Chapter 43 The Immune System. Animal Immunity INNATE IMMUNITY Recognition of traits shared by broad ranges of pathogens, using a small set of receptors

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.

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

I. Innate Immunity

• Innate defenses include barrier defenses, phagocytosis, antimicrobial peptides.

• Defenses are unique to vertebrates: the inflammatory response and natural killer cells.


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


B. Cellular Innate Defenses

• White blood cells = leukocytes engulf pathogens in the body (phagocytosis) then fuses with a lysosome to destroy the microbe.


• 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


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.


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.


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.


• 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


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


• 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


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


• 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


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.

+

+ +


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

+

+ +

+


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


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

+


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


IV. Active Immunization

• Active immunity = in response to an infection or vaccination

• Body creates antibodies to fight off infection


• 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


VI. Immune Disruption


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


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


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


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)


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)


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


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.


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.


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.


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.

Documents

Chapter 43 The Immune System. Animal Immunity INNATE IMMUNITY Recognition of traits shared by broad ranges of pathogens, using a small set of receptors