The Lymphatic System System which launches fight against infections.

The Lymphatic SystemThe Lymphatic System

System which launches fight System which launches fight against infectionsagainst infections

Lymphatic SystemLymphatic System

The major components of the lymphatic system are lymphatic vessels, lymph, lymph nodes, and some other lymphatic organs

Lymphatic vessels carry lymph, a colorless liquid, throughout the body. Along lymph vessels are small bean-shaped glandular nodules called lymph nodes.

Other lymphatic organs are:Tonsil: clusters of lymphatic tissues just under the mucous membranes that line the nose, mouth, and pharynx.Spleen: it is similar to a lymph node in shape and structure but it is much larger.

Thymus: a soft organ with two lobes that is located anterior to the ascending aorta and posterior to the sternum.Peyer patch: lymphoid tissue on the visceral surface of the small intestine.

Lymphatic SystemLymphatic System

Primary Lymphoid OrgansPrimary Lymphoid Organs– Bone marrow and ThymusBone marrow and Thymus

Secondary Lymphoid OrgansSecondary Lymphoid Organs– Spleen, tonsils, Peyer’s patchesSpleen, tonsils, Peyer’s patches

Lymphatic system, upper respiratory Lymphatic system, upper respiratory system and muscular system ALL contain system and muscular system ALL contain lymphatic vesselslymphatic vessels

Lymphatic VesselsLymphatic Vessels

Lymphatic vesselsLymphatic vessels carry excess fluid from carry excess fluid from tissues and return it to the bloodstream.tissues and return it to the bloodstream.

Have Have flaplike valvesflaplike valves that help prevent that help prevent backflow of lymphbackflow of lymph

Vessels lead to Vessels lead to lymph nodeslymph nodes

After leaving the nodes, the vessels merge After leaving the nodes, the vessels merge to form to form lymphatic trunkslymphatic trunks

Lymphatic CapillariesLymphatic Capillaries

Thinned walled Thinned walled capillaries which allow capillaries which allow fluid to enter.fluid to enter.

Fluid inside is called Fluid inside is called ““lymphlymph””LactealsLacteals: lymphatic : lymphatic capillaries located in capillaries located in lining of small lining of small intestines which absorb intestines which absorb fat and transport them fat and transport them to venous circulationto venous circulation

Lymph nodes Lymph nodes and ductsand ducts

The right lymphatic duct drains lymph from the upper R side, whereas the thoracic duct drains lymph from the rest of the body.

Lymphatic capillary

Lymphatic vessel

Lymph node

Lymphatic vessel

Lymphatic trunk

Collecting duct

Subclavian vein

Lymph nodesLymph nodesGlands which are located along the lymphatic Glands which are located along the lymphatic pathwayspathways

Contain large #s of Contain large #s of lymphocyteslymphocytes and and macrophagesmacrophages

Located in Located in neck, thoracic cavity, armpit neck, thoracic cavity, armpit (axillary), abdomen, pelvic area, inguinal area (axillary), abdomen, pelvic area, inguinal area and supratrochlear nodesand supratrochlear nodes (where is this???) (where is this???)

2 functions: filtration and providing 2 functions: filtration and providing lymphocytes and macrophages for immunitylymphocytes and macrophages for immunity

Do Do not trap wbcsnot trap wbcs but they do trap bacteria, and but they do trap bacteria, and toxinstoxins

ImmunologyImmunology

The body’s defense systemThe body’s defense system

TerminologyTerminology

ImmunologyImmunology: the study of how body : the study of how body components respond and interactcomponents respond and interact

Immunoglobulins: Immunoglobulins: class of proteins that class of proteins that make up antibodiesmake up antibodies

PhagocytosisPhagocytosis: process where cells engulf and : process where cells engulf and destroy foreign particles such microorganisms or destroy foreign particles such microorganisms or damaged cells. damaged cells. MacrophagesMacrophages and and segmented segmented neutrophilsneutrophils are the most important phagocytic are the most important phagocytic cellscells


