AIDS, HIV and The Immune System


Introduction

The virus responsible for the condition known as AIDS (Acquired Immunodeficiency Syndrome), is named HIV (Human Immunodeficiency Virus). AIDS is the condition whereby the body's specific defense system against all infectious agents no longer functions properly. There is a focused loss over time of immune cell function which allows intrusion by several different infectious agents, the result of which is loss of the ability of the body to fight infection and the subsequent acquisition of diseases such as pneumonia. We will examine the virus itself, the immune system, the specific effect(s) of HIV on the immune system, the research efforts presently being made to investigate this disease, and finally, how one can try to prevent acquiring HIV.

The Virus

HIV is one member of the group of viruses known as retroviruses. The term "retrovirus" stems from the fact that these kinds of viruses are capable of copying RNA into DNA. No other organism so far discovered on earth is capable of this ability. The virus has two exact copies of single-stranded RNA as its basic genetic material (genome) in the very center of the organism. The genome is surrounded by a spherical core made of various proteins in tightly-packed association with one another. The core is itself surrounded by a membrane (called an "envelope", made of fat [lipids] and various membrane-bound proteins). One of the membrane-bound proteins can bind to a particular protein on the surface of certain immune cells, called T-cells (we'll talk about these in a minute) which results in the virus becoming physically attached. Upon binding, the virus is brought inside of the T-cell (cells do this kind of thing all of the time), and the envelope is removed by enzymes normally present inside the cell. The internal core is thus exposed, and it too is broken-down. This last phase results in exposure of the virus's RNA genetic material. An enzyme attached to the RNA, known as "reverse transcriptase", begins to make a complimentary base-pair single-strand copy of the RNA into DNA (please see What the Heck is PCR? ). The single strand of DNA is also copied by the same enzyme to form double-stranded DNA. This DNA inserts somewhere into one of the 46 chromosomes within our cells, and there it is used as a template for production of all of the things necessary to form new virus particles ( replication of the virus). These new virus particles can be subsequently released from the infected cell, and can infect adjacent cells.

The Immune System

The immune system is a system within all vertebrates (animals with a backbone) which in general terms, is comprised of two important cell types: the B-cell and the T-cell. The B-cell is responsible for the production of antibodies (proteins which can bind to specific molecular shapes), and the T-cell (two types) is responsible either for helping the B-cell to make antibodies, or for the killing of damaged or "different" cells (all foreign cells except bacteria) within the body. The two main types of T-cells are the "helper"T-cell and the cytotoxic T-cell. The T-helper population is further divided into those which help B-cells (Th2) and those which help cytotoxic T-cells (Th1). Therefore, in order for a B-cell to do its job requires the biochemical help of Th2 helper T-cells; and, for a cytotoxic T-cell to be able to eliminate a damaged cell (say, a virally-infected cell), requires the biochemical help of a Th1 helper T-cell.

Whenever any foreign substance or agent enters our body, the immune system is activated. Both B- and T-cell members respond to the threat, which eventually results in the elimination of the substance or agent from our bodies. If the agent which gains entry is the kind which remains outside of our cells all of the time (extracellular pathogen), or much of the time (virus often released) the "best" response is the production by B-cells of antibodies which circulate all around the body in the bloodstream, and eventually bind to the agent. There are mechanisms available which are very good at destroying anything which has an antibody bound to it. On the other hand, if the agent is one which goes inside one of our cells and remains there most of the time (intracellular pathogens like viruses or certain bacteria which require the inside of one of our cells in order to live), the "best" response is the activation of cytotoxic T-cells (circulate in the bloodstream and lymph), which eliminate the agent through killing of the cell which contains the agent (agent is otherwise "hidden"). Both of these kinds of responses (B-cell or cytotoxic T-cell) of course require specific helper T-cell biochemical information as described above. Usually, both B-cell and cytotoxic T-cell responses occur against intracellular agents which provides a two-pronged attack. Normally, these actions are wonderfully protective of us. The effect of HIV on the immune system is the result of a gradual (usually) elimination of the Th1 and Th2 helper T-cell sub-populations.

How HIV Specifically Affects the Immune System

Remember about the proteins which are part of the envelope of HIV? Well, one of these proteins, named gp 120, (a sugar-containing protein called a glycoprotein, of approximately 120,000 molecular weight), "recognizes" a protein on helper T-cells named CD4, and physically associates with it. The CD4 [Cluster of Differentiation Antigen No. 4] protein is a normal part of a helper (both Th1 and Th2) T-cell's membrane. Thus, CD4 is a specific receptor for HIV. This virus however, can also infect other cells which include macrophages and certain other kinds of cells which can engulf substances through a process known as phagocytosis. As a consequence of the interaction with CD4 on helper T-cells, HIV specifically infects the very cells necessary to activate both B-cell and cytotoxic T-cell immune responses. Without helper T-cells, the body cannot make antibodies properly, nor can infected cells containing HIV (an intracellular pathogen) be properly eliminated. Consequently, the virus can: multiply, kill the helper T-cell in which it lives, infect adjacent helper T-cells, repeat the cycle, and on and on, until eventually there is a substantial loss of helper T-cells.

