Immune System

Immune System IMMUNE SYSTEM IMMUNITY - 187 - (L. immunis – freedom exempt) Immunity is the ability of an individual host to resist the development of disease and allergy even after receiving an infective dose of pathogen with complete virulence and the various allergens. Immune system is the system of human body which protects it from various pathogens/infectious agents/allergens and cancer. Immunology is the science of development of immunity against particular pathogen/pathogens/allergens. Thefoundation of science of immunology was laid by three workers: (i) Edward Jenner (1796). A risky inoculation of small pox pustule through a scratch on a vein was performed in Turkey and other eastern countries prior to Jenner. Jenner noticed that milk-maids did not suffer from small pox though they did developsimilar scabs of cowpox. He transferred the material from the scab of milkmaid Sarah Nelmes to a young boyof eight years James Phipps (on May 14, 1796). Later on he inoculated the boy with live small pox material (July, 1796). The disease did not appear. The procedure was tried on others with equal success. Jenner also coined the term vaccine. (ii) Louis Pasteur (1879), Developed the technique of weakening or attenuation of pathogen by heat, cold or starvation for preparation of vaccine. (iii) Von Behring (1891). He discovered the technique of passive immunization by injecting diphtheria pathogen into sheep and preparing serum from its blood after sometime. The agents which invite action of immune system are microorganisms, their products, certain food items, chemicals, drugs, pollen and pollutants. NONSPECIFIC BODY DEFENCE It is natural defence system of the body with which an individual is born and which is always available to protect the body against various types of discomfort causing environmental agents. This is done by providing barriers to the entry of foreign agents and disposing them off them as soon as they enter the body. Nonspecific body defence does not involve antigen recognition. It is also called innate, inborn, familial or natural immunity, There are a number of components of innate immunity – anatomic, physiological, phagocytic inflammatory, natural killer cells and complement system. Innate immunity or non specific body defence is also called the first line of defence for most humans. 1. Anatomic Barriers. They do not allow the foreign agents and pathogens to enter the body. Anatomical barriers include skin, membranes and friendly microorganisms. (i) Skin. Keratinised dead outer cells of horny layer, stratum corneum, do not allow entry of pathogens. Oil from sebaceous glands and sweat from soporiferous glands make the skin acidic with pH 3 – 5,and possess bactericidal as well as fungicidal properties. (ii) Nostril Hair. They filter out dust and microorganisms from inhaled air. (iii) External Friendly Microorganisms/Friendly Bacteria. Many friendly bacteria live on skin, produce acids and secrete chemicals harmful to pathogens. (iv) Mucous Membranes. They line digestive, respiratory and urinogenital tracts so as to prevent entry of germs into body tissues. (v) Mucus and Cilia. Mocous membrane of the nasal tract possesses cilia for pushing back dust and germs. It also secrets mucus for trapping and killing them. (vi) Internal Friendly Microorganisms. They occur in intestine and vagina. Intestinal microorganisms secrete chemicals harmful to other microbes. Bacteria present in vagina secrete lactic acid for keeping it free from other microbes. 2. Physiological Barriers. They are barriers related to body temperature, pH and chemicals of body secretions which inhibit growth of pathogens. Immune System (i) Fever. There is raising of body temperature due to toxins released by pathogens and pyrogens produced by leucocytes. Fever stimulates phagocytosis and inhibits growth of many pathogens. (ii) External Secretions. Sweat, oil and secretions of external friendly bacteria are acidic to prevent growth of many pathogens. (iii) Lysozyme. It is a bacteriolytic enzyme present in sweat, tears, saliva and mucus. Lysozymes bring about hydrolysis/breakdown of bacterial cell walls. (iv) Activity of Stomach. HCl of gastric juice kills most of microorganisms ingested with food and drinks. (v) Bile. It does not allow growth of microorganisms. (vi) Cerumen (Ear Wax). It is secretion of ceruminous glands present in external auditory canal. Cerumen traps dust particles, kills bacteria and repesl insects. (vii) Interferons. They are glycoproteins which are produced in small amount by certain kinds of cell when infected with virus. Interferons make the surrounding cells resistant to viral infection. 