Anatomy & Physiology II – Lymphatic & Immune Systems

Chapter Objectives

Understand:
- Structure & function of the lymphatic system
- Differences between innate (non-specific) and adaptive (specific) immunity
- Differences between cell-mediated and antibody-mediated immunity
- Effects of stress and aging on immune function

Functions of the Lymphatic System

Fluid recovery
- Capillaries continuously filter plasma into interstitial spaces
- Life‐threatening within hours if lost water/proteins are not returned
Immunity
- Lymph passes through nodes → immune cells monitor & attack foreign material
Transport of dietary lipids
- Lacteals in small intestine absorb lipids & fat-soluble vitamins that capillaries cannot

Major Components of the Lymphatic System

Lymph (fluid)
Lymphatic vessels & capillaries
Lymphatic tissues
Lymphatic organs
- Tonsils, lymph nodes (cervical, axillary, inguinal, etc.), thymus, spleen, red bone marrow, MALT (e.g., Peyer’s patches, appendix)
Two principal ducts
- Right lymphatic duct (drains right head, arm, thorax)
- Thoracic duct (drains remainder of body; begins at cisterna chyli)

Lymph: Characteristics & Formation

Clear, colorless; similar to plasma but ↓ protein
Originates as interstitial fluid
Contents vary with location & may include:
- Macrophages, hormones, bacteria/viruses, debris, metastatic cancer cells
Fluid dynamics
- Outflow at arterial end → $\text{capillary hydrostatic pressure}$
- Inflow at venous end ← $\text{blood colloid osmotic pressure}$ (plasma proteins)
- Escaped proteins + residual fluid returned by lymphatics
- Respiratory & skeletal muscle pumps assist return; failure → edema

Lymphatic Vessels & Capillaries

Begin as blind, highly permeable capillaries
Absent in: bone, cartilage, cornea, teeth, bone marrow, CNS
Structural adaptations for one-way entry
- Anchoring filaments prevent collapse
- Overlapping endothelial “mini-valves” open when interstitial pressure ↑
Specialized GI capillaries: lacteals (lymph = chyle)
Capillaries → vessels (thin walls, many valves) → trunks → ducts → subclavian veins (bloodstream)
Flow forces (no pump)
- Rhythmic vessel contractions (intrinsic)
- Valves, skeletal/respiratory pumps, arterial pulsations

Lymphatic Cells

Natural killer (NK) cells
T lymphocytes (T cells)
B lymphocytes (B cells)
Macrophages
Dendritic cells (in epidermis = Langerhans)
Reticular cells (form stroma of lymphatic organs)

Lymphatic Organs & Tissues

Primary (site of immunocompetence acquisition)
- Red bone marrow: hematopoiesis
- Thymus: T-cell maturation; only lymphatic organ that does NOT directly fight antigen
Secondary (sites where immune responses occur)
- Lymph nodes
- Spleen
- Lymphatic nodules (tonsils, Peyer’s patches, appendix, diffuse MALT)

Lymph Nodes

$\sim 450{-}600$ bean-shaped organs (≤ $3\,\text{cm}$ )
Concentrated in cervical, axillary, mammary, & inguinal regions
Only lymphatic structures that FILTER lymph
- Macrophages remove pathogens before fluid re-enters blood
Immune surveillance sites for lymphocytes
More afferent than efferent vessels → slows flow for filtration

Spleen

Largest lymphatic organ (fist-sized) in left hypochondriac region
Functions
- Lymphocyte proliferation & surveillance
- Removes aged/damaged RBCs & platelets
- Platelet reservoir
- Fetal RBC production

Lymphatic Nodules (MALT)

Unencapsulated lymphoid masses in mucosae of GI, respiratory, urinary, reproductive tracts
Examples: tonsils, Peyer’s patches (ileum), appendix

Overview of the Immune System

1st line: Surface barriers (skin, mucosa)
2nd line: Internal innate defenses (phagocytes, NK cells, inflammation, fever, antimicrobial proteins)
3rd line: Adaptive immunity (humoral/B cells & cellular/T cells)

Innate (Non-Specific) Immunity

General Features

Present at birth; rapid response; no memory; same response to all pathogens
Two lines of defense

1st Line – Mechanical & Chemical Barriers

Mechanical: intact epidermis, mucous membranes, tears, saliva, mucus, cilia, epiglottis, urine flow, defecation, vomiting
Chemical: sebum (acidic film), lysozyme (tears, saliva, mucus), gastric juice (HCl + enzymes), vaginal acidity

