Basics of the Immune System

Overview of the Immune System’s Architecture

• Two grand divisions

  • External (first-line) defenses

  • Physical barriers: skin, mucous membranes lining respiratory, digestive, reproductive, urinary tracts

  • Chemical barriers blended into these surfaces (acids, lysozymes, sebum)

  • Internal defenses

  • Cellular and molecular components that respond after a pathogen breaches surface barriers

  • Housed or supported by lymphatic structures (lymph nodes, spleen, etc.)

• Constant theme: a pathogen must penetrate external barriers ➜ recognition must occur ➜ internal defenses activate

Recognition, Antigens & the “Should I Respond?” Question

• All immune reactions hinge on molecular recognition

  • Requires binding between a host antigen receptor (on antibody or leukocyte) and a foreign antigen

  • If binding occurs ➜ immune response; if not ➜ no response

• Antigen = any molecule capable of being bound and flagged as “non-self”

  • Can be protein, carbohydrate, glycoprotein, etc.

• Visual metaphor used: antibody arms with curved binding pockets that “lock” onto antigens

• Future discussion teaser: binding may lead to agglutination (clumping of targets)

Self-Tolerance, Blood Typing & Autoimmune Disease

• Every cell (even self) owns antigens ➜ immune system must be tolerant to self‐antigens

• Blood transfusion compatibility is an immune issue

  • Donor RBC antigens + recipient antibodies that bind them = dangerous agglutination & hemolysis

• Errors in antigen-receptor formation (gene mutation or post-translational modification) ➜ self-binding ➜ autoimmune disease

  • Different tissues express distinct antigens → determines which tissue is under attack (e.g., pancreas in Type 1 diabetes, joints in rheumatoid arthritis)

Innate (Non-Specific) Immunity – “Built-In & Broad”

1. External Innate Defenses

• Skin

  • Epidermis = stratified squamous epithelium; outer layers keratinized, dehydrated, dead → tough barrier

• Mucous membranes

  • Line internal tracts; kept moist by mucus; non-keratinized (“mucosa is moist”)

• Chemical shields

  • Sebum → weak acid mantle on skin (suppresses bacterial/fungal growth)

  • Gastric HCl (pH≈1–2) destroys microbes swallowed

  • Lysozymes in tears, saliva, nasal mucus, sweat → enzymatically lyse bacterial walls while secretions perform other duties (lubrication, cooling, washing)

2. Internal Innate Defenses

a. Phagocytes (“eating cells”)

• Neutrophils, macrophages, monocytes, eosinophils, natural killer cells

• Perform phagocytosis → engulf ➜ lysosomal enzymes digest target

• NK cells & some others can also release toxic granules for contact killing

b. Interferons (“viral neighborhood watch”)

• Protein messengers released by virus-infected cells & activated lymphocytes

• Nearby cells respond by:

  • Down-regulating protein synthesis (blocks viral replication)

  • Triggering apoptosis (self-destruct to deny viruses a factory)

  • Alerting and activating immune cells

c. Inflammation – vascular fast-track for WBC delivery

• Goal: accelerate leukocyte arrival at infection site

• Key chemical: histamine from mast cells (plus heparin, cytokines)

  • Histamine ➜ arteriolar vasodilation + ↑ capillary permeability (endothelial gaps widen)

• Cardinal signs & causes

  • Redness & heat: more blood (blood = red, carries heat)

  • Swelling (edema): fluid shifts

  • Capillary hydrostatic pressure rises (arteriole dilation)

  • Proteins leak → interstitial oncotic pressure ↑

  • Net filtration pressure equation reminder: NFP = (HPC - HPI) - (\piC - \piI); both terms shift toward filtration

  • Pain: edema puts pressure on nerve endings

• Leukocyte trafficking sequence

  1. Cytokines induce margination & adhesion (WBCs stick to endothelium)

  2. Diapedesis – cell squeezes through enlarged cleft

  3. Chemotaxis – follows chemical gradient (cytokines, bacterial toxins) via amoeboid crawling

• Systemic extension = fever

  • Hypothalamus resets set‐point ➜ shivering & vasoconstriction raise body temp

  • Benefits: enzymes work faster; many microbes replicate slower at elevated temps

