सूक्ष्मजीवशास्त्र Microbiology

थोडक्यात सारांश

Bacteriophages (phages) are viruses that infect bacteria. They were discovered by Frederick Twort (1915) and Félix d'Hérelle (1917), who named them. This topic covers phage structure (T4 as the model), the lytic and lysogenic cycles, one-step growth curve, plaque assay and uses of phages.

महत्त्वाचे मुद्दे

• Phages are specific to their host bacteria.
• T4 phage (infects E. coli) has a complex structure: icosahedral-like elongated head containing dsDNA, a collar, a contractile tail sheath around a hollow tail core, a base plate with tail pins and six long tail fibres.
• Genome types: dsDNA (T4, lambda), ssDNA (φX174, M13), ssRNA (MS2), dsRNA (φ6).
• Adsorption: tail fibres attach to receptors on the cell wall.
• Penetration: sheath contracts; DNA is injected; the protein coat stays outside.
• Biosynthesis: host DNA is broken down; early proteins, phage DNA, then late (structural) proteins are made.
• Maturation/assembly: heads filled with DNA; tails and fibres join.
• Release: phage lysozyme (and holin) breaks the cell wall; about 100–200 new phages released per cell.
• Lytic (virulent) cycle — T4:
• Lysogenic cycle — lambda (λ): phage DNA circularises and integrates into the host chromosome at a specific site (between gal and bio genes) as a prophage. The repressor protein (cI) keeps lytic genes off. UV light or chemicals can cause induction → lytic cycle.
• Temperate phage: can follow either cycle.
• Lysogenic conversion: prophage genes change the host's properties, e.g. Corynebacterium diphtheriae makes diphtheria toxin only when lysogenized by phage β; cholera toxin genes are carried by phage CTXφ.
• One-step growth curve (Ellis and Delbrück, 1939): shows eclipse period (no infective phage inside cells), latent period (no rise in free phage count), and rise period (burst). Burst size = phages released per infected cell.
• Plaque assay: phage + host on soft agar overlay; each clear zone (plaque) comes from one phage; count gives PFU/mL.
• Uses: phage therapy (treating bacterial infections, renewed interest against drug-resistant bacteria), phage typing of bacteria (e.g. Salmonella typhi, S. aureus), cloning vectors (lambda, M13), phage display, transduction studies.

महत्त्वाच्या संज्ञा

• Prophage – integrated phage DNA.
• Lysogen – bacterium carrying a prophage.
• Burst size – number of phages released from one infected cell.
• PFU – plaque forming unit.
• Eclipse period – stage when no complete infective phage is present inside the host.

सूत्रे

• Titre (PFU/mL) = number of plaques ÷ (dilution × volume plated in mL)
• Example: 120 plaques from 0.1 mL of 10⁻⁶ dilution → 120 ÷ (10⁻⁶ × 0.1) = 1.2 × 10⁹ PFU/mL.
• Burst size = (final phage titre after burst − unadsorbed phage) ÷ number of infected cells (simplified: phages released ÷ infected cells).

५ महत्त्वाचे प्रश्न

Q1. What is a temperate phage?

A phage that can enter either the lytic cycle or the lysogenic cycle, in which its DNA integrates into the host chromosome as a prophage. Example: lambda phage.

Q2. Calculate the phage titre if 85 plaques are formed from 0.1 mL of a 10⁻⁷ dilution.

Titre = 85 ÷ (10⁻⁷ × 0.1) = 85 × 10⁸ = 8.5 × 10⁹ PFU/mL.

Q3. Describe the structure of T4 phage with a labelled diagram.

• Head: elongated icosahedron, protein capsid, dsDNA inside.
• Collar: joins head and tail.
• Tail: hollow core with contractile sheath.
• Base plate with six tail pins and six tail fibres.
• Function of each part in infection.

Q4. Explain the lytic cycle of T4 phage.

• Adsorption, penetration, biosynthesis, assembly, lysis (details above).
• Early and late genes.
• Host DNA degraded.
• About 100–200 progeny per cell.
• Takes about 20–30 min at 37 °C.

Q5. Describe the lysogenic cycle and lysogenic conversion.

• Lambda DNA enters, circularises.
• Integrase inserts it at att site → prophage.
• Repressor blocks lytic genes; prophage replicates with chromosome.
• Induction by UV → excision → lytic cycle.
• Lysogenic conversion: diphtheria toxin (phage β), cholera toxin (CTXφ).
• Immunity of lysogen to superinfection by the same phage.

परीक्षेसाठी टीप

Draw the T4 diagram neatly with all six labels; it is the most common diagram question in this unit.

