The Lymphatic and Immune Systems

Immune Surveillance

Immune surveillance: NK cells constantly patrol the body for pathogens or defective host cells; utilize perforins and granzymes 1. Perforins: a group of proteins which polymerize in a ring and "punch" a hole in the plasma membrane of the invader 2. Granzymes: a group of proteins that act as enzymes which degrade proteins (digest proteins)

Immunity - Active vs Passive and Natural vs Artificial

*Active Immunity*: body makes its own antibodies or T cells *Natural active immunity*: get sickness, next time your body fights it *Artificial active immunity*: production of one's own antibodies or T cells as a result of vaccination; vaccine consists of either dead or attenuated pathogens; may require booster shots *Passive Immunity*: body acquires them from another person or animal *Natural passive immunity*: temporary immunity that results from acquiring antibodies produced by another person. E.g. fetus acquiring antibodies through the placenta *Artificial passive immunity*: temporary immunity that results from the injection of an immune serum obtained from another person or animals. E.g. snakebite, botulism - Two forms of active immunity involve immune memory - Passive immunity only last for 2-3 weeks

Antigens

*Antigen*: any molecule that triggers an immune responses; some antigens are free molecules (venoms & toxins) others are components of plasma membranes and bacterial cell walls; only certain regions of an antigen stimulate immune responses *Haptens*: molecules too small to cause an immune response themselves, must bind to a host macromolecule. E.g. penicillin allergy, animal dander; after the first exposure a hapten may stimulate an immune response without needing to bind to another molecule; can result in anaphylactic shock (penicillin)

Specific Immunity: Cellular vs Humoral Immunity

*Cellular (cell-mediated) immunity*: employs lymphocytes, which attack and destroy foreign cells or diseased host cells; intracellular viruses, bacteria, yeast, and protozoans *Humoral (antibody-mediated) immunity*: mediated by antibodies, tag pathogens for destruction; effective against extracellular viruses, bacteria, yeasts, protozoans and molecular pathogens, e.g. toxins, venoms and allergens

1st line of defense: Non-Specific (Innate)

*External barriers* *(dry, acidic protein - antibacterial, thick layer of dead cells) 1. *Skin and mucous membranes* 2. External skin is composed of keratin, a tough protein that few pathogens can penetrate 3. Also the skin is coated with antimicrobial chemicals eg defensins and lactic acid - Defensins: peptides that kill microbes by creating holes in their membranes; are also produced by neutrophils and other cells - Cathelicidins: a peptide produced by keratinocytes, neutrophils, macrophages, and other cells, that destroys bacteria, fungi, and viruses - Acid mantle: a thin film of lactic acid from sweat - Dermicidin: an antibacterial peptide found in sweat 4. The digestive, respiratory, urinary, and reproductive tracts have mucous secretions which trap organisms but also contain lysozyme an enzyme that destroys the bacterial cell wall 5. The areolar connective tissue located beneath the skin and mucous membranes contain hyaluronic acid which gives it a viscous consistency; some organisms have hyaluronidase which breaks down the hyaluronic acid

Fever

*Fever (a.k.a. Pyrexia)*: abnormal elevation of body temperature; the term febrile means pertaining to fever - Can result from trauma, infections, drug reactions brain tumors, and other causes - Is an adaptive mechanism that in moderation does more good than harm - *Pyrogen*: fever producing agent exogenous pyrogens such as the surface glycolipids of bacteria and viruses; or endogenous pyrogens released by neutrophils and macrophages as they attack pathogens; these chemicals secrete the anterior hypothalamus to secrete prostaglandin E2 which in turn raises the hypothalamic set point - Beneficial because - Promotes interferon activity - Elevates metabolic rate and accelerates tissue repair - Inhibits reproduction of bacteria and viruses - *Antipyretic*: fever reducing agents - Fevers above 40.50 C (1050 F) can make a person delirious - Convulsions, coma and death can cause irreversible brain damage in the range 440 - 460 C (111 to 115 F)

