Chapter 21 – The Immune System (A&P II)

Learning Objectives

  • Describe innate (nonspecific) defenses and the key cellular/molecular players involved.

  • Detail the sequence of inflammatory events and explain how each step eliminates pathogens.

  • Define "antigen" and "antibody," and outline how their interaction drives immunity.

  • Compare origin, maturation, activation, and effector roles of B versus T lymphocytes.

  • Identify antigen-presenting cells (APCs) and clarify their indispensable support for adaptive immunity.

  • Trace every step of humoral immunity, including immunological memory and antibody actions.

  • Distinguish active vs. passive and natural vs. artificial acquisition of immunity.

  • Define cellular immunity, list the specialized T-cell subsets, and summarize their functions.

  • Discuss practical/clinical topics: transplant rejection, immunodeficiencies, autoimmunity, and hypersensitivities.

Big-Picture Purpose of the Immune System

  • Shields the body from two broad assault types:
    • External: microorganisms such as bacteria, viruses, helminths (worms).
    • Internal: rapidly dividing abnormal cells, e.g., metastatic cancers.

  • Orchestrates multilayered defenses that escalate from broad, fast barriers to slow, exquisitely specific attacks.

Functional Categories of Immunity

  • Innate (nonspecific)
    • First line: external body membranes—skin, hair, mucus.
    • Second line: internal weapons—phagocytes, NK cells, antimicrobial proteins, inflammation, fever.
    • Traits: present at birth, react instantly, recognize broad pathogen patterns.

  • Adaptive (specific)
    • Third line: tailored responses that recognize molecular fingerprints (antigens).
    • Traits: slower to mobilize (requires "priming"), systemic, possesses memory, more potent on re-exposure.

First Line of Defense – Barrier Mechanisms

  • Physical
    • Intact epidermis + keratin; continuous mucous membranes.
    • Respiratory cilia sweep debris toward pharynx; nasal hairs trap particulates.

  • Chemical micro-environment
    • Acid mantle (skin pH ≈ <5) discourages bacterial growth.
    • Enzymes: lysozyme in saliva, lacrimal fluid, and respiratory mucus; gastric enzymes/acids.
    • Defensins: broad-spectrum antimicrobial peptides.
    • Sebum & sweat: lipid components toxic to some microbes.

  • Mucin
    • Forms sticky traps in GI and respiratory tracts.

  • When breached (cuts, burns, punctures) ⇒ immediate activation of second line.

Second Line of Defense – Innate Internal Arsenal

Pattern-Recognition Receptors (PRRs)

  • Expressed by innate cells; bind conserved microbial "signatures" (PAMPs) ⇒ rapid response before harm.

Phagocytes

  • Neutrophils
    • Most abundant WBC; become highly phagocytic upon encountering microbes; die after battle (source of pus).

  • Macrophages
    • Monocyte-derived; long-lived, robust.
    • Free macrophages wander (e.g., alveolar macrophages). Fixed macrophages are stationed (e.g., Kupffer cells in liver).

  • Phagocytosis stages

    1. Adherence via pathogen "signature" or opsonins (antibodies/complement).

    2. Pseudopods engulf → phagosome.

    3. Phagosome + lysosome → phagolysosome.

    4. Digest; residual bodies exocytosed.

    5. If enzymes insufficient, Helper T cells command macrophages to unleash ROS, O_2^-, and raise lysosomal pH.

Natural Killer (NK) Cells

  • Large granular lymphocytes; non-phagocytic.

  • Patrol blood & lymph, inducing apoptosis in virus-infected or cancerous cells even before adaptive immunity responds.

Inflammation – "The Fire Alarm"

  • Triggers: trauma, heat, chemicals, infection.

  • Classical signs: redness, heat, swelling, pain (and sometimes impaired function).

  • Chemical mediators
    • Histamine (mast cells), kinins, prostaglandins, complement, cytokines.

  • Vascular events

    1. Vasodilation ⇒ hyperemia ⇒ redness & heat.

    2. ↑ capillary permeability ⇒ exudate into tissues ⇒ edema; swelling presses on nociceptors ⇒ pain.