3. Phagocytic Barriers. Phagocytosis is carried out by leucocyte sand macrophages. The two act as soldiers of defence and scavenger of the body. Phagocytic leucocytes are neutrophils (most abundant) and monocytes. They come out of blood capillaries through diapedesis, engulf and digest most of the microorganisms (Metchinkoff, 1982). Macrophages are modified monocytes. They are large phagocytic cells of two types – fixed (inside lymph nodes, spleen, liver, bone marrow) and wandering (connective tissue). They constitute reticulo-endothelial system. Macrophages of liver are present along sinusoids and are called kupffers cells. Macrophages attack germs and inorganic substances that happen to enter tissues and engulf them. Pus may collect. Pus is a thick liquid formed in the region of wound and is composed of tissue fluid, damaged body cells, dead phagocytes, some leucocytes and microorganisms. 4. Inflammatory Barriers. Inflammation is reaction of living tissues to injury, irritation or infection which is characterized by pain, swelling, redness and heat. Inflammatory response can be localised (area of injury or infection) or systemic (whole body). The injured regions attract mast cells (histaminocytes of connective tissue and basophils of blood. They release prostaglandins and histamine (C5H9N3). Histamine dilates blood capillaries and other small blood vessels. Therefore, more blood flows into the area of injury making it red and warm. Histamine also makes fine blood vessels more permeable, lowers blood pressure, allows greater leakage of phagocyte and plasma (histamine also stimulates gastric secretions and uterine contractions). Increased influx of phagocytes allows destruction of microorganisms. Plasma contains serum proteins with antimicrobial activity. Accumulation of tissue fluid causes swelling and dilution of toxins produced by pathogens. 5. Natural Killer Cells. They are small lymphocytes/cells of immune system which are specialised to kill virus inflected and tumour cells. Killer cells produce perforins. The later produce pores in the plasma membrane of the target cells. Water enters the perforated cells. They swell up and burst. Cellular remains are then cleared by phagocytes. 6. Complement System. It is a system of over 30 proteins which participate in both innate and aquired immunities in a cascade fashion for protecting the individual from pathogens. Many of the proteins of complement system function as enzymes precursors. In acquired immunity the system becomes active in response to antigen-antibody complex. It is also called classical p athway. In innate immunity, the complement system is activated directly in response to bacterial endotoxins, microbial polysaccharides, cell wall and other components of invading microorganism. It is called alternate pathway as well as properdin system. The pathway helps in dealing with invading microorganisms even before a person becomes sensitized against them. Certain proteins of this system cleave and form two components, membrane attack complex and biologically active fragments. Membrane attack complex functions as lytic complex which produces trans membrane pores in the microbes. Water enters the microbes and they burst and die. Biologically active fragments produce opsonins, anaphylotoxins and chemotactic factors. They form a coat over the invading microbes and attract phagocytes (neutrophils and macrophages) for engulfing them. Complement system also causes agglutination of microbes, neutralisation of viruses, activation of mast cells and basophils and has some direct inflammatory effect. SPECIFIC BODY DEFENCE It is immunity obtained during the life of an individual against a particular microorganisms due to previous infection, vaccination or inoculation of antiserum. Specific body defence is also called acquired, adaptive Immune System or specific immunity. This type of immunity occurs only in vertebrates (humans). It supplements protection provided by innate or inborn immunity. However it takes a few to several days to