Inflammation

*Inflammation*: local defense response to tissue injury of any kind, including trauma and infection; general purposes include 1) to limit spread of pathogen and ultimately destroy them; 2) remove debris of damaged tissue; and 3) initiate tissue repair *Cardinal signs - redness, swelling, heat, and pain* Regulated by a class of proteins called *cytokines*, secreted by leukocytes and alter the physiology of the receiving cell; these are referred to as *paracrine* and *autocrine effects* Inflammation involves three major processes: 1. Mobilization: of the body's defenses 2. Containment & destruction of pathogens 3. Tissue cleanup and repair *Mobilization of Defenses* 1. *Hyperemia*: increased blood flow to the affected area; achieved by local vasodilation, also the vasoactive chemicals stimulate the endothelial cells to separate slightly widening the intercellular clefts to increase thereby increasing the permeability 2. *Selectins*: a group of cell adhesion molecules that are released by the endothelial cells to make the vessel wall more sticky 3. *Margination: adhesion of leukocytes to the vessel wall* (in capillaries - endothelial cells cause wbc to stick 4. *Diapedesis*/emigration: leukocytes crawl through gaps in the endothelium In summary, the basis for the four cardinal signs of inflammation are: 1. Heat: due to hyperemia 2. Redness: due to hyperemia, and sometimes extravasation of erythrocytes into the tissue such as occurs in sunburn 3. Swelling: due to increased fluid filtration from the capillaries 4. Pain: due to direct injury to the nerves, pressure on the nerves due to edema, stimulation of pain receptors by prostaglandins, some bacterial toxins, and *bradykinin* *Containment & destruction of Pathogens* - The clots form a sticky mesh that walls off and isolates (sequesters) bacteria and other microbes - *Chemotaxis*: exhibited as neutrophils are attracted to chemicals such as bradykinin and leukotrienes - Neutrophils also recruit macrophages and additional neutrophils by releasing cytokines; *colony stimulating factors* increase leukocyte production; within a matter of hours neutrophil count can rise as high as 25,000 (neutrophilia) *Tissue Cleanup and Repair* - Monocytes are the major agents of tissue cleanup and repair, arrive at the site within 8-12 hours; can change into macrophages and APCs - Edema also contributes to tissue cleanup, by reducing venous drainage and forcing open the valves and promoting lymphatic drainage; - *Pus: a collection of dead cells, tissue debris, and fluid; is generally absorbed* - *Abscess*: accumulation of pus in a tissue cavity - *Platelet-derived growth factor*: secreted by the blood platelets and endothelial cells in the area; stimulates fibroblasts to reproduce and synthesize collagen; pain helps to limit activity and allow for repair (clotting, anti-clotting and tissue growth factors)

3rd line of defense (Specific Immunity)

*Specific immunity*: is that aspect of your body's defenses against pathogens and other foreign material that acts against specific molecules, usually requiring that your immune system "learn" the properties of specific molecules over a number of days or weeks before mounting an effective response against the foreign material *cells learn to fight only certain specific things* The two characteristics that distinguish specific immunity from non specific immunity is: 1. *Specificity*: immunity that is directed towards a particular pathogen 2. *Memory*: exists so that when the body is reexposed to the same pathogen, it reacts quickly

Antigen-Presenting Cells

*T-cells require the help of APCs to recognize and attack foreign antigens* - *Antigen presenting cells*: a cell that phagocytizes an antigen and displays fragments of it on its surface for recognition by other cells of the immune system a process called antigen processing; includes B-cells, *macrophages*, reticular cells, and dendritic cells function as APCs - Major histocompatibility complex: proteins on the surface that hold the foreign antigen, also serve as identification tags Function to alert the T-cells to the presence of a foreign antigen Lymphocytes and APCs talk to each other with cytokines called *interleukins* *MHC I - self* *MHC II - non-self*

Pathways for activation of complement

*don't know all details of pathways, just be aware there are three* 1. *Classical pathway*: requires an antibody molecule to get started, is part of the specific immunity, the antibody binds to an antigen on the surface of the pathogen; thus forming an antigen-antibody complex, which changes the shape of the antibody, and exposes a pair of complement-binding sites, binding of the first complement to these sites sets off a reaction cascade; this cascade reaction is called *complement fixation*; 2. *Alternative pathway*: does not require an antibody and therefore belongs to non specific defenses; C3b binds directly to targets such as human tumor cells, viruses, bacteria and yeasts; triggering a reaction cascade causing an autolytic effect; in which c3b eventually leads to the accelerated splitting of more C3 and production of even more C3b 3. *Lectin pathway*: plasma proteins that bind to carbohydrates; part of non specific defenses; lecithin binds to certain sugars of a microbial cell surface and sets off yet another reaction cascade leading to C3b production

