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Chapter 43Chapter 43
The Immune System
Animal Immunity
INNATE IMMUNITY
Recognition of traitsshared by broad rangesof pathogens, using asmall set of receptorsNon-specific
•
•Rapid response
•Recognition of traitsspecific to particularpathogens, using a vastarray of receptors
•Slower response
ACQUIRED IMMUNITY
Pathogens(microorganisms
and viruses)
Barrier defenses:SkinMucous membranesSecretions
Internal defenses:Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells
Humoral response:Antibodies defend againstinfection in body fluids.
Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.
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I. Innate Immunity
• Innate defenses include barrier defenses, phagocytosis, antimicrobial peptides.
• Defenses are unique to vertebrates: the inflammatory response and natural killer cells.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
A. Barrier Defenses
• Skin and mucous membranes
• Body fluids (saliva, mucus, and tears) are hostile to microbes.
• Low pH of skin and the digestive system prevents growth
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B. Cellular Innate Defenses
• White blood cells = leukocytes engulf pathogens in the body (phagocytosis) then fuses with a lysosome to destroy the microbe.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Different types of phagocytic cells:
– Neutrophils: engulf and destroy microbes.
– Macrophages: part of the lymphatic system and found throughout body.
– Eosinophils: discharge destructive enzymes.
– Dendritic cells: stimulate development of acquired immunity.
Lymphatic System
Adenoid
Tonsil
Lymphnodes
Spleen
Peyer’s patches(small intestine)
Appendix
Lymphaticvessels Lymph
nodeMasses ofdefensive cells
Bloodcapillary
Lymphaticvessel
Tissuecells
Interstitial fluid
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C. Inflammatory Responses
• After injury, mast cells release histamine
– increase local blood supply and more phagocytes and antimicrobial proteins to enter tissues.
• Pus = a fluid (rich in white blood cells, dead microbes, and cell debris) accumulates at the site
Major events in a local Inflammatory Response
Pathogen Splinter
Macrophage
Mast cell
Chemicalsignals
Capillary
Phagocytic cellRed blood cells
Fluid
Phagocytosis
1. 2. 3.
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D. Natural Killer Cells
• All body cells (except RBC) have a class I MHC protein on their surface.
• MHC = Major Histocompatibility Complex , part of the extracellular matrix.
• Class II MHC protein molecules are found on specialized cells
• Cancerous or infected cells no longer express this MHC protein; natural killer (NK) cells attack these damaged cells.
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II. Acquired Immunity
• Lymphocytes recognize and respond to antigens
• Lymphocytes from thymus (T cells) and from bone marrow (B cells)
• Lymphocytes contribute to immunological memory,
• Cytokines = secreted by macrophages and dendritic cells to recruit and activate lymphocytes.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• B cells and T cells have receptor proteins that can bind to antigens (each cell binds to one antigen)
Antigen receptors on lymphocytes
Antigen-bindingsite
Antigen-binding site
Antigen-bindingsite
Disulfidebridge
Variableregions
Constantregions
Transmembraneregion
Plasmamembrane
Lightchain
Heavy chains
T cell
chain chain
Disulfide bridge
Cytoplasm of T cell
T cell receptor
Cytoplasm of B cell
B cell receptorB cell
V
V
C C
V
V
C C C C
VV
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A. Role of the MHC
• In infected cells, MHC molecules bind and transport antigen fragments to the surface (antigen presentation)
• T cell can then detect the antigen fragment
Antigen Presentation by an MHC molecule
Antigen
Top view: binding surfaceexposed to antigen receptors
Plasmamembrane ofinfected cell
AntigenClass I MHCmolecule
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• Class I MHC molecules are found on almost all nucleated cells of the body.
– They display antigens to cytotoxic T cells.
• Class II MHC molecules are found on specialized cells: macrophages, B cells, and activated T cells
Interaction of T cells with Antigen-Presenting Cells
Infected cell
Antigenfragment
Class I MHCmolecule
T cellreceptor
(a)
Antigenassociateswith MHCmolecule
T cellrecognizescombination
Cytotoxic T cell (b)Helper T cell
T cellreceptor
Class II MHCmolecule
Antigenfragment
Antigen-presentingcell
Microbe
1
11
2
22
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B. Amplifying Lymphocytes
• The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly (clonal selection)
• Two types: short-lived effector cells (fight current battle) and long-lived memory cells… for future attacks by same pathogen.
Clonal Selection of B cells
B cells thatdiffer inantigen specificity
Antibodymolecules
Antigenreceptor
Antigen molecules
Clone of memory cells Clone of plasma cells = effectors
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• First exposure to an antigen represents the primary immune response.
– During this time, effector B cells = plasma cells are generated, and T cells are activated to their effector forms.
• Secondary immune response = memory cells facilitate a faster, more efficient response.
Antibodiesto A
Antibodiesto B
Secondary immune response toantigen A produces antibodies to A.Primary immune response to antigenB produces antibodies to B.
Primary immune responseto antigen A producesantibodies to A.
An
tib
od
y co
nce
ntr
atio
n(a
rbit
rary
un
its)
Exposureto antigen A
Exposure toantigens A and B
Time (days)
104
103
102
101
100
0 7 14 21 28 35 42 49 56
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III. Acquired immunity
• Humoral immune response = activation of B cells, production of antibodies.
• Cell-mediated immune response = activation of cytotoxic T cells.
• Helper T cells aid both responses.