become effective. It has four unique characteristics : (i) Specificity. It is specific for each and every type of pathogen. (ii) Diversity. It operates against the whole diversity of pathogenic organisms, their toxins and pollutants. (iii) Discrimination between Self and Nonself. It can differentiate molecules and cells of foreign origin form those of self and body. (iv) Memory. The immunity against a pathogen developed during an initial infection/vaccination is retained by the individual so that second encounter with the pathogen invites a hightened immune response. Types. Acquired immunity or specific body defence is of two types, active and passive. (i) Active (Acquired) Immunity. It is immune response generated in an individual due to previous contraction of disease (naturally acquired active immunity) or vaccination (artificially acquired active immunity). In many cases it is life long (e.g., against measles). (ii) Passive (Acquired) Immunity. It is acquired immunity produced in an individual due to inoculation of antiserum and from mother through placenta. Passive immunity is immediate but afterwards lasts for shorter duration. Antigen. An antigen (antibody generating) or immunogen is any foreign substance like protein or polysaccharide present in the external coating of pathogen, toxin of pathogen, white of egg, feathers, constituent of a vegetable, fruit, meat, drug, chemical, tissue or organ transplant which induces the immune system to produce antibodies. Sites over the antigens that are recognized by antibodies and receptors found on B and T-cells are called antigen determinants (epitope). An antigen may have one to several types of antigen determinants. Antibody. Antibodies are glycoproteins which are of innumerable types, each specific to a specific antigen. They occur in blood plasma as gammaglobulins or immunoglobulins (Ig). About 20% of plasma proteins are antibodies. Each antibody consist of four polypeptides, two long heavy or H-chains and two short, light or L-chains. They are held together in a Y-shaped configuration. Long H-chains are present throughout while short L-chains are restricted to the two arms. The tips of the two arms possess a specific architecture that fits over the antigen determinant in a lock and key fashion to form antigen-antibody complex. The antigen binding fragment (Fab) of arms is called variable or V-region while the stem and basal parts of arms of antibody form constant or crystalline fragment (FC). The latter determines diffusivity and adherence of the antibody. Immune System Components of Immune System. Immune system has two components, humeral and cell mediate. (i) Humoral/Antibody Medical Immune System (AMIS). The immune system comprises antibodies present in body humours (blood lymph). The antibodies are produced by plasma cells rich in endoplasmic reticulum. They are formed by B-lymphocytes. Antibodies protect the body from pathogens that happen to Immune System enter blood and lymph. (ii) Cell Mediated Immune System (CMIS). The immune system comprises T-lymphocytes which defend the body against pathogens, cancers and foreign structure like tissue transplants. Cells of Immune System. They are lymphocytes and antigen presenting cells like macrophages. A healthy human has about a trillion lymphocytes. Lymphocytes are of two types, T-lymphocytes (T-cells) and Blymphocytes (B-cells). Both of them develop in bone marrow (in foetus from yolk sac and then from liverspleen complex) from lymphatic stem cells by the process called haematopoiesis. Some of the young lymphocytes migrate into thymus for preprocessing. They are called T-lymphocytes. Afterwards they pass on to all the lymphoid tissues of the body and get lodged there. The other types of lymphocytes remain in the bone marrow and get preprocessed there. They are called B-lymphocytes. After being preprocessed Blymphocytes also migrate to all the lymphoid tissues of the body where they reside near but separate from T-lymphocytes. Activation of Adaptive/Acquired Immunity. An antigen is processed by antigen presenting cells like macrophages and B-lymphocytes. A type of T-cells (T-helper cells) interacts with presented antigen and becomes activated. The activated T-cells not only form a clone of T-cells but also B-lymphocytes. Cell Mediated Immunity/Action of T-cells. The cells are long-lived small