    3. Exudate sweeps antigens into lymphatics.

    4. Fibrin meshwork localizes invaders, serving as repair scaffold.

  • Phagocyte mobilization

    1. Leukocytosis (↑
      neutrophils in blood).

    2. Margination (cling to capillary endothelium).

    3. Diapedesis (squeeze out of vessels).

    4. Chemotaxis (follow inflammatory chemicals).

  • Clinical sequelae
    • Pus: dead neutrophils + debris + microbes.
    • Abscess: collagen walls off pus; may require surgical drainage.

Antimicrobial Proteins

  • Interferons (IFNs)
    • Released by virus-infected cells; "warn" neighbors to synthesize antiviral proteins.

  • Complement (≈>20 plasma proteins)
    • Circulate inactive; activation → membrane attack complex (MAC), opsonization, inflammation amplification.

Fever

  • Pyrogens (from leukocytes/macrophages) reset hypothalamic thermostat ⇒ body temp ↑.

  • Moderate fever benefits:
    • Liver & spleen sequester Fe/Zn (nutrients microbes need).
    • Metabolism ↑ \Rightarrow faster tissue repair.

Transition to Adaptive Immunity

  • Innate slows the infection but cannot fully eradicate highly evolved pathogens.

  • Adaptive response, though delayed, is specific and often decisive.

Characteristics of Adaptive Immunity

  • Specificity: unique lymphocyte receptors bind unique antigens.

  • Systemic: protective effects extend throughout body.

  • Memory: secondary responses are faster, stronger, symptom-free.

Branches of Adaptive Defense

  • Humoral (Antibody-Mediated)
    • B cells → plasma cells → antibodies circulating in fluids.
    • Targets: extracellular pathogens, toxins; act by tagging for elimination.

  • Cellular (Cell-Mediated)
    • T cells directly kill or regulate.
    • Targets: intracellular pathogens, cancer cells, grafts.

Antigens

  • Any molecule that provokes an adaptive response; usually large, complex, and "non-self".

  • Two key functional properties
    • Immunogenicity – stimulates specific lymphocyte proliferation.
    • Reactivity – reacts with activated lymphocytes/antibodies.

  • Haptens: small molecules (e.g., poison ivy urushiol) that become immunogenic after binding self-proteins ⇒ sometimes cause harmful self-attack.

  • One antigen possesses multiple antigenic determinants ⇒ many distinct antibodies may bind one microbe.

Antibodies (Immunoglobulins)

  • Produced exclusively by plasma cells.

  • Each antibody binds the antigen that originally activated its parent B cell.

  • Functions (mnemonic "NAPP-C")
    • Neutralization – mask toxic/viral sites.
    • Agglutination – clump cells.
    • Precipitation – pull soluble antigens out of solution.
    • Complement fixation/activation – trigger MAC and cell lysis.

  • Research tool: monoclonal antibodies (lab-generated, single specificity) for diagnostics, therapies, and cancer targeting.

Cellular Players of Adaptive Immunity

Lymphocytes

  • Origin: \text{red bone marrow} (hematopoietic stem cells).

  • Maturation (≈ 2{-}3 days)
    • B cells in bone marrow; T cells in thymus.
    • Develop immunocompetence (one receptor specificity) + self-tolerance (non-reactivity to self).

  • Seeding
    • Naïve yet immunocompetent cells colonize secondary lymphoid organs (nodes, spleen, tonsils) & circulate.

  • Activation
    • Encounter with antigen matches receptor ⇒ clonal selection.

  • Proliferation & Differentiation
    • Clones → effector cells (plasma, helper, cytotoxic) + memory cells (long-lived sentinels).

Antigen-Presenting Cells (APCs)

  • Professional APCs:
    • Dendritic cells – most potent; patrol skin/mucosa; migrate to nodes to activate T cells.
    • Macrophages – present to TH cells, which in turn activate macrophages (positive feedback). • B cells – present antigen to TH for help in full activation.

  • Mechanism: engulf antigen → process → load peptides on MHC molecules → display to T cells.

Humoral Immune Response in Depth

  • B-cell Activation

    1. Antigen binds membrane Ig receptors.

    2. Endocytosis & presentation (often with T_H assistance).

    3. Clonal expansion.

  • Effector Outcome
    • Plasma cells pump out ≈2000 antibodies/second for \approx 4–5 days.
    • Memory B cells silently patrol for future encounters.

  • Immunological Memory
    • Primary response: lag 3{-}6 days; antibody peak \approx10 days; symptoms present.
    • Secondary response: onset within <24 h; peak 2{-}3 days; titers higher & linger weeks-months; usually asymptomatic.

