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Functions of the Lymph System

1) Maintains volume and pressure of extracellularfluid by returning excess water and dissolvedsubstances from the interstitial fluid to thecirculation.

2) Lymph nodes and other lymphoid tissues arethe site of clonal production of immunocompetent lymphocytes andmacrophages in the specific immune response.

The first function relates to our discussion of the filtration which occursfrom the arterial end of capillaries (Starlings Law of the capillaries).
http://classvideos.net/anatomy/mp3/238lymph02.mp3

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Drainage into the Lymph System

Figure 20.1

Filtration intointersitial fluid osmosis

Excess fluid enterslymph capillaries

minivalves

Pressure gradient

Filtration forces water and dissolved substances from the capillaries intothe interstitial fluid. Not all of this water is returned to the blood byosmosis, and excess fluid is picked up by lymph capillaries to becomelymph. From lymph capillaries fluid flows into lymph veins (lymphaticvessels) which virtually parallel the circulatory veins and are structurallyvery similar to them, including the presence of semilunar valves. Lymphcapillaries have flap-like minivalves which allow fluid to enter whenpressure gradient is normal, but close to prevent backflow whenpressure is higher in the lymph capillary.

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Hierarchy of Lymph Vessels

Lymphcapillaries

Lymphaticveins

Lymphnodes

Lymphducts

Lymphaticveins

Semilunarvalves

Lymph veins (also known as lymphatic vessels) both enter and leavethe lymph nodes as they pass from one node to another beforeeventually reaching the lymph duct.

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The Flow of Lymph

See the video clip on the Lymph System in Realmedia format.
http://classvideos.net/anatomy/rm/rm380205.rmhttp://classvideos.net/anatomy/rm/rm380205.rmhttp://classvideos.net/anatomy/rm/rm380205.rmhttp://classvideos.net/anatomy/mp3/238lymph05.mp3http://classvideos.net/anatomy/rm/rm380205.rm

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Drainage into rightlymph duct

Drainage into leftlymph duct

(thoracic duct)

Axillary nodes

Inguinal nodes

Cervical nodes

GI nodes

Chyle cistern

Figure 20.2

Note the unequal drainage of the lymph system into the two ducts. Thenodes shown are the high concentration areas only, which occur at theconvergence of lymph vessels from the body regions. It has beenestimated that lymph cannot pass more than a few centimeters withoutpassing through at least one node.

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Chyle cisternLymph from

legs andGI tract

Thoracic duct

Brachiocephalic veins

Right lymph duct

Figure 20.2

The lymphatic veins flow into one of two lymph ducts. The right lymphduct drains the right arm, shoulder area, and the right side of the headand neck. The left lymph duct, or thoracic duct, drains everything else,including the legs, GI tract and other abdominal organs, thoracicorgans, and the left side of the head and neck and left arm andshoulder. These ducts then drain into the subclavian veins on each sidewhere they join the internal jugular veins to form the brachiocephalicveins.

azygous vein

hemiazygous vein
http://classvideos.com/anatomy/mp3/238lymph07.mp3

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Lymphokinetic Motion- the flow of the lymph.

1) Lymph flows down the pressure gradient.

2) Muscular and respiratory pumps push lymphforward due to function of the semilunar valves.

Some other mammals utilize muscular contractions to move the lymph,but humans rely entirely on the pumps and pressure gradient.

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Pressure in Lymphokinetic Motion

Lymphcapillaries

Lymphaticveins

Lymphnodes

Lymphducts

Highpressure

Lowpressure

Brachiocephalicveins and Vena

Cavae

Lowest pressureBlood capillaries

Interstitial fluid

Highest pressure

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Structure of a Lymph Node

Afferent lymphveins

Efferent lymph veins

Germinal center sourceof lymphocytes

Medullary region source of macrophages

Figure20.4

Lymph nodes: Lymph nodes are small encapsulated organs locatedalong the pathway of lymphatic vessels. They vary from about 1 mm to1 to 2 cm in diameter and are widely distributed throughout the body,with large concentrations occurring in the areas of convergence of lymph vessels. They serve as filters through which lymph percolates onits way to the blood. Antigen-activated lymphocytes differentiate andproliferate by cloning in the lymph nodes.

