Ch17 - Adaptive ImmunityA

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Copyright 2010 Pearson Education, Inc.Lectures prepared by Christine L. Case

Chapter 17

AdaptiveImmunity: Specific

Defenses of the

Host

Copyright 2010 Pearson Education, Inc.

An Overview of the Body s Defenses

Figure 16.1


The Adaptive Immune System


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Immunity

Innate immunity: Defenses against any pathogen Adaptive immunity: Induced resistance to a

specific pathogen


Dual Nature of Adaptive Immunity

Figure 17.8


Dual Nature of Adaptive Immunity

T and B cells develop from stem cells in red bonemarrow

Humoral immunity B cells mature in the bone marrow

-Chickens: Bursa of Fabricius Due to antibodies

Cellular immunity Due to T cells T cells mature in the thymus


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Anatomy of the Lymphoid System

Lymphoid system: collection of tissues and

organs designed to bringB and T cells in contact

with antigens (pathogens

and other foreign bodies)

Includes:- Lymphatic vessels- Secondary lymphoid

organs

- Primary lymphoid organs


Lymphatic vesselsCarry lymph fluid to body tissues

-Lymph formed as result of bodyscirculatory system

Lymph travels through vessels to lymphnodes

-Material such as protein is removed-Fluid portion empties back into

blood stream



Secondary lymphoid organs Sites where lymphocytes gather to encounter antigens Organs include

-Lymph nodes-Spleen-Tonsils-Adenoids-Appendix



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Primary lymphoid organs Bone marrow and thymus are pr imary lymphoid

organs

-Location where stem cells destined tobecome B and T cells mature

-B cells mature in bone marrow-T cells mature in thymus

-Once mature, cells leave primarylymphoid organs and migrate to

secondary lymphoid organs



Antigens and Antibodies


The Nature of Antigens

Antigen (Ag): A substance that causes the body toproduce specific antibodies or sensitized T cells

Antibodies (Ab) interact withepitopes or antigenicdeterminants

Hapten: Antigen is combined with carriermolecules


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Antigens

Figure 17.1


Haptens

Figure 17.2


The Nature of Antibodies

Globular proteins called immunoglobulins The number ofantigen-binding sites determines

valence


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Antibodies

Figure 17.3a,b


Antibodies

Figure 17.3c


Monomer 80% of serum Abs Fix complement In blood, lymph, and intestine Cross placenta Enhance phagocytosis; neutralize toxins and

viruses; protects fetus and newborn

Half-life = 23 days

IgG Antibodies


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Pentamer 510% of serum Abs Fix complement In blood, in lymph, and on B cellsAgglutinates microbes; first Ab

produced in response to infection

Half-life = 5 days

IgM Antibodies


IgA Antibodies

Dimer 1015% of serum Abs In secretions Mucosal protection Half-life = 6 days


Monomer 0.2% of serum Abs In blood, in lymph, and on B cells On B cells, initiate immune response Half-life = 3 days

IgD Antibodies


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Monomer 0.002% of serum Abs On mast cells, on basophils, and in

blood

Allergic reactions; lysis of parasiticworms

Half-life = 2 days

IgE Antibodies


B Cells and Humoral Immunity


Major histocompatibility complex (MHC)expressedon mammalian cells

T-dependent antigensAg presented with (self) MHC to TH cell TH cell produces cytokines that activate the B cell

T-independent antigens Stimulate the B cell to make Abs

Activation of B Cells


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Figure 17.4



Figure 17.6


Clonal Selection

Figure 17.5


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B cells differentiate intoAntibody-producing plasma cells Memory cells

Clonal deletion eliminates harmful B cells


The Results of Ag-Ab Binding

Figure 17.7


Agglutination

Figure 17.7


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Opsonization

Figure 17.7


Neutralization

Figure 17.7

ANIMATION Humoral Immunity: Antibody Function


Complement Fixation

Figure 17.7


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Antibody-Dependent Cell-MediatedImmunity

Figure 17.7


ADCC

Antibody-dependent cell-mediated cytotoxicity

Figure 17.15b


ADCC

Figure 17.15a


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T Cells and Cellular Immunity


Helper T Cells (CD4, TH)TH1 Activate cells related to cell-mediated

immunity

TH2 Activate B cells to produceeosinophils, IgM, and IgE

Cytotoxic T Cells (CD8, TC)Destroy target cells with perforin and

granzymes



Delayed Hypersensitivity T Cells (TD)Associated with allergic reaction, transplant

rejection, and tuberculin skin test

Regulatory (Suppressor) T cells (TR) CD4 and CD25 on surface Turn off immune response when Ag no longer

present

Suppress T cells against self



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T cells mature in the thymus Thymic selection eliminates many immature T cells

T cells respond to Ag by T-cell receptors (TCRs) T cells require antigen-presenting cells (APCs) Pathogens entering