IMMUNOLOGY — HIGH-YIELD EXAM NOTES (TNMGRMU Pattern)
Format for each answer: Definition → Classification/Diagram → Mechanism/Points → Clinical/Exam tip. Draw diagrams exactly as described — examiners give marks for correctly labelled diagrams even if text is short.
SECTION A — ESSAY QUESTIONS (15 MARKS)
1. Structure and Functions of Immunoglobulins
Definition: Immunoglobulins (Ig) are glycoprotein molecules produced by plasma cells (differentiated B-lymphocytes) that function as antibodies, binding specifically to antigens.
Diagram to draw — Basic Y-shaped Ig monomer:
Antigen-binding site Antigen-binding site
\ /
\ /
VL \ / VL
\ /
VH----\--------------/----VH } FAB REGION
\ S-S / (Fragment, antigen binding)
CL------\----------/------CL
\ /
==========HINGE=========
| |
CH2 CH2
| S-S | } FC REGION
CH3--------CH3 (Fragment, crystallizable)
(Carbohydrate attached here)
- 2 identical Heavy chains (H) + 2 identical Light chains (L), joined by disulfide (S-S) bonds → "Y" shape.
- Each chain has a Variable (V) region (top, antigen-specific) and Constant (C) region (bottom).
- Fab fragment = antigen binding (2 per molecule) — made of VL+CL+VH+CH1.
- Fc fragment = effector functions (complement fixation, binding to phagocytes, placental transfer).
Classification — 5 classes (write as table):
| Class | Structure | Key Feature |
|---|
| IgG | Monomer | Most abundant (75%), crosses placenta, secondary response |
| IgM | Pentamer | First antibody in primary response, good agglutinator |
| IgA | Dimer (secretory) | Found in saliva, tears, milk, mucosal immunity |
| IgD | Monomer | On B-cell surface, receptor function |
| IgE | Monomer | Allergy/hypersensitivity, binds mast cells/basophils |
Functions of Antibody (Fc-mediated):
- Neutralization of toxins/viruses
- Opsonization (coating for phagocytosis)
- Agglutination of particulate antigens
- Precipitation of soluble antigens
- Complement activation (classical pathway)
- Antibody-Dependent Cell Cytotoxicity (ADCC)
- Placental transfer of immunity (IgG only)
2. Hypersensitivity Reactions
Definition: Exaggerated/inappropriate immune response to an antigen causing tissue damage. Classified by Gell and Coombs into 4 types.
Flowchart to draw:
HYPERSENSITIVITY REACTIONS
|
---------------------------------------------------
| | | |
TYPE I TYPE II TYPE III TYPE IV
(Anaphylactic) (Cytotoxic) (Immune complex) (Delayed/Cell mediated)
IgE mediated IgG/IgM Ag-Ab-Complement T-lymphocyte mediated
| Type | Mechanism | Time | Example |
|---|
| I - Anaphylactic | Ag binds IgE on mast cells/basophils → degranulation → histamine release | Seconds-minutes | Asthma, urticaria, anaphylaxis, allergic rhinitis |
| II - Cytotoxic | IgG/IgM binds antigen on cell surface → complement/NK cell lysis | Minutes-hours | Hemolytic disease of newborn, blood transfusion reaction, Goodpasture syndrome |
| III - Immune complex | Ag-Ab complexes deposit in tissue → complement activation → neutrophil damage | 3-8 hours | Serum sickness, SLE, post-streptococcal glomerulonephritis, Arthus reaction |
| IV - Delayed type | Sensitized T-cells release cytokines → macrophage activation (no antibody involved) | 24-72 hours | Tuberculin (Mantoux) test, contact dermatitis, graft rejection, TB granuloma |
Diagram — Type I (simplest, most asked):
Allergen ---> binds IgE on Mast cell surface
|
cross-links IgE
|
Mast cell degranulation
|
Histamine, Leukotrienes released
|
Vasodilation + Bronchospasm + Itching
3. Complement System
Definition: A group of ~30 heat-labile serum proteins (C1-C9) that act in a cascade to help destroy pathogens, working with antibodies ("complements" antibody action).
