11

Maintain fluid balanceMaintain fluid balance Protect body from infection and diseaseProtect body from infection and disease

Lymphatic and Immune Lymphatic and Immune SystemsSystems

22

ImmunityImmunity fluids from all capillary beds are filteredfluids from all capillary beds are filtered immune cells stand ready to respond to foreign cells or immune cells stand ready to respond to foreign cells or

chemicals encounteredchemicals encountered

Lipid absorptionLipid absorption Lacteals in small intestine absorb dietary lipidsLacteals in small intestine absorb dietary lipids

Fluid recoveryFluid recovery absorbs plasma proteins and fluid from tissues and returns absorbs plasma proteins and fluid from tissues and returns

it to the bloodstreamit to the bloodstream• interference with lymphatic drainage leads to severe edemainterference with lymphatic drainage leads to severe edema

Functions of Lymphatic SystemFunctions of Lymphatic System

33

Lymph and Lymphatic Lymph and Lymphatic CapillariesCapillaries

LymphLymph clear, colorless fluid, similar to plasma but much clear, colorless fluid, similar to plasma but much

less proteinless protein Lymphatic capillariesLymphatic capillaries

closed at one endclosed at one end tethered to surrounding tissue by protein filamentstethered to surrounding tissue by protein filaments endothelial cells loosely overlapped endothelial cells loosely overlapped

• allow bacteria and cells entrance to lymphatic capillaryallow bacteria and cells entrance to lymphatic capillary• creates valve-like flaps that open when interstitial fluid creates valve-like flaps that open when interstitial fluid

pressure is high, and close when it is lowpressure is high, and close when it is low

44

Lymphatic CapillaryLymphatic Capillary

55

Lymphatic VesselsLymphatic Vessels

Larger ones composed of 3 layersLarger ones composed of 3 layers tunica interna: endothelium and valvestunica interna: endothelium and valves tunica media: elastic fibers, smooth muscletunica media: elastic fibers, smooth muscle tunica externa: thin outer layertunica externa: thin outer layer

66

Valve in a Lymphatic VesselValve in a Lymphatic Vessel

77

Route of Lymph FlowRoute of Lymph Flow Lymphatic capillariesLymphatic capillaries Collecting vessels: Collecting vessels: course through many lymph nodescourse through many lymph nodes

Lymphatic trunks: Lymphatic trunks: drain major portions of bodydrain major portions of body

Collecting ducts : Collecting ducts : right lymphatic duct – receives lymph from R arm, R side of right lymphatic duct – receives lymph from R arm, R side of

head and thorax; empties into R subclavian veinhead and thorax; empties into R subclavian vein thoracic duct - larger and longer, begins as a prominent thoracic duct - larger and longer, begins as a prominent

sac in abdomen called the cisterna chyli; receives lymph sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, L arm, L side of head, neck and from below diaphragm, L arm, L side of head, neck and thorax; empties into L subclavian veinthorax; empties into L subclavian vein

88

The Fluid CycleThe Fluid Cycle

99

Lymphatic Drainage of Lymphatic Drainage of Mammary and Axillary RegionsMammary and Axillary Regions

1010

Drainage of ThoraxDrainage of Thorax

1111

Mechanisms of Lymph FlowMechanisms of Lymph Flow Lymph flows at low pressure and speedLymph flows at low pressure and speed Moved along by rhythmic contractions of lymphatic Moved along by rhythmic contractions of lymphatic

vesselsvessels stretching of vessels stimulates contractionstretching of vessels stimulates contraction

Flow aided by skeletal muscle pumpFlow aided by skeletal muscle pump Thoracic pump aids flow from abdominal to thoracic Thoracic pump aids flow from abdominal to thoracic

cavitycavity Valves prevent backward flowValves prevent backward flow Rapidly flowing blood in subclavian veins, draws Rapidly flowing blood in subclavian veins, draws

lymph into itlymph into it Exercise significantly increases lymphatic returnExercise significantly increases lymphatic return

1212

Cells are created in the bone Cells are created in the bone marrowmarrow

Lymphocytes are created in the bone Lymphocytes are created in the bone marrow. 2 types- T and B cellsmarrow. 2 types- T and B cells

B cells mature in the bone marrowB cells mature in the bone marrow T cells mature in the thymus gland by T cells mature in the thymus gland by

secretion of thymosinsecretion of thymosin

1313

Lymphatic CellsLymphatic Cells Natural killer (NK) cellsNatural killer (NK) cells

responsible for immune surveillanceresponsible for immune surveillance

T lymphocytes- T helper and suppressorT lymphocytes- T helper and suppressor mature in thymusmature in thymus