थोडक्यात सारांश

Immunity (प्रतिकारशक्ती) is the body's ability to resist infection and disease. It has two arms: innate (natural) immunity, present from birth and non-specific, and acquired (adaptive) immunity, which is specific and has memory. This topic covers both arms, the cells and organs of the immune system, and active and passive immunity.

महत्त्वाचे मुद्दे

• Innate immunity — first line: physical and chemical barriers — skin, mucous membranes, cilia, tears and saliva (lysozyme), stomach acid, normal microflora.
• Innate immunity — second line: phagocytes (neutrophils, macrophages), natural killer (NK) cells, inflammation, fever, complement system, interferons.
• Phagocytosis steps: chemotaxis → attachment → ingestion (phagosome) → fusion with lysosome (phagolysosome) → killing and digestion → release of waste.
• Inflammation signs: redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function.
• Acquired immunity — third line: specific, has memory, and distinguishes self from non-self. Carried out by lymphocytes.
• Humoral (antibody-mediated) immunity: B lymphocytes become plasma cells that secrete antibodies. Effective against extracellular microbes and toxins.
• Cell-mediated immunity: T lymphocytes — helper T cells (CD4⁺) activate other cells; cytotoxic T cells (CD8⁺) kill virus-infected and cancer cells.
• Primary immune organs: bone marrow (B cells mature here and all blood cells arise), thymus (T cells mature). Secondary organs: lymph nodes, spleen, MALT (tonsils, Peyer's patches).
• Primary response: slow, low, mainly IgM. Secondary response: fast, strong, long-lasting, mainly IgG — due to memory cells. This is the basis of booster doses.
• Antigen-presenting cells (macrophages, dendritic cells, B cells) display antigen on MHC molecules: MHC class I → CD8⁺ T cells; MHC class II → CD4⁺ T cells.
• Natural active: after recovering from infection.
• Artificial active: by vaccination.
• Natural passive: antibodies from mother to baby via placenta (IgG) and colostrum (IgA).
• Artificial passive: injection of ready-made antibodies (antitoxin, anti-rabies immunoglobulin, anti-venom).
• Types of acquired immunity:

महत्त्वाच्या संज्ञा

• Antigen – substance that triggers a specific immune response.
• Antibody – protein made by plasma cells that binds a specific antigen.
• Complement – group of blood proteins that help kill microbes.
• Interferon – protein released by virus-infected cells that protects nearby cells.
• Herd immunity – protection of a community when most people are immune.

महत्त्वाची माहिती

५ महत्त्वाचे प्रश्न

Q1. Differentiate active and passive immunity.

In active immunity the body makes its own antibodies after infection or vaccination; it is slow but long-lasting with memory. In passive immunity ready-made antibodies are given (from mother or by injection); it is immediate but short-lived.

Q2. What are the cardinal signs of inflammation?

Redness, heat, swelling, pain and loss of function.

Q3. Describe the mechanism of phagocytosis.

• Chemotaxis: phagocyte moves toward microbe.
• Adherence, helped by opsonins (antibodies, complement C3b).
• Ingestion by pseudopodia → phagosome.
• Fusion with lysosome → phagolysosome.
• Killing by enzymes and reactive oxygen species (oxidative burst).
• Exocytosis of residues.

Q4. Compare humoral and cell-mediated immunity.

• Cells: B cells vs T cells.
• Mediators: antibodies vs cytokines and direct killing.
• Targets: extracellular bacteria, toxins vs intracellular viruses, cancer cells, transplants.
• Transferred by serum vs by cells.
• Examples of role: neutralizing tetanus toxin vs killing virus-infected cells.

Q5. Explain primary and secondary immune responses.

• Primary: first contact; lag of about a week or more; low antibody titre, mainly IgM; declines quickly.
• Secondary: on re-exposure; short lag; higher, longer titre, mainly IgG; higher affinity.
• Due to memory B and T cells.
• Basis of vaccines and boosters.
• Draw graph of antibody titre vs time.

परीक्षेसाठी टीप

Learn the four types of acquired immunity with one example each — natural/artificial × active/passive.

थोडक्यात सारांश

An antigen is a substance that the immune system recognises as foreign and that reacts with antibodies or T cells. An antibody (immunoglobulin) is a Y-shaped protein made by plasma cells to bind a specific antigen. This topic covers properties of antigens, antibody structure, the five classes of immunoglobulins, antigen–antibody reactions and monoclonal antibodies.