The fight between the virus and the immune system for supremacy is continuous. Our body responds to this onslaught through production of more T-cells, some of which mature to become helper T-cells. The virus eventually infects these targets and eliminates them, too. More T-cells are produced; these too become infected, and are killed by the virus. This fight may continue for up to ten years before the body eventually succumbs, apparently because of the inability to any-longer produce T-cells. This loss of helper T-cells finally results in the complete inability of our body to ward-off even the weakest of organisms (all kinds of bacteria and viruses other than HIV) which are normally not ever a problem to us. This acquired condition of immunodeficiency is called, AIDS.

Research

This virus has been under intense scrutiny for several years, now (since approximately 1985), and an astonishing amount of information has been gathered. One must wonder, "why isn't there a cure?" There isn't a cure primarily because there isn't a cure for most viruses. We do not yet know how to specifically kill a virus which spends most of the time hiding inside of our cells. The substances which we know can directly harm such a virus, unfortunately can also harm our own cells. Unlike our immune system, we do not yet know how to direct an attack on only those cells which are infected with the virus. Our knowledge so far allows us only to attack all of our cells (much like we do in chemotherapy for cancer treatments). We can't even sort-of focus an attack, as one can do with radiation treatment - if radiation treatment were used for HIV infections, this treatment would significantly hurt our immune system's ability to function, which is the opposite of what we want. To date, the most effective treatment against viruses is to develop a vaccine - which stimulates our own immune system to enable our immune system to better fight the virus. Thus, we have vaccines against poliovirus, smallpox virus, measles virus, influenza viruses, and others. The vaccine per se does not fight the virus, but instead causes an immune response specifically directed against the particular virus from which the vaccine is made - this response directly increases the number of specific B- and T-cells available to respond against a live virus infection encountered at some later time. Unfortunately, the fact that HIV is a retrovirus causes serious problems in vaccine development. The enzyme which generates RNA and DNA copies of the virus's RNA genetic material, makes errors. These errors are sometimes not lethal to the virus, but instead result in a different strain of a given virus - a different "looking" virus. Indeed, HIV is approximately 65-times more likely to undergo such changes as influenza virus (before HIV, the greatest variant producer - Please see The Flu Season is Upon us).

Our immune system's ability to recognize any foreign substance or agent, depends entirely upon how the substance or agent "looks" with respect to the molecular shapes displayed - just as your elbow looks different than someone else's elbow - even though each are clearly elbows. Therefore, while an individual may become infected with a single strain of HIV, over several years of many, many viral generations, an individual may have 10 different strains of HIV present. Further, to date no two people have been identified to have been infected with the same strain of HIV. Consequently, against which strain should a population be immunized? In such cases, one tries to identify molecular shapes which are common to all known strains - in this way, all strains would theoretically be recognizable by our immune system. Sadly, this research has failed to provide an effective vaccine. This virus is subtle, and can do some very covert things using biochemical mechanisms we do not yet understand. Because of recent basic research in the field of immunology (the discipline which develops an understanding of the intricate workings of the immune system), based upon years of previous basic research in this and other fields however, some light is beginning to emerge which may help us.

It is becoming clear that the two helper T-cell types identified only a few years ago may be significantly more important than first assumed. Remember, the Th1 helper-cell helps generate a cytotoxic T-cell response, and the Th2 helper-cell helps generate an antibody response. As it turns out, certain intracellular pathogens primarily elicit a Th2 response in certain in-bred strains of mice, while in a different in-bred mouse strain, the same pathogen primarily elicits a Th1 response. In this example, all mice which respond primarily with antibody (B-cell; Th2 help), die; and, all mice which primarily respond with a cytotoxic T-cell response (Th1 help), live! Such is not the case for every intracellular pathogen - some responses are very balanced with respect to B-cell and cytotoxic T-cell contributions, and others are imbalanced in one or the other direction. The balance in contribution of these two paths to an immune response, appears to not only depend upon the particular infectious organism, but also upon the particular genetic background of the infected animal. Thus, one can imagine that one may be able to find a way to tip the balance towards the most effective response path against a given organism, e.g., either antibody production by B-cells, or development of cytotoxic T-cells. This research is one of the prime areas under investigation with regard to HIV. There are very limited data to date; but, those individuals who have had HIV for a really long time, but have not yet acquired AIDS (there are indeed now a number of such individuals), appear to have their immune response shifted towards the cytotoxic side (Th1 help). This limited information on HIV, in combination with basic research information on several different diseases using animal models (mice), has generated a quick response within the research community. Consequently, there are efforts currently underway to identify the biochemical substances which are involved in directing a response along the Th1 path, and efforts to determine how the immune system might be manipulated to direct a response along a given path. Such experimentation is long and difficult, and requires money, skill, unflinching commitment, and an abiding faith that this problem can be solved.

