The Lymphatic System

• The lymphatic system mediates immunity by providing resistance to damage or disease.
• Susceptibility is vulnerability to damage or disease.
• Pathogens include disease-causing microorganisms like bacteria, fungi, viruses, and parasites.
• The lymphatic system consists of lymph plasma, or simply lymph, and associated vessels and organs
• The lymphatic system circulates and drains excess body fluids.
• The lymphatic system defends the body against disease and damage.
• The lymphatic system transports dietary lipids.
• Lymph is richer in dietary lipids as it exits the GI tract, compared to interstitial fluid and blood
• Lymph is carried in lymphatic vessels, while interstitial fluid is outside of vessels.
• Lymph is filtered through lymphoid tissues and/or in lymphoid organs.

Lymph Circulation

• Lymphatic circulation begins at lymphatic capillaries located between tissue cells.
• The tips of lymphatic capillaries allow interstitial fluid (IF) to enter but not exit.
• Endothelial cell edges overlap in lymphatic capillaries.
• Fluid enters lymphatic vessels when interstitial fluid pressure is greater than the pressure inside the lymph vessels.
• Endothelial cell edges press close when lymph pressure is greater than the pressure in interstitial fluid.
• Lymphatic capillaries attach to surrounding tissue cells with anchoring filaments made of elastic fibres.
• Anchoring filaments pull endothelial cells wide open when tissues swell from excess fluid, allowing more IF to enter lymphatic vessels
• Lacteals are specialized lymphatic capillaries that specifically exist at small intestines
• Lacteals absorb dietary lipids from digestion
• Lipid-rich lymph is creamy white and known as chyle
• Lymphatic capillaries merge to form lymphatic vessels.

Blood vs Lymphatic Capillaries

• Both blood and lymphatic capillaries are very thin (~1 cell thick).
• Blood capillaries have a smaller diameter of 5-10 μm, while lymphatic capillaries are slightly larger at 10-60 μm.
• Blood capillaries form an interconnected loop, with no closed ends, while lymphatic capillaries have closed tips that overlap
• Blood capillaries have bidirectional exchange with IF, but lymphatic capillaries only permit one-way fluid entry.
• Lymphatic vessels carry lymph to lymph nodes and lymphoid tissues.
• Lymph plasma gets filtered through the lymphatic vessels
• Lymphatic vessels merge to form lymph trunks as they exit lymph nodes
• Lymph trunks drain lymph coming from specific lymph nodes in the body
• Lymph trunks merge to form lymphatic ducts.
• The right lymphatic duct is absent in some people.
• The right lymphatic duct frequently has 3 independent trunks.
• Lymph independently drains to the right subclavian vein.
• The left thoracic duct is the main path for lymph to return to circulation.
• The left thoracic duct is the largest lymph vessel in the body.
• The left thoracic duct starts at the cisterna chyli.
• The left thoracic duct drains into the left subclavian vein, where it meets the left internal jugular vein.
• The three trunks on the right lymphatic duct drain into the right brachiocephalic vein.
• The thoracic duct + bronchomediastinal trunk independently drain into the left brachiocephalic vein.
• The brachiocephalic veins drain into the superior vena cava.
• The right lymphatic duct or trunks drain lymph from the head, neck, and right upper limb.
• The thoracic duct drains lymph from the remaining part of the body.