महत्त्वाचे मुद्दे

• Immunogen: substance that can induce an immune response. Hapten: small molecule that is not immunogenic alone but becomes so when joined to a carrier protein (e.g. penicillin).
• Factors affecting antigenicity: foreignness, large molecular size (usually over about 10,000 Da), chemical complexity, stability, route and dose. Proteins are the best antigens; polysaccharides are good; lipids and nucleic acids are weak.
• Epitope (antigenic determinant): the small part of an antigen that binds an antibody. Paratope: the part of an antibody that binds the epitope.
• Antibody structure (Porter and Edelman): four polypeptide chains — two heavy (H) and two light (L) — joined by disulphide bonds into a Y shape.
• Each chain has variable (V) and constant (C) regions. The V regions at the tips form two antigen-binding sites.
• Papain digestion gives two Fab fragments (antigen binding) and one Fc fragment (crystallizable; binds cells and complement).
• Light chains: kappa (κ) or lambda (λ). Heavy chain type decides the class: γ (IgG), α (IgA), μ (IgM), δ (IgD), ε (IgE).
• Hinge region gives flexibility.
• Precipitation: soluble antigen + antibody → visible precipitate (e.g. Ouchterlony double diffusion, radial immunodiffusion).
• Agglutination: particulate antigen (cells) clumps (e.g. blood grouping, Widal test for typhoid).
• Neutralization: antibody blocks toxin or virus (antitoxins).
• Complement fixation: complement used up when antigen–antibody complex forms.
• ELISA: enzyme-labelled antibody gives colour (e.g. HIV screening).
• Immunofluorescence: fluorescent dye-labelled antibodies.
• Antigen–antibody reactions:
• Monoclonal antibodies: identical antibodies from one clone, made by hybridoma technology (Köhler and Milstein, 1975) — fusion of a B cell with a myeloma cell, selected in HAT medium. Used in diagnosis (pregnancy kits), therapy and research.

महत्त्वाच्या संज्ञा

• Valency – number of antigen-binding sites (IgG = 2; pentameric IgM = 10).
• Affinity – strength of binding of one site to one epitope; avidity – overall binding strength of the whole antibody.
• Titre – highest dilution of serum that still gives a visible reaction.
• Prozone – false negative due to antibody excess.
• Isotype – antibody class determined by heavy chain.

महत्त्वाची माहिती

५ महत्त्वाचे प्रश्न

Q1. What is a hapten?

A small molecule that can bind an antibody but cannot by itself trigger antibody production; it becomes immunogenic only when linked to a large carrier protein. Example: penicillin, dinitrophenol.

Q2. Differentiate agglutination and precipitation.

Agglutination is clumping of particulate antigens like cells by antibodies (e.g. blood grouping). Precipitation is formation of an insoluble complex from soluble antigens (e.g. Ouchterlony test).

Q3. Describe the structure of an antibody with a diagram.

• Y shape: 2 identical heavy and 2 identical light chains.
• Inter-chain disulphide bonds.
• Variable regions (VH, VL) form antigen-binding site; constant regions (CH, CL).
• Hinge region.
• Fab and Fc fragments on papain digestion.
• Functions of Fab (binding) and Fc (complement, cell binding).

Q4. Write the properties of the five classes of immunoglobulins.

• Use the table: structure, location, special roles.
• IgG – placenta, opsonization.
• IgA – mucosal immunity, colostrum.
• IgM – first response, pentamer, J chain.
• IgD – B cell receptor.
• IgE – allergy, parasites.

Q5. Explain hybridoma technology for monoclonal antibodies.

• Immunise mouse with antigen; collect spleen B cells.
• Fuse with myeloma cells (using PEG).
• Select hybrids in HAT medium (unfused myeloma cells die; unfused B cells die naturally).
• Screen clones for desired antibody (ELISA).
• Grow selected clone in culture or mouse.
• Uses: diagnostics, cancer therapy, blood typing.

परीक्षेसाठी टीप

Draw the antibody diagram with all labels (heavy chain, light chain, V and C regions, hinge, disulphide bonds, Fab, Fc). Learn the Ig table thoroughly.

थोडक्यात सारांश

The complement system is a group of about 30 plasma and membrane proteins that "complement" (help) antibodies and phagocytes in killing microbes. Its proteins are present in inactive form and are switched on one after another in a cascade. Complement can be activated by three pathways — classical, alternative and lectin — which all meet at C3 and end in the membrane attack complex that punches holes in cells. It was discovered by Jules Bordet (1890s) as a heat-labile serum factor.