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Thymus

Tonsils

Spleen

Peyers patches GALT

MALT

Other LymphoidOrgans

Figure 20.5

Diffuse Lymphatic Tissue and Lymphatic nodules: The alimentarycanal, respiratory passages, and genitourinary tract are guarded byaccumulations of lymphatic tissue that are not enclosed by a capsule(i.e. they are diffuse ) and are found in connective tissue beneath theepithelial mucosa. These cells intercept foreign antigens and then travelto lymph nodes to undergo differentiation and proliferation. Localconcentrations of lymphocytes in these systems and other areas arecalled lymphatic nodules . In general these are single and random butare more concentrated in the GI tract in the ileum, appendix, cecum,and tonsils. These are collectively called the Gut Associated LymphaticTissue ( GALT ). MALT (Mucosa Associated Lymphatic Tissue) includesthese plus the diffuse lymph tissue in the respiratory tract.

The spleen: The spleen filters the blood and reacts immunologically toblood-borne antigens. This is both a morphologic (physical) andphysiologic process. In addition to large numbers of lymphocytes the

spleen contains specialized vascular spaces, a meshwork of reticular cells and fibers, and a rich supply of macrophages which monitor theblood. Connective tissue forms a capsule and trabeculae which containmyofibroblasts, which are contractile. The human spleen holdsrelatively little blood compared to other mammals, but it has thecapacity for contraction to release this blood into the circulation duringanoxic stress. White pulp in the spleen contains lymphocytes and isequivalent to other lymph tissue, while red pulp contains large numbersof red blood cells that it filters and degrades.

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Immunocompetence - the ability to recognize self vs. non-self antigens.

Antigen a protein or other substance whichstimulates recognition by immunocompetentlymphocytes.

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Sites of Immunocompetence

T-cells B-cells

?Bursa of fabricus inchickens; bursaequivalent in humans:bone marrow, possiblythe distal bowel.

Thymus

Immunocompetent lymphocytestravel to lymph nodes and otherlymph tissue where they

proliferate and mature in responseto antigenic stimulation and thenenter the circulation.

Figure 20.8

The B in B-cells comes from the Bursa of Fabricus , a structure in birdswhere the cloaca and gut join. This is where B-cells were first identified.

In humans, which have no bursa, immuncocompetence is believed tooccur in the bone marrow, and in other areas which act as bursaequivalents. The bulk of immunocompetence occurs by the end of puberty and slowly decreases with age. The thymus eventuallyatrophies and disappears.

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B-Cell Response Humoral Immunity

Immunocompetentgeneric B-Cell

Non-self antigen

Antigen challenge

Plasma cells Memory cells3:1

antibodies

Primaryresponse

Secondary

responseMore memory cells

Immunocompetent B-cells in the lymph nodes and elsewhere arecapable of responding to bacterial and some viral antigens. This iscalled antigen challenge and causes the activated B-cell to cloneproducing plasma cells and memory cells . The plasma cells secreteantibodies against the antigen, called monoclonal antibodies . (SeeAntibody Actions in slides 16 and 17.) This is called the primaryresponse and takes about 7 to 10 days to reach its peak. The memorycells retain the ability to quickly produce large numbers of plasma cellsand more memory cells should a subsequent exposure to the antigenoccur, called the secondary response . Secondary responses peak inabout 1 day. Your ability to produce a secondary response to a diseasedue to the presence of memory cells is called active immunity , andcan last for many years.

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B-CellResponse

Receptors(IgD antibodies)

Monoclonalantibodies

Figure 21.9

Plasma cellsMemory cells

Plasma cells Memory cells

Note that several immunocompetent B-cell lymphocytes are shown withdifferent receptors (IgD antibodies) on their surface. A large variety of B-cells with different receptors helps to ensure that most bacterial andmany viral antigens of the appropriate types will find a receptor whichmatches them.

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Antibody Actions:

Agglutination exemplified by blood typing reactions.

Opsonization labeling, promotes phagocytosis.

Neutralization binds to active sites of toxins.

Precipitation makes soluble antigens insoluble.

Fixes and activates complement causes opsonization,inflammation, and cell lysis.

See the next slide.

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Figure 22.13

Figure 21.13

Opsonization

Monomer antibodies have the shape of a Y (See next slide) with twoantigen attachment points. The pentamer antibody can attach to fivetimes as many antigens.

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Antibody Structure

Note the constant regions (C) which are always present, the variableregions (V) which determine the specific binding characteristics, thecomplement binding site which activates complement (See slide 21),and the macrophage binding site which stimulates opsonization.

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Table 22.3

B-Cell receptors

Early releaseduring primary

response

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Table 22.3

Becomes mostimportant and

prevalent antibody

Present in secretions

Stimulates mast cellsand basophils toproduce inflammation

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Complement

Activation

Complement can be activated by contact with antibodies (see slide 18)or by contact with certain bacteria.