ImmunogenicityImmunogenicity: the degree to which an : the degree to which an antigen elicits an immune responseantigen elicits an immune response

ImmunogenImmunogen: antigen that stimulates an : antigen that stimulates an immune responseimmune response

Soluble antigenSoluble antigen: free floating antigen : free floating antigen recognized by B cell receptorsrecognized by B cell receptors


EpitopeEpitope: the small piece of an antigen that : the small piece of an antigen that is bound by an antibody or a T cell is bound by an antibody or a T cell receptorreceptor

ChemotaxisChemotaxis: release of substances which : release of substances which attract phagocytic wbc to bacteria. Cells attract phagocytic wbc to bacteria. Cells move from an area of low to high move from an area of low to high concentration of chemokines.concentration of chemokines.

Immune SystemImmune System

Immune SystemImmune System: : cells in our bone cells in our bone marrow, thymus, and the lymphatic system marrow, thymus, and the lymphatic system of ducts and nodes, spleen, and blood that of ducts and nodes, spleen, and blood that function to protect us. function to protect us.

FunctionFunction is to recognize self from nonself is to recognize self from nonself and to defend the body against nonself.and to defend the body against nonself.

Lines of DefenseLines of Defense

11stst line of Defense line of Defense– Non specificNon specific

Innate or inbornInnate or inbornGeneral response which protects us dailyGeneral response which protects us daily

Non Specific ResponsesNon Specific Responses– InflammationInflammation– PhagocytosisPhagocytosis– Physical barriersPhysical barriers– Chemical barriersChemical barriers


11stst line of defense: line of defense: – Skin and mucosal membrane surfacesSkin and mucosal membrane surfaces– SecretionsSecretions: mucous on membranes in nose : mucous on membranes in nose

trap microorganisms and are secreted trap microorganisms and are secreted through sneezing. What other secretions can through sneezing. What other secretions can you think of?you think of?

Tears, saliva, ear wax, sweat, production and Tears, saliva, ear wax, sweat, production and elimination of urineelimination of urine

– Phagocytic wbcPhagocytic wbc in the mucous membrane in the mucous membrane


11stst line of defense continued: line of defense continued:– Normal flora Normal flora deter penetration of deter penetration of

microorganismsmicroorganisms– pH pH of body fluids such as gastric juicesof body fluids such as gastric juices– Cilia movementCilia movement helps protect the respiratory helps protect the respiratory

tracttract– The enzymeThe enzyme lysozyme lysozyme which is found in tears which is found in tears

and saliva attacks and destroys the cell wall of and saliva attacks and destroys the cell wall of susceptible bacteria especially some gram susceptible bacteria especially some gram positive bacteriapositive bacteria


Non specific cellular and chemical responseNon specific cellular and chemical response– Fever productionFever production resulting from resulting from pyrogenicpyrogenic secretions secretions

from pathogensfrom pathogens– Interleukin 1Interleukin 1 produced resulting from stimulated produced resulting from stimulated

macrophages.macrophages.Polypeptide secreted by macrophages, enhance T cell Polypeptide secreted by macrophages, enhance T cell activation and activityactivation and activity

– PhagocytosisPhagocytosis: process of surrounding and engulfing : process of surrounding and engulfing foreign matter. foreign matter.

Antibodies coating an invading microbe for phagocytosis is Antibodies coating an invading microbe for phagocytosis is called called opsonizationopsonization..

Activation of the Complement Activation of the Complement SystemSystem

Complement SystemComplement System

Activation of complement proteinsActivation of complement proteins

OpsonizationOpsonization: enhancing phagocytosis of Ags: enhancing phagocytosis of Ags

ChemotaxisChemotaxis: attracting macrophages and : attracting macrophages and neutrophilsneutrophils

LysisLysis: rupturing membranes of foreign cells: rupturing membranes of foreign cells

ClumpingClumping of Ag bearing agents of Ag bearing agents

Altering the molecular structureAltering the molecular structure of viruses of viruses

Inflammatory ResponseInflammatory Response

Involves granulocytes such as basophils Involves granulocytes such as basophils and eosinophils.and eosinophils.