महत्त्वाचे मुद्दे

• Complement proteins are made mainly by the liver (hepatocytes) and also by macrophages.
• They are named C1 to C9 (and factors B, D, P); fragments are labelled "a" (usually small) and "b" (usually large), e.g. C3 → C3a + C3b. (For C2 the larger piece is traditionally called C2a in many texts.)
• Complement is heat-labile: heating serum at 56 °C for 30 minutes inactivates it (used in serological tests).
• Starts when C1q binds the Fc region of antigen-bound IgM (one pentamer is enough) or IgG (two or more molecules needed).
• C1 (C1q, C1r, C1s) cleaves C4 and C2 → C3 convertase (C4b2a) → cleaves C3 → C5 convertase (C4b2a3b).
• Classical pathway (antibody-dependent, part of adaptive immunity):
• C3 slowly breaks down on its own ("tick-over"); C3b binds microbial surfaces such as LPS, yeast walls (zymosan).
• Factor B binds, factor D cleaves it → C3bBb (C3 convertase), stabilized by properdin (factor P); C3bBb3b is the C5 convertase.
• Alternative pathway (antibody-independent, innate):
• Lectin pathway: mannose-binding lectin (MBL) binds mannose on microbial surfaces; MBL-associated serine proteases (MASPs) cleave C4 and C2, like C1.
• Terminal (lytic) pathway common to all: C5 → C5a + C5b; C5b binds C6, C7, C8 and several C9 molecules → membrane attack complex (MAC, C5b–9) → a pore → cell lysis (especially Gram-negative bacteria, enveloped viruses, foreign RBCs).
• Lysis of cells by MAC.
• Opsonization: C3b coats microbes so phagocytes (with C3b receptors) engulf them easily.
• Inflammation: C3a and C5a are anaphylatoxins — they make mast cells release histamine and increase vascular permeability.
• Chemotaxis: C5a attracts neutrophils.
• Clearance of immune complexes from blood.
• Biological functions:
• Regulation protects host cells: C1 inhibitor, factor H, factor I, decay-accelerating factor (DAF), CD59 (blocks MAC).
• Deficiencies: C3 deficiency → repeated bacterial infections; C5–C9 deficiency → recurrent Neisseria infections; C1 inhibitor deficiency → hereditary angioedema.
• Complement fixation test (CFT) uses consumption of complement to detect antigen or antibody (e.g. the old Wassermann test for syphilis).

महत्त्वाच्या संज्ञा

• Cascade – chain of reactions where each activated protein activates the next.
• Convertase – enzyme complex that cleaves C3 or C5.
• Opsonin – molecule that coats a microbe and promotes phagocytosis (C3b, IgG).
• Anaphylatoxin – complement fragment (C3a, C5a) that triggers inflammation.
• Membrane attack complex – C5b–C9 pore that lyses target cells.

महत्त्वाची माहिती

५ महत्त्वाचे प्रश्न

Q1. What are anaphylatoxins?

C3a and C5a (C4a weakly). They cause mast cells and basophils to release histamine, increase blood vessel permeability and smooth-muscle contraction, and so promote inflammation.

Q2. Why is serum heated at 56 °C before some serological tests?

To inactivate the heat-labile complement proteins, so that complement in the patient's serum does not interfere with the test (e.g. in complement fixation test).

Q3. Describe the classical pathway of complement activation.

• Antigen–antibody complex; C1q binding (IgM, IgG).
• Activation of C1r, C1s.
• Cleavage of C4 and C2; C3 convertase.
• C3 cleavage; C5 convertase.
• Terminal pathway and MAC (flow chart).

Q4. Explain the alternative and lectin pathways.

• Spontaneous C3 hydrolysis; factor B, D, properdin; amplification loop.
• MBL binding to mannose, MASPs, C4 and C2 cleavage.
• Both work without antibody — early defence.

Q5. Write the biological functions and regulation of complement.

• Lysis, opsonization, inflammation, chemotaxis, immune complex clearance.
• Regulatory proteins and their roles.
• Diseases due to deficiency.

परीक्षेसाठी टीप

Draw one combined flow chart showing the three pathways meeting at C3 and ending at C5b–9; it answers both short notes and long questions.

थोडक्यात सारांश

Hypersensitivity is an exaggerated or harmful immune response to an antigen, usually on second exposure, which damages the body's own tissues. Common examples are allergies, asthma, blood transfusion reactions and the tuberculin skin test. Gell and Coombs (1963) classified hypersensitivity into four types based on the mechanism. Types I–III are antibody-mediated (immediate), while Type IV is cell-mediated (delayed).