How One Can Try Not to Become HIV-Infected

HIV can enter one's body by several different routes: indirectly through eye, oral, anal, vaginal, or urethral (female/male urine canal) contact, and directly through the bloodstream via any opening in the skin. The walls of all tissue (the eye, upper and lower respiratory, genital, urethral, intestinal) except the skin, which are exposed to the environment are lined with mucosal tissue. Within and beneath this tissue are cells which can engulf anything which invades the tissue. After engulfment of an agent, these particular cells travel to a regional area where B- and T-cells are concentrated and organized into a complex arrangement of tissue called a lymph node. Also, the engulfment process may generate a local inflammatory response, which in turn calls on the arrival of B- and T-cells from the bloodstream, across the endothelial wall of the blood-vessel, and into the tissue at the focus of the inflammatory response. If an agent enters the bloodstream via a direct injection into a vein (needle puncture made through intravenous illicit drug use, or by receipt of needed blood products, e.g., transfusion), it will enter the spleen (an organized tissue primarily containing B- and T-cells, and also various lymph nodes via lymphatic and blood vessels connected to the spleen). It is in these ways that HIV eventually associates with helper T-cells. Any abrasion in the skin or mucosal tissue provides access to the tissue and bloodstream by any infectious agent.

Under normal circumstances, the design of the immune system's various tissues and connections, allows the agent to be focused within a regional lymph node, which greatly improves the probability of an effective defensive response. In the case of HIV, however, this ability either brings the target cells to the virus, or brings the virus to the target cells. Consequently, the only way to prevent exposure to the virus, is to avoid situations which allow the potential for entry of the virus. Such situations are overwhelmingly associated with sexual intercourse, intravenous drug use, and exposure of a cut in one's skin to the bodily fluids (secretions, blood) of an HIV-infected individual. Such situations do not include hugging, touching, or other nonfluid-exchange expressions of caring for someone infected with HIV.

Oral, vaginal, and anal intercourse can lead to tiny abrasions of the mucosal tissue in these areas; and, within the tissues of the mouth (gums in particular) there will almost always be tiny abrasions present under any circumstances. These openings provide access by the virus to the blood and lymphatic streams, as well as to cells within the tissue. If a person is infected with HIV, there will be virus within the secretions of the person (particularly the seminal fluid of males), and in the blood of the person. Consequently, the direct exposure to bodily fluids (secretions, blood) can potentially occur between both partners (female/female, male/male, female/male) during any kind of sexual intercourse, whether or not ejaculation by a male partner occurs. While the body may be able to ward-off a small amount of virus, repeated exposure to such amounts places a person, particularly women having vaginal intercourse, and men and women having anal intercourse with an HIV-infected partner, at significant risk of HIV infection. Under any circumstance, there is a risk of HIV infection through only one sexual intercourse encounter. The use of a condom for the male partner, in combination with chemical substances which kill viruses, is recommended. Multiple sexual partners, unprotected sexual intercourse, anal sexual intercourse, the presence of other sexually-transmitted disease, and intravenous drug usage significantly increase the risk of HIV infection.

One can be tested for the presence of HIV through an appointment with one's local Health Department (state-supported). Health department test results are completely confidential and inaccesible to anyone but the patient and testing physician at the public-health clinic. While a personal physician's records are also confidential, these records are however, subject to examination at any time by the health insurer(s) of the physician. No matter where one chooses to be examined, one will be required to undergo a pre-test and post-test psychological counseling session.

Recent Statistics (January, 1995): The CDC report showed 401,749 cases of AIDS in the U.S. through the middle of 1994, while approximately one-million within the U.S. are infected with HIV. Twenty percent of all AIDS cases within the U.S. are within the 20s age-group - (apparently contracted HIV while teenagers).

The CDC AIDS Hotlines are:
English: 800-342-2437 (800-342-AIDS)
Spanish: 800-344-7432 (800-344-SIDA)
Deaf: 800-243-7889.
Your local Health Department is also a good source of information. Become informed.

Recent Information About Therapy Involving the Use of Protease Inhibitors
Copyright John C. Brown, 1995
Last Updated: January, 1997

Please See the Following for Information and Support:
AIDS Virtual Library
Michigan Electronic Library - AIDS Information



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