  • Forms of Humoral Immunity
    • Active × Natural = infection-induced immunity.
    • Active × Artificial = vaccination with attenuated/dead pathogen.
    • Passive × Natural = maternal IgG across placenta & IgA in milk.
    • Passive × Artificial = injection of exogenous antibodies (e.g., antivenom). Provides immediate, short-term protection; no memory.

Cellular Immune Response

  • T cells defend against intracellular threats (viruses, some bacteria/parasites), cancer, and transplanted tissue.

  • Classes & Key Functions
    • Helper T (CD4^+) – "generals"; activate B & T cells, stimulate macrophages, amplify innate defense; without them, adaptive immunity collapses (e.g., HIV/AIDS).
    • Cytotoxic T (CD8^+) – "hit men"; search and destroy infected or foreign cells via perforin-granzyme pore formation and apoptosis signals.
    • Regulatory T – immune "brakes"; secrete suppressive cytokines to prevent excessive/inappropriate responses (autoimmunity prevention).
    • Memory T – ensure swift secondary cellular responses.
    • NK cells – innate relatives; detect lack of MHC or antibody coating; induce apoptosis without prior sensitization.

Antigen Recognition & Activation

  • T cells only see antigens when displayed on MHC:
    • MHC I (on all nucleated cells) presents endogenous peptides → recognized by CD8^+.
    • MHC II (on APCs) presents exogenous peptides → recognized by CD4^+.

  • Activation requires: (1) antigen recognition; (2) costimulatory signals (cytokines, surface molecules).

  • Proliferation peaks ≈7 days; contraction via apoptosis at 7{-}30 days to avoid cytokine storms.

Clinical & Real-World Connections

Transplants & Rejection

  • Success hinges on matching ABO, other blood antigens, and MHC loci.

  • Lifelong immunosuppression necessary ⇒ increased infection/cancer risk; ~50\% grafts rejected by year 10.

Immunodeficiencies

  • Congenital: SCID (genetic; absent B & T) – fatal without bone-marrow transplant.

  • Acquired: Hodgkin’s lymphoma (malignant B cells); AIDS (HIV targets CD4^+ T_H).
    • AIDS signs: cachexia, night sweats, lymphadenopathy; opportunistic infections (Pneumocystis, Kaposi sarcoma).

Autoimmune Diseases (Loss of Self-Tolerance)

  • Examples & targets:
    • Rheumatoid arthritis – joints.
    • Myasthenia gravis – neuromuscular junction.
    • Multiple sclerosis – CNS myelin.
    • Graves’ disease – thyroid.
    • Type 1 diabetes mellitus – pancreatic \beta cells.
    • Systemic lupus erythematosus – multi-organ.
    • Glomerulonephritis – renal glomeruli.

  • Therapies: broad immunosuppression (corticosteroids, anti-TNF, cytokine blockers) ⇒ ethical need to balance infection risk.

Hypersensitivities ("Too Much of a Good Thing")

  • Immediate (Type I; IgE-mediated): first exposure sensitizes; re-exposure → histamine flood, allergy symptoms; severe form = anaphylactic shock (massive vasodilation, BP collapse) → treat with epinephrine.

  • Subacute (Types II & III): antibody-driven but slower (hours); e.g., mismatched transfusion, lupus complexes.

  • Delayed (Type IV): T-cell-mediated; onset 1{-}3 days; e.g., contact dermatitis, TB skin test.

Ethical, Philosophical & Practical Considerations

  • Vaccination: harnesses adaptive memory while sparing disease—public-health triumph but requires societal trust.

  • Immunosuppression vs. Quality of Life: organ recipients’ dilemma—long-term drug side effects vs. graft survival.

  • Monoclonal antibodies: cutting-edge therapeutics (e.g., checkpoint inhibitors in oncology) raise cost-access debates.

  • Autoimmunity research: understanding self-tolerance breakdown informs therapies and transplant tolerance.

These bullet-point notes integrate every major and minor detail from the transcript, clarify complex mechanisms with step-by-step logic, enumerate all examples, insert approximate quantitative data (3{-}6 day lag, 10 day peaks, 50\% rejection, etc.), and connect the content to clinical realities and broader ethical implications. The structure mirrors a comprehensive study outline capable of substituting for the original lecture slides.