AcquiredImmuneResponse
Humoral (antibody-mediated) immune response
B cell
Plasma cells
Cell-mediated immune response
Key
Stimulates
Gives rise to
+
+
++
+
+
+Memory B cells
Antigen (1st exposure)
Engulfed by
Antigen-presenting cell
MemoryHelper T cells
Helper T cell Cytotoxic T cell
MemoryCytotoxic T cells
ActiveCytotoxic T cells
Antigen (2nd exposure)
Secretedantibodies
Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.
Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.
+
+ +
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A. Helper T Cells
• Secrete cytokines that stimulate other lymphocytes.
The central role of helper T cells in humoral and cell-mediated immune responses
Antigen-presentingcell
Peptide antigen
Cell-mediatedimmunity = attack on
infected cells.
Class II MHC moleculeCD4
TCR (T cell receptor)
Helper T cell
Humoralimmunity
= secretion ofantibodies byplasma cells.
Cytotoxic T cell
CytokinesPositive Feedback …
B cell
Bacterium
+
+ +
+
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B. Cytotoxic T Cells
• Effector cells in cell-mediated immune response.
– Activated cytotoxic T cell secretes proteins that destroy the infected target cell.
The killing action of cytotoxic T cells
Cytotoxic T cell
Perforin
Granzymes
TCRCD8
Class I MHCmolecule
Targetcell
Peptideantigen
Pore
Released cytotoxic T cell
Dying target cell
1. 2.3. lysis
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C. B Cells
• Humoral response = secretion of antibodies by B cells.
B cell activation in the humoral immune response
Antigen-presenting cell
Endoplasmicreticulum ofplasma cell
Secretedantibodymolecules
Bacterium
B cellPeptideantigen
Class II MHCmolecule
TCR CD4
Helper T cellActivatedhelper T cell
Cytokines
Clone of memoryB cells
Clone of plasma cells
2 µm
+
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D. Role of Antibodies
• Neutralization = pathogen can no longer infect a host because it is bound to an antibody.
• Opsonization = antibodies bound to antigens increase phagocytosis.
Antibody-mediated mechanisms of antigen disposal
Viral neutralization
Virus
OpsonizationBacterium
Macrophage
Activation of complement system and pore formation
Complement proteins
Formation ofmembraneattack complex
Flow of waterand ions
Pore
Foreigncell
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IV. Active Immunization
• Active immunity = in response to an infection or vaccination
• Body creates antibodies to fight off infection
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• Passive immunity = immediate, short-term protection.
• Antibodies from mother to infant in breast milk or injected anitbodies
V. Passive Immunity
Passive immunization of an infant occurs during breast-feeding
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VI. Immune Disruption
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A. Allergies
• Exaggerated (hypersensitive) responses to antigens (allergens)
– Ex. hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells. Next time the allergen enters the body, it binds to mast cell–associated IgE molecules.
• Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms.
Mast cells, IgE, and the allergic response
Allergen
IgE
Granule
Mast cell
Histamine
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B. Autoimmune Diseases
• Immune system loses tolerance for self and turns against certain molecules of the body.
– Ex. rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis.
X-ray of a hand deformed by rheumatoid arthritis
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C. Immunodeficiency Diseases
• Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses.
• Acquired immunodeficiency results from exposure to chemical and biological agents.
– Acquired immunodeficiency syndrome (AIDS) caused by HIV
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VII. Immune System Evasion by Pathogens
• Pathogens have evolved mechanisms to attack immune responses.
• Through antigenic variation, some pathogens are able to prevent recognition.
• Human viruses exchange genes with the viruses of domesticated animals.
• Immune systems are unable to recognize the new viral strain. (Bird or Swine flu)
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A. Latency
• Some viruses may remain in a host in an inactive state
– Herpes simplex viruses can be present in a human host without causing symptoms (cold sores, genital warts)
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B. Attack on the Immune System: HIV
• Human immunodeficiency virus (HIV) infects helper T cells.
• The loss of helper T cells impairs both the humoral and cell-mediated immune responses and leads to AIDS.
• HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA.
The progress of an untreated HIV infection
Latency
Relative antibodyconcentration
AIDSH
elp
er T
cel
l co
nce
ntr
atio
nin
blo
od
(ce
lls/m
m3 )
Helper T cellconcentration
Relative HIVconcentration
Years after untreated infection0 1 2 3 4 5 6 7 8 9 10
0
200
400
600
800
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You should now be able to:
1. Distinguish between innate and acquired immunity.
2. Name and describe four types of phagocytic cells.
3. Describe the inflammation response.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
4. Distinguish between the following pairs of terms: antigens and antibodies; antigen and epitope; B lymphocytes and T lymphocytes; antibodies and B cell receptors; primary and secondary immune responses; humoral and cell-mediated response; active and passive immunity.
5. Explain how B lymphocytes and T lymphocytes recognize specific antigens.
6. Explain why the antigen receptors of lymphocytes are tested for self-reactivity.
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7. Describe clonal selection and distinguish between effector cells and memory cells.
8. Describe the cellular basis for immunological memory.
9. Explain how a single antigen can provoke a robust humoral response.
10. Compare the processes of neutralization and opsonization.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
11. Describe the role of MHC in the rejection of tissue transplants.
12. Describe an allergic reaction, including the roles of IgE, mast cells, and histamine.
13. Describe some of the mechanisms that pathogens have evolved to thwart the immune response of their hosts.
14. List strategies that can reduce the risk of HIV transmission.
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