B lymphocytesB lymphocytes activation causes proliferation and differentiation into activation causes proliferation and differentiation into

plasma cells that produce antibodiesplasma cells that produce antibodies

Antigen Presenting CellsAntigen Presenting Cells macrophages macrophages (from monocytes)(from monocytes) dendritic cells dendritic cells (in epidermis, mucous membranes and lymphatic (in epidermis, mucous membranes and lymphatic

organs)organs) reticular cells reticular cells (also contribute to stroma of lymph organs)(also contribute to stroma of lymph organs)

1414

Lymphatic OrgansLymphatic Organs

At well defined sites; have CT capsulesAt well defined sites; have CT capsules Primary lymphatic organsPrimary lymphatic organs

site where T and B cells become site where T and B cells become immunocompetentimmunocompetent

red bone marrow and thymus red bone marrow and thymus Secondary lymphatic organsSecondary lymphatic organs

immunocompetent cells populate these immunocompetent cells populate these tissuestissues

lymph nodes, tonsils, and spleenlymph nodes, tonsils, and spleen

1515

LymphadenopathyLymphadenopathy

Collective term for all lymph node Collective term for all lymph node diseasesdiseases

LymphadenitisLymphadenitis swollen, painful node responding to foreign swollen, painful node responding to foreign

antigenantigen Lymph nodes are common sites for Lymph nodes are common sites for

metastatic cancermetastatic cancer swollen, firm and usually painlessswollen, firm and usually painless

1616

Lymph NodeLymph Node

Fig. 21.12 a and b

1717

Location of TonsilsLocation of Tonsils

Palatine tonsilsPalatine tonsils pair at posterior margin of oral cavitypair at posterior margin of oral cavity most often infected most often infected

Lingual tonsilsLingual tonsils pair at root of tonguepair at root of tongue

Pharyngeal tonsil (adenoid)Pharyngeal tonsil (adenoid) single tonsil on wall of pharynxsingle tonsil on wall of pharynx

1818

ThymusThymus

1919

SpleenSpleen

2020

Defenses Against PathogensDefenses Against Pathogens Nonspecific defenses - broadly effective, no prior exposure – Cell Nonspecific defenses - broadly effective, no prior exposure – Cell

mediated – T lymphocytemediated – T lymphocyte Cell mediated = T cell attacks cells that have been infected with a Cell mediated = T cell attacks cells that have been infected with a

bacteria or virusbacteria or virus first line of defensefirst line of defense

• external barriersexternal barriers second line of defensesecond line of defense

• phagocytic cells, antimicrobial proteins, inflammation and phagocytic cells, antimicrobial proteins, inflammation and feverfever

Specific defense - results from prior exposure, protects against only Specific defense - results from prior exposure, protects against only a particular pathogen – Humoral response – B lymphocyte- antibody a particular pathogen – Humoral response – B lymphocyte- antibody

third line of defensethird line of defense• immune systemimmune system

2121

External BarriersExternal Barriers SkinSkin

toughness of keratintoughness of keratin dry and nutrient-poordry and nutrient-poor defensins: peptides, from neutrophils attack defensins: peptides, from neutrophils attack

microbesmicrobes Mucous membranesMucous membranes

stickiness of mucus stickiness of mucus lysozyme: enzyme destroys bacterial cell wallslysozyme: enzyme destroys bacterial cell walls

Subepithelial areolar tissueSubepithelial areolar tissue tissue gel: viscous barrier of hyaluronic acidtissue gel: viscous barrier of hyaluronic acid

• hyaluronidase: enzyme used by pathogens to spreadhyaluronidase: enzyme used by pathogens to spread

2222

Complement SystemComplement System

Complement (C) proteins in blood that Complement (C) proteins in blood that must be activated by pathogens. Named must be activated by pathogens. Named because they “compliment” the work of because they “compliment” the work of antibodies.antibodies.