Mast cellsMast cells are activated during an allergic are activated during an allergic reaction and release reaction and release histaminehistamine

Delayed hypersensitivityDelayed hypersensitivity is also called is also called Cell Cell MediatedMediated response response

Immune ResponsesImmune Responses

22ndnd line of Defense line of Defense– SpecificSpecific– Production of Abs in response to AgProduction of Abs in response to Ag

Specific ResponsesSpecific Responses– Associated with Ag and Ab reactionAssociated with Ag and Ab reaction– Ab response occurs after exposure to AgAb response occurs after exposure to Ag– Ab may neutralize, kill, or cause clumping of foreign Ab may neutralize, kill, or cause clumping of foreign

microorganismsmicroorganisms– Complement system also works w/Abs to destroy the Complement system also works w/Abs to destroy the

invaderinvaderComplement system is a group of proteins produced in the Complement system is a group of proteins produced in the liver, circulating in the plasma and enhance the work of Absliver, circulating in the plasma and enhance the work of Abs

Types of ImmunityTypes of Immunity ExampleExample

Active natural immunityActive natural immunity Having a disease like Having a disease like the mumpsthe mumps

Active artificial immunityActive artificial immunity Receiving a vaccination Receiving a vaccination like (MMR)like (MMR)

Passive natural Passive natural immunityimmunity

Abs produced by the Abs produced by the body itself or received body itself or received from momfrom mom

Passive artificial Passive artificial immunityimmunity

Injection of antibodiesInjection of antibodies

Types of Immunity

Natural ImmunityNatural Immunity

Also known as Also known as innate (inherited) immunityinnate (inherited) immunity

Mechanism which kicks in after bacteria Mechanism which kicks in after bacteria gets past the first lines of defensegets past the first lines of defense

Natural immunity is a Natural immunity is a non specific non specific mechanismmechanism

Natural ImmunityNatural Immunity

Components of Natural Immune SystemComponents of Natural Immune System– Cellular componentsCellular components

Mast cellsMast cells

Neutrophils: most abundant and 1Neutrophils: most abundant and 1stst to arrive to arrive

MacrophagesMacrophages

– Humoral (fluid)Humoral (fluid)ComplementComplement

LysozymeLysozyme

InterferonInterferon

LeukocytesLeukocytesTypeType FunctionFunction

Polymorphonuclear Polymorphonuclear (granulocytes)(granulocytes)

PhagocytosisPhagocytosis

NeutrophilsNeutrophils Phagocytosis, most active and voraciousPhagocytosis, most active and voracious

EosinophilsEosinophils Allergic responseAllergic response

BasophilsBasophils Release histamine (so do mast cells)Release histamine (so do mast cells)

MonocytesMonocytes Become macrophages and phagocytesBecome macrophages and phagocytes

MacrophagesMacrophages PhagocytosisPhagocytosis

LymphocytesLymphocytes

T LymphocytesT Lymphocytes Cell mediated immunityCell mediated immunity

B LymphocytesB Lymphocytes Humoral immunityHumoral immunity

Plasma cellsPlasma cells Antibody productionAntibody production

Effector Cells Effector Cells

Plasma cellsPlasma cells: derived from lymphocytes : derived from lymphocytes (white blood cells) and are the cells which (white blood cells) and are the cells which secrete antibodies. They live a short time secrete antibodies. They live a short time and are constantly being replaced.and are constantly being replaced.

MacrophagesMacrophages: derived from monocytes : derived from monocytes (wbc) w/primary function of phagocytosis(wbc) w/primary function of phagocytosis

Adaptive ImmunityAdaptive Immunity

Also known as Also known as acquired immunityacquired immunity

Active immunity can leave the host Active immunity can leave the host w/specific w/specific immunologic memoryimmunologic memory which which allows the host to respond more effectively allows the host to respond more effectively if re-infection with the same if re-infection with the same microorganism occursmicroorganism occurs

Specific Immune ResponseSpecific Immune ResponsePrimary Immune ResponsePrimary Immune Response: 10 to 17 days after : 10 to 17 days after initial exposure to Ag. Selected lymphocytes initial exposure to Ag. Selected lymphocytes generate a maximum effector cell response.generate a maximum effector cell response.