Flowchart to draw — 3 activation pathways converging:
CLASSICAL PATHWAY ALTERNATIVE PATHWAY LECTIN PATHWAY
(Ag-Ab complex, (Microbial surface, (Mannose on
C1q binds) C3, Factor B, D) pathogen, MBL binds)
| | |
-------------------------------------------------------
|
C3 CONVERTASE FORMED
|
C3 --> C3a + C3b
|
C5 CONVERTASE FORMED
|
C5 --> C5a + C5b
|
C5b + C6 + C7 + C8 + C9(n)
|
MEMBRANE ATTACK COMPLEX (MAC)
|
CELL LYSIS (pore formation)
Biological functions (write as list):
- Cell lysis – via MAC (C5b-9)
- Opsonization – C3b coats pathogen for phagocytosis
- Anaphylatoxins – C3a, C5a cause mast cell degranulation, chemotaxis
- Chemotaxis – C5a attracts neutrophils
- Clearance of immune complexes
- Viral neutralization
4. Antigen-Antibody Reactions and their Applications
Definition: In-vitro reaction between antigen and its specific antibody, forming the basis of serological diagnostic tests.
Flowchart of types:
ANTIGEN-ANTIBODY REACTIONS
|
-----------------------------------------------------
| | | | |
Agglutination Precipitation Complement Neutralization Labelled
(particulate (soluble Ag) fixation (toxin- (ELISA,
Ag) test antitoxin) RIA, IF, WB)
Key tests (table — high yield):
| Test | Principle | Use |
|---|
| Agglutination | Particulate Ag + Ab → visible clumping | Blood grouping, Widal test, VDRL |
| Precipitation | Soluble Ag + Ab → insoluble complex | Immunodiffusion, counter-current electrophoresis |
| ELISA | Enzyme-labelled Ab/Ag, colour change measured | HIV, Hepatitis screening |
| Western Blot | Proteins separated by size, probed with labelled Ab | HIV confirmatory test |
| Immunofluorescence | Fluorescent-labelled antibody detected under UV microscope | Rabies, Autoimmune disease diagnosis |
| RIA (Radioimmunoassay) | Radioactive-labelled antigen | Hormone assays |
| CFT (Complement Fixation Test) | Measures complement used up in Ag-Ab reaction | Viral serology |
Diagram — ELISA (most commonly asked in this group):
Antigen coated on well
|
Add patient serum (has Ab if positive)
|
Wash (remove unbound)
|
Add Enzyme-linked secondary antibody
|
Add substrate --> Colour change = POSITIVE
5. Humoral Immunity vs Cell-Mediated Immunity
Definition: Two arms of the adaptive (acquired) immune system.
Diagram — Branching flowchart:
ADAPTIVE IMMUNITY
|
---------------------------------
| |
HUMORAL IMMUNITY CELL-MEDIATED IMMUNITY
(B-lymphocyte mediated) (T-lymphocyte mediated)
| |
Antigen presented Antigen presented
| |
B-cell activated T-helper (CD4) activated
| |
Proliferates into Activates:
Plasma cells + Memory cells - Cytotoxic T (CD8) -> kills infected cells
| - Macrophages -> phagocytosis
Plasma cells secrete - B cells (help)
ANTIBODIES |
| Memory T-cells formed
Antibody neutralizes/
opsonizes free antigen
(extracellular pathogens,
bacteria, toxins) (intracellular pathogens -
viruses, TB, fungi, tumor cells,
graft rejection)
Comparison table:
| Feature | Humoral | Cell-Mediated |
|---|
| Cell involved | B lymphocyte | T lymphocyte |
| Effector molecule | Antibody | Cytokines, cytotoxic cells |
| Target | Extracellular pathogens/toxins | Intracellular pathogens, tumor, grafts |
| Memory | Memory B cells | Memory T cells |
| Example | Bacterial infection immunity | TB, viral infection, graft rejection |
6. Vaccines — Types and Schedule
Definition: A biological preparation that provides active acquired immunity by stimulating the immune system to produce antibodies without causing disease.
Flowchart — classification:
VACCINES
|
-----------------------------------------------
| | | |
LIVE ATTENUATED KILLED/ TOXOID SUBUNIT/
INACTIVATED RECOMBINANT
| | | |
BCG, OPV, Salk (IPV), Diphtheria, Hepatitis B,
Measles, MMR, Rabies, Tetanus HPV
Yellow fever Pertussis
Points to write:
- Live attenuated – weakened organism, strong long-lasting immunity, single dose often sufficient, contraindicated in immunocompromised (risk of reactivation).
- Killed/Inactivated – heat/chemical killed organism, safe but needs boosters, weaker immunity.
- Toxoid – inactivated bacterial toxin (formalin-treated), stimulates antitoxin antibodies.
- Subunit/Recombinant – only immunogenic part of organism used, very safe.
