Human Health and Disease

Public health measures against infectious diseases: 1. Vaccination (immunisation): • Vaccines provide active immunity against specific pathogens • National immunisation programs: BCG, DPT, MMR, polio, hepatitis B • Herd immunity protects unvaccinated individuals when high percentage is vaccinated 2. Safe drinking water and sanitation: • Proper treatment and chlorination of water supplies • Sewage treatment prevents waterborne diseases (cholera, typhoid, hepatitis A) • Safe disposal of human waste 3. Vector control: • Control of mosquitoes: insecticides, drainage of stagnant water, use of larvicides • Prevents malaria, dengue, filariasis, Japanese encephalitis • Rodent control for plague, leptospirosis 4. Food safety: • Proper cooking, storage, and handling of food • Prevents food-borne infections (Salmonella, Staphylococcal food poisoning) • Inspection of food products 5. Personal hygiene: • Regular handwashing with soap • Use of clean personal items (not sharing towels, razors) • Proper respiratory hygiene (covering mouth when coughing) 6. Surveillance and reporting: • Early detection and notification of outbreaks • Contact tracing and quarantine of infectious cases 7. Health education: • Awareness about transmission routes and prevention • Sex education to prevent STIs 8. Antibiotic and antiviral stewardship: • Proper use of antibiotics to prevent resistance 9. Travel health measures: • Vaccination requirements for international travel • Screening at borders during outbreaks

Biology has contributed to controlling infectious diseases in numerous ways: 1. Understanding pathogens: • Microbiology revealed the causative agents of diseases (germ theory — Koch, Pasteur) • Identification of bacteria (Koch's postulates), viruses, fungi, protozoa, and helminths as disease-causing agents 2. Development of vaccines: • Understanding of antigen-antibody interactions led to development of vaccines • Smallpox eradicated (1980) through global vaccination • Polio, measles, diphtheria drastically reduced • Recombinant DNA technology → Hepatitis B vaccine, HPV vaccine 3. Antibiotics and antimicrobials: • Understanding bacterial metabolism led to development of antibiotics (penicillin by Fleming, 1928) • Antifungals, antivirals (e.g., antiretrovirals for HIV) 4. Immunology: • Understanding of immune system → immunotherapy, monoclonal antibodies • Blood typing → safe blood transfusions • Organ transplantation through understanding of histocompatibility 5. Vector biology: • Study of mosquito life cycle → targeted vector control (larvicides, insecticides, biological control) • Genetic modifications of mosquitoes to reduce population 6. Diagnostic techniques: • ELISA, PCR, Western blot for rapid, accurate diagnosis • Rapid antigen tests (e.g., malaria RDTs, COVID tests) 7. Epidemiology: • Mathematical modelling of disease spread • Contact tracing, quarantine strategies 8. Biotechnology: • Recombinant vaccines, monoclonal antibodies • CRISPR-based diagnostics

(a) Amoebiasis: • Causative agent: Entamoeba histolytica (protozoan parasite) • Transmission: Faecal-oral route – Ingestion of food or water contaminated with cysts of E. histolytica – Contamination via infected human faeces • Houseflies act as mechanical vectors (carry cysts on body) • Common in areas with poor sanitation • Causes: intestinal amoebiasis (amoebic dysentery) and extra-intestinal amoebiasis (amoebic liver abscess) (b) Malaria: • Causative agent: Plasmodium species (P. vivax, P. falciparum, P. malariae, P. ovale) • Vector: Female Anopheles mosquito • Transmission: Bite of infected female Anopheles mosquito – Infected mosquito injects sporozoites into human bloodstream – Sporozoites infect liver cells, then red blood cells • Can also spread: blood transfusion, sharing needles, mother to foetus (congenital malaria — rare) • P. falciparum causes most severe (cerebral) malaria (c) Ascariasis: • Causative agent: Ascaris lumbricoides (roundworm — helminth) • Transmission: Faecal-oral route (same as amoebiasis) – Ingestion of food, water, or soil contaminated with embryonated (infective) Ascaris eggs – Eggs passed in faeces of infected person → contaminate soil and water • Common in children who play in contaminated soil • Larvae hatch in intestine → migrate through liver, lungs → mature in small intestine (d) Pneumonia: • Causative agents: Streptococcus pneumoniae (most common bacteria), Haemophilus influenzae; also viruses (influenza, RSV), fungi (Pneumocystis jirovecii) • Transmission: Airborne droplet infection – Inhaling droplets released by coughing, sneezing, or talking by an infected person – Sharing utensils, direct contact with secretions – Aspiration of oral bacteria into lower respiratory tract • Risk factors: Immunocompromised individuals, elderly, infants, smokers

