The Lymphatic System

• The lymphatic system is the immune system, referring to vessels and structures carrying cells participating in the immune response.
• Lymphatic vessels run parallel with blood vessels, carrying lymph, a blood filtrate product.
• Lymph circulates and enters filtering structures like lymph nodes and tonsils.

Lymphatic Vasculature

• The lymphatic vasculature is a dead-end circuit, not a closed circuit like blood vessels.
• It starts with closed capillaries within tissues, draining excess interstitial fluid.
• Capillaries merge into vessels, then ducts, and lymph re-enters blood circulation.
• Lymphatic capillaries resemble blood capillaries with simple squamous epithelium walls.
• Vessels are thin-walled, multi-layered, resembling veins but lacking muscle.
• Vessels have valves preventing backflow of lymph.
• Vessels empty into the right lymphatic duct (right side of head, neck, shoulder, thoracic region, and right arm) and the thoracic duct (left side, abdomen, intestinal tract and lower appendages).
• These ducts empty into the subclavian veins.

Lymph Formation and Composition

• Interstitial fluid enters lymphatic capillaries.
• Blood flows through capillaries, higher pressure forces plasma and small solutes into tissue space.
• Filtered plasma in tissue space is interstitial fluid.
• Some interstitial fluid re-absorbed into capillaries at the venous end, but excess remains.
• Lymphatic capillaries have overlapping squamous cells, becoming leaky with increasing interstitial fluid pressure, allowing fluid to enter.
• Once inside lymphatic capillaries, the fluid is called lymph.
• Lymph contains white blood cells and proteins (clotting proteins, antibodies).

Lymph Movement

• Lymphatic vessels merge, running close to arteries.
• Valves in lymphatic vessels aid in forward movement of lymph against gravity.
• Lymphatic vessels merge into right lymphatic duct and thoracic duct.
• Thoracic duct drains more lymph than the right lymphatic duct.
• Ducts empty into subclavian veins, then the superior vena cava, re-entering blood circulation.

Lymphedema

• Impeded lymph flow causes lymphedema, fluid buildup in tissue space.
• Can be due to surgery removing lymph nodes/vessels or filarial worm infections.
• Severe lymphedema is called elephantitis.

White Blood Cells

• White blood cells mediate immune responses, protecting against infectious agents, foreign particles, and cancer cells.
• Phagocytic cells (neutrophils, macrophages) and lymphocytes (T cells, B cells) are important.
• Found in blood, lymph, and lymphatic organs/structures (lymph nodes, tonsils).

Lymphatic Organs and Structures Locations

• Lymph nodes are at junctures: head/shoulders, arms/torso, legs/torso, neck, armpit, groin, digestive tract (Peyer's patches), pharyngeal region (tonsils, adenoids).
• Primary lymphatic organs: thymus and bone marrow.
• Secondary lymphatic organs/structures: lymph nodes, spleen, tonsils, mucosal-associated lymphatic tissue (MALT).

Primary Lymphatic Organs

• Thymus (atop the heart) and bone marrow (in spongy bone).
• Sites of lymphocyte maturation: T cells mature in the thymus, B cells in the bone marrow.

Secondary Lymphatic Organs/Structures

• Filter lymph (lymph nodes) or blood (spleen), trapping antigens/pathogens.
• Isolate/sequester substances for elimination by white blood cells.
• Examples: lymph nodes, spleen, tonsils, MALT (mucous membranes of intestinal tract).

Lymphatic Tissue Composition

• Largely composed of reticular connective tissue.
• Fibroblasts lay down a connective tissue matrix with reticular fibers.
• Meshwork designed for filtering.
• White blood cells reside within meshwork.

Lymph Node Structure

• Located along lymphatic vessels, filtering lymph.
• Afferent vessels flow into the node, efferent vessels allow lymph to flow out.
• Reticular connective tissue under a fibrous capsule.
• Cortex (outer region) and medulla (inner region).
• Trabeculae (capsule infolds) divide cortex into compartments filled with lymphatic follicles (white blood cell collections).
• Germinal center: center of lymphatic follicle, with different cell population.
• Medullary region: cells aligned in strings/cords (medullary cords).
• Afferent lymphatic vessels more numerous than efferent, slowing fluid flow for filtering.