महत्त्वाचे मुद्दे

• The antigen that triggers an allergy is called an allergen (pollen, dust mites, peanuts, penicillin, insect venom).
• First contact sensitizes the person; harm appears on later contact.
• Mediated by IgE bound to mast cells and basophils (through Fc receptors).
• On re-exposure the allergen cross-links IgE → mast cells degranulate and release histamine, leukotrienes, prostaglandins.
• Occurs within minutes (about 2–30 min).
• Examples: hay fever (allergic rhinitis), asthma, urticaria, food allergy, anaphylactic shock (penicillin, bee sting). Atopy is an inherited tendency to Type I allergy.
• Treatment: antihistamines, adrenaline (epinephrine) for anaphylaxis, desensitization; tested by skin prick test.
• Type I – Immediate (anaphylactic) hypersensitivity
• IgG or IgM bind antigens on the surface of cells → complement lysis, phagocytosis or ADCC.
• Examples: ABO-mismatched blood transfusion reaction, haemolytic disease of the newborn (Rh incompatibility; prevented by anti-D injection to the Rh-negative mother), autoimmune haemolytic anaemia, drug-induced cytopenias.
• Type II – Cytotoxic (antibody-dependent) hypersensitivity
• Soluble antigen–antibody (IgG) complexes deposit in blood vessel walls, kidneys and joints → complement activation → neutrophils → inflammation.
• Occurs in hours (about 4–8 h for the local Arthus reaction; days for serum sickness).
• Examples: Arthus reaction (local), serum sickness (after animal antiserum), post-streptococcal glomerulonephritis, systemic lupus erythematosus (SLE), farmer's lung.
• Type III – Immune complex hypersensitivity
• No antibody; sensitized T cells (TH1 cells release cytokines that activate macrophages; cytotoxic T cells kill).
• Appears after 48–72 hours.
• Examples: tuberculin (Mantoux) test, contact dermatitis (nickel, poison ivy, cosmetics), granulomas in tuberculosis and leprosy, graft rejection.
• Type IV – Delayed-type (cell-mediated) hypersensitivity (DTH)
• Mantoux test: purified protein derivative (PPD) injected intradermally in the forearm; induration of 10 mm or more at 48–72 h is commonly read as positive (cut-offs vary by guideline) and shows past exposure or BCG vaccination.

महत्त्वाच्या संज्ञा

• Allergen – antigen that causes allergy.
• Sensitization – first exposure that primes the immune system.
• Degranulation – release of granule contents (histamine) from mast cells.
• Anaphylaxis – sudden, severe, whole-body Type I reaction; can be fatal.
• Induration – raised, hard swelling of skin, as in a positive Mantoux test.

महत्त्वाची माहिती

५ महत्त्वाचे प्रश्न

Q1. What is anaphylaxis? How is it treated?

Anaphylaxis is a severe, rapid, body-wide Type I reaction (falling blood pressure, airway narrowing) after exposure to an allergen such as penicillin or bee venom. Immediate injection of adrenaline (epinephrine) is the main treatment, with antihistamines and oxygen.

Q2. Why is the tuberculin test called delayed hypersensitivity?

Because the reaction is caused by T cells and macrophages, which take time to gather at the site; induration appears only after 48–72 hours, not within minutes.

Q3. Explain Type I hypersensitivity in detail.

• Sensitization: IgE production, binding to mast cells.
• Re-exposure: cross-linking, degranulation.
• Mediators and their effects.
• Examples; diagnosis by skin test; treatment.
• Flow diagram.

Q4. Describe Types II and III hypersensitivity with examples.

• Type II: antibodies against cell-surface antigens; transfusion reaction, Rh disease and its prevention.
• Type III: immune complex deposition; Arthus reaction, serum sickness, glomerulonephritis.
• Difference between the two.

Q5. Classify hypersensitivity reactions (Gell and Coombs) and compare immediate and delayed types.

• Four types in a table.
• Immediate (I–III): antibody-mediated, can be transferred by serum.
• Delayed (IV): T-cell mediated, transferred by lymphocytes, not by serum.

परीक्षेसाठी टीप

Learn the table row-wise: type, mediator, time, example. Mantoux test (Type IV) and Rh incompatibility (Type II) are favourite short notes.

थोडक्यात सारांश

A vaccine is a preparation of a killed or weakened microbe, its parts, or its toxin made harmless, which trains the immune system without causing disease. Immunization gives protection either actively (the body makes its own antibodies and memory cells) or passively (ready-made antibodies are given). Vaccines have eradicated smallpox and nearly eradicated polio; India's Universal Immunization Programme protects millions of children every year.