cells (4 – 5) years, some throughout life) which have upto 100,000 receptors sites on their surface for binding antigens. The cells develop antigen specificity through previous contact. They are often called competent lymphocytes. The later respond to specific antigen by forming a clone of cells. The cells then differentiate into following types: 1. Cytotoxic or Killer T-cells. The cells reach the site of infection or agglutination and get attached to antigen containing microorganisms. They secrete perforins that produce holes in the attached cell. The killer T-cells then pass toxic chemicals (lymphotoxins) into attached cell for killing the same. Afterwards they move away for attacking new antigen containing cells. Killer T-cells attack virus invaded cells, cancer cells and cells of transplanted organs. They also destroy helper T-cells when the latter are invaded by HIV. AIDS is due to deficiency of helper T-cells. The killed cells are removed by phagocytes. 2. Helper T-cells. They constitute more than 75% of total T-cells. They regulate immune functions by secreting lymphokines (interleukins, monocyte colony stimulating factor). Interleukin-2 has positive feedback system for helper T-cells, stimulate growth and proliferation of other T-cells. Interleukins 4, 5 and 6 stimulate B-lymphocytes. Macrophages are attracted to the site of infection and stimulate phagocytosis by lymphokines. 3. Suppressor T-cells. The cells act as negative feedback and keep the activity of other T-cells under check. This protects the body tissues and chemicals from attack of phagocytes and their antibodies. 4. Memory T-cells. They are sensitized T-cells which retain memory of antigen-specificity for future, some time life long. Other T-cells are amplifier T-cells and delayed hypersensitivity T-cells. Killer, helper and suppressor T-cells are also called effector cells. Antibody-Mediated/Humoral Immunity or Action of B-cells. B-lymphocytes are activated either by helper T-cells or directly by antigen. The activated B-lymphocytes enlarge, formed plasmoblasts and then plasma cells. Plasma cells are rich in endoplasmic reticulum. In the presence of antigen plasma cells formed antibodies at the rate of 2000 molecules per cell/per second, a total of 20 trillions per day. Antibody action (Effector Mechanism). (i) Neutralisation. Some antibodies function as antitoxins and neutralize the toxins produced by pathogens/foreign chemical. (ii) Agglutination. Antibodies called agglutinins cause immobilization and clumping of antigens (precipitation) and antigen containing pathogen. (iii) Opsonisation /Adherence. Antibodies called opsonins (e.g., IgG) attach themselves to surfaces of antigen containing cells so as to be recognized by phagocytes. (iv) Complement Mediated Cell Lysis. Antigen containing cells are perforated by enzymes produced with the help of lysin antibodies (IgM-IgG) and cytotoxic T-cells. (v) Phagocytosis. The lysed immobilized clumped pathogen are engulfed by phagocytes. Immune System Clonal Selection. Formation of a clone of cells by each activated T-lymphocytes and antibody producing plasma cells by activated B-lymphocytes, each exhibiting the specificity for the same antigen is called clonal selection. The cells are of course of more than one type and perform different functions. One type of cloned lymphocytes do not function as effector cells but instead develop into long lived memory cells. Primary and Secondary Immune Responses. Primary immune response is the first immune response developed during the first encounter with the antigen. It is feeble but longer. Secondary immune response is a quick heightened immune response against a subsequent encounter with the same antigen. It is due to the presence of memory cells against that antigen. It persists for long while the primary response declines rapidly. A person having caught chicken pox or measles only once becomes immune to the subsequent attack of the pathogen. LYMPHOID ORGANS They are those organs that have lymphatic tissues where maturation and proliferation of lymphocytes occur. The sites where T-lymphocytes and B-lymphocytes mature and developed antigen – specific receptor are called primary lymphoid organs, viz., thymus for T-lymphocytes and bone marrow for B-lymphocytes. Secondary lymphoid organs are those organs which have lymphatic tissues where