Lymph Node Details

• Photomicrographs show the cortical region (with darker follicles and lighter germinal centers).
• Germinal centers contain mostly B cells.
• Regions around germinal centers contain T cells and macrophages.
• Lymph nodes enlarge when substances are trapped and being worked on due to follicle enlargement (germinal center).
• Germinal centers enlarge during infection due to B lymphocyte division and increased antibody production.

Spleen

• Secondary organ that filters blood.
• Red pulp (reddish) and white pulp (lighter/darker blue clusters) visible in splenic tissue.
• Red pulp: storage for red blood cells, clearing site for old/damaged red blood cells, and macrophages.
• White pulp: similar to lymphatic follicles, contains lymphocytes clustered around small arteries, and T cells, macrophages and B cells.
• Lymphocyte division increases size of white pulp areas.

Immune Mechanisms

• Nonspecific (innate) and specific mechanisms.
• Nonspecific mechanisms: triggered generically, innate (inborn), and do not grant immunity.
• Specific mechanisms: targeted, grant immunity, and targeted against a specific trigger.

Nonspecific Mechanisms: Protective Coverings

• Skin and mucous membranes (first line of defense).
• Skin: multi-layered stratified squamous epithelium, heavily keratinized (waterproof, tough).
• Mucous membranes: lack keratin, protected by mucus (traps pathogens) and cilia/hairs (move pathogens).

Nonspecific Mechanisms: Coatings/Rinses

• Tears: salty (inhibits growth), contain antibodies and lysozyme (antimicrobial).
• Sebum (skin oil/hair oil): lipid mixture, acidic (inhibits microbial growth), moisturizing.

Nonspecific Mechanisms: Chemicals

• Lysozyme: antimicrobial, found in saliva, tears, inhibits bacterial growth.
• Interferons: antiviral, secreted by virally infected cells, and trigger gene expression in healthy cells to inhibit viral entry/replication.

Nonspecific Mechanisms: Complement Proteins

• Formed by body cells, circulate inactive, and activate in a cascade.
• Assemble to form a molecular arrow that punctures the membrane of infected cells (membrane attack complex).

Nonspecific Mechanisms: Cells - Natural Killer (NK) Cells

• Non-specific patrollers of tissue.
• Respond to non-self cues (certain membrane proteins).
• Release a molecular arrow similar to complement proteins, effectively killing the cell.

Nonspecific Mechanisms: Macrophages

• Phagocytic cells attracted to irritation areas.
• Phagocytose irritating substances, especially during inflammation.

Nonspecific Mechanisms: Inflammation

• Traps infectious/irritating substance to prevent dispersal.
• Cells release chemicals (mediators) initiating, regulating, and controlling the entire process.
• Mediators trigger vasodilation (redness, heat) and increased capillary permeability.
• Clotting proteins, complement proteins, and antibodies enter the area.
• Phagocytic cells move via chemotaxis, marginate (adhere to the blood vessel), emigrate (leave the blood vessel), and phagocytose.
• Histamine is an example of these mediators.
• Inflammation needs to be regulated because long term inflammation damages healthy cells.

Nonspecific Mechanisms: Fever

• Elevation of body temperature.
• Chemicals released by infected cells bind to macrophages, which then release interleukin one, leading to prostaglandin protection.
• Prostaglandins bind in the hypothalamus (controls body temperature), raising body temperature.
• Hypothalamus initiates shivering (simultaneous contraction of antagonistic muscles) to generate heat.
• Elevated temperature inhibits reproduction of infectious agents.
• High temperatures can denature body proteins.
• Fever reducers (aspirin, ibuprofen) eliminate prostaglandin production, stopping input to the hypothalamus.