महत्त्वाचे मुद्दे

• History: Edward Jenner (1796) used cowpox to protect against smallpox; Louis Pasteur made vaccines against chicken cholera, anthrax (1881) and rabies (1885). Smallpox was declared eradicated by WHO in 1980; India was declared polio-free (WHO South-East Asia region certified) in 2014.
• Active immunity: produced by the person's own immune system, after infection (natural) or vaccination (artificial). Slow to develop (days to weeks) but long-lasting, with memory cells.
• Passive immunity: ready-made antibodies; natural (mother to baby through placenta (IgG) and colostrum (IgA)) or artificial (antitoxins, immunoglobulin, e.g. anti-rabies immunoglobulin, anti-tetanus serum). Immediate but short-lived (weeks to months), no memory.
• Live attenuated: weakened living organisms — BCG (M. bovis), oral polio vaccine (Sabin), MMR, rotavirus, yellow fever. Strong, long immunity, often a single dose; not for immunocompromised people.
• Killed (inactivated): whole organisms killed by heat or formalin — injectable polio vaccine (Salk, IPV), rabies cell-culture vaccine, whole-cell pertussis. Safer, need boosters.
• Toxoids: toxins inactivated by formalin — tetanus and diphtheria toxoids.
• Subunit / recombinant: only the protective antigen — hepatitis B surface antigen (HBsAg) made in yeast, HPV vaccine.
• Conjugate: polysaccharide linked to a protein carrier to work in infants — Hib, pneumococcal conjugate vaccine.
• Newer types: mRNA vaccines and viral-vector vaccines (used for COVID-19, e.g. Covishield is a viral-vector vaccine), DNA vaccines.
• Types of vaccines:
• Adjuvants (e.g. aluminium salts/alum) increase the immune response to a vaccine.
• Primary and secondary response: the first dose gives a slow, weak response (mainly IgM); a booster gives a fast, strong, long-lasting response (mainly IgG) because of memory cells — the reason for booster doses.
• Herd immunity: when most of a population is immune, spread is blocked and even unvaccinated people are protected.
• Cold chain: vaccines must be kept cool (usually 2–8 °C) from manufacture to use.
• India's UIP (started 1985 from the 1978 EPI) includes BCG, OPV, IPV, hepatitis B, pentavalent (DPT + HepB + Hib), rotavirus, PCV, measles-rubella, JE (in endemic districts) and Td. Check the current national schedule, as vaccines are added from time to time.

महत्त्वाच्या संज्ञा

• Attenuation – weakening of a pathogen so it cannot cause disease but still gives immunity.
• Toxoid – toxin made harmless but still antigenic.
• Booster dose – later dose that strengthens and prolongs immunity.
• Herd immunity – community protection when a high proportion is immune.
• Antiserum (antitoxin) – serum containing ready-made antibodies.

महत्त्वाची माहिती

५ महत्त्वाचे प्रश्न

Q1. What is a toxoid? Give two examples.

A toxoid is a bacterial exotoxin treated (usually with formalin) so it is no longer toxic but still produces protective antibodies. Examples: tetanus toxoid and diphtheria toxoid.

Q2. Differentiate between Salk and Sabin polio vaccines.

Salk (IPV) is an injectable, killed (inactivated) vaccine. Sabin (OPV) is an oral, live attenuated vaccine that also gives gut (IgA) immunity and is easy to give in mass campaigns.

Q3. Classify vaccines with examples, advantages and limitations.

• Live attenuated, killed, toxoid, subunit/recombinant, conjugate, mRNA and vector.
• Advantages and limitations of live vs killed.
• Role of adjuvants and cold chain.

Q4. Compare active and passive immunity.

• Natural and artificial forms of each with examples.
• Comparison table.
• Uses of passive immunity: rabies, tetanus, snakebite antivenom.

Q5. Write a note on India's Universal Immunization Programme.

• Aim: protect infants, children and pregnant women.
• Vaccines in the schedule (birth: BCG, OPV-0, Hep B; 6, 10, 14 weeks: OPV, pentavalent, rotavirus, IPV, PCV; 9 months: MR, etc.).
• Achievements: polio-free status, measles reduction.
• Mission Indradhanush to raise coverage.

परीक्षेसाठी टीप

Give one example for every vaccine type and remember "toxoid = tetanus, diphtheria; recombinant = hepatitis B". Mention primary vs booster response with a small antibody graph.

थोडक्यात सारांश

Epidemiology is the study of how diseases are distributed in a population and what factors decide their occurrence, so that they can be controlled. For infectious diseases this means understanding the source of the microbe, how it spreads, who is susceptible, and how outbreaks are recognized and stopped. This topic covers basic terms, the chain of infection, modes of transmission, disease frequency measures and control measures, including India's surveillance system.