While effector cells are developing an infected While effector cells are developing an infected person may become ill but eventually the person may become ill but eventually the symptoms of the illness disappear as Abs and symptoms of the illness disappear as Abs and effector T cells clear antigens from the body.effector T cells clear antigens from the body.

Secondary Immune ResponseSecondary Immune Response: later exposure to : later exposure to the Ag that results in a much faster (2-7 days), the Ag that results in a much faster (2-7 days), much faster, and more prolonged response by much faster, and more prolonged response by Abs and effector T cellsAbs and effector T cells

Immunoglobulin StructureImmunoglobulin Structure

Composed of Composed of glycoproteinsglycoproteins4 protein chains held together w/ 4 protein chains held together w/ disulfide bondsdisulfide bondsFcFc regionregion: constant region dictates the type of : constant region dictates the type of immunoglobulin A, E, D, M, or Gimmunoglobulin A, E, D, M, or GFab portionFab portion: antigen binding region of the Ab. : antigen binding region of the Ab. This region is highly diverse so that the variety of This region is highly diverse so that the variety of antigens recognized by these receptors is antigens recognized by these receptors is extremely numerousextremely numerousHeavyHeavy chains chainsLightLight chains chains

Immunoglobulin StructureImmunoglobulin Structure

Composed of 2 identicalHeavy chains and 2identical light chains

Constant regions are located on both the light and heavy chains

The very end of the variable Regions is called the hypervariable as that is the region where the amino acid sequencing varies the most

AntibodiesAntibodies

Variable regionVariable region is what determines the is what determines the antigen specificityantigen specificity

The constant region (The constant region (FcFc) is what ) is what determines the antibody immunological determines the antibody immunological class or class or isotypeisotype (A,E,M,G, D) (A,E,M,G, D)

Antibodies do not destroy antigens directlyAntibodies do not destroy antigens directly– NeutralizeNeutralize– Target for eliminationTarget for elimination

Agglutination, precipitation, complement fixationAgglutination, precipitation, complement fixation


IgM: first type of antibody secreted during IgM: first type of antibody secreted during a primary immune response (promotes a primary immune response (promotes agglutination or clotting)agglutination or clotting)

IgG: major type of antibody secreted IgG: major type of antibody secreted during a secondary immune responseduring a secondary immune response

IgE: type most associated with allergic IgE: type most associated with allergic reactions (promotes release of histamine)reactions (promotes release of histamine)


IgA: this is the antibody found in most IgA: this is the antibody found in most abundance in bodily secretions such as saliva abundance in bodily secretions such as saliva and mother’s milkand mother’s milk

IgD: this antibody serves as a B cell surface IgD: this antibody serves as a B cell surface receptor.receptor.

Soluble antibodies are involved in the followingSoluble antibodies are involved in the following– Cause clottingCause clotting– Can bind active sites on toxinsCan bind active sites on toxins– Tag foreign microbes for destructionsTag foreign microbes for destructions


IgM and IgD are the first antibodies expressed IgM and IgD are the first antibodies expressed by a B cellby a B cell

Each B cell has ~ 100,000 IgM or IgD receptors Each B cell has ~ 100,000 IgM or IgD receptors on its surfaceon its surface

These antibodies can bind free Ags whereas T These antibodies can bind free Ags whereas T cell receptors can only bind to Abs when they cell receptors can only bind to Abs when they are presented by Ag presenting cells (discussed are presented by Ag presenting cells (discussed later)later)


Binding the IgM or IgD on the B cell surface Binding the IgM or IgD on the B cell surface provokes a primary immune response resulting provokes a primary immune response resulting in secretion of IgM, B cell division, and clonal in secretion of IgM, B cell division, and clonal expansionexpansion