Produced in the liverProduced in the liver

2323

Complement SystemComplement System

Mechanisms of actionMechanisms of action enhanced inflammationenhanced inflammation phagocytosis phagocytosis

• promoted by opsonizationpromoted by opsonization cytolysis cytolysis

• membrane attack complex forms on target cellmembrane attack complex forms on target cell immune clearanceimmune clearance

• RBCs carry Ag-Ab complexes to macrophages in RBCs carry Ag-Ab complexes to macrophages in liver and spleenliver and spleen

2424

Membrane Attack ComplexMembrane Attack Complex Complement proteins form ring in plasma Complement proteins form ring in plasma

membrane of target cell causing cytolysismembrane of target cell causing cytolysis

2525

Immune SurveillanceImmune Surveillance

NK cells NK cells destroy bacteria, transplanted cells, cells destroy bacteria, transplanted cells, cells

infected by viruses, and cancer cellsinfected by viruses, and cancer cells• release perforins and granzymesrelease perforins and granzymes

2626

Action of NK cellAction of NK cell

Fig. 21.17

2727

InflammationInflammation

Defensive response to tissue injuryDefensive response to tissue injury1.1. limits spread of pathogens, then destroys limits spread of pathogens, then destroys

themthem2.2. removes debrisremoves debris3.3. initiates tissue repairinitiates tissue repair

CytokinesCytokines small proteins regulate inflammation and small proteins regulate inflammation and

immunity; includeimmunity; include• interferons, interleukins, tumor necrosis factor, interferons, interleukins, tumor necrosis factor,

and chemotactic factorsand chemotactic factors

2828

InflammationInflammation Suffix Suffix -itis -itis denotes inflammation of denotes inflammation of

specific organsspecific organs Cardinal signsCardinal signs

redness redness (erythema) caused by hyperemia ((erythema) caused by hyperemia ( blood flow)blood flow)

swelling swelling (edema) caused by (edema) caused by capillary capillary permeability and filtrationpermeability and filtration

heat heat caused by hyperemiacaused by hyperemia pain pain caused by inflammatory chemicals caused by inflammatory chemicals

(bradykinin, prostaglandins) secreted by damaged (bradykinin, prostaglandins) secreted by damaged cells, pressure on nervescells, pressure on nerves

2929

InflammationInflammation

Three major processesThree major processes1.1. mobilization of body defensesmobilization of body defenses

2.2. containment and destruction of pathogenscontainment and destruction of pathogens

3.3. tissue clean-up and repairtissue clean-up and repair

3030

Mobilization of DefensesMobilization of Defenses

Histamine and leukotrienes are secreted by Histamine and leukotrienes are secreted by damaged cells, basophils and mast cellsdamaged cells, basophils and mast cells stimulates vasodilation that leads to hyperemiastimulates vasodilation that leads to hyperemia

• causes redness and heatcauses redness and heat local metabolic rate, promotes cell multiplication and local metabolic rate, promotes cell multiplication and

healinghealing

• dilutes toxins, provides Odilutes toxins, provides O22, nutrients, waste removal, nutrients, waste removal

stimulates stimulates permeability of blood capillaries permeability of blood capillaries• allows blood cells, plasma proteins (antibodies, complement allows blood cells, plasma proteins (antibodies, complement

proteins, fibrinogen) into tissueproteins, fibrinogen) into tissue• clotting sequesters bacteria, forms scaffold for tissue repairclotting sequesters bacteria, forms scaffold for tissue repair

3131

Mobilization of DefensesMobilization of Defenses Leukocyte Leukocyte

DeploymentDeployment marginationmargination

• selectins cause selectins cause leukocytes to leukocytes to adhere to blood adhere to blood vessel wallsvessel walls

diapedesis diapedesis (emigration)(emigration)• leukocytes leukocytes

squeeze between squeeze between endothelial cells endothelial cells into tissue spaceinto tissue space

3232

Containment and Destruction of Containment and Destruction of PathogensPathogens

Fibrinogen Fibrinogen now in tissue clots, trapping pathogensnow in tissue clots, trapping pathogens

Heparin Heparin prevents clotting at site of injuryprevents clotting at site of injury pathogens are in a fluid pocket surrounded by clotpathogens are in a fluid pocket surrounded by clot

ChemotaxisChemotaxis leukocytes are attracted to chemotactic chemicals leukocytes are attracted to chemotactic chemicals

Neutrophils are quickest to respond Neutrophils are quickest to respond phagocytosis phagocytosis respiratory burstrespiratory burst secrete cytokines for recruitment of macrophages and secrete cytokines for recruitment of macrophages and

neutrophilsneutrophils macrophages and T cells secrete colony-stimulating factor macrophages and T cells secrete colony-stimulating factor

to stimulate leukopoiesis to stimulate leukopoiesis

3333

Tissue CleanupTissue Cleanup

Monocytes the primary agents of cleanup Monocytes the primary agents of cleanup arrive in 8 to 12 hours, become arrive in 8 to 12 hours, become macrophages, macrophages,

