Download - Lymphatic System: Functions
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Lymphatic System: Functions
• Returns interstitial fluid and leaked plasma proteins back to blood
• Together with lymphoid organs provide the structural basis of immune system
Copyright © 2010 Pearson Education, Inc. Figure 20.1
Lymphaticsystem:Lymph ductLymph trunkLymph node
Lymphaticcapillary
Bloodcapillaries
Lymphaticcollecting vessels, with valves
HeartArterial systemVenous system
Tissuefluid
Tissue cell Bloodcapillaries
Lymphaticcapillaries
(a) Structural relationship between a capillary bed of the blood vascular system and lymphatic capillaries.
Filaments anchoredto connective tissue
Fibroblast in looseconnective tissue
Endothelial cell
Flaplike minivalve
(b) Lymphatic capillaries are blind-ended tubes in which adjacent endothelial cells overlap each other, forming flaplike minivalves.
Copyright © 2010 Pearson Education, Inc. Figure 20.2a
Cervical nodesEntrance of rightlymphatic duct into vein
Internal jugular vein
Entrance of thoracicduct into vein
Thoracic duct
Cisterna chyli
Lymphaticcollecting vessels
Axillary nodes
Aorta
Inguinal nodes
Regionallymph nodes:
(a) General distribution of lymphatic collecting vessels and regional lymph nodes.
Drained by the rightlymphatic ductDrained by thethoracic duct
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Lymphoid Cells
• Lymphocytes - warriors of immune system
• Two types• T cells (T lymphocytes)
• B cells (B lymphocytes)
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Lymphocytes
• T cells and B cells protect against antigens• Anything the body perceives as foreign
• Bacteria and their toxins; viruses
• Mismatched RBCs or cancer cells
• Provides a proliferation site for lymphocytes
• Furnishes a surveillance vantage point
Copyright © 2010 Pearson Education, Inc. Figure 20.3
Macrophage
Medullary sinusReticular fiber
Lymphocytes
Reticular cells onreticular fibers
Copyright © 2010 Pearson Education, Inc. Figure 20.4
Afferentlymphaticvessels
Efferentlymphaticvessels
Capsule
Trabeculae
Hilum
Cortex• Lymphoid follicle• Germinal center• Subcapsular sinus
Medulla:• Medullary cord• Medullary sinus
Follicles
Trabecula
Subcapsularsinus
Capsule
Medullarycords
Medullarysinuses
(b) Photomicrograph of part of a lymph node (72x)(a) Longitudinal view of the internal structure
of a lymph node and associated lymphatics
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Spleen
• Largest lymphoid organ
• Functions• Site of lymphocyte proliferation and immune
surveillance and response
• Cleanses the blood of aged cells and platelets and debris
Copyright © 2010 Pearson Education, Inc. Figure 20.6c
(c) Photograph of the spleen in its normal position in the abdominal cavity, anterior view.
Diaphragm
Spleen
Adrenalgland
SplenicarteryPancreas
Leftkidney
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Thymus
• Size with age• Infants, in inferior neck
• Increases in size, most active during childhood
• Stops growing during adolescence and then gradually atrophies
• It functions strictly in T lymphocyte maturation
Copyright © 2010 Pearson Education, Inc. Figure 20.7
CortexMedulla
Thymic (Hassall’s)corpuscle
Copyright © 2010 Pearson Education, Inc. Figure 20.8
Tonsil
Tonsillar cryptGerminal centersin lymphoid follicles
Pharyngeal tonsilPalatine tonsilLingual tonsil
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Immunity
• Resistance to disease
• Immune system has two parts• Innate (nonspecific) defense system
• Adaptive (specific) defense system
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Immunity
1. Innate defense system has two lines of defense• First line of defense is external body
membranes (skin and mucosae)• Second line of defense is antimicrobial
proteins, phagocytes, and other cells • Inhibit spread of invaders • Inflammation is its most important
mechanism
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Immunity
2. Adaptive defense system • Third line of defense attacks particular
foreign substances
• Takes longer to react than the innate system
• Innate and adaptive defenses are deeply intertwined
Copyright © 2010 Pearson Education, Inc. Figure 21.1
Innatedefenses
Surface barriers• Skin• Mucous membranes
Internal defenses• Phagocytes• NK cells• Inflammation• Antimicrobial proteins• Fever
Humoral immunity• B cells
Cellular immunity• T cells
Adaptivedefenses
Copyright © 2010 Pearson Education, Inc. Figure 21.2b
Lysosome
Phagosome(phagocyticvesicle)
Acidhydrolaseenzymes
(b) Events of phagocytosis.