Antimicrobial Proteins

- Antimicrobial proteins: two groups of proteins that inhibit microbial reproduction, thereby providing short-term, nonspecific resistance to pathogenic bacteria and viruses Can be divided into two categories: - *Interferons*: certain cells especially leukocytes infected with viruses release the proteins interferons to alert neighboring cells, also activates NK cells and macrophages; can confer resistance to cancer cells - *Complement System*: group of thirty or more globulins that contribute to both nonspecific and specific immunity; synthesized mainly by the liver; circulate in the blood in the inactive form and are activated in the presence of pathogens; this is the principle means of pathogen destruction in antibody mediated immunity

Lymph returned to blood stream

- Begin with lymphatic capillaries (terminal lymphatics), lymphatic capillaries are absent from the CNS, cartilage, cornea, bone and bone marrow - Lymphatic capillaries are closed at one end - Endothelial cells loosely overlap each other - The overlapping of the edges acts as valve like flaps - Construction of lymphatic vessels is similar to veins - Lymph flows under the same forces that govern venous return - Primary is rhythmic contraction of the lymphatic vessels - Skeletal muscle pump - Arterial pulsations - Thoracic (respiratory) pump - Rapid flow of lymphatic fluid in the large vessels pulls additional fluid into the vessels - Lymphatic vessels converge and become lager and larger Hence the route is: Lymphatic capillaries → collecting vessels → six lymphatic trunks →two collecting ducts → subclavian veins Valves aren't actual structure, but one cell being pushed into the end of another cell, creates valve to prevent backflow

Humoral Immunity: Recognition

- Begins when an antigen binds to several of the receptors - Antigens are linked together and taken into the cell - Digests the antigen - Links the epitopes to MHC-II and displays them - Helper t cell binds to this Ag-MHC-II complex - Helper T cell then secretes interleukins to activate the B-cell - B-cell under goes mitosis (clonal selection) - Differentiate into plasma cells which secretes antibodies, initially IgM later exposures IgG *stops invader from getting into cell* (like the airforce - drone cells) B cells - found in bone marrow B cells -- plasma cells -- chemicals (antibodies) into blood stream, prevent invaders from getting into cell

Three Lines of Defense

1. *First line defense*: consists of external barriers; e.g. skin and mucous membranes which are impenetrable to most pathogens 2. *Second line defense*: consists of several nonspecific defense mechanisms against pathogens that break through the skin or mucous membranes, includes leukocytes, macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever 3. *Third line of defense*: the immune system which defeats a pathogen but leaves the body with a "memory" of it - First two are referred to as *non-specific resistance (defense)*; guard against a broad range of pathogens - Immunity is called a *Specific defense*; results from a prior exposure, provides future protection against that one invader

Lymphatic Cells

1. *Natural Killers (NK) Cells*: are large lymphocytes that *attack and destroy bacteria, transplanted tissue cells and host cells that are infected with viruses or turned cancerous*; they are responsible for a mode of defense called immune surveillance are large granular lymphocytes, considered to be a type of cytotoxic lymphocyte which play a major role in the rejection of tumors and cells infected by viruses; kill by releasing cytotoxic granules of perforins and granzyme that cause the target to die by apoptosis or osmotic lysis; they gained their name natural killer because they do not require activation in order to kill cells 2. *Lymphocytes (T cells)*: lymphocytes that *mature in the thymus* and later depend on thymic hormones; there are several subclasses "born" in the red bone marrow as descendants of pleuripotent stem cells; are released into the blood stream as undifferentiated stem cells; migrate to the thymus and form colonies; mature in the thymus where they develop surface antigen receptors *(immunocompetent)*, reticular epithelial cells test these cells for competency; if they pass move unto the medulla of the thymus and undergo positive selection; *naïve lymphocytes pool* meaning they are immunocompetent but untested in actual battle, colonize lymphatic tissues and organs 3. *B lymphocytes (B cells)*: lymphocytes that differentiate into plasma cells, secrete the antibodies of the immune system; *mature in bone marrow* another group of fetal stem cells; those that respond to self-antigens undergo clonal deletion; self tolerant B cells produce surface receptors for antigens and produce clones; found in lymph nodes, they are abundant in the spleen, bone marrow and mucous membranes 4. *Macrophages*: very large, and active phagocytic cells of the connective tissues; develop from monocytes that have emigrated from the blood stream; phagocytize and destroy tissue debris, dead neutrophils, bacteria, and other foreign material; also process foreign matter and present antigenic fragments to certain T cells, alerting the immune system to the presence of an enemy; thus are called *antigen-presenting cells (APCs)* 5. Dendritic cells: branched mobile APC's found in the epidermis, mucous membranes, and lymphatic organs; often called Langerhans cells in the skin; alert the immune system to pathogens that have breached the body surfaces; engulf cells by receptor mediated endocytosis rather than phagocytosis 6. Reticular cells: branched stationary cells that contribute to the stroma (connective framework) of lymphatic organs and act as APCs in the thymus