B-and T-cells are settle after maturation and where they undergo proliferation/differentiation on being activated by specific antigen, e.g., lymph nodes, spleen, tonsils. VACCINATIOIN AND IMMUNISATION Immunisation is the phenomenon of increasing specific antibody production and development of memory Band T-cells against the potential attack of a pathogen. It is carried out through vaccination and injection of antiserum. When an immunised person is attacked by the pathogen, the existing antibodies immediately attack the antigen while the memory T and B cells give rise to a massive crop of lymphocytes and antibodies. Vaccination (L. vacac – cow). Vaccination is a process of inoculation of harmless antigenic material (attenuated pathogen or its toxoid) into healthy person for providing active acquired immunity against the disease. A single vaccination may not give adequate immunity. Therefore, 2 – 3 booster doses of vaccine are administered later on at specific intervals. Vaccine. It is suspension/extract of weakened/attenuated/dead germs or antigen containing component of the pathogens.When injected into a healthy person they provide active acquired immunity to the disease. (i) Edward Jenner (1796) prepared the first vaccine when he injected fluid from the sore of milkmaid suffering from cowpox into the body of a healthy boy which did not later catch small pox even when he was injected with fluid containing small pox germs. (ii) Louis Pasteur (1879) found that ageing cultures of cholera bacteria did not cause the disease in chicken and also made them immune to fowl cholera. By refining the technique of attenuation, Pasteur (1885) developed vaccine against rabies. (iii) It was found that injecting small doses of tetanus toxin made the person immune to the disease. By the end of 1920s, vaccines against tetanus, diphtheria, pertussis (whooping cough) and tuberculosis became available. (iv) instead of attenuated pathogen, their antigenic polypeptides were separated and used as vaccines. They are called second generation vaccines. Another line of immunization is administration of toxoids. Toxoids are toxins usually inactivated by formalin which retain their antigenic activity. A toxoid stimulates antitoxin formation and protects the body from exotoxin producing organism, e.g., tetanus toxoid, diphtheria toxoid. (v)With the help of genetic engineering or recombinant DNA technology, antigenic polypeptides of the pathogens are synthesized in transgenic organisms, i.e. hepatitis-B vaccine from transgenic yeast. (vi) Third generation vaccines are pure synthetic antigenic polypeptides or their genes extracted from the pathogens. Immune System Aritiserum/Serum. It is fibrinogen free serum or blood plasma of an animals which has antibodies or antitoxins against a particular pathogen/toxin because the animal has been injected with safe dose of pathogen at regular intervals, e.g., diphtheria, tetanus, snake bite. Monoclonal Antibodies. They are identical antibody molecules, specific for a particular antigen, which have developed from a single source like hybridoma. Hybridoma. Hybrid cell culture formed of antigen sensitized cells, fused with myeloma/cancerous bone marrow cells for indefinite production of monoclonal antibodies. BLOOD GROUPS Blood groups are based on antigenic determinants present on the surface of red blood corpuscles. There are about 30 antigens giving rise to an equal number of blood groups. However, in transfusion, two types of blood groups are important – ABO blood group system and Rh blood group system. A proper matching is required otherwise the immune system of recipient can cause agglutination of transfused cells and blocking of blood capillaries. ABO Blood Group System. It is determined by three alleles IA, IB and I (IQ) giving rise to four blood groups (A, B, AB and O) and six genotypes (IA IA, IAi, IB IB, IBi, I AIB, ii). Blood group A has A antigen over erythrocytes and antibodies b against B antigen in plasma, blood group B has B antigen over erythrocytes and antibodies (a) against A antigen in plasma, blood group AB has both A and B antigens but no antibodies in plasma while blood group O has no antigen but both types of antibodies (a and b) against A and B antigen in plasma. Blood group AB recipient can receive blood of any group (AB, A, B, O) because of the absence of any