Secretion of the IgM Abs stimulates the Secretion of the IgM Abs stimulates the activation of the complement systemactivation of the complement system

IgG Abs are then produced and promote IgG Abs are then produced and promote phagocytosisphagocytosis

Antibody Response GraphAntibody Response Graph

B Cell MaturationB Cell Maturation

Stem cell Pro- B cell Pre B cellStem cell Pro- B cell Pre B cellImmature B cell mature B cell Immature B cell mature B cell

During this time of development the Ab/Ag During this time of development the Ab/Ag specificity is being determined through a process specificity is being determined through a process of of random genetic recombinationrandom genetic recombination. Also . Also undergoes a process of undergoes a process of negative selectionnegative selection to to screen for self versus non self molecules. screen for self versus non self molecules. During the immature B cell stage: if the antigen During the immature B cell stage: if the antigen receptor matches with a receptor matches with a self antigenself antigen the cell dies the cell dies by apoptosis called by apoptosis called Clonal DeletionClonal Deletion

B Cell Maturation and FunctionB Cell Maturation and Function

When antigen binds to the B cell receptor, When antigen binds to the B cell receptor, the B cell is activated and begins to the B cell is activated and begins to undergo undergo clonal expansionclonal expansion, which results in , which results in the proliferation of the proliferation of exact duplicatesexact duplicates of the of the original B cell.original B cell.

When B cells are mature the must When B cells are mature the must undergo a process to determine undergo a process to determine self self tolerancetolerance. This process is Ag dependent.. This process is Ag dependent.

Humoral Immunity SummaryHumoral Immunity Summary

Involves the production of Abs that circulate in Involves the production of Abs that circulate in the blood and lymph to defend against free the blood and lymph to defend against free bacteria, toxin, and virusesbacteria, toxin, and virusesInvolves Involves B cellsB cells that eventually differentiate into that eventually differentiate into plasma cellsplasma cells or memory cells or memory cellsAlso requires the use of Helper T cells and Also requires the use of Helper T cells and certain cytokines such as IL-2certain cytokines such as IL-2Plasma cells produce antibodies while memory Plasma cells produce antibodies while memory cells wait for re-exposurecells wait for re-exposureAntibodies tag foreign microbes for destruction Antibodies tag foreign microbes for destruction through several processesthrough several processes

Cell Mediated Response OverviewCell Mediated Response Overview

Involves Involves direct killingdirect killing of infected cells via T of infected cells via TCC cells cells

Does Does notnot involve the production of Abs involve the production of Abs

Requires both the activation of TRequires both the activation of THH cells and T cells and TCC

cellscells

Some cells will become effector cells and some Some cells will become effector cells and some cells will become memory cells to wait for re-cells will become memory cells to wait for re-exposureexposure

Most important cell is the Most important cell is the TTHH cell cell

Overlaps with Humoral ResponseOverlaps with Humoral Response

T LymphocytesT Lymphocytes

Originate in the bone marrow but mature in the Originate in the bone marrow but mature in the thymusthymus

Stored in the secondary lymphatic tissueStored in the secondary lymphatic tissue

Basis for Basis for Cell Mediated immunityCell Mediated immunity

Lifespan: resting 1-3 weeks, activated 3-4 days, Lifespan: resting 1-3 weeks, activated 3-4 days, memory years/lifetimememory years/lifetime

Respond to specific Ag and Respond to specific Ag and cancercancer cells cells

Do not produce AbsDo not produce Abs

2 Primary types: cytotoxic and helper T cells2 Primary types: cytotoxic and helper T cells

T Cell MaturationT Cell Maturation

Stem Cell Pro T cell Pre T cellStem Cell Pro T cell Pre T cellDouble positive T cell Double positive alpha beta TCR Double positive T cell Double positive alpha beta TCR

T cell Single positive T alpha beta TCR cellT cell Single positive T alpha beta TCR cell

During this time of development T cell receptor (TCR) During this time of development T cell receptor (TCR) specificity is being determinedspecificity is being determined