Lymphatic System Details

• The lymphatic system empties excess fluid into circulation.
• Not all filtered fluid is reabsorbed.
• 15% of fluid (approximately 3 L/day) is returned to circulation via the lymphatic system.
• Skeletal muscle and respiratory pumps move fluid through lymphatic vessels.
• Primary lymphatic organs enable stem cell division and immunocompetence
• Secondary lymphatic organs enable immunocompetent functions.
• Lymphatic tissues have immune functions but lack a capsule.
• Mucosa-associated lymphoid tissue (MALT) consists of lymphatic tissues found in the lamina propria of mucous membranes.
• Aggregated lymphoid follicles (Peyer’s patches) are located in the ileum of the small intestine.
• Tonsils consist of a pharyngeal tonsil, 2 palatine tonsils, and 2 lingual tonsils.
• Red bone marrow has multipotent stem cells and is where B and T lymphocytes are formed.
• The thymus is a bilobed gland in the anterior portion of the mediastinum.
• The thymus shrinks with age.
• The thymus is where T lymphocytes become immunocompetent.
• Each lobe of the thymus consists of an outer cortex and inner medulla.
• The cortex of the thymus contains epithelial cells that train immature T cells.
• The medulla of the thymus contains mature T cells
• The medulla of the thymus contains masses of epithelial cells that die and release keratohyalin, forming thymic corpuscles.
• The function of thymic corpuscles is unknown, but functions as site of T cell death
• The spleen is located in the left hypochondriac region of the abdomen
• The spleen is intermediate to the stomach and diaphragm.
• The visceral peritoneal membrane wraps the capsule of the spleen.
• The spleen contains the largest mass of lymphatic tissue in the body.
• The outer capsule of the spleen contains dense CT, reticular fibres, and fibroblasts
• The capsule projects into the organ, forming trabeculae that provide passage for blood vessels.
• The inner parenchyma contains white and red pulp.
• White pulp contains lymphocytes and macrophages.
• Lymphatic tissue is clustered around a splenic artery.
• The spleen surveils blood that enters and defends against infection.
• Red pulp contains erythrocytes, macrophages, lymphocytes, and other immune cells.
• The spleen removes worn-out or damaged blood cells.
• The spleen participates in hemopoiesis and stores platelets.
• Lymph nodes are bean-shaped organs, clustered in specific anatomical locations.
• The exterior capsule of the lymph nodes is made of dense CT.
• The interior of Lymph nodes is called the stroma
• The stroma forms trabeculae.
• The parenchyma includes the inner/outer cortex and medulla, lymphoid nodules in the outer cortex, and clusters of B cells
• The inner cortex contains mostly T cells and dendritic cells with T cell activity but no lymphoid nodules.
• The medulla contains reticular fibre matrix, activated B cells (plasma cells), and macrophages.
• Lymph flows into lymph nodes = afferent.
• Lymph flows out of lymph nodes = efferent.

Immunity

• Immunity is resistance to damage or disease.
• Innate immunity consists of nonspecific and fast defenses in all animals
• Adaptive immunity consists of specific defenses in vertebrates that must be activated.
• External defenses are the first line of innate defense against infection and invasion.
• The epidermis consists of keratinized stratified squamous epithelium.
• The epidermis provides a physical barrier to invaders with densely packed cells
• Sebum from sebaceous glands is catabolized by normal microbiota of skin into fatty acids, which keeps the skin acidic.
• Sweat from sudoriferous glands keeps skin salty
• Salty skin restricts possible species of organisms that colonize the skin
• Mucous membranes are covered in mucus that traps invaders.
• Hair filters air in the nasal cavity, around eyes, and genitals.
• Cilia sweeps mucus through the respiratory tract.
• Tears are produced by the lacrimal apparatus of the eyes
• Tears contains lysozyme to destroy bacterial membranes
• Antimicrobial secretions of the body consist of urine, vaginal secretions, and gastric juices.
• Defecation and vomiting help flush microbes from the body.
• Internal defenses come into use if external defenses fail
• Interferons are proteins made by virally-infected body cells that produce antiviral responses in neighboring cells.
• Complement proteins enhances phagocytosis, stimulate cell lysis of invaders and also stimulates inflammation
• Iron-binding proteins limit available iron from any microbes
• Antimicrobial proteins (AMPs) are small proteins that stimulate or enhance leukocyte activity, stimulate cell lysis of invaders.
• Natural killer cells (NKCs) consist of 5-10% of lymphocytes in blood and lymphatic organs
• Natural killer cells attack any cells presenting foreign plasma membrane proteins.
• Natural killer cells secrete perforins that poke holes in cell membranes, leading to cell lysis or cytolysis.
• Natural killer cells secrete granzymes to induce apoptosis.
• Phagocytes are cells that engulf other cells or large particles to destroy them.
• Neutrophils respond first to bacterial infections and tissue damage during inflammation.
• Macrophages differentiate from monocytes once they leave blood.
• Macrophages attend to tissue damage relatively late
• Inflammation is an immune response to tissue damage
• The inflammatory response is nonspecific
• Damaged tissues cells release chemical signals like histamine
• Histamine causes nearby endothelial cells to express membrane proteins
• Leukocytes in blood bind to membrane proteins on endothelial cells near tissue damage with receptors on leukocyte membranes.
• Leukocytes "roll" along the endothelial surface as a result of histamine, enabling them to respond to the threat
• Emigration is when increased vascular permeability allows leukocytes to squeeze through intercellular gaps
• Fluid and cells leave blood vessels during emigration.
• Chemotaxis is when leukocytes follow chemical trails to the site of tissue damage.
• Tissue disinfection takes place when leukocytes perform defensive roles, like phagocytizing invaders and natural killer cells cause cytolysis
• Macrophages arrive later than neutrophils to phagocytize cell debris.
• Chemical signals other than histamine participate in inflammation.
• Kinins are proteins that promote vasodilation and increase vascular permeability
• Kinins enhance leukocyte chemotaxis and modulate pain responses.
• Prostaglandins and leukotrienes are eicosanoid lipids that enhance leukocyte chemotaxis and phagocyte adherence.
• Complement proteins promote histamine release, act as chemoattractants for neutrophils, and enhance phagocytosis.
• Inflammation triggers pain, redness, immobility, swelling, and heat

Fever Details

• Fever is unusually high body temperature.
• Fever is a product of changes by the hypothalamus of the brain
• Bacterial toxins cause body cells to release cytokines, which then stimulates hypothalamic changes.