antibody while blood group O person can donate blood to any other person due to the absence of any antigen. Rh (Rhesus) Blood Group System. Erythrocytes can carry another three sets of antigens – C, D and E. Out of them D is vary strongly antigenic. It determines either Rh+ (having D antigen) or Rh¯ (lacking D antigen) of blood. The name Rh has been given after the discovery of this antigen first in Rhesus monkey. Rh+ antigen (Dantigen) produces a strong immunogenic response in Rh¯ individuals. Therefore, determination of Rh and its matching is important in blood transfusion, Rh factor also causes haemolytic disease of newborn. (HDN) or erythroblastosis foetalis. An Rh¯mother gets sensitized by her first Rh+ baby due to Rh+ RBCs of foetus, entering her circulatory system and during delivery of this child. She produces anti Rh antibodies. A second Rh+ foetus will invite anti Rh antibodies of the mother resulting in HDN. Such a lady must be injected with defective anti Rh antibody during every pregnancy carrying Rh+ fetus Immune System . ORGAN TRANSPLANTS AND ANTIBODIES Skin grafts and transplants can be successful only if they have been matched properly through tissue typing forhuman leucocyte antigens or HLA proteins. Major hisitocompatibility complex or MCH that is involved in this acceptability or rejection is a group of closely linked genes located over chromosome 6. In humans it is called human leucocyte antigen or HLA complex. HLA system is highly polymorphic with each gene having a number of alleles, e.g., A-32, B-55, C-14, and D-85. The alleles are co dominants. A large rather indefinite combination of alleles is possible resulting in virtually indefinite number of phenotypes. Two unrelated persons are unlikely to have similar HLA phenotypes. Further, being closely linked, HLA alleles present on a chromosome are likely to be inherited en bloc. It is called haplotype. Each individual has two HLA haplotypes, one from each parent. Only the twins have identical HLA haplotypes. Two siblings have 25% chances of having similar HLA haplotypes. Therefore, siblings (brothers and sisters) have more chances of being antigenically similar either than either of the parents and the latter more than unrelated person. Therefore, for organ or tissue transplantation the preference order for transplant donor is identical twin > sibling > parent > unrelated donor. As there are antigens, which are likely to be attacked by recipient T-cells and antibodies, the recipients of organ/tissue transplants are always given immunosuppressant. IMMUNOSUPPRESENTS They are chemicals, which suppress immune reaction to the body towards transplanted organs (e.g., kidney, parts of intestine, heart), e.g., cyclosporine. IMMUNE SYSTEM DISORDERS Immune system is a multicomponent interactive system. A healthy immune system protects the body from various infections. Any defect in the system results in discomfort, disease or even death. There are three types of defects – hypersensitivity/allergy,antimmune deceases and immunodeficiency. HYPERSENSITIVITY /ALLERGY Allergy is noninfectious unusual reaction or hypersensitivity of an individual to a foreign substance or agent that is harmless to other individuals. Allergen is a foreign substance or agent that produces hypersensitivity in an individual, e.g., pollen, spores, dust, scent, woolen, silk or nylon, lotions, nail polish, lipstick, drug (e.g., penicillin), egg white, fur, feathers, shell fish, etc. the allergen on first contact functions as a mild antigen. The process is called sensitization. It produces antibodies that remain attached to mast cells. Whenever, the allergen enters the body of a sensitized person, it causes antigen-antibody reaction and lysis of mast cell. This releases histamine (a chemical formed from histidine. Histamine and IgE antibodies act as allergy mediator. It dilates arteries and causes fluid accumulation. Allergy may appear as local or systemic. Important allergy reactions are (i) Sneezing. (ii) Coughing. (iii) Watering of eyes. (iv) Oedema or accumulation of tissue fluid below skin. (v) Asthma. It is a common manifestation of allergy. Asthma is a disorder characterized by narrowing of bronchi, bronchospasm, wheezing and difficulty in expiration. Dust mites seem to be responsible for 40% of the cases. (vi)Hay Fever. Allergic swelling and secretion of