Immunity, AIDS and Substance Abuse — Notes

Immunity is the overall ability of the host to fight disease-causing organisms. Innate immunity is non-specific and present at birth. It consists of four kinds of barriers:

1. Physical barriers — skin prevents entry of microbes; mucus lining the respiratory, gastrointestinal and urogenital tracts traps microbes.
2. Physiological barriers — acid in the stomach, saliva in the mouth and tears from the eyes prevent microbial growth.
3. Cellular barriers — certain leucocytes: polymorpho-nuclear leucocytes (PMNL-neutrophils), monocytes and natural killer lymphocytes in blood, and macrophages in tissues, phagocytose and destroy microbes.
4. Cytokine barriers — virus-infected cells secrete proteins called interferons, which protect non-infected cells from further viral infection.

Interferons limit the spread of viruses; α-interferon is also used as a biological response modifier in cancer treatment.

Acquired immunity is pathogen-specific and is characterised by memory. The first encounter produces a primary response of low intensity; a subsequent encounter with the same pathogen produces a highly intensified secondary (anamnestic) response (in the model graph, peaks of about 19 and 108 units).

Two kinds of lymphocytes carry it out:

• B-lymphocytes produce antibodies into blood and lymph — humoral (antibody-mediated) immune response.
• T-lymphocytes do not secrete antibodies but help B-cells and attack infected cells — cell-mediated immunity (CMI). CMI is responsible for graft rejection: the body distinguishes self from non-self, so tissue and blood-group matching are essential before transplants, and patients take immunosuppressants.

Active immunity — the host’s own body produces antibodies on exposure to antigens (live or dead microbes or proteins), by natural infection or vaccination; it is slow but long-lasting. Passive immunity — ready-made antibodies are given: colostrum supplies IgA to the newborn; the foetus receives IgG through the placenta; injected antitoxins (tetanus) and antivenom (snake bite). It is immediate but short-lived.

Lymphoid organs: primary — bone marrow (all blood cells, including lymphocytes, are produced) and thymus (T-lymphocytes mature; it is large at birth and shrinks with age); lymphocytes become antigen-sensitive here. Secondary — spleen (filters blood, reservoir of erythrocytes), lymph nodes (trap microbes in lymph), tonsils, Peyer’s patches of the small intestine and the appendix; here lymphocytes interact with antigens and proliferate. MALT (mucosa-associated lymphoid tissue) lines the respiratory, digestive and urogenital tracts and makes up about 50 percent of lymphoid tissue.

Antibody structure: each antibody molecule has four polypeptide chains — two heavy and two light — joined by disulfide bonds, written H₂L₂. The molecule is Y-shaped; the tips of its arms are antigen-binding sites.

Classes of antibodies (immunoglobulins):

• IgG — most abundant in serum (about 75–80 percent); monomer; crosses the placenta, giving passive immunity to the foetus; main antibody of the secondary response.
• IgA — in body secretions: colostrum, saliva, tears, mucus; usually a dimer; protects body surfaces and the newborn’s gut.
• IgM — pentamer (5 units, 20 chains), the largest; first antibody formed in a primary response; efficient at agglutination.
• IgD — on the surface of B-cells; acts as an antigen receptor that helps activate B-cells.
• IgE — least abundant; binds mast cells and basophils; involved in allergic reactions and defence against parasitic worms.

Vaccination and immunisation: a vaccine is a preparation of antigenic proteins of a pathogen or inactivated/weakened pathogen. It generates antibodies and memory B and T cells, so the real pathogen meets a rapid, intense secondary response. Recombinant DNA technology produces antigenic polypeptides in bacteria or yeast (for example the hepatitis B vaccine made in yeast). Active immunisation uses vaccines; passive immunisation gives pre-formed antibodies or antitoxins (tetanus antitoxin, snake antivenom) when a quick response is needed.

Autoimmunity: due to genetic and other unknown reasons, the body sometimes attacks self-cells, resulting in damage — autoimmune diseases such as rheumatoid arthritis.

AIDS (Acquired Immuno Deficiency Syndrome) is a deficiency of the immune system acquired during life; first reported in 1981, it has spread worldwide. It is caused by HIV (Human Immunodeficiency Virus), a retrovirus with an RNA genome and an envelope.

Transmission: (a) sexual contact with an infected person; (b) transfusion of contaminated blood and blood products; (c) sharing infected needles (intravenous drug users); (d) from infected mother to child through the placenta. It does not spread by touch or physical contact. There is a long incubation period (a few months to many years, usually 5–10).

Replication of HIV: the virus enters macrophages, where its RNA is copied into viral DNA by reverse transcriptase. The viral DNA is integrated into the host cell’s DNA and directs the infected cell to make virus particles; the macrophage continues to produce virus — an HIV factory. HIV also enters helper T-lymphocytes (T_H), replicates and produces progeny viruses that attack other helper T-cells. The number of helper T-lymphocytes falls progressively; the patient has fever, diarrhoea and weight loss, and becomes prone to opportunistic infections by bacteria (Mycobacterium), viruses, fungi and parasites such as Toxoplasma.

Diagnosis: ELISA (Enzyme-Linked Immunosorbent Assay) detects antibodies against HIV; the colour produced in a well is compared with a cut-off from negative controls.

Treatment and prevention: anti-retroviral drugs are only partially effective, prolonging life. Prevention: NACO and NGOs educate people; blood is screened in blood banks; disposable needles and syringes; free distribution of condoms; avoiding drug abuse; regular check-ups for susceptible groups; World AIDS Day on 1 December.

Commonly abused drugs:

• Opioids bind opioid receptors in the central nervous system and gastrointestinal tract. Heroin (“smack”, diacetylmorphine) is a white, odourless, bitter crystalline compound made by acetylation of morphine, extracted from the latex of the poppy, Papaver somniferum. It is a depressant and slows down body functions.
• Cannabinoids interact with cannabinoid receptors in the brain. Natural cannabinoids come from the inflorescences of Cannabis sativa; marijuana, hashish, charas and ganja are inhaled or taken orally and affect the cardiovascular system.
• Cocaine (coke, crack) comes from the coca plant, Erythroxylum coca, native to South America. It interferes with the transport of dopamine and has a potent stimulating action on the CNS, producing euphoria and increased energy; excessive doses cause hallucinations.
• Barbiturates, amphetamines, benzodiazepines and similar drugs, normally used as medicines for depression and insomnia, are often abused. Plants such as Atropa belladonna and Datura have hallucinogenic properties.

Tobacco and smoking: tobacco contains nicotine, an alkaloid that stimulates the adrenal gland to release adrenaline and noradrenaline, raising blood pressure and heart rate. Smoking is associated with cancers of the lung, urinary bladder and throat, bronchitis, emphysema, coronary heart disease and gastric ulcer; tobacco chewing with oral cancer. Smoke raises carbon monoxide in blood, reducing the oxygen carried by haemoglobin.

Alcohol: chronic use damages the nervous system and liver (cirrhosis); use during pregnancy harms the foetus.

Adolescence and addiction: reasons include curiosity, adventure, excitement, experimentation, peer pressure, escape from stress and failure, family history and the false perception that it is “cool”. Repeated use causes addiction (psychological attachment) and dependence: when intake is stopped abruptly, withdrawal syndrome (anxiety, shakiness, nausea, sweating) appears.

Prevention and control: avoid undue peer pressure; education and counselling; seek help from parents and peers; look for danger signs (falling grades, withdrawal, changes in sleep and appetite); professional and medical help from de-addiction and rehabilitation centres.