National Immunization Schedule (India — high yield):
| Age | Vaccine |
|---|
| Birth | BCG, OPV-0, Hep B-1 |
| 6,10,14 weeks | DPT, OPV, Hep B, Hib, Rotavirus |
| 9 months | Measles/MR, Vitamin A |
| 16-24 months | DPT booster, MR-2 |
| 5-6 years | DPT booster 2 |
| 10 & 16 years | TT |
7. AIDS / HIV
Definition: Acquired Immunodeficiency Syndrome — caused by Human Immunodeficiency Virus (HIV, a retrovirus), leading to progressive destruction of CD4+ T-helper cells.
Diagram — HIV structure:
gp120 (surface spike)
\ /
____\/____
/ gp41 \ <- Envelope (lipid bilayer)
| p17 matrix |
| ___________ |
| | p24 capsid| |
| | RNA (2) | |
| | RT enzyme| |
| ----------- |
\_____________/
Flowchart — Pathogenesis:
HIV enters via gp120 --> binds CD4 receptor + CCR5/CXCR4 co-receptor
|
Fusion & entry into CD4+ T-helper cell
|
Reverse transcriptase: RNA --> DNA
|
Integration into host genome (integrase)
|
New viral particles produced --> bud out, kill host cell
|
Progressive CD4+ cell depletion
|
Immunodeficiency --> Opportunistic infections (TB, Candida, PCP)
|
AIDS
Transmission: Sexual contact, blood/blood products, mother-to-child (vertical), needle sharing.
Diagnosis:
- ELISA – screening test
- Western Blot – confirmatory test
- CD4 count – monitors disease progression (AIDS if <200 cells/µL)
- Viral load (PCR) – monitors treatment response
Management: HAART (Highly Active Anti-Retroviral Therapy) – combination of NRTI + NNRTI/PI.
8. Organs of the Immune System (Lymphoid Organs)
Definition: Organs where lymphocytes are produced, mature, and mount immune responses. Classified as Primary and Secondary.
Diagram/flowchart:
LYMPHOID ORGANS
|
--------------------------------
| |
PRIMARY (Central) SECONDARY (Peripheral)
- site of lymphocyte - site where mature lymphocytes
origin & maturation meet antigen & respond
| |
1. Bone marrow (B-cell 1. Lymph nodes
maturation, origin of 2. Spleen
all blood cells) 3. Tonsils
2. Thymus (T-cell 4. MALT (mucosa-associated
maturation) lymphoid tissue - Peyer's
patches, appendix)
Points:
- Bone marrow – pluripotent stem cells → B cells mature here (in humans); site of origin of all leukocytes.
- Thymus – T-cell precursors migrate from bone marrow, undergo positive/negative selection; involutes with age.
- Lymph node – filters lymph, site of antigen trapping by dendritic cells, has cortex (B cells), medulla, germinal centers.
- Spleen – filters blood, removes old RBCs, site of immune response to blood-borne antigens (red pulp = RBC filtration, white pulp = lymphocytes).
- MALT – protects mucosal surfaces (gut, respiratory tract).
SECTION B — SHORT NOTES (5 MARKS)
1. Antigen
- Definition: Any substance capable of inducing a specific immune response and reacting with the products of that response (antibody or sensitized T cell).
- Properties: Foreignness, high molecular weight, chemical complexity, rigidity.
- Terms: Immunogen (induces immune response), Hapten (small molecule, antigenic only when bound to carrier protein), Epitope/antigenic determinant (part of antigen that binds antibody).
- Diagram: draw an oval labelled "Antigen" with small projecting bumps labelled "Epitopes" - each epitope binds one antibody paratope.
2. Types of Immunity
IMMUNITY
|
-----------------------------
| |
INNATE (Natural) ACQUIRED (Adaptive)
- Non-specific - Specific, has memory
- Skin, mucosa, phagocytes |
- Present from birth -------------------
| |
ACTIVE PASSIVE
(body produces own (ready-made Ab
antibody; slow but given; fast but
long-lasting) short-lasting)
| |
Natural: infection Natural: maternal Ab
Artificial: vaccine Artificial: antiserum/
immunoglobulin injection
3. Interferons (IFN)
- Definition: Antiviral glycoproteins produced by virus-infected host cells, inhibit viral replication in neighbouring cells.
- Types: IFN-α, IFN-β (Type I, from leukocytes/fibroblasts - antiviral), IFN-γ (Type II, from T cells/NK cells - immunomodulatory).
- Mechanism (flow): Virus infects cell → cell produces IFN → IFN binds receptors on neighbouring cells → activates antiviral proteins (blocks viral protein synthesis) → neighbouring cells become resistant.
- Uses: Hepatitis B/C treatment, some cancers, multiple sclerosis (IFN-β).
4. Cytokines / Interleukins
- Definition: Small signalling proteins secreted by immune cells that regulate immunity, inflammation, and hematopoiesis.
