Comprehensive Immune System & Antibody Review

Antibody (Immunoglobulin) Classes

• General architecture
  • All antibodies are “Y”-shaped molecules; tips of the “Y” = antigen-binding (variable) regions.
  • Stem of the “Y” = Fc region (constant for the isotype, calls in phagocytes/complement).
  • IgA = a dimer (two Y’s joined); IgM = a pentamer (five Y’s joined).
• IgM — “Main / First Responder”
  • First antibody to spike during a primary exposure to any pathogen.
  • Large pentameric structure → excellent at agglutination & complement activation.
  • Drives the classical complement pathway (complement binds to IgM already attached to antigen).
• IgG — “General Infantry”
  • Most abundant class (largest proportion of serum antibodies).
  • Dominant antibody during secondary exposures; spikes quickly because body "remembers" the antigen.
  • Crosses placenta; crucial for long-term immunity and opsonization.
• IgA — “Secretory Antibody”
  • Found almost exclusively in secretions: breast milk, saliva, tears, mucus, etc.
  • Key for mucosal immunity; major NCLEX focus = provides passive immunity to newborns via breast milk.
  • Produced by modified apocrine (sudoriferous) glands in the mammary tissue.
• IgE — “E for Eosinophils, AllergiEs, and parasitEs”
  • Binds strongly to basophils & mast cells → triggers histamine release in allergic reactions.
  • Cooperates with eosinophils to combat parasites.
• IgD — “Don’t know / Don’t care” (minimal clinical emphasis)
  • Functions mainly as B-cell receptor; rarely a focus of board questions.

Antibody Functional Regions

• Arm (Fab) region binds antigen.
• Fc region (“F for Phagocyte Call”) sticks out and
  • Recruits macrophages/neutrophils for opsonization (marks pathogen for phagocytosis).
  • Binds complement proteins (classical pathway).

Complement System (Innate but Antibody-Linked)

• > 30 plasma proteins that assemble in cascades (analogous to coagulation).
• Classical pathway: Complement binds to antibody (IgM/IgG) already bound to antigen.
• Alternative pathway: Complement binds directly to polysaccharides on bacterial/fungal walls.
• Key outcome terms
  • Opsonization: coating that enhances phagocytosis.
  • MAC (membrane attack complex): forms pores that lyse pathogens (mentioned conceptually).

Interferons (IFN)

• Cytokines released by virus-infected cells.
• “Interfere” with viral replication & warn neighboring cells; part of innate, non-specific response.

Innate (Non-Specific) Immunity Overview

First, Second, Third Lines of Defense

1. First line: Barriers (skin, mucous membranes, secretions, normal flora).
2. Second line: Inflammation, fever, complement, interferons, phagocytes, NK cells.
3. Third line: Adaptive (B & T lymphocytes, antibodies).

Inflammation

• Cardinal signs (know all five)
  1. Redness (rubor)
  2. Heat (calor)
  3. Swelling (tumor)
  4. Pain (dolor)
  5. Loss of function (functio laesa)
• Chemical mediators
  • Histamine → vasodilation & capillary permeability (antihistamines block this → decongestion).
  • Leukotrienes → bronchoconstriction; targeted by anti-asthma drugs.
  • Prostaglandins → pain & fever; inhibited by NSAIDs (non-steroidal anti-inflammatory drugs).
  • Bradykinin → directly stimulates pain receptors; remembered as the kinin tied to pain.

Vascular & Cellular Events

• CAMs (cell-adhesion molecules) displayed on inflamed endothelium capture leukocytes.
• Margination: WBCs cling to endothelium via CAMs.
• Diapedesis: WBCs squeeze through endothelium into tissues ("diapedesis" = cell through tiny gap).
• Chemotaxis: WBCs follow chemical gradient toward injury/pathogen.
• Warmth arises because blood is \approx 0.5^{\circ}\text{C} hotter than core body temperature, and metabolic activity rises at the site.

Exudate & Pus

• Exudate: Protein-rich fluid leaving capillaries to “wash” injured tissue; contains debris + microbes.
• When exudate is loaded with dead neutrophils & bacteria → pus (malodorous).

Cellular Players

• Granulocytes: Neutrophils, Eosinophils (allergy/parasite), Basophils (histamine release).
• Monocytes → Macrophages (professional phagocytes).
• Lymphocytes:
  • B cells (plasma cells → antibodies).
  • T cells (CD4 helper, CD8 cytotoxic).
  • Natural Killer (NK) cells (induce apoptosis of abnormal cells).

Adaptive Immunity – T-Cell Maturation Snapshot (preview)

• Immature "pre-T" cells leave bone marrow → thymus.
• Initially express both CD4 & CD8; then
  • Cells destined to be Helper T (Th) keep CD4 (lose CD8).
  • Cells destined to be Cytotoxic T (Tc) keep CD8 (lose CD4).
• Mature T cells recognize antigen only when presented on MHC proteins (detailed next lecture).

Immunogenicity vs. Hypersensitivity

• Immunogenicity: Property of an antigen describing its ability to provoke an immune response.
  • Increases with size, complexity (proteins > polysaccharides > lipids), & foreignness.
• Hypersensitivity: Host’s exaggerated response (allergy). Example: shellfish has high immunogenicity for some individuals → allergic reaction.

Secretory & Gland Review

• Apocrine (a type of sudoriferous/sweat gland): produce breast milk; also in axillae & urogenital area.
• Eccrine/Merocrine: standard sweat glands for thermoregulation.

Coagulation Cascade Connection

• Inflammation recruits platelets & triggers the 12 clotting factors via intrinsic/extrinsic pathways (monitored clinically by PT/INR & aPTT). Heat + clotting contribute to local temperature rise.

Mnemonics & Board-Exam Pearls

• "M is Main; G is General; A is sAlivA; E is for Eosinophils/allErgiEs/parasites; D = Don’t care."
• IgM spikes first; IgG spikes second and larger → measure titers to judge primary vs. secondary infection.
• Question stem mentioning breast-fed newborn + passive immunity → answer IgA.
• Allergy question involving basophils/eosinophils → think IgE.
• CAM + margination → diapedesis → chemotaxis sequence.
• Bradykinin = pain; NSAIDs block prostaglandins; anti-histamines block histamine.
• Complement classical pathway requires antibody (IgM/IgG); alternative does not (binds microbe wall directly).