Adaptive Immunity

• Adaptive immunity consists of specific defenses activated with tailored responses
• Lymphocytes are the primary adaptive immune defenses
• Lymphocytes descend from the lymphoid stem cell lineage

Lymphocytes

• Immunocompetent B and T cells expresses membrane proteins called antigen receptors to bind antigens (molecules that evoke immune response)
• Recognition of unique shape of antigens is a function of Lymphocytes
• Antigen receptors of a single lymphocyte bind to the same antigen only
• Lymphocytes can both occur by cell-mediated and antibody-mediated (humoral) immunities
• T cells mediates cell-mediated immunity
• B cells mediates antibody-mediated immunity
• Helper T cells are needed to activate both types of immunity
• T cells expresses additional notable membrane proteins
• Helper T lymphocytes (HTLs) expresses a protein called cluster of differentiation 4 (CD4)
• Cytotoxic T lymphocytes (CTLs) expresses a protein called CD8.
• CD proteins identify/distinguish lymphocytes
• CD proteins function as co-receptors during immune signalling.
• Major histocompatibility complex (MHC) antigens identify the body
• Class I MHC (MHC-I) antigens are found in the membranes of all body cells except erythrocytes
• Class II MHC (MHC-II) antigens are found on the membranes of antigen-presenting cells (APCs).
• Unique combination of MHC antigens helps immune system recognize tissues as "self" but donated tissues as "foreign”.

Adaptive Immunity Types

• Cell-mediated immunity uses CTLs to directly kill invaders.
• CTLs guard against intracellular pathogens
• Activateds B cells participate in antibody-mediated/humoral immunity to guards against extracellular pathogens circulating in body fluids
• Invaders must evade the innate defenses and enter tissues for any action
• Binding of antigens on an invader to antigen receptors on a lymphocyte results in Lymphocytes activation
• Clonal antigen selection occurs after Lymphocytes activation occurs
• During clonal selection lymphocyte produce Effector cells (large population and short lived that carry out lymphocyte's defensive roles)
• Lymphocytes produce Memory cells to look out for exact same antigen that triggered clonal selection; may be long-lived but do not actively kill/attack invaders
• Effector and Memory cells express same antigen receptors as the first lymphocyte to be activated
• Antigens must be processed by those cells and presented to the lymphocytes
• Exogenous antigens circulate in fluids, like bacteria, worms, pollen, viruses
• A processed Exogenous antigens can be phagocytosis or endocytosis by an antigen-presenting cell, digested, produces MHC-II antigen
• Exogenous antigens also is then fused and processed bound to lymphocyte antigen binds MHC-II.
• Inside of body cells present inside Antigens for processes
• Endogenous antigens are then released out of cell to come into contact with lymphocytes to be defended against
• Endogenous antigen may be Viruses, toxins, or tumors inside of APC

T Cells

• T cell receptors (TCRs) bind endogenous foreign antigen bound to MHC-I when presented by cytokine
• Protein on CTL interacts with MHC-I to stabilize the relationship
• T cells need stimulation from protein division and create
• Cell-mediated, and antibody-mediated activities need cytokine hormones
• Infection and immune system destruction lead to T-Cell destruction
• Activated HTLs undergo clonal selection

Antibody-Mediated Immunity

• Foreign antigen is imported to B cells via endocytosis.
• Antigen is processed and displayed on B cells bound to MHC-II.
• B cells are then processed before release
• The body can undergo various malfunctions with homeostasis.
• Immunodeficiency, autoimmune disorders, and hypersensitivities are types of Homeostatic Imbalances
• Acquired Immunodeficiency causes HIV (human immunodeficiency virus) that then infects
• There is no treatment for HIV infections
• Anaphylaxis occur
• Helper T cells are required to activate both types of immunity
• The T cell are then triggered to release the required resources

Once CTLs are activated, they undergo clonal selection:

• Effector cells, which are Active CD8+ T cells secrete Perforins and Granzymes to cause destruction.
• Memory cells: Memory CTLs
• Adaptive immunity helps the immune system to self-recognize the various threats to body through similar processes

Lymphocytes

• Adaptive immunity helps the immune system to self-recognize what body materials are needed as well
• Thymus during Positive Selection is in charge of making sure the required material is still accepted, or else cells get destroyed
• Failure to properly divide result in potential autoimmunity
• The most important is the ability to recognize body requirements and the ability to eliminate threats in the end for any effective immune system