Immune System Disorder

1. *Type I (acute) hypersensitivity*: includes most common allergies e.g. anaphylaxis/anaphylactic shock 2. *Type II (antibody-dependent cytoxic) hypersensitivity*: occurs when IgG or IgM binds to cell surfaces and interferes with their function e.g. hemolytic disease of the newborn; myasthenia gravis (learning curve), mother's cells hijack your cells and tell body to attack orginal person's cells 3. *Type III (immune complex) hypersensitivity*: occurs when IgG or IgM forms Ag-Ab complexes triggering inflammation; e.g. autoimmune diseases, e.g. Rheumatoid Arthritis, Serum Sickness, Acute Glomerulonephritis (destroying kidneys) 4. *Type IV (delayed) hypersensitivity*: cell-mediated immunity e.g. poison ivy, allergies to cosmetics (use something many times, takes body a while to decide)

Cellular Immunity: Recognition of enemy cells

1. Antigen presentation: cytotoxic and helper T cells patrol, if encounter an antigen with an MHCP , an immune response is initiated - MHC-I proteins occur on every nucleated cell in the body except erythrocytes - MHC-II proteins: human leukocyte antigens, occur only on APCs and only display foreign antigens 2. T cell activation: the T cell checks twice before undergoing clonal selection *by ADC cell Macrophage tells immature T cell if you see ___ you kill it -- becomes mature T cell*

Autoimmune Diseases

1. Cross-reactivity: some Ab react to similar self-antigens 2. Abnormal exposure of self antigens to the blood: breakdown of BBB or BTB resulting in sterility Change in the structure of self antigens: viruses and drugs 3. change the structure of self antigens resulting in our immune system attacking our own cells; e.g. type I diabetes mellitus body attacks itself, because it's bored - giving it to fight can sometimes help

Lymphocytes

1. Cytotoxic T (Tc) cells 2. Helper T (Th) cells 3. Regulatory T (Tr) cells (T-regs) 4. Memory T (Tm) cells *immature T cell -- Thymus -- mature cells -- splits into memory, helper and cytotoxic*

Cellular Immunity: Attack of enemy cells

1. Helper T cells: coordinate both humoral and cellular immunity - Recognizes an AG-MHCP; secretes interleukin which results in three effects - Attraction of neutrophils and natural killer cells - Attract macrophages stimulate phagocytic activity, inhibit them from leaving the site - Stimulate T and B cell mitosis 2. Cytotoxic T cells: recognizes a complex of antigen-MHCP, "docks" on the cell and injects a lethal hit of cytotoxic chemicals - Perforins and granzymes kill target cell - Interferons inhibit viral replication, recruit and activate macrophages - Tumor necrosis factor aids in macrophage activation and kills cancer cells