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The T-Cell Response Cell-mediated Immunity

Cytotoxic (killer)T-Cells

Infected body cell

or tumor cell

ActivatedT-Cells

MemoryT-Cells

MHC I proteins

Lymphokines/Cytokines

MHC = Major HistocompatibilityComplex recognition proteins.

MHC I presentall bodycells

MHC II present on cells of theimmune system

MHC = Major HistocompatibilityComplex recognition proteins.

MHC I present in all bodycells

MHC II present on cells of theimmune system

MHC (Major Histocompatibility Complex ) are proteins used for recognition by immune system cells. MHC I proteins are displayed by allcells of the body (important for non-immune cell recognition) and MHC IIproteins are displayed by cells of the immune system (important for immunecell recognition).These are then displayed along with proteins from an infectious organismor tumor cell and trigger the T-cell response.

D8 receptors on cytotoxiccells are part of immunecognition along with theHC I proteins.

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Cytotoxic T-CellActivation

Cytotoxic (killer) T-cells are activated by coming into contact with aninfected body cell or tumor cell. They recognize the MHC I proteinspossessed by the body cells in combination with the processed viralantigen. CD8 proteins

are antigens that are part of the recognition

process of the cytotoxic T-cells. In response to activation the T-cellsclone to produce mature (activated) cytotoxic T-cells and memory cells.

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Lymphokines/Cytokines:

a. interleukin I - costimulator for activated T-cells

b. interleukin II - stimulates both B and T-cellproliferation

c. MAF - macrophage activating factor

d. MIF - macrophage migration inhibiting factor

e. perforin - causes cell lysis

f. lymphotoxin - kills cells by fragmenting their DNA

g. tumor necrosis factor -

Cytotoxic T-cells secrete lymphokines and cytokines . Here are someof them.

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HelperT-Cells

Infected body cell

or tumor cell

Activated

macrophage

ActivatedT-Cells

MemoryT-Cells

Antigen presentationMHC II proteins

MHC I proteins

Interleukin I

Interleukin II


Acts as a co-stimulator or

inducer

B-Cellresponse

MHC II proteins are displayed by cells of the immune system. Theseare then displayed along with proteins from an infectious organism or tumor cell and presented to the Helper T-cells to activate them.

CD4 receptors on helperT-cells are part of immunerecognition along with theMHC II proteins.

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Role of Helper-Inducer T-Cells

Helper T-cells express CD4 proteins and are activated bymacrophages (APCs ) using MHC II recognition proteins. Helper T-cells then stimulate both cell-mediated and humoral immune responses.The human immunodeficiency virus (HIV) uses the CD4 receptor toinfect Helper T-cells, macrophages, and other immunologic cells.

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HelperT-Cells

SupressorT-Cells

Infected body cell

or tumor cell

Activated

macrophage

ActivatedT-Cells

MemoryT-Cells

Antigen presentationMHC II proteins

MHC I proteins

Acts as a co-stimulatorInterleukin I

Interleukin II Modulateauto-

responses

?


B-Cellresponse

Not much is known about supressor T-cells which help to supressantigen-dependent responses.

Regulatory T cells (also known as suppressor T cells) are aspecialized subpopulation of T cells that act to suppress activationof the immune system and thereby maintain immune systemhomeostasis and tolerance to self. The existence of a dedicatedpopulation of "suppressor" T cells was the subject of significantcontroversy among immunologists for many years. However, recent

advances in the molecular characterization of this cell populationhave firmly established their existence and their critical role in thevertebrate immune system. Interest in regulatory T cells has beenheightened by evidence from experimental mouse modelsdemonstrating that the immunosuppressive potential of these cellscan be harnessed therapeutically to treat autoimmune diseases andfacilitate transplantation tolerance or specifically eliminated topotentiate cancer immunotherapy.

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Hypersensitivity1. Type I Hypersensitivity - allergic reactions. Memory

cells to non-pathogenic antigens release IgE antibodieswhich bind to basophils and mast cells. Produces allergyand anaphylaxis.2. Type II Hypersensitivity - autoimmunity.Examples: multiple sclerosis, myasthenia gravis, Gravesdisease, and some forms of Type 1 diabetes mellitus.3. Type III Hypersensitivity (a.k.a. immune complexdisease) antigen-antibody complexes lodge in endothelialcells inducing inflammation by triggering the complement

pathway with resulting cell lysis, hemorrhage, and tissuedestruction. Examples include: systemic lupuserythematosus (SLE), rheumatoid arthritis and acuteglomerulonephritis.

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