Innate Immunity (Non-specific immunity): • The natural, inborn resistance to disease that a person is born with • Non-specific — provides general protection against all pathogens • Does NOT require prior exposure to a pathogen • Responds immediately to infection • Does not have memory (does not improve with repeated exposure) • Provides the first and second lines of defence Barriers of Innate Immunity: 1. Physical / Anatomical Barriers (First line of defence): • Skin: Tough, keratinised outer layer acts as mechanical barrier; prevents penetration of most pathogens • Mucous membranes: Line respiratory, gastrointestinal, urogenital tracts; trap pathogens in mucus • Cilia: In respiratory tract; sweep mucus with trapped pathogens up and out (mucociliary escalator) 2. Physiological / Chemical Barriers: • Stomach acid (HCl, pH ~2): Kills most ingested pathogens • Saliva, tears, mucus: Contain lysozyme — enzyme that breaks down bacterial cell walls • Normal body temperature: Inhibits growth of some pathogens • Interferons: Proteins secreted by virus-infected cells; warn neighbouring cells; inhibit viral replication • Complement proteins: In blood — form pores in bacterial membranes (lysis) 3. Phagocytic Barriers (Cellular barriers): • Phagocytes: Neutrophils and macrophages engulf (phagocytose) and destroy pathogens • Natural killer (NK) cells: Kill virus-infected and tumour cells without prior sensitisation • Mast cells: Release histamine in inflammation 4. Inflammatory Barriers: • Inflammation response: Increased blood flow, phagocyte recruitment to infection site • Fever: Elevated temperature inhibits pathogen growth; accelerates immune responses

(a) Innate vs Acquired Immunity: Innate Immunity: • Present from birth — inherited • Non-specific — acts against all pathogens equally • Immediate response (within minutes to hours) • No memory — response same on first and subsequent exposures • Components: physical barriers (skin), phagocytes, NK cells, complement, interferons • Does not involve lymphocytes (primarily) Acquired (Adaptive) Immunity: • Develops during an individual's lifetime through exposure to antigens • Specific — responds to specific antigens • Slower initial response (days to weeks) • Has MEMORY — faster, stronger response on second exposure • Components: B lymphocytes (humoral immunity — antibodies), T lymphocytes (cell-mediated immunity) • Can be active or passive (b) Active vs Passive Immunity: Active Immunity: • Organism's own immune system produces antibodies in response to antigen exposure • Develops after: natural infection OR vaccination • Slow to develop (days to weeks) • Long-lasting (years to lifetime) due to memory cells • Self-generated — body does the work • Examples: recovery from measles, vaccination with MMR vaccine Passive Immunity: • Ready-made antibodies are transferred from another source • Antibodies are NOT produced by the recipient's own immune system • Provides immediate protection • Short-lived (weeks to months) — no memory cells formed • Natural passive immunity: maternal antibodies to foetus via placenta (IgG) and to infant via breast milk (IgA) • Artificial passive immunity: Injection of antiserum/immunoglobulins (e.g., anti-tetanus serum, anti-rabies immunoglobulin) • Examples: Anti-snake venom (antivenom), anti-tetanus immunoglobulin after wound