- Types (list): Interleukins (IL-1 to IL-37), Interferons, TNF, Chemokines, Colony stimulating factors (CSF).
- Key examples: IL-1 & IL-6 (fever/inflammation), IL-2 (T-cell growth factor), TNF-α (inflammation, septic shock), IL-4 (B-cell/IgE switching).
- Draw simple diagram: Cell A --(secretes cytokine)--> binds receptor on Cell B --> triggers response in Cell B.
5. MHC / HLA
- Definition: Major Histocompatibility Complex — set of genes on chromosome 6 (called HLA in humans) coding for surface glycoproteins involved in antigen presentation.
MHC
|
-----------------
| |
CLASS I CLASS II
(HLA-A,B,C) (HLA-DP,DQ,DR)
present on present on
ALL nucleated ANTIGEN PRESENTING
cells CELLS (macrophage,
| dendritic cell, B cell)
presents to |
CD8+ cytotoxic presents to
T cells CD4+ helper T cells
- Importance: Organ transplant matching, graft rejection, disease association (e.g., HLA-B27 with ankylosing spondylitis).
6. Autoimmunity / Autoimmune Diseases
- Definition: Loss of self-tolerance → immune system attacks the body's own tissues/antigens.
- Mechanism (flow): Self-tolerance breakdown (due to molecular mimicry/genetic/hormonal factors) → autoreactive T/B cells activated → autoantibodies produced → tissue damage.
- Classification with examples:
- Organ-specific: Hashimoto's thyroiditis, Type 1 Diabetes mellitus, Myasthenia gravis
- Systemic: SLE (Systemic Lupus Erythematosus), Rheumatoid arthritis
7. Immunodeficiency Disorders
IMMUNODEFICIENCY
|
--------------------------
| |
PRIMARY SECONDARY (Acquired)
(Congenital/genetic) (due to external cause)
| |
e.g. Bruton's e.g. AIDS, malnutrition,
agammaglobulinemia, chemotherapy, radiation,
DiGeorge syndrome, diabetes, chronic steroid use
SCID (Severe Combined
Immunodeficiency)
8. Monoclonal Antibodies
- Definition: Antibodies produced from a single clone of B cells, hence identical and specific to one epitope.
- Production (flowchart): Immunize mouse with antigen → B cells isolated from spleen → fused with myeloma cells (using PEG) → hybridoma formed → screened & cloned → antibody harvested.
- Uses: Diagnostic kits (pregnancy test), cancer therapy (Rituximab, Trastuzumab), autoimmune disease treatment (Infliximab).
9. ELISA (Enzyme-Linked Immunosorbent Assay)
- Principle: Detects antigen or antibody using an enzyme-labelled reagent; enzyme acts on substrate to give colour change measured by spectrophotometer.
- Diagram (same as essay #4 above) — reproduce: Antigen coated → serum added → wash → enzyme-linked antibody → substrate → colour = positive.
- Uses: HIV, Hepatitis B/C screening, hormone assays (pregnancy test).
10. Widal Test / VDRL (Serological Tests)
- Widal test – slide/tube agglutination test detecting antibodies (agglutinins) against Salmonella typhi O and H antigens in typhoid fever.
- VDRL (Venereal Disease Research Laboratory) – flocculation test detecting reagin antibody in syphilis, uses cardiolipin antigen.
- Both are examples of agglutination/flocculation Ag-Ab reactions (link back to essay Q4).
11. T Cells and B Cells
| Feature | T cell | B cell |
|---|
| Site of maturation | Thymus | Bone marrow |
| Function | Cell-mediated immunity | Humoral immunity (antibody) |
| Subtypes | CD4 (helper), CD8 (cytotoxic), memory, suppressor | Plasma cells, memory B cells |
| Surface marker | CD3 | CD19, CD20, surface Ig |
12. Natural Killer (NK) Cells
- Definition: Large granular lymphocytes of innate immunity, kill virus-infected and tumor cells without prior sensitization (no memory, non-specific).
- Mechanism: Release perforin and granzymes → induce apoptosis in target cell. Also recognize cells with low/absent MHC-I ("missing self" hypothesis).
- Difference from Cytotoxic T cell: NK cell = innate, no antigen specificity, no memory; Cytotoxic T (CD8) = adaptive, antigen-specific, has memory.
Exam strategy tip: For 15-mark essays, spend the first 2-3 minutes just drawing the flowchart/diagram neatly with labels — examiners often award diagram marks separately from text marks. For 5-mark short notes, one clean diagram + 4-5 bullet points is sufficient; don't overwrite.