End Results of Complement System

1. Inflammation: C3a stimulates mast cells and basophils to secrete histamine and other inflammatory chemicals 2. Immune clearance: C3b binds Ag-Ab complexes to red blood cells, as the RBCs circulate through the liver and spleen the macrophages of these organisms strip off and destroy the Ag-Ab complexes and leave the rbcs unharmed; is the principle means of clearing foreign antigens from the blood stream *(sticks antibody with invader attached onto rbc, goes to spleen and gets washed off)* 3. Phagocytosis: bacteria, viruses, and other pathogens are phagocytized by neutrophils and macrophages; C3b assists phagocytes to internalize "naked" microorganisms by *opsonization* (stick antibodies on small object, make it look big) whereby microbial cells are coated with C3b thus serving as a binding site for phagocyte attachment 4. Cytolysis: C3b splits another complement protein C5 into C5a and C5b which joins C3a in proinflammatory actions; this reaction goes on to bind 17 molecules of complement C9 to form a ring called the membrane attack complex; this complex forms a hole in the target cell; resulting in the target cell unable to maintain homeostasis and the cell eventually ruptures *(punches hole so cell leaks guts and dies)*

Six Major Lymphatic Trunks

1. Jugular 2. Subclavian 3. Bronchomediastinal 4. Intercostals 5. Intestinal 6. Lumbar

Lymphatic System - Components

1. Lymph: usually a clear, colorless fluid similar to blood plasma but low in protein, may also contain macrophages, hormones, bacteria, viruses, cellular debris, and possible cancer cells **2. Lymphatic vessels: larger lymphatic vessels are similar to blood vessels except thinner, begin with 1. capillaries-> 2. collecting vessels-> 3. lymphatic trunks-> 4. collecting ducts-> 5. subclavian veins lymphatic capillaries are not found in the central nervous system, cartilage, cornea, and bone 3. Lymphatic tissue: composed of aggregates of lymphocytes and macrophages that populate many organs of the body 4. Lymphatic organs: lymphocytes, and macrophages are especially concentrated and set off from surrounding organs by connective tissue capsules Doesn't have pump so fluid gets back into cardiovascular system by: 1. gravity 2. skeletal muscles 3. cardiovascular pump 4. blood going by in vein pulls fluid into system

Lymphatic Organs

1. Lymphatic (lymphoid) organs: well defined anatomical sites and at least partial connective tissue sites; e.g. red bone marrow, thymus, spleen, tonsils, and lymph nodes: a. Primary lymphatic organs: red bone marrow and thymus, where T & B lymphocytes become immunocompetent b. Secondary lymphatic organs: includes lymph nodes, tonsils and spleen, populated with immunocompetent lymphocytes which have matured in the primary lymphatic organs

Lymphatic Tissue

1. Lymphatic (lymphoid)Tissues: aggregations of lymphocytes in the connective tissues of mucous membranes and various organs a. Diffuse lymphatic tissue: these are the simplest form in which lymphocytes are scattered lymphocytes rather than densely clustered; 1. Bronchus associated lymphatic tissue (BALT) 2. Gut associated lymphatic tissue (GALT) 3. Mucosa associated lymphatic tissue (MALT) 2. Lymphatic nodules: congregations of dense masses of lymphocytes and macrophages, come and go as pathogens invade tissues a. Peyer's patches: lymphatic nodules found in the ileum

Humoral Immunity: Memory

1. Primary Response: person is exposed to an allergen for the first time, and mounts an immune response 2. Secondary (anamnestic) response: second immune response if exposed to the allergen again 3. Memory B cells: some clonal cells become memory cells 4. `Antibody titer: plasma cells begin producing antibodies

Lymphatic Collecting Ducts

1. Right Lymphatic Duct: receives lymphatic drainage from the right arm, right side of thorax, and head; empties into the right subclavian vein 2. Thoracic Duct: two lumbar trunks form the *cisterna chyli* (chyle: fatty intestinal lymph); collectively drains all of the body below the diaphragm left upper limb, and left side of head, neck, and thorax

Cellular Immunity: Memory of enemy cells

1. T cell recall response: some Tc and Th cells become memory cells, - T cell recall response

Humoral Immunity: Attack

5 classes of antibodies: 1. *IgA*: found in mucus, tears, milk, saliva; prevents pathogens from adhering to epithelia (stops them from being able to attach hooks) 2. *IgD*: transmembrane protein of B cells, function in activation of B cells by antigens (in B cells activation) 3. *IgE*: transmembrane protein of *basophils and mast cells*, *stimulates release of histamine and other chemical mediators attracts eosinophils to sites of parasitic infection* 4. *IgG*: *most abundant*, crosses placenta and confers immunity on the fetus (protect from disease) 5. *IgM*: secreted in *primary* immune response; responsible for agglutination reactions in transfusion reactions