Structure of an antibody (immunoglobulin) molecule: Basic structure — Y-shaped molecule: 1. Heavy chains (H): Two identical heavy polypeptide chains (long) 2. Light chains (L): Two identical light polypeptide chains (short) • Connected by disulfide bonds (–S–S–) • Two light chains + two heavy chains form the Y-shape Regions: • Variable region (V region): – Tips of both arms of the Y – Found on both heavy and light chains – Antigen-binding site — unique for each antibody – Two antigen-binding sites per antibody (bivalent) – Also called Fab region (Fragment antigen-binding) • Constant region (C region): – Rest of the molecule (stem of Y and lower arms) – Same for all antibodies of the same class – Determines the class of antibody (IgG, IgM, IgA, IgD, IgE) – Fc region (Fragment crystallisable): stem of Y; binds complement, Fc receptors on cells • Hinge region: – Flexible region between Fab and Fc – Allows antigen-binding arms to move apart Classes of immunoglobulins: • IgG: Most abundant; crosses placenta; provides passive immunity to newborn • IgM: First antibody produced; pentamer; very effective at complement activation • IgA: Found in secretions (breast milk, saliva, tears) • IgD: B-cell receptor • IgE: Involved in allergic reactions and antiparasitic immunity

HIV (Human Immunodeficiency Virus) transmission routes: HIV is found in blood, semen, vaginal secretions, breast milk. Transmission requires contact with infected body fluids. 1. Sexual transmission (most common globally): • Unprotected sexual intercourse (vaginal, anal, or oral sex) with an infected partner • Anal intercourse carries highest risk • Heterosexual, homosexual, and bisexual transmission 2. Blood-borne transmission: • Sharing needles, syringes, or other drug injection equipment with an infected person • Needle-stick injuries in healthcare workers • Blood transfusion of infected blood (now largely prevented by screening) • Use of unsterilised medical/dental equipment 3. Mother to child (vertical transmission): • During pregnancy (across placenta) • During childbirth (exposure to maternal blood) • Through breastfeeding (virus present in breast milk) HIV is NOT transmitted through: • Casual contact (handshakes, hugging, sharing utensils) • Coughing, sneezing, air • Mosquito bites or other insect vectors • Sharing toilets or swimming pools • Saliva (extremely low risk) Pathology: • HIV attacks CD4+ T helper cells → progressive immunodeficiency • AIDS (Acquired Immunodeficiency Syndrome) — final stage when CD4 count < 200 cells/μL • Opportunistic infections (PCP, toxoplasmosis, CMV) and AIDS-defining cancers (Kaposi's sarcoma, NHL) Prevention: Condom use, clean needles, blood screening, antiretroviral therapy (ART) reduces viral load and transmission risk to near zero

HIV destruction of the immune system — step by step: 1. Entry of HIV: • HIV uses its envelope glycoprotein gp120 to bind to CD4 receptor on CD4+ T helper cells (also macrophages and dendritic cells) • Co-receptor (CXCR4 or CCR5) also required for fusion • HIV enters the cell and releases its RNA genome 2. Reverse transcription: • HIV's reverse transcriptase converts viral RNA → viral DNA • Viral DNA integrates into the host cell genome as provirus (via integrase enzyme) • Provirus may remain latent or actively replicate 3. Viral replication and budding: • When CD4+ T cell is activated, provirus is transcribed • New HIV particles bud from the cell surface • Host cell is eventually destroyed (lysed) in the process 4. Progressive depletion of CD4+ T cells: • Normal CD4+ count: 500–1500 cells/μL • HIV continuously kills CD4+ T helper cells • The body initially compensates by producing new T cells • Over years (average 8–10 years without treatment), CD4 count progressively falls 5. Collapse of immune response: • CD4+ T cells are the master coordinators of the immune system • They activate B cells → antibody production impaired • They activate cytotoxic T cells (CD8+) → cell-mediated immunity impaired • Without T helper cell signals, the entire adaptive immune response collapses 6. AIDS: • CD4 count < 200/μL • Severe immunodeficiency → unable to fight infections • Opportunistic infections: PCP, oral candidiasis, CMV retinitis, tuberculosis, toxoplasmosis • AIDS-defining cancers: Kaposi's sarcoma, non-Hodgkin lymphoma Treatment: Antiretrovirals (ART) block viral replication; can maintain CD4 count and prevent AIDS progression, though cannot eliminate the provirus.