Undergoes process of both positive and negative Undergoes process of both positive and negative screening for productive gene arrangement, self versus screening for productive gene arrangement, self versus non-self molecules, and appropriate CD surface protein non-self molecules, and appropriate CD surface protein moleculesmolecules

CD 8 = Cytotoxic T cell, CD 4 = Helper T cellCD 8 = Cytotoxic T cell, CD 4 = Helper T cell

Stem Cell differentiationStem Cell differentiation

Stem cells originate in the bone marrow

AntigensAntigens

Elicit an immune response Elicit an immune response 2 general types exist2 general types exist– Exogenous: foreign from outside the hostExogenous: foreign from outside the host– Endogenous: foreign from within the hostEndogenous: foreign from within the host

Viruses, bacteria, fungi, protozoa, and Viruses, bacteria, fungi, protozoa, and parasites are all antigensparasites are all antigens

Antigenic determinants = epitopeAntigenic determinants = epitope

AntigensAntigens

Chemical composition are Chemical composition are proteinsproteins and and large polysaccharideslarge polysaccharides (carbs) (carbs)

Proteins Proteins make the best immunogens due make the best immunogens due to their high MW and structural complexityto their high MW and structural complexity

PolysaccharidesPolysaccharides (carbs or sugars)(carbs or sugars) are OK are OK immunogens but their small size make immunogens but their small size make them less effective than proteinsthem less effective than proteins

AntigensAntigens

Lipids are inferiorLipids are inferior antigens because of antigens because of their relative simplicity and lack of their relative simplicity and lack of structural stabilitystructural stability

Nucleic acidsNucleic acids are poor Ag due to lack of are poor Ag due to lack of molecular flexibility and rapid degradationmolecular flexibility and rapid degradation

Antigen ReceptorsAntigen Receptors

The way that B cells and T cells recognize The way that B cells and T cells recognize specific molecules and trigger an immune specific molecules and trigger an immune responseresponse

Plasma membrane boundPlasma membrane bound

All antigen receptors on a B cell or T cell have All antigen receptors on a B cell or T cell have the same specificitythe same specificity

Determined by random genetic eventsDetermined by random genetic events– Occurs before any contact w/foreign antigen is madeOccurs before any contact w/foreign antigen is made– Allows for an enormous variety of B and T Allows for an enormous variety of B and T

lymphocyteslymphocytes

AutoimmunityAutoimmunity

Immune system Immune system fails to distinguish self fails to distinguish self from non selffrom non self producing autoantibodies producing autoantibodies and cytotoxic T cells that attack and and cytotoxic T cells that attack and damage the body’s tissuesdamage the body’s tissues

May be caused by a May be caused by a virus replicating virus replicating within a host cellwithin a host cell or or faulty T cellsfaulty T cells or or antigen which closely resembles self Agantigen which closely resembles self Ag (example strep infection in heart valves)(example strep infection in heart valves)

Autoimmunity diseases and conditionsAutoimmunity diseases and conditionsCancer of the lymph nodesCancer of the lymph nodes: when lymphocytes : when lymphocytes undergo a mutation and multiply out of controlundergo a mutation and multiply out of controlRheumatoid arthritisRheumatoid arthritis: involves the : involves the jointsjoints, RF factor is , RF factor is test methodtest methodGrave’s diseaseGrave’s disease: : hyperthyroidismhyperthyroidism, affects young , affects young women, goiter is common side effect as well as women, goiter is common side effect as well as exophthalmos exophthalmos (protrusion of the eyes)(protrusion of the eyes)

Pernicious anemiaPernicious anemia: mucous lining of : mucous lining of stomachstomach does does not secrete protein called intrinsic factor which is not secrete protein called intrinsic factor which is needed for B12 absorption resulting in anemianeeded for B12 absorption resulting in anemiaHIV infection: HIV infection: reverse transcriptionreverse transcription coverts viral coverts viral RNA into DNARNA into DNA

The Lymphatic System System which launches fight against infections.

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