Helper T cells

A.K.A. T4, CD4, or CD 4+ promote action of Tc cells, and play key role in humoral immunity and non specific defense; all other T-cells are involved in cellular immunity only coordinates activities between two systems -- speed and who goes where and teaching other t cells

Cytotoxic T cells

A.K.A. T8, CD8 or CD8+ are the "effectors" of cellular immunity carry out attack on enemy cells, also called killer T cells not to be confused with NK cells

Immunodeficiency

AIDS (acquired immunodeficiency syndrome) gets past the 1st and 2nd line of defense and APC cells because it is so small invades one group of helper T cells and lives there (how fast/hard to react) messes up whole system - how much/little to attack, how hard/soft to attack Helper T cells destroyed so it can't defend against normal functions we normally wouldn't have a problem with

Complement System

Activated complement: can bring about pathogen destruction in one of four ways 1. Inflammation: C3a stimulates mast cells and basophils to secrete histamine and other inflammatory chemicals; also attracts neutrophils and macrophages a. Pain b. Swelling - more contents (basophils/histamine) c. Redness - more blood (basophils/histamine) d. Heat - blood ^ heat ^ (basophils/histamine) 2. Immune clearance: C3b stimulates and binds Ag-Ab complexes to red blood cells, 3. Phagocytosis: accomplished by opsonization , performed by neutrophils and macrophages 4. Cytolysis: C3b splits another complement protein which leads to a cascade of reactions eventually leading to a hole in the plasma membrane of the target cell

Functions

Functions of the immune system include: 1. Fluid recovery: ~15% of the fluid in tissue is not reabsorbed by - the capillaries, but is reabsorbed by the lymphatic system, as also ¼-1/2 of the plasma protein 2. Immunity: foreign cells and chemicals are picked up in the tissues, and as the lymph is filtered, these substance can be detected and an immune response is initiated 3. Lipid absorption: lacteals in the small intestine absorb certain dietary lipids and are taken to the vascular system

Secondary Lymphatic Organ - Lymph Nodes

Lymph nodes: most numerous lymphatic organs; serve two functions: 1) cleanse the lymph, macrophages & reticular cells remove 99% of the impurities before the fluid leaves the node, and 2) act as a site of T & B cell activation; structured organ composed of a capsule, cortex and medulla, have afferent and efferent vessels Disorders: *Lymphadenitis*: swollen, painful lymph node *Lymphadenopathy*: collective term for lymph node swelling

Lymph formed

Lymphatic fluid: originates as tissue fluid that was not taken up by the cardiovascular system, but is picked up by the lymphatic vessels

Problems with lines of defense

Our immune system is very complex - it is easy to have errors 1. System can go haywire and overload system: storm T cells don't tell other cells to stop attacking, doesn't put the brakes on (bee venom) - when older immune system doesn't work as well = less storms 2. Getting past system - ways: 1. be very smal 2.overwhelm entire system (septic shock)

2nd line of defense: Non-specific (Innate)

Phagocytes: phagocytic cells *chemicals - kill by releasing toxins* *Complement system - 31 proteins, tag things and destroy all not tagged* *Inflammation - non-specific response* *Fever - non-specific response to invader * There are five types of leukocytes: 1. *Neutrophils*: spend their time by wandering in connective tissues, primarily kill bacteria by phagocytosis and digestion; or discharge a cloud of bactericidal chemicals into the tissue fluid, which creates a respiratory burst which results in destruction of the bacteria but also the neutrophil *kill and eat bacteria" 2. *Eosinophils*: found primarily in mucous membranes; guard against parasites, allergens, and other pathogens; are especially concentrated at sites of allergy, inflammation, or parasitic infections; produce superoxide, hydrogen peroxide, and other toxic proteins including a neurotoxin; promote actions of basophils and *mast cells (wbc in CT protection)*; degrade antigen-antibody complexes; secrete enzymes that degrade and limit histamine and other inflammatory chemicals 3. *Basophils*: secrete chemicals that aid the mobility and action of other leukocytes (leukotrienes), activate and attract neutrophils and eosinophils, the vasodilator histamine speeds the delivery of leukocytes to the area, and the anticoagulant heparin which inhibits the formation of blood clots; these substances are also produced by mast cells are similar to basophils; eosinophils promote basophil and mast cell action by stimulating them to release these secretions *secrete histamine - vasodilator* 4. *Lymphocytes*: look the same in blood, three basic categories: 1) *NK cells*, 2) T cells, and 3) B cells; in circulating blood 80% are T-cells, 15% B cells, and 5% NK cells/stem cells 5. *Monocytes*: are leukocytes that emigrate from the blood into connective tissues and transform into macrophages which is referred to as the *macrophage system*; dendritic cells are included in this system; macrophages are widely distributed in loose connective tissue and sometimes are referred to as histiocytes *eat anything/clean things up after attack* - Macrophage (lymphoid-macrophage) system: all the body's phagocytic cells except leukocytes, and dendritic cells are included in this system; histiocytes (macrophages in loose connect tissues); other specialized forms with specific localities include: - Microglia: found in the CNS - Alveolar macrophages: found in lungs - Hepatic macrophages: found in the liver