Adaptive (Specific) Immunity – “Custom-Built & Memory-Forming”

Core players

• B lymphocytes → humoral (antibody-mediated) immunity

• T lymphocytes → cell-mediated immunity

Clonal Selection & Memory

• Initial antigen recognition triggers massive mitosis → clones

  • ~50 % become effector cells (immediately fight)

  • Cytotoxic T cells (Tc) release perforins or phagocytose small targets

  • Plasma cells (activated B) secrete antibodies matching parent receptor

  • Remaining ~50 % become memory cells

  • Lodge in lymph nodes/spleen; can persist years–life

  • Enable rapid secondary response (immunological memory)

T Cell Effector Mechanisms

• Perforins insert into target membrane ➜ pore formation ➜ osmotic lysis

• Additional cytokines attract macrophages, enhance killing

Antibody (Ab) Effector Mechanisms

• Each Ab has ≥2 identical binding sites → Y-shaped “multigrip”

• Major reactions

  • Agglutination – Ab crosslinks pathogens; clumps limit spread & ease phagocytosis (same mechanism causes transfusion clumping)

  • Opsonization – Ab-coated target recognized faster by phagocyte Fc receptors (acts as molecular “seasoning”)

  • Neutralization – Ab coats viral or bacterial surface proteins

  • Blocks virus entry & toxin release

  • (Also complement activation & precipitation, though not detailed in transcript)

Routes of Acquiring Immunity

Active Acquisition (body manufactures its own Abs & memory)

• Natural active: infection in everyday life

• Artificial active (vaccination)

  • Vaccine contains non-infectious antigenic fragments (e.g., seasonal flu shot’s viral protein cocktail)

  • Body mounts full adaptive response → memory ready before real pathogen arrives

Passive Acquisition (ready-made Abs and/or cells obtained externally)

• Natural passive

  • Maternal IgG crosses placenta during gestation

  • Maternal IgA transferred via breast milk post-partum

• Artificial passive

  • Injection of pre-formed antibodies from another organism (e.g., antiserum for snake venom, occasionally equine or bovine sources)

  • Temporary; donor Abs eventually degrade

Clinical, Ethical & Real-World Connections

• Blood transfusion protocols rest on antigen/antibody compatibility to avoid lethal agglutination

• Autoimmune diseases (lupus, MS, Type 1 diabetes) highlight danger of failed self-tolerance; gene editing and immunotherapies raise ethical debates

• Inflammation therapeutics

  • Weigh benefit (faster WBC delivery) vs harm (pain, tissue pressure, compromised perfusion)

  • Decision to administer NSAIDs or steroids is a case-by-case clinical judgment

• Fever management: antipyretics improve comfort yet might slow immune kinetics; guidelines suggest treating only high or dangerous fevers

• Interferon-based drugs (e.g., IFN-β for multiple sclerosis) repurpose a natural innate molecule

• Vaccination: individual immunity + herd immunity concepts; ethical duty vs personal autonomy debates

Quick Numerical & Formula Highlights

• Gastric HCl pH: \approx 1\text{–}2 (strong enough to kill many microbes)

• Sebum pH: slightly acidic (<7) → “acid mantle”

• Capillary fluid shift underpinning edema expressed by filtration equation above

• Fever set-point elevation: typically +1^{\circ}\text{C to }+4^{\circ}\text{C} over baseline

Suggested Study Flow & Memory Hooks

• First, memorize barrier → recognition → response pathway; every detail slots under one of these steps

• Map innate vs adaptive on a two-column chart; note which cells and chemicals belong where

• Use the “ARMY” metaphor for adaptive immunity: clone volunteers (memory) + active soldiers (plasma/Tc) drafted after first contact

• For antibodies, remember “G O N A” (Glue-Opsonize-Neutralize-Activate complement) to recall key reactions

• Practice clinical vignettes: mismatched transfusion ➜ query agglutination; virus reinfection ➜ recall memory cells; large swollen ankle ➜ apply inflammation cascade & edema math