Lymphatic System & Immunity: Structure, Function, and Defense Mechanisms

Lymphatic system: 3 main components

Lymphatic vessels (lymphatics), lymph (the fluid), and lymph nodes

4 functions of the lymphatic system

Return excess tissue fluid to the blood, return leaked proteins to the blood, carry pathogens to lymph nodes, carry absorbed fat from the intestine to the blood (via lacteals)

Why does lymph form?

Capillary hydrostatic/osmotic pressures force out more fluid than gets reabsorbed; the difference (up to 3 L/day) becomes interstitial fluid that lymphatics collect and return to the blood

Lymphatic capillaries: structure

Begin in spaces between cells, closed at one end, larger in diameter than blood capillaries

Where are lymphatic capillaries absent?

Bones (including bone marrow) and teeth

Lymphatic capillary minivalves

Endothelial cells overlap loosely to form one-way flaps; anchoring (collagen) filaments pull them open as interstitial fluid volume rises, letting fluid in; rising pressure inside the capillary forces the flaps shut, preventing lymph from leaking back out

Lacteals

Specialized lymphatic capillaries in each villus of the small intestine; absorb digested fat, forming a fatty lymph called chyle

Lymph flow mechanisms

Skeletal muscle pump, respiratory pump, and one-way valves -- the same mechanisms that drive venous return

Lymphatic vessel hierarchy (small to large)

Capillaries -> vessels -> trunks -> ducts

Right lymphatic duct

About 1/2 inch long; drains the upper right side of the body (right arm and head)

Thoracic (left) duct

Main collecting duct of the lymphatic system; 38-45 cm long; drains 75% of the body; begins as the cisterna chyli

Cisterna chyli

A dilated sac at the start of the thoracic duct, located anterior to the 2nd lumbar vertebra

Lymphoid cells (4 types)

Lymphocytes (B and T cells), macrophages, dendritic cells, reticular cells

B lymphocytes (humoral immunity)

Develop into plasma cells that produce antibodies; antibody-antigen complexes prevent the antigen from interacting with other cells; memory B cells stay dormant until future exposure

T lymphocytes: 4 types

Cytotoxic (killer) T cells destroy foreign invaders; helper T cells assist B and cytotoxic T cells; suppressor T cells end the immune response; memory T cells stay dormant until re-exposure

Macrophage (as a lymphoid cell)

Phagocytizes foreign substances and helps activate T cells

Dendritic cells

Capture antigens and transport them to lymph nodes; activate T lymphocytes

Reticular cells

Similar to fibroblasts; produce the reticular fibers (stroma) that support other cells in lymphoid organs

Diffuse lymphatic tissue vs. lymphoid follicles

Diffuse = few scattered reticular tissue patches found in nearly every organ; follicles (nodules) = solid, uncapsulated balls of packed lymphoid cells with a germinal center of dendritic and B cells

Peyer's patches

Aggregated lymphoid nodules; large clusters of lymphoid follicles in the wall of the distal small intestine

Primary lymphoid organs

Red bone marrow and the thymus -- where B and T cells mature (B cells mature in marrow, T cells mature in the thymus; both originate in marrow)

Secondary lymphoid organs

Lymph nodes, spleen, and MALTs (tonsils, Peyer's patches, appendix) -- where mature B and T cells first encounter antigen and are activated

Thymus gland: location & aging

Two lobes between the sternum and aorta; atrophies starting around age 20

Thymus: cortex vs. medulla

Outer cortex screens and stimulates proliferation/maturation of immature T cells; inner medulla is where mature T cells enter the bloodstream

Thymus: unique features

No follicles (no B cells); doesn't directly fight antigens; has a blood-thymus barrier isolating immature T cells from antigens; stroma is epithelial cells, not reticular fibers

Lymph nodes: shape & location

Oval, bean-shaped; deep or superficial, concentrated along the respiratory tree, GI tract, mammary glands, axillae, and groin; filter lymph to trap pathogens, debris, and tumor cells

Lymph node structure

Fibrous capsule with internal trabeculae; stroma of reticular fibers; cortex (follicles/germinal centers with dividing B cells, plus T cells in transit) and medulla (medullary cords with both B and T cells)

Lymph node circulation path

Afferent vessels -> subcapsular sinus -> smaller sinuses -> medullary sinus -> hilum -> efferent vessels; fewer efferent than afferent vessels, so lymph stagnates, giving lymphocytes/macrophages time to act

Lymph sinuses

Large lymphatic capillaries crisscrossed by reticular fibers, found throughout the lymph node; macrophages sit on the fibers to phagocytize foreign matter

Unique fact about lymph nodes

They are the ONLY lymphoid organ that filters lymph

Buboes vs. metastasis (in lymph nodes)