mucous membrane of nose, throat and conjunctiva in response to pollen and spores. (vii) Urticaria. Allergic skin eruptions characterized by multiple, circumscribed raised pinkish itchy blisters persisting for a few days. (viii) Eczema. A dermatitis that starts with reddening of skin, formation of vesicles rupturing of vesicles and forming of scales. (ix) Anaphylaxis (Anaphylactic Shock). It is a hypersensitive reaction of the body to a foreign substance like bee sting, penicillin, serum protein, etc. that results in breathless pallor and collapse due to marked dilation of arteries, very low blood pressure, collection of tissue fluid below skin, little supply of blood to brain and other vital organs which may prove fatal. Allergic reactions are countered by the administration of antihistamines like phenindamine, diphenhydramine and cyclizine. AUTOIMMUNITY It is abnormal immune reaction in which the body immune system begins to reject substances and tissues of the body. The diseases caused by autoimmunity are known as autoimmune diseases. Some substances/tissue of the patient’s body develop antigenic activity and hence are known as self antigens/auto antigens, e.g., chronic anemia (auto antigen – RBCs), myasthenia gravis (autoantigen – muscle cells), chronic hepatitis (autoantigen –liver cells), juvenile or insulin dependent diabetes (auto antigen – β-cells), multiple sclerosis (antibodies attack myelin sheath of nerve cells), rheumatoid arthritis. IMMUNODEFICIENCY DISEASES Immune System They are disorders of immune system where one or more components of innate or acquired immunity become defective due to gene mutations, infections, malnutrition or accidents. SCID or severe combined immunodeficiency is a genetic defect in which the patient lacks adenosine deaminase. Very few Tlymphocytes are formed. B-lymphocytes are also deficient. As a result the patient dies of even minor infection. Such children can survive only in germ free isolation chambers. Immunity can now be restored through bone marrow/fetal tissue transplant. AIDS. It is acquired (immuno) immune deficiency syndrome, which is characterised by reduction in the number of CD4 or helper T4–lymphocytes because of infection of HIV (human immunodeficiency virus). It is also called slim disease. ARC is AIDS related complex, which is characterized by swollen lymph nodes, fever, night sweats and weight loss. It is mild or early form of AIDS. 25% ARC patients may later develop full-blown AIDS. AIDS was first detected in a homosexual male in U.S.A. (1981) Its virus was isolated by Montagnier et al (1983) in France and later by Gallo et al in U.S.A. (1981). Virus was named variously as HCLV III (human cell leukemia virus III), HTLV III (human T-lymphotrophic virus III), LAV (lymphadenopathy associated virus) and ultimately HIV (1986 by International Committee on Taxonomy of Viruses). It is of two types, HIVI (more common in India, Europe and America) and HIV-II (more common Africa). In India the first AIDS case was reported in 1986. Spread of Disease. The disease is rapidly spreading throughout the world. Daily some 8500 persons become infected with virus. However, vigorous campaign against this disease has resulted in slowing down thespread of disease. Nationwide sentinel surveillance believes that the number of HIV infected persons in India was 3.97 million in 2001 out of the total of some 20 million worldwide. Cumulative number of AIDS cases till May 2002 was 35.567. High-risk groups include prostitutes, drug addicts, homosexual males, and person with extra-martial relations and recipients of unscreened blood transfusions. In India HIV positivism had reached high proportions in areas adjoining golden triangle (Laos, Thailand, Myanmar) due to intravenous drug addiction. Transmission. There are three routes of transmission. (i) Parenteral Route. It is through blood contact involving unscreened transfusion of blood, tattooing, infected razors of barbers, poorly sterilized dental instruments, sharing of injection needles and organ transplant. (ii) Sexual Route. It accounts for 85% of HIV infection due to multiple sex partners, prostitutes, homosexuality and artificial insemination. Virus is present in sufficient strength in semen and vaginal secretions of infected persons. (iii) Tran placental Route. Infection can occur from infected mother to