2nd Line – Internal Defenses

a) Antimicrobial Proteins
- Interferons (IFNs)
- Secreted by virus-infected leukocytes
- Protect neighboring cells; activate NK cells & macrophages
- Complement (≈ $30$ plasma proteins from liver)
- Enhance inflammation, immune clearance, opsonization (↑ phagocytosis), cytolysis (MAC)
b) Phagocytes
- Neutrophils: most abundant WBC; die in process
- Macrophages (fixed & wandering) derived from monocytes
- Steps: Chemotaxis → Adherence → Ingestion (phagosome) → Digestion (phagolysosome) → Exocytosis of residual body
c) Natural Killer (NK) Cells
- Continual patrol; attack bacteria, virus-infected, cancer, transplanted cells
- Release perforins & granzymes → target lysis/apoptosis
d) Inflammation
- Trigger: tissue injury (trauma, infection)
- Purposes: limit spread, dispose debris, initiate repair
- 3 major processes
1. Mobilization (vasodilation = hyperemia, ↑ permeability → exudate, leukocyte emigration)
2. Containment & destruction of pathogens (fibrinogen walls-off; phagocytosis)
3. Cleanup & repair (macrophages, mitosis, fibroblasts)
- Cardinal signs: Pain, Redness, Immobility, Heat, Swelling ("PRISH")
- Cellular sequence (leukocyte mobilization): Leukocytosis → Margination → Diapedesis → Chemotaxis → Phagocytosis
e) Fever
- Systemic ↑ body temperature; hypothalamic set-point reset by pyrogens
- Exogenous (bacterial/viral glycolipids)
- Endogenous (IL-1, TNF from leukocytes)
- Phases: Onset (chills) → Stadium (oscillation) → Defervescence (sweating, vasodilation)
- Benefits
- Kills heat-labile microbes
- ↓ serum Fe, Zn, Cu (starves bacteria)
- Switches host metabolism to fats/proteins
- Promotes neutrophil activity & interferon efficacy
- Treat only if prolonged or > critical level (risk: enzyme denaturation, seizures, brain damage)

Adaptive (Specific) Immunity

Attributes: specificity & memory; slower to start but stronger on repeat exposure
Requires antigen recognition; involves lymphocytes & APCs
Two arms
- Cell-mediated (T cells) → intracellular targets
- Antibody-mediated / Humoral (B cells) → extracellular targets

Antigens & Receptors

Antigen: substance recognized as foreign (non-self) that provokes response; exhibits
- Immunogenicity (triggers proliferation)
- Reactivity (ability to react with antibodies/cells)
Epitope (antigenic determinant): specific segment recognized; immune system capable of recognizing ≈ $10^9$ different epitopes
Major Histocompatibility Complex (MHC)
- Self antigens on all nucleated cells
- Type I (MHC-I): present endogenous peptides to $\text{CD8}^+$ T cells
- Type II (MHC-II): present exogenous peptides on APCs to $\text{CD4}^+$ T cells
- Highly polymorphic; cause of graft rejection/transfusion reactions
Immunocompetence
- Ability to distinguish self/non-self; acquired in primary organs (thymus, bone marrow)
- $\approx 98\%$ of developing lymphocytes failing self-tolerance undergo apoptosis

Antigen Processing & Presentation

Exogenous pathway (APCs): pathogen phagocytosis → peptide-MHC-II display for helper T recognition
Endogenous pathway (infected body cell): viral/tumor proteins → peptide-MHC-I display for cytotoxic T recognition

Cell-Mediated Immunity (CMI)

Antigen recognition & binding
T-cell activation (requires co-stimulation: costimulatory molecules or cytokines)
- $\text{CD4}^+$ Helper T (TH): coordinate immunity; secrete IL-2, other cytokines
- $\text{CD8}^+$ Cytotoxic T (TC): only T cell that directly kills (perforin, granzymes, lymphotoxin)
- Memory T (TM): long-lived; rapid secondary response; usually symptom-free
Clonal selection → proliferation & differentiation into effector & memory clones
Pathogen/tumor/transplant elimination

Response peaks ≈ 1 wk, then wanes unless reinforced by antigen

Antibody-Mediated (Humoral) Immunity

Antigen binds specific B-cell receptor → internalized & processed → displayed with MHC-II
Helper T binds & secretes cytokines → B-cell activation & co-stimulation
Clonal selection →
- Plasma cells (antibody factories; life $4{-}5$ days)
- Memory B cells (long-lived, mount swift secondary response)
Antibodies (immunoglobulins)
- Classes: IgM, IgA, IgG, IgD, IgE (covered in lab)
- Mechanisms / defensive actions
  - Neutralization (block sites)
  - Immobilization (prevent motility)
  - Agglutination & precipitation (clumping/insoluble complexes)
  - Complement activation (classical pathway)
  - Opsonization / enhanced phagocytosis

Immunological Memory

Primary response (1st exposure)
- Few specific lymphocytes; lag; peak antibody days-weeks; produce memory cells
Secondary response (subsequent exposure)
- Memory cells proliferate within hours → higher, longer antibody titer; often subclinical

Psychoneuroimmunology (PNI) & Stress

Nervous, endocrine, immune systems are interlinked
Thoughts, emotions, beliefs can modulate immune competence & disease course
- Chronic stress → elevated cortisol → immunosuppression

Aging & the Immune System

↑ Susceptibility to infections & malignancies
↑ Autoantibody production
↓ Vaccine efficacy
Cellular explanations
- Thymic involution, ↓ thymic hormones → less responsive T cells
- B cells slower & produce fewer antibodies

Key Numbers, Terms & Symbols (Quick Reference)

Lymph node count: $\sim 450{-}600$
Node size: ≤ $3\,\text{cm}$
Two main ducts: Right lymphatic & Thoracic
Cardinal signs of inflammation: $\text{PRISH}$ (Pain, Redness, Immobility, Heat, Swelling)
Epitope diversity: $\sim 1 \times 10^9$

Ethical / Practical Implications

Fever management: treat only when prolonged/high to avoid enzyme denaturation & neurological damage
Transplant medicine: MHC compatibility critical; immunosuppressants required
Vaccination: leverages immunological memory for protective secondary response; efficacy declines with age, necessitating boosters or adjuvants