Edema Edema venous flow, venous flow, lymphatic flow that lymphatic flow that favors removal of bacteria and debrisfavors removal of bacteria and debris

Formation of pusFormation of pus mixture of tissue fluid, cellular debris, dying mixture of tissue fluid, cellular debris, dying

neutrophils and microbesneutrophils and microbes

3434

FeverFever Defense mechanism: can be harmfulDefense mechanism: can be harmful

promotes interferon activitypromotes interferon activity accelerating metabolic rate and tissue repairaccelerating metabolic rate and tissue repair inhibiting pathogen reproductioninhibiting pathogen reproduction

A cytokine, interleukin 1, called a pyrogenA cytokine, interleukin 1, called a pyrogen secreted by macrophages, stimulates anterior secreted by macrophages, stimulates anterior

hypothalamus to secrete PGE which resets body hypothalamus to secrete PGE which resets body thermostat higherthermostat higher

> 105> 105F may cause delirium, 111F may cause delirium, 111F- 115F- 115F, coma-deathF, coma-death

Stages of feverStages of fever onset, stadium, defervescenceonset, stadium, defervescence

3535

Course of a FeverCourse of a Fever

3636

Specific ImmunitySpecific Immunity

Specificity and memorySpecificity and memory Cellular immunity: cell-mediated (T cells)Cellular immunity: cell-mediated (T cells) Humoral immunity: antibody mediated (B Humoral immunity: antibody mediated (B

cells)cells)

3737

Passive and Active ImmunityPassive and Active Immunity

Natural active immunity Natural active immunity (produces memory cells)(produces memory cells) production of one’s own antibodies or T cells as a production of one’s own antibodies or T cells as a

result of infection or natural exposure to antigenresult of infection or natural exposure to antigen Artificial active immunity Artificial active immunity (produces memory cells)(produces memory cells)

production of one’s own antibodies or T cells as a production of one’s own antibodies or T cells as a result of vaccinationresult of vaccination

Natural passive immunity Natural passive immunity (through placenta, milk)(through placenta, milk) temporary, fetus acquires antibodies from mothertemporary, fetus acquires antibodies from mother

Artificial passive immunity Artificial passive immunity (snakebite, rabies, tetanus)(snakebite, rabies, tetanus) temporary, injection of immune serum (antibodies)temporary, injection of immune serum (antibodies)

3838

Life Cycle of T cellsLife Cycle of T cells

Stem cells in red bone marrowStem cells in red bone marrow Mature in thymusMature in thymus

thymosins stimulate maturing T cells to thymosins stimulate maturing T cells to produce antigen receptorsproduce antigen receptors

immunocompetent T cell has antigen immunocompetent T cell has antigen receptors in placereceptors in place

DeploymentDeployment naïve T cells colonize lymphatic tissue and naïve T cells colonize lymphatic tissue and

organsorgans

3939

Antigen ProcessingAntigen Processing

4040

InterleukinsInterleukins

Chemical messengers between leukocytesChemical messengers between leukocytes Used by lymphocytes to communicate with Used by lymphocytes to communicate with

one anotherone another

4141

Cellular ImmunityCellular Immunity T cells attack foreign cells and diseased host T cells attack foreign cells and diseased host

cellscells Three classes of T cellsThree classes of T cells

1.1. Cytotoxic T cells (TCytotoxic T cells (Tcc cells) carry out attack cells) carry out attack

2.2. Helper T cells: help promote THelper T cells: help promote Tcc cell and B cell cell and B cell

action and nonspecific defense mechanismsaction and nonspecific defense mechanisms

3.3. Memory T cells: provide immunity from future Memory T cells: provide immunity from future exposure to antigenexposure to antigen

4242

Attack Phase: Role of Helper T Attack Phase: Role of Helper T CellsCells

Secretes interleukinsSecretes interleukins attract neutrophils, NK attract neutrophils, NK

cells, macrophagescells, macrophages stimulate phagocytosisstimulate phagocytosis stimulate T and B cell stimulate T and B cell

mitosis and maturationmitosis and maturation

Coordinate humoral Coordinate humoral and cellular immunityand cellular immunity

4343

Attack Phase: Attack Phase: Cytotoxic T CellsCytotoxic T Cells

Only T cells directly attack enemy cellsOnly T cells directly attack enemy cells Lethal hit mechanism Lethal hit mechanism

docks on cell with antigen-MHC-I protein complexdocks on cell with antigen-MHC-I protein complex