महत्त्वाचे मुद्दे

• John Snow (1854) traced a London cholera outbreak to the Broad Street water pump — often called the start of modern epidemiology.
• Sporadic – occasional, scattered cases (tetanus).
• Endemic – constantly present at a usual level in an area (malaria in parts of India).
• Epidemic (outbreak) – cases clearly above the expected level in a place and time (cholera after floods, dengue in monsoon).
• Pandemic – epidemic spread over many countries or continents (influenza 1918, COVID-19 declared by WHO in March 2020).
• Patterns of occurrence:
• Chain of infection (six links): infectious agent → reservoir → portal of exit → mode of transmission → portal of entry → susceptible host. Breaking any link stops spread.
• Reservoirs: humans (cases and carriers, e.g. typhoid carrier "Typhoid Mary"), animals (zoonoses: rabies, plague, leptospirosis), and environment (soil – tetanus; water – cholera).
• Direct: contact (skin, sexual), droplets (within about 1–2 m; influenza), vertical (mother to fetus; HIV, rubella).
• Indirect: airborne droplet nuclei (tuberculosis, measles), vehicle-borne (food, water, blood – hepatitis A, cholera, hepatitis B), vector-borne (mosquito – malaria, dengue; flea – plague), fomites (towels, door handles).
• Modes of transmission:
• Incubation period: time from infection to first symptoms (cholera hours–5 days; rabies weeks–months).
• Incidence = new cases in a period ÷ population at risk.
• Prevalence = all existing cases at a time ÷ total population.
• Morbidity (illness rate) and mortality (death rate); case fatality rate = deaths from the disease ÷ cases × 100.
• R₀ (basic reproduction number): average number of new cases from one case in a fully susceptible population; R₀ > 1 means spread.
• Measures of frequency:
• Infectious disease cycle: entry, multiplication, symptoms, shedding, transmission.
• Emerging and re-emerging diseases: new (COVID-19, Nipah in Kerala, Zika) or returning/resistant ones (MDR-TB, dengue, chikungunya).
• Control of epidemics: early detection and lab confirmation, isolation and treatment, quarantine of contacts, vaccination, vector control, safe water and sanitation, health education, and travel measures.
• Surveillance in India: Integrated Disease Surveillance Programme (IDSP, 2004) and its digital platform IHIP; National Centre for Disease Control (NCDC), Delhi.
• Typing methods that trace outbreak strains: phage typing, serotyping, ELISA, PCR and DNA fingerprinting.

महत्त्वाच्या संज्ञा

• Carrier – person who carries and spreads a pathogen without showing disease.
• Zoonosis – disease naturally transmitted from animals to humans.
• Vector – living carrier (usually an arthropod) that transmits a pathogen.
• Fomite – non-living object that carries infection.
• Quarantine – limiting the movement of healthy contacts during the incubation period; isolation separates the sick.

सूत्रे

• Incidence rate = (new cases during period ÷ population at risk) × 1000.
• Prevalence = (existing cases at a time ÷ total population) × 1000.
• Case fatality rate (%) = (deaths due to disease ÷ number of cases) × 100.
• Example: a town of 50,000 has 250 new dengue cases in a year and 5 deaths. Incidence = 250 ÷ 50,000 × 1000 = 5 per 1000 per year; CFR = 5 ÷ 250 × 100 = 2%.

५ महत्त्वाचे प्रश्न

Q1. Distinguish between endemic and epidemic.

An endemic disease is constantly present at a usual level in an area. An epidemic is a sudden rise of cases clearly above the expected level in a place and time.

Q2. What is a carrier? Give an example.

A person who harbours and sheds a pathogen without showing symptoms, e.g. a chronic typhoid carrier with Salmonella Typhi in the gall bladder. Carriers silently spread infection.

Q3. Explain the chain of infection with examples.

• Six links in a flow diagram.
• Example: tuberculosis — agent M. tuberculosis, reservoir patient, exit by cough, airborne spread, entry by inhalation, susceptible host.
• Ways to break each link.

Q4. Describe the modes of transmission of infectious diseases.

• Direct: contact, droplet, vertical.
• Indirect: airborne, vehicle (food, water, blood), vector (mechanical and biological), fomites.
• One disease example for each.

Q5. How are epidemics recognized and controlled?

• Surveillance and rise above expected cases; lab confirmation and typing.
• Control: isolation, quarantine, treatment, immunization, vector control, sanitation, education.
• Role of public health system (IDSP, NCDC, WHO).

परीक्षेसाठी टीप

Practise one incidence/CFR calculation and draw the chain of infection. Learn the four patterns (sporadic, endemic, epidemic, pandemic) with Indian examples.