Buboes = inflamed, swollen, painful lymph nodes; metastasis = cancer cells trapped in a lymph node, not painful

Spleen: location & structure

Largest mass of lymphoid tissue in the body; located between the stomach and diaphragm; has a fibrous capsule with its own artery, vein, and efferent lymph vessels

Spleen: white pulp

Site where some B cells mature into plasma cells; provides immune function

Spleen: red pulp

Site of lymphocyte proliferation; macrophages phagocytize bacteria, worn-out RBCs, and platelets (blood cleansing); stores platelets and iron; site of fetal erythrocyte production (normally stops after birth)

MALT

Mucosa-Associated Lymphoid Tissue; located in mucous membranes; includes Peyer's patches, tonsils, and the appendix

Tonsils

Simplest lymphoid organ; form a ring around the throat entrance; not fully encapsulated; tonsillar crypts trap bacteria, which then move into tissue and are destroyed; palatine tonsils are largest and most frequently infected

Lymphadenopathy

Increased drainage/enlargement of lymph nodes due to inflammatory lesion or infection

Hodgkin's disease

Cause unknown, though Epstein-Barr virus contributes to most cases; one of the most curable cancers

Burkitt lymphoma

A type of non-Hodgkin's lymphoma; the cancerous cell is a B cell; about half are cured with extensive chemotherapy

Burkitt lymphoma: African (endemic) type

Associated with Epstein-Barr virus; commonly involves the jaw

Burkitt lymphoma: American (sporadic) type

Not associated with EBV; causes extensive marrow replacement

Burkitt lymphoma: immunodeficiency-associated type

Associated with 90% of HIV cases, as well as immunosuppressive drugs

Innate vs. adaptive defense

Innate = nonspecific, present from birth; adaptive = specific, antigen-targeted, has memory

First line of defense

Skin and mucous membranes -- mechanical barriers that prevent pathogen entry

Acid mantle of the skin

Sweat and sebum make the skin surface acidic, inhibiting bacterial growth, and contain bactericidal chemicals

Keratin (first-line defense role)

Provides resistance against acids, alkalis, and bacterial enzymes

Mucus, nasal hairs, cilia (first-line defense)

Mucus traps microorganisms; nasal hairs filter/trap them; cilia propel debris-laden mucus away from the respiratory passages

Gastric juice (first-line defense)

Concentrated HCl and protein-digesting enzymes destroy pathogens in the stomach

Lacrimal secretions & saliva

Continuously lubricate/cleanse the eyes and mouth; contain lysozyme, an enzyme that destroys microorganisms

Second line of defense (5 elements)

Phagocytes, natural killer (NK) cells, inflammation, antimicrobial proteins, fever

Phagocytes: 2 major types

Neutrophils and macrophages (macrophages derive from monocytes)

Fixed (resting) macrophages

Reside permanently in specific organs -- e.g., Kupffer cells (liver) and microglia (brain)

Pattern recognition receptors (PRRs)

Found on macrophages and boundary epithelial cells; recognize molecular shapes common to pathogens and trigger inflammation

Opsonization

Coating a pathogen with opsonins (complement proteins or antibodies) that act as "handles," greatly accelerating phagocytosis

Natural killer (NK) cells

Large granular lymphocytes; nonspecific killers that respond to a lack of self-antigens; kill virus-infected/tumor cells using perforin and granzymes (not phagocytosis); secrete chemicals that enhance inflammation

5 signs of inflammation

Redness, heat, swelling, pain, loss of function

4 functions of inflammation

Prevent the spread of damage, dispose of pathogens/debris, alert the adaptive immune system, set the stage for tissue repair

Inflammation Stage 1: vasodilation

Injured cells release histamine, kinins, prostaglandins, cytokines, and complement proteins, causing vasodilation, increased permeability, and recruitment of phagocytes/lymphocytes

Hyperemia

Increased blood flow from vasodilation; causes the redness and heat of inflammation and brings in more immune cells/chemicals

Exudate

Fluid containing clotting factors and antibodies that leaks into tissue spaces due to increased capillary permeability; sweeps foreign material into lymphatic vessels

Why does inflammation cause pain?

