA by reverse transcription (Fig. 13.3). EVOLUTION OF VIRULENCE New diseases are usually virulent-- they make many hosts seriously ill or kill them. As hosts evolve defenses, disease organisms become less virulent-- fewer hosts are killed. Only if the pathogens can spread rapidly once again can they once again become virulent and kill their hosts without dying out because they have meanwhile spread to new hosts. C. HIV INFECTION PROGRESSES IN CERTAIN PATTERNS, OFTEN LEADING TO AIDS EVENTS IN INFECTED HELPER T CELLS HIV kills or incapacitates CD4 T lymphocytes by various mechanisms: causing cells to fuse with one another to form giant cells (which cannot function as T cells) causing cell rupture (lysis) causing cells to commit cellular suicide (apoptosis) noncytopathic strains of HIV impair T-cell functioning without killing the cells. PROGRESSION FROM HIV INFECTION TO AIDS Stage 1. Initial infection: As virus spreads, antibodies are produced against it (seroconversion to HIV positive) and many CD4 T-lymphocytes are killed. Stage 2. Asymptomatic phase: Virus particles become hard to detect in blood; CD4 cells are killed at slower rate. Asymptomatic phase may last for months or years. Stage 3. The disease progresses to full-blown AIDS: virus levels increase; CD4 cell counts diminish greatly; death often occurs from opportunistic infections. TESTS FOR HIV INFECTION: ELISA antibody tests can detect antibodies to HIV. Results are reported as HIV- or HIV+. The process in which a person becomes HIV+ by developing antibody to HIV is called seroconversion. Western blot tests also detect antibodies. The test is more expensive but it gives fewer false positive results (test results that appear positive when the person really was not). Both of these tests have low rates of false negatives (results that are negative when the person really has the condition being tested for). Both tests are thus sensitive (low rate of false negatives). The Western blot test has higher specificity (meaning a lower rate of false positives). PCR tests detect viral nucleic acids instead of antibodies. Testing everyone for AIDS would result in very many false positives. A VACCINE AGAINST AIDS? Vaccines stimulate specific cells of the immune system to divide. In HIV infection, stimulating the infected CD4 cells to divide may actually spread the infection and causes it to progress to a more dangerous phase. Vaccines also require healthy CD4 cells in order for the vaccine to work. For these reasons, traditional vaccines may not be possible for AIDS. DRUG THERAPY FOR PEOPLE WITH AIDS Current drugs against AIDS prevent reverse transcription and thus interfere with the HIV life cycle. These include both Zidovudine (ZDV, formerly called AZT) and didanosine (DDI). D. KNOWLEDGE OF HIV TRANSMISSION CAN HELP YOU AVOID AIDS RISKS RISK BEHAVIORS: Risk is the probability of transmission. High risk behaviors increase the likelihood of transmission: unprotected sex with an infected person (especially anal sex) sharing needles with an infected person COMMUNICABILITY Transmission is the passage of a pathogen from one individual to another. Transmission routes for HIV include: transmission via semen, vaginal fluids, or blood during sexual intercourse transmission by blood via hypodermic needles, during birth, or by any other contact with another person's blood AIDS is NOT transmitted by touching, saliva, eating utensils, toilets, or mosquitoes. SUSCEPTIBILITY VERSUS HIGH RISK: All humans are susceptible-- if exposed to sufficient levels of the virus, we are likely to become infected. Other species are not susceptible to HIV. High risk depends on individual behavior, not on membership in a group. The following behaviors will increase your risks: unprotected sex anal sex multiple sex partners intravenous drug use poor self-esteem and poor refusal skills High risk groups are those in which a high percentage of people are infected. PUBLIC HEALTH AND PUBLIC POLICY Public health measures are those which seek to minimize disease risks in populations. Policy varies from country to country and also sometimes more locally. Educational programs work, but they are often hampered by disagreements over what messages to convey. The messages need to be tailored to different target groups. Testing for HIV is a controversial issue. Most jurisdictions prohibit disclosing results. WORLDWIDE PATTERNS OF INFECTION Incidence rates vary by country and continent. Africa currently has the highest rates. The greatest rates of increase are in Asia. In Africa and Asia, incidence rates are comparable among men and women. In North America, South America, and Europe, incidence rates are high among men. ---------------------------------- Dec., 2003 PERMISSION IS HEREBY GRANTED to instructors who have adopted the book BIOLOGY TODAY for classroom use to download, modify, and use these notes as needed to aid them in in their teaching. Students of such instructors may likewise use and modify these notes as study aids.