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IMMUNOLOGY – Antibody Classes, Inflammation, Complement & Early Adaptive Concepts

Immunoglobulins (Antibodies)

  • “Immunoglobulin” (Ig) is another word for antibody.

  • 5 main classes: IgG, IgA, IgM, IgE, IgD (easy mnemonic: “GAMED”).

  • Basic Y-shaped protein produced by B-lymphocytes; each arm binds a specific antigen.

  • Overall functions: neutralisation, agglutination, precipitation, complement activation, opsonisation, antibody-dependent cell-mediated cytotoxicity (ADCC).

IgM – “Main / 1st Responder”

  • Structure: pentamer (5 Y’s → 10 antigen-binding sites).

  • First antibody to spike in a primary infection.

  • Functions: strong agglutination, efficient complement activation.

  • Clinical pearl: a serum rise in IgM = recent or first-time exposure.

IgG – “General Infantry / Most Abundant”

  • Monomer; ≈ 80\% of serum antibodies.

  • Dominates the secondary response (memory response).

  • Only Ig class that crosses placenta → passive neonatal immunity.

  • Versatile: neutralises toxins & viruses, opsonises, fixes complement.

  • Board-style question: “Patient has high IgG but low IgM → indicates previous exposure/re-infection.”

IgA – “Secretions & Maternity”

  • Dimer (2 Y’s) when secreted; monomer in serum.

  • Found in mucosal secretions: saliva, tears, mucus, breast milk (colostrum).

  • Protects external openings & infant GI tract.

  • Breast milk is produced by modified apocrine sweat glands (mammary glands).

IgE – “Allergies & Parasites”

  • Monomer; binds Fcε receptors on mast cells & basophils.

  • Triggers degranulation → histamine release → type I hypersensitivity.

  • Important for defence against helminths (parasites).

  • Memory aid: E for Eosinophils, Edema, External parasites.

IgD – “Don’t Know / B-Cell Receptor”

  • Surface receptor on naïve B cells; exact serum role unclear.

  • Low concentration, short half-life.

Primary vs Secondary Antibody Response

  • Primary infection: large IgM peak → slower, shorter IgG rise.

  • Subsequent infection with same antigen: rapid, higher IgG peak; modest/absent IgM rise.

  • Graphically: IgM spike first, IgG dominates later exposures.

Innate vs Adaptive Immunity (“Lines of Defence”)

  1. First line – physical & chemical barriers (skin, mucosa, secretions).

  2. Second line – innate cellular & chemical responses (inflammation, complement, phagocytes).

  3. Third line – adaptive, specific immunity (B & T lymphocytes; antibodies).

  • Antibodies are adaptive but cooperate with innate components (e.g., complement).

Inflammation – Cardinal Signs & Mediators

  • Signs: redness, heat, swelling, pain.

  • Vasodilation & ↑ permeability due to histamine, kinins, prostaglandins.

  • NSAIDs (non-steroidal anti-inflammatory drugs) inhibit prostaglandin synthesis.

  • Temperature rises because of increased blood flow & metabolic activity at site.

Kinins (e.g., Bradykinin)

  • Peptides produced during inflammation; potent vasodilators.

  • Cause pain, ↑ vascular permeability, recruit leukocytes.

  • Board emphasis: \text{Bradykinin} = swelling & pain mediator.

Leukocyte Recruitment & Extravasation

  1. Margination – leukocytes cling to endothelial CAMs (cell-adhesion molecules).

  2. Diapedesis – squeezing through endothelium into tissue.

  3. Chemotaxis – migration along chemical gradients (e.g., cytokines, bacterial peptides).

White Blood Cell Classes

  • Granulocytes: neutrophils, eosinophils, basophils (→ “new, easy, basic granulocytes”).

  • Monocytes → differentiate into macrophages in tissue.

  • Lymphocytes: B cells, T cells, NK cells.

Complement System

  • >30 plasma proteins activated in cascade.

  • Classical pathway: C1 binds antibody–antigen complexes.

  • Alternative pathway: direct binding to bacterial/fungal polysaccharides (no antibody needed).

  • Lectin pathway: mannose-binding lectin binds pathogen sugars.

  • Opsonisation (C3b): “tags” pathogen → ↑ phagocytosis likelihood.

  • MAC (membrane-attack complex) forms pores → lysis.

  • Opsonin definition: molecule (antibody or complement) that enhances phagocytosis.

Antibody Structure Nuances

  • Variable region (Fab) – antigen-binding.

  • Constant region – class-specific functions.

  • Fc region (“Fragment, crystallisable”) – binds Fc receptors on phagocytes & activates complement; “calls the eater.”

Cytokines – Short Half-Life Messengers

  • Rapidly produced & degraded to allow tight control of immune signaling.

Immunogenicity

  • Degree to which an antigen triggers an immune response.

  • Factors increasing immunogenicity:
    • Molecular complexity (proteins > polysaccharides > lipids).
    • Size (larger molecules > smaller).
    • Foreignness (more non-self).
    • Structural heterogeneity.

  • Clinical example: shellfish proteins highly immunogenic to some people → severe allergy.

Adaptive Cellular Arm (Preview)

  • T-lymphocyte maturation: precursors leave bone marrow → thymus.

  • Double-positive cells (CD4 & CD8) → differentiate:
    • Helper T = CD4^+.
    • Cytotoxic T = CD8^+.

Pharmacology Tie-Ins (Term 4 Preview)

  • NSAIDs block prostaglandin synthesis (COX inhibition) → ↓ pain, fever, inflammation.

  • Glucocorticoids dampen multiple inflammatory mediators (e.g., IL-1, TNF-α).

Numerical / Structural Highlights

  • IgM pentamer: 5 subunits, 10 binding sites.

  • IgA dimer: 2 subunits, 4 binding sites.

  • IgG concentration: ≈ 80\% of total serum antibody.

  • Complement proteins: >30 identified components.