1 Phagocyteadheres to pathogens or debris.
2 Phagocyte formspseudopods that eventually engulf the particles forming a phagosome.
3 Lysosome fuseswith the phagocytic vesicle, forming a phagolysosome.
4 Lysosomal enzymes digest the particles, leaving a residual body.
5 Exocytosis of thevesicle removes indigestible andresidual material.
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Inflammatory Response
• Cardinal signs of acute inflammation:
1. Redness
2. Heat
3. Swelling
4. Pain
(And sometimes 5. Impairment of function)
Copyright © 2010 Pearson Education, Inc. Figure 21.3
Tissue injury
Release of chemical mediators(histamine, complement,kinins, prostaglandins, etc.)
Vasodilationof arterioles
Increased capillarypermeability
Local hyperemia(increased blood
flow to area)
Locally increasedtemperature increasesmetabolic rate of cells
Leaked protein-richfluid in tissue spaces
Leaked clottingproteins form interstitialclots that wall off area
to prevent injury tosurrounding tissue
Temporary fibrinpatch forms
scaffolding for repair
Healing
Capillariesleak fluid
(exudate formation)
Attract neutrophils,monocytes, andlymphocytes to
area (chemotaxis)
Release of leukocytosis-inducing factor
Leukocytosis (increased numbers of whiteblood cells in bloodstream)
Leukocytes migrate toinjured area
Margination (leukocytes cling to
capillary walls)
Diapedesis (leukocytes pass through
capillary walls)
Phagocytosis of pathogensand dead tissue cells
(by neutrophils, short-term;by macrophages, long-term)
Area cleared of debris
Pus may form
Signs of inflammation
Initial stimulusPhysiological response
Result
Innate defenses Internal defenses
Possible temporarylimitation of
joint movement
Heat Redness Pain Swelling
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Phagocyte Mobilization
• Neutrophils, then phagocytes flood to inflamed sites
Copyright © 2010 Pearson Education, Inc. Figure 21.4
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Diapedesis.Neutrophils flatten andsqueeze out of capillaries.
Chemotaxis.Neutrophilsfollow chemicaltrail.Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2 3
4
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Antimicrobial Proteins
• Interferons (IFNs) and complement proteins• Attack microorganisms directly
• Hinder microorganisms’ ability to reproduce
Copyright © 2010 Pearson Education, Inc. Figure 21.6
Spontaneous activation
Stabilizing factors (B, D, and P)
No inhibitors on pathogensurface
Alternative pathway
Enhances inflammation:
Insertion of MAC and cell lysis(holes in target cell’s membrane)
Complementproteins(C5b–C9)
Pore
Membraneof target cell
++
stimulates histamine release,increases blood vessel permeability, attracts phagocytes by chemotaxis, etc.
complex
Opsonization:
+
coats pathogensurfaces, which enhances phagocytosis
Antigen-antibody complexClassical pathway
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Fever
• Systemic response
• Leukocytes secrete pyrogens
• Pyrogens reset the body’s thermostat upward
• High fevers are dangerous because heat denatures enzymes
• Benefits of moderate fever• Causes the liver to sequester iron and zinc
• Increases metabolic rate, speeds up repair
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Adaptive Defenses
• Adaptive immune response• Is specific
• Is systemic
• Has memory
• Two separate overlapping arms
1. Humoral (antibody-mediated) immunity
2. Cellular (cell-mediated) immunity
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Antigens
• Substances that can mobilize the adaptive defenses and provoke an immune response
• Most are large, complex molecules not normally found in the body (nonself)
Copyright © 2010 Pearson Education, Inc. Figure 21.7
Antigenic determinantsAntigen-bindingsitesAntibody A
Antibody BAntibody C
Antigen
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Self-Antigens
• Protein molecules (self-antigens) on the surface of cells
• Antigenic to others in transfusions or grafts
• Example: MHC proteins• Coded for by genes of the major
histocompatibility complex (MHC) and are unique to an individual
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Cells of the Adaptive Immune System
• Two types of lymphocytes• B lymphocytes (B cells)—humoral immunity
• T lymphocytes (T cells)—cell-mediated immunity
• Antigen-presenting cells (APCs)• Do not respond to specific antigens
Copyright © 2010 Pearson Education, Inc. Figure 21.8
1
2
3
Red bone marrow: site of lymphocyte origin
Secondary lymphoid organs: site ofantigen encounter, and activation to becomeeffector and memory B or T cells
Primary lymphoid organs: site ofdevelopment of immunocompetence as B orT cells
Lymphocytes destined to become T cellsmigrate (in blood) to the thymus and develop immunocompetence there. B cells develop immunocompetence in red bone marrow.
Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. They “seed” the lymph nodes, spleen, and other lymphoid tissues where they encounter their antigen.
Antigen-activated immunocompetent lymphocytes (effector cells and memory cells) circulate continuously in the bloodstream and lymph and throughout the lymphoid organs of the body.
Redbone marrow
Bone marrowThymus
Lymph nodes,spleen, and otherlymphoid tissues
Immaturelymphocytes
Adaptive defenses Humoral immunityCellular immunity
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Clonal Selection
1. B cell is activated when antigens bind to its surface receptors
2. Bound antigen enters cell
3. Stimulated B cell grows to form a clone of identical cells bearing the same antigen-specific receptors(T cells required to help B cells achieve full activation)
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Fate of the Clones
• Most clone cells become plasma cells• secrete antibodies at rate of 2000 per second
for 4 - 5days
• Secreted antibodies• Circulate in blood or lymph
• Bind to free antigens
• Mark the antigens for destruction
Copyright © 2010 Pearson Education, Inc. Figure 21.11 (1 of 2)
Primary response(initial encounterwith antigen)
Antigen bindingto a receptor on aspecific B lymphocyte (B lymphocytes with non-complementary receptors remain inactive)
Proliferation toform a cloneActivated B cells
Plasma cells(effector B cells)Secretedantibodymolecules
Memory B cell—primed to respond to same antigen
Adaptive defenses Humoral immunity
Antigen
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Immunological Memory
• Primary immune response• Occurs on first exposure to specific antigen
• Lag period: three to six days
• Peak levels of antibody reached in 10 days
• Antibody levels then decline
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Immunological Memory
• Secondary immune response• Occurs on re-exposure to same antigen
• Sensitized memory cells respond within hours
• Antibody levels peak in 2 – 3 d at higher levels
• Antibodies bind with greater affinity
• Antibody level remain high for weeks to months
Copyright © 2010 Pearson Education, Inc. Figure 21.11
Primary response(initial encounterwith antigen)
Antigen bindingto a receptor on aspecific B lymphocyte(B lymphocytes withnon-complementaryreceptors remaininactive)
Proliferation toform a cloneActivated B cells
Plasma cells(effector B cells)
Secretedantibodymolecules
Memory B cell—primed to respondto same antigen
Clone of cellsidentical toancestral cells
Subsequentchallenge by same antigenresults in more rapid response
Secondary response(can be years later)
MemoryB cells
Plasmacells
Secretedantibodymolecules
Adaptive defenses Humoral immunity
Antigen
Copyright © 2010 Pearson Education, Inc. Figure 21.12
Time (days)
Anti-bodiesto A
First exposureto antigen A
Second exposure to antigen A;first exposure to antigen B
Anti-bodiesto B
Primary immuneresponse to antigenA occurs after a delay.
Secondary immune response toantigen A is faster and larger; primaryimmune response to antigen B issimilar to that for antigen A.
Copyright © 2010 Pearson Education, Inc. Figure 21.13
PassiveActive
Humoralimmunity
ArtificiallyacquiredInjection ofimmune serum (gamma globulin)
Naturallyacquired
Antibodiespass from mother tofetus via placenta; or to infant in her milk
ArtificiallyacquiredVaccine;dead or attenuated pathogens
Naturallyacquired
Infection;contact with pathogen
Copyright © 2010 Pearson Education, Inc. Figure 21.14a
Antigen-bindingsite
Stemregion
Hingeregion
Light chainconstant regionDisulfide bond
Light chainvariable region
Heavy chainconstant region
Heavy chainvariable region
(a)
Copyright © 2010 Pearson Education, Inc. Figure 21.15
Inactivates by
Antigen Antibody
Fixes and activates
Enhances Enhances Leads to
Phagocytosis
Chemotaxis
Histaminerelease
Inflammation Cell lysis
Agglutination(cell-bound antigens)
Precipitation(soluble antigens)
Neutralization(masks dangerousparts of bacterial
exotoxins; viruses)
Complement
Antigen-antibodycomplex
Adaptive defenses Humoral immunity
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Monoclonal Antibodies
• Commercially prepared pure antibody
• Proliferate indefinitely and have the ability to produce a single type of antibody
• Used in research, clinical testing, and cancer treatment
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Cell-Mediated Immune Response
• T cells defend against intracellular antigens
• Major types of T cells• CD4 cells become helper T cells (TH)
• CD8 cells become cytotoxic T cells (TC) that destroy cells harboring foreign antigens
• Other types of T cells• Regulatory T cells (TREG)
• Memory T cells
Copyright © 2010 Pearson Education, Inc. Figure 21.16
Maturation
CD4cell
T cellreceptor
T cellreceptor
CD4
Helper T cells(or regulatory T cells)
Cytotoxic T cells
APC(dendritic cell)
APC(dendritic cell)