Lymphatic System

R. Lymphatic duct - drains into right subclavian Thoracic duct - drains into left subclavian not in the hepatic portal system Lymph needs: wbc lymphocytes macrophages Blood circulates through and fluid leaks through capillaries 15% needs to be picked up from tissues Lymphatic system - picks up and brings it back to the vascular system: Blood stream

Primary Lymphatic Organs - Red Bone Marrow

Red bone marrow: characteristically is soft, loosely organized, highly vascular material separated from osseous tissue by endosteum; in adults limited to parts of axial skeleton and proximal heads of humerus and femur, produces all classes of formed elements in blood; sinusoids drain in to *central longitudinal vein*

Secondary Lymphatic Organ - Spleen

Spleen: largest lymphatic organ; the parenchyma is composed of *red pulp* associated with erythrocytes and *white pulp* consists of lymphocytes and macrophages; highly vascular and vulnerable to trauma; results in the necessity to remove the spleen, the end result is increased number of infections for the patient; the spleen functions as a reserve area for rbcs, as an erythrocyte graveyard, produces rbcs in the fetus, and can later in adult life if necessary, monitors the blood for foreign antigens, and can help to stabilize blood volume

Cellular Immunity

T-lymphocytes directly attack and destroy diseased or foreign cells (marines of the cells - hand to hand combat) immature t cell -- leaves BM, go to Thymus -- mature t cell attack directly affected cell 3 types of bacteria per mature T cell

Overview

The lymphatic system consists of an extensive network of vessels, tissues nodes, and organs. The lymphatic system is concerned with the transportation of a watery clear fluid the lymph. Lymph is actually the interstitial fluid left behind by the circulatory system. The lymphatic system's primary function is to return this fluid to the circulatory system. The lymphatic organs also have a considerable overlap with the immune system. Thus the lymphatic system assists in distributing immune cells and other factors throughout the body in effort to defend the body against disease. Lastly, lymphatic vessels absorb lipids from the intestines and transport them to the blood.

Primary Lymphatic Organs - Thymus

Thymus: is a member of the lymphatic, immune, and endocrine systems; begins to undergo atrophy after age 14; the cortex contains *reticular epithelial cells*, which form the blood-thymus barrier; later developing lymphocytes migrate to the medulla where they mature and are released into blood or lymphatic vessels; RES cells also secret *thymosin, thymopoietin, thymulin, interleukins* and an *interferon*

Secondary Lymphatic Organ - Tonsils

Tonsils: are patches of lymphatic tissue; tonsillar crypts deep pits surrounding the tonsils; 3 main sets 1. Pharyngeal tonsil (a.k.a. adenoids): single tonsil, located on the wall of the pharynx just behind the nasal cavity 2. Palantine tonsils: paired, located at the posterior margin of the oral cavity; are the largest and most often infected 3. Lingual tonsil: concentrated on each side of the tongue

Regulatory T cells

a.k.a. T-regs inhibit multiplication and cytokine secretion by other T-cells limiting the immune response

Definition

an organ system consisting of lymphatic vessels, lymph nodes, the tonsils, spleen and thymus organ, vessels, fluid - return fluid to cardiovascular system

Memory T cells

are descended from cytotoxic T-cells; responsible for memory in cellular immunity *booster/tetanus shot - stimulate Tm cells*

Pathogen

environmental agents capable of producing disease