Increased tissue fluid causes edema, which presses on adjacent nerve endings

Inflammation Stage 2: phagocyte mobilization

Leukocytosis-inducing factors boost neutrophil production, followed by margination, diapedesis, and chemotaxis of WBCs

Margination, diapedesis, chemotaxis

Margination = WBCs pavement/line up against the capillary wall; diapedesis = amoeboid movement of WBCs through the capillary wall; chemotaxis = WBCs migrate toward the chemical trail at the injury site

Neutrophils vs. monocytes: arrival speed

Neutrophils arrive rapidly; monocytes arrive more slowly

Inflammation Stage 3: tissue repair

Tissue regrowth and repair of damage, or scar formation if damage is severe

Pus

Creamy yellow mixture of dead/dying neutrophils, broken-down tissue cells, and living/dead pathogens

Infectious granuloma

An area of infected macrophages surrounded by uninfected macrophages and an outer fibrous capsule; bacteria may stay dormant forever or reactivate if immunity drops

Antimicrobial proteins

Enhance innate defenses by directly attacking microorganisms or hindering their reproduction; the two most important are interferon and complement

Interferon (IFN)

Produced by virus-infected cells; diffuses to uninfected cells and stimulates antiviral protein production (not virus-specific); IFN-alpha/beta also activate NK cells; IFN-gamma (from lymphocytes) has widespread immune-mobilizing effects

Complement system

20 inactive plasma proteins that, once activated, enhance immune/allergic/inflammatory responses and kill bacteria and other cells (our own cells are immune to it)

Complement: 3 activation pathways

Classical (antibody-triggered), lectin (lectins binding microbial sugars), and alternative (spontaneous activation on microbe surfaces lacking complement inhibitors)

Complement: convergence at C3

All 3 pathways converge on C3, which cleaves into C3a (enhances inflammation) and C3b (initiates the membrane attack complex and causes opsonization)

Membrane Attack Complex (MAC)

Formed by C3b; causes cell lysis by disrupting the cell's ability to control intracellular Ca2+

Fever

An abnormally high body temperature triggered by pyrogens (from leukocytes/macrophages) acting on the hypothalamus

3 benefits of fever

Increases T lymphocyte/monocyte migration into lymph nodes, increases metabolic rate (speeding repair and T cell production), and suppresses bacterial growth by limiting available iron

Adaptive defense: key traits

Antigen-specific, systemic, and has memory; amplifies inflammation and activates complement

Adaptive defense: 2 arms

Humoral (antibody-mediated) immunity and cellular (cell-mediated) immunity

Antigen

Any substance that provokes a specific immune response; antigenic determinants are the specific parts of the antigen that trigger the response

Complete antigens

Large, complex molecules (usually proteins, sometimes carbs/lipids); immunogenic (stimulate lymphocyte proliferation/antibody production) and reactive

Incomplete antigens (haptens)

Small molecules that are NOT immunogenic alone; react with antibodies but need a protein carrier to trigger an immune response (e.g., poison ivy allergen)

MHC antigens

Unique to each individual's cells; help identify self vs. foreign

MHC Class I

Found on all body cells except RBCs; recognized by cytotoxic (CD8) T cells

MHC Class II

Found only on antigen-presenting cells, thymus cells, and activated T cells; recognized by helper (CD4) T cells

3 key cell types in adaptive immunity

B lymphocytes (humoral immunity), T lymphocytes (cellular immunity), and antigen-presenting cells (APCs, which don't respond to specific antigens but play auxiliary roles)

Immunocompetent naive B/T cells

Display a unique receptor for one specific antigen before ever encountering it; genes (not antigen exposure) determine what the immune system can recognize

T cell self-tolerance: positive selection

Occurs in the thymic cortex; selects T cells with a weak response to self-MHC molecules; non-selected cells die by apoptosis

T cell self-tolerance: negative selection

Occurs in the inner thymic cortex; eliminates T cells that react strongly to self-antigens, ensuring T cells don't attack self-antigens on self-MHC

Antigen-Presenting Cells (APCs): 3 major types

Dendritic cells (activate T cells), macrophages (maintain/become activated), B cells (present antigen to helper T cells for their own activation help)

Humoral immunity

B-cell-mediated immunity; antibodies target extracellular antigens

Clonal selection (B cells)

An antigen binds a matching B cell receptor, causing that B cell to grow and divide, forming clones bearing the same antigen-specific receptors

Fate of B cell clones

Most become plasma cells secreting specific antibodies; others become memory cells for future exposures

Antibody structure

4 polypeptide chains linked by disulfide bonds; constant regions are the same within an antibody class and determine function; variable regions of heavy/light chains form the antigen-binding site

IgD

Monomer on the surface of B cells; important in B cell activation

IgM

Pentamer released during the primary immune response; activates complement

IgG

Monomer; most abundant/diverse antibody; crosses the placenta (passive immunity); activates complement

IgA

Dimer; prevents pathogens from attaching to epithelial surfaces; found in milk and saliva

IgE

Monomer; binds mast cells/basophils, triggering histamine release when activated

Antibody defense mechanisms (4)

Neutralization, agglutination, precipitation, and complement fixation

Neutralization

Antibodies bind/block sites on viruses or exotoxins, preventing them from binding to tissue cell receptors

Agglutination vs. precipitation

Agglutination clumps cell-bound antigens (cross-linked into lattices); precipitation cross-links soluble antigens into insoluble complexes, making them easier for phagocytes to engulf