Activation Activation
Memorycells
CD8cell
CD8
Lymphoidtissues andorgans
Blood plasma
ThymusClass I MHCprotein
Class II MHCprotein
Effectorcells
Adaptive defenses Cellular immunity
Immaturelymphocyte
Red bone marrow
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T Cell Activation
• APCs migrate to lymph nodes to present their antigens to T cells
• T cell activation is a two-step process
1. Antigen binding
2. Co-stimulation
Copyright © 2010 Pearson Education, Inc. Figure 21.18
1 Dendritic cell engulfs an exogenous antigen, processes it, and displays its fragments on class II MHC protein.
2 ImmunocompetentCD4 cell recognizes antigen-MHC complex. Both TCR and CD4 protein bind to antigen-MHC complex.
3 CD4 cells are activated,proliferate (clone), and become memory and effector cells.
Viral antigen
Dendriticcell
Class lI MHCproteindisplayingprocessedviral antigenCD4 protein
Immunocom-petent CD4T cell
ActivatedhelperT cells
Helper Tmemory cell
T cell receptor(TCR)
Cloneformation
Adaptive defenses Cellular immunity
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Roles of Helper T(TH) Cells
• Play a central role in the adaptive immune response
• Once primed by APC presentation of antigen, they• Help activate T and B cells
• Induce T and B cell proliferation
• Activate macrophages and recruit other immune cells
• Without TH, there is no immune response
Copyright © 2010 Pearson Education, Inc. Figure 21.19a
(a)B cell (being activated)
MHC II proteinof B cell displayingprocessed antigenIL- 4 and othercytokines
Helper T cellCD4 protein
T cell receptor (TCR)
Activated helperT cell 1
2
TH cell binds with the self-nonself complexes of a B cell that has encountered its antigen and is displaying it on MHC II on its surface.
TH cell releases interleukins as co-stimulatory signals to complete B cell activation.
TH cell help in humoral immunity
Copyright © 2010 Pearson Education, Inc. Figure 21.19b
Class II MHCprotein
Class IMHC protein
APC (dendritic cell)
IL-2
CD4 protein
CD8 T cell
Helper T cell
CD8protein
(b)
1
2
Previously activated TH cell binds dendritic cell. TH cell stimulates dendritic cell to express co-stimulatory molecules (not shown) needed to activate CD8 cell.
3 Dendritic cell can now activate CD8 cell with the help of interleukin 2 secreted by TH cell.
TH cell help in cell-mediated immunity
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Roles of Cytotoxic T(TC) Cells
• Targets• Virus-infected cells
• Cells with intracellular bacteria or parasites
• Cancer cells
• Foreign cells (transfusions or transplants)
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Organ Transplants
• Four varieties• Autografts: from one body site to another in
the same person
• Isografts: between identical twins
• Allografts: between individuals who are not identical twins
• Xenografts: from another animal species
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Prevention of Rejection
• Depends on the similarity of the tissues
• Patient is treated with immunosuppressive therapy• Corticosteroid drugs to suppress inflammation
• Antiproliferative drugs
• Immunosuppressant drugs
• Many of these have severe side effects
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Immunodeficiencies
• Congenital and acquired conditions that cause immune cells, phagocytes, or complement to behave abnormally
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Acquired Immune Deficiency Syndrome (AIDS)• Cripples the immune system by interfering
with the activity of helper T cells
• Opportunistic infections occur, including pneumocystis pneumonia and Kaposi’s sarcoma
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Autoimmune Diseases
• Immune system loses the ability to distinguish self from foreign
• Production of autoantibodies and sensitized TC cells that destroy body tissues
• Examples include multiple sclerosis, myasthenia gravis, Graves’ disease, type I diabetes mellitus, systemic lupus erythematosus (SLE), glomerulonephritis, and rheumatoid arthritis
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Anaphylactic Shock
• Systemic response to allergen that directly enters the blood• Basophils and mast cells are throughout the body• Systemic histamine releases may cause• Constriction of bronchioles • Sudden vasodilation and fluid loss from the
bloodstream• Hypotensive shock and death
• Treatment: epinephrine