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.