1.1. releases perforin, granzymes - kills target cellreleases perforin, granzymes - kills target cell

2.2. interferons - decrease viral replication and interferons - decrease viral replication and activates macrophagesactivates macrophages

3.3. tumor necrosis factor: kills cancer cellstumor necrosis factor: kills cancer cells

4444

Cytotoxic T Cell FunctionCytotoxic T Cell Function

Cytotoxic T cell binding to cancer cellCytotoxic T cell binding to cancer cell

4545

Destruction of Cancer CellDestruction of Cancer Cell

4646

MemoryMemory

Memory T cellsMemory T cells following clonal selection some T cells following clonal selection some T cells

become memory cellsbecome memory cells long-lived; in higher numbers than naïve cellslong-lived; in higher numbers than naïve cells

T cell recall responseT cell recall response upon reexposure to same pathogen, memory upon reexposure to same pathogen, memory

cells launch a quick attackcells launch a quick attack

4747

Humoral ImmunityHumoral Immunity RecognitionRecognition

B cell receptors bind antigen, take in and digest B cell receptors bind antigen, take in and digest antigen antigen

After costimulation by TAfter costimulation by TH H cell, divide repeatedly, cell, divide repeatedly, differentiate into plasma cells, produce antibodies differentiate into plasma cells, produce antibodies specific to that antigenspecific to that antigen

AttackAttack antibodies bind to antigen, render it harmless, ‘tag antibodies bind to antigen, render it harmless, ‘tag

it’ for destructionit’ for destruction MemoryMemory

some B cells differentiate into memory cellssome B cells differentiate into memory cells

4848

Humoral Immunity - RecognitionHumoral Immunity - Recognition

4949

Antibody StructureAntibody Structure

5050

Antibody ClassesAntibody Classes

By amino acid sequences of C region of By amino acid sequences of C region of antibodyantibody

IgA:IgA: mucus, saliva, tears, milk, intestinal secretions, mucus, saliva, tears, milk, intestinal secretions, prevents adherence to epitheliaprevents adherence to epithelia

IgD: IgD: B cell membrane antigen receptorB cell membrane antigen receptor IgE: IgE: mast cells; stimulates release of histamines, mast cells; stimulates release of histamines,

attracts eosinophils; immediate hypersensitivity reactionsattracts eosinophils; immediate hypersensitivity reactions IgG:IgG: 80% circulating, crosses placenta to fetus, 2 80% circulating, crosses placenta to fetus, 2

immune response, complement fixationimmune response, complement fixation IgM:IgM: 10% in plasma, 1 10% in plasma, 1 immune response, agglutination, immune response, agglutination,

complement fixationcomplement fixation

5151

Antibody DiversityAntibody Diversity

Immune system capable of as many as 1 Immune system capable of as many as 1 trillion different antibodiestrillion different antibodies

Somatic recombinationSomatic recombination DNA segments shuffled and form new DNA segments shuffled and form new

combinations of base sequences to produce combinations of base sequences to produce antibody genesantibody genes

Somatic hypermutationSomatic hypermutation B cells in lymph nodules rapidly mutate B cells in lymph nodules rapidly mutate

creating new sequencescreating new sequences

5252

Humoral Immunity - AttackHumoral Immunity - Attack NeutralizationNeutralization

antibodies mask pathogenic region of antigenantibodies mask pathogenic region of antigen

Complement fixationComplement fixation antigen binds to IgM or IgG, antibody changes shape, antigen binds to IgM or IgG, antibody changes shape,

initiates complement binding; primary defense against initiates complement binding; primary defense against foreign cells, bacteriaforeign cells, bacteria

AgglutinationAgglutination antibody has 2-10 binding sites; binds to multiple enemy antibody has 2-10 binding sites; binds to multiple enemy

cells immobilizing themcells immobilizing them

PrecipitationPrecipitation antibody binds antigen molecules (not cells); creates antibody binds antigen molecules (not cells); creates

antigen-antibody complex that precipitates, phagocytized antigen-antibody complex that precipitates, phagocytized by eosinophil by eosinophil

5353

Agglutination and PrecipitationAgglutination and Precipitation