fetus (vertical transmission) across placenta and to infants through milk (prenatal transmission). Misconceptions. AIDS does not spread through mosquito bites, hugging, kissing, and sharing meals, toilets towels or utensils, shaking hands, coughing, sneezing or looking after AIDS patients. Structure of HIV. HIV is a retrovirus having rounded outline. The core has two single strands of genomic RNA, enzyme reverse transcriptase, protein P-15 associated with genomic RNA, inner covering of P-24 and outer of P-18. Genome has both overlapping and split genes (8 in HIV-I and 9 in HIV –II). Core is surrounded by host-derived envelope with spikes containing protein components complementary to CD-4 or T-4 antigen receptor present on surface of helper T cells, monocytes, macrophages and some nerve cells. Virus Multiplication. Helper T-cells, other cells of immune system and certain nerve cells possess viral or T-4 antigen receptors over their surface. If HIV comes in contact with receptor site, it sticks to it and later passes into the cell. The freed genomic RNA synthesizes copy DNA with the help of reverse transcriptase and biochemical of the host. Copy DNA forms complement strand and the duplex attaches to host DNA in the form of provirus. Provirus may multiply with host cell. Ultimately it forms genomic RNA and messenger RNA. Messenger RNA synthesizes viral proteins. Genomic RNA and viral proteins are packed together to produce virions. The later bud out of the host cell, get covered by envelope and attack new cells. Infected host cells are ultimately killed. This reduces the number of cells belonging to immune system. Incubation Period. It is 2 – 10 years (commonly 27 – 28 months). The first 2 – 6 months are window period when laboratory tests do not indicate infection. Later HIV positivism can be known from the presence of P-24 and antiviral antibodies. There is reduction in number of helper T-cells. 10% of patients develop full blown disease or AIDS. Immune System HIV Tests. Two common tests are (i) ELISA Test (Enzyme Linked Immune Sorbent Assay). For negative 100% correct. 5–6% false positive. Result within 2-½ hrs. (ii) Western Blot. Testing of antibodies against HIV proteins. (iii) Polymerase Chain Reaction or PCR test. - 194 Symptoms. (i) Repeated episodes of diarrhea. (ii) Unexplained loss of weight. (iii) Prolonged cough, night sweating, continuous low grade fever for more than one month. (iv) Tuberculosis (common in India). (v) Candidosis (moniliasis) of mouth and esophagus. (vi) Atypical pneumonia by fungus Pneumocystis carinii. (vii) Brain damage. AIDS dementia is related to Herpes Zoster Virus. (viii) Kaposi’s sarcoma (cancer of skin and lymph nodes) (ix) Ulcers. (x) Reduced number of helper T-cells. Most of the symptoms are due to opportunistic infections that appear when immunity of the body decreases. Treatment. Currently triple drug treatment is employed – protease inhibitor, reverse transcriptase inhibitor and AZT (azidothymidine). Interleukin has been added to this in order to make the treatment more effective. The treatment is costly and prolonged. Vaccines like RGP – 10 are under test. Chicory acid extracted from green coffee beans has been found to prevent HIV multiplication inside human cells (Robinson et al, 1998). VaccineTG AAC09 is under clinical trial. Prevention. (i) Education. National AIDS Control Programme began in India in 1987. A National AIDS Control Organisation has been set up under the Ministry of Health and Family Welfare. Awareness is being imparted through all means of publicity and NGOs in schools, colleges, factories, farms, panchayats, commercial areas, etc. (ii) Screening. It is compulsorily carried out in case of all blood donors, organs donors, semen donors, donors of growth hormones, foreigners, sex workers. (iii) AIDS Positive. Prevention of sexual contact and pregnancy in case of AIDS positive persons (iv) Ban on Prostitution. (v) Safer Sex. It should be between single partners. Condom and barrier cream (e.g., dextrin sulphate) are effective in checking HIV transmission (vi) Disposables. Only disposable needles, syringes, blood bags, and dialyzing sets should used. (vii) Razors, blades and dental equipment must be thoroughly sterilized. (e.g., 70% alcohol, 3.5 sodium hypochlorite, 5% formaldehyde, boiling for 15 minutes or autoclaving). Immune System