थोडक्यात सारांश

Antimicrobial agents are chemicals that kill or stop the growth of microbes inside the body. Antibiotics are substances made by microorganisms that act against other microbes. This topic covers the history, classification by target, mode of action, testing of drug sensitivity and the problem of antibiotic resistance.

महत्त्वाचे मुद्दे

• Paul Ehrlich introduced chemotherapy and the idea of a "magic bullet"; his drug Salvarsan (arsphenamine, 1910) treated syphilis.
• Gerhard Domagk (1930s) introduced the sulpha drug Prontosil.
• Alexander Fleming discovered penicillin (1928); Florey and Chain purified it for use (1940s).
• Selman Waksman discovered streptomycin (1943) from Streptomyces griseus and coined the word "antibiotic".
• Selective toxicity: the drug harms the microbe but not the host — the key property of a good drug.
• Spectrum: narrow (e.g. penicillin G — mainly Gram-positive) or broad (e.g. tetracycline, chloramphenicol).
• Bactericidal drugs kill (penicillin, aminoglycosides); bacteriostatic drugs stop growth (tetracycline, sulphonamides, chloramphenicol).
• Cell wall synthesis – penicillins, cephalosporins (β-lactams; block transpeptidation of peptidoglycan), vancomycin.
• Cell membrane – polymyxin B, colistin (bacteria); amphotericin B, nystatin (fungi; bind ergosterol).
• Protein synthesis – on 30S subunit: aminoglycosides (streptomycin), tetracyclines; on 50S: chloramphenicol, macrolides (erythromycin).
• Nucleic acid synthesis – quinolones/fluoroquinolones (ciprofloxacin; inhibit DNA gyrase), rifampicin (inhibits RNA polymerase).
• Metabolic pathways (antimetabolites) – sulphonamides (compete with PABA in folic acid synthesis), trimethoprim.
• Modes of action (targets):
• Antifungal: azoles (fluconazole), polyenes; antiviral: acyclovir (herpes), zidovudine/AZT (HIV), oseltamivir (influenza).
• Antibiotic sensitivity testing: Kirby–Bauer disc diffusion on Mueller–Hinton agar; measure the zone of inhibition. MIC found by broth dilution.
• Resistance mechanisms: enzymatic inactivation (β-lactamase), altered target (changed penicillin-binding proteins in MRSA), reduced permeability, efflux pumps, alternative metabolic pathway.
• Resistance spreads by mutation and by gene transfer (R plasmids, transposons). Misuse of antibiotics speeds it up.

महत्त्वाच्या संज्ञा

• Antibiotic – antimicrobial substance produced by a microorganism.
• Chemotherapeutic agent – any chemical used to treat disease.
• MIC – lowest drug concentration that prevents visible growth.
• MBC – lowest concentration that kills 99.9% of the bacteria.
• MDR – multi-drug resistant.

महत्त्वाची माहिती

५ महत्त्वाचे प्रश्न

Q1. What is selective toxicity?

The ability of a drug to harm the pathogen without harming the host, because it acts on a target present only in the microbe, e.g. peptidoglycan for penicillin.

Q2. Define MIC.

Minimum inhibitory concentration — the lowest concentration of an antimicrobial agent that prevents visible growth of a microorganism under standard conditions.

Q3. Explain the modes of action of antibiotics with examples.

• Cell wall: penicillin, cephalosporin, vancomycin.
• Cell membrane: polymyxin, amphotericin B.
• Protein synthesis: streptomycin, tetracycline (30S); erythromycin, chloramphenicol (50S).
• Nucleic acid: ciprofloxacin, rifampicin.
• Antimetabolites: sulphonamides, trimethoprim.
• Draw a bacterial cell showing these targets.

Q4. Describe the Kirby–Bauer disc diffusion method.

• Standardised inoculum (0.5 McFarland) swabbed on Mueller–Hinton agar.
• Antibiotic discs placed on surface.
• Incubate at 35–37 °C for 16–18 hours.
• Measure diameter of zone of inhibition.
• Compare with standard chart: sensitive, intermediate, resistant.

Q5. Discuss mechanisms of antibiotic resistance and its prevention.

• β-lactamase destroys penicillin.
• Target change (MRSA, altered PBP).
• Efflux pumps (tetracycline).
• Reduced uptake (porin changes).
• Spread by plasmids and transposons.
• Prevention: complete course, no self-medication, no use as growth promoters, infection control, new drugs.

परीक्षेसाठी टीप

Classify antibiotics by target site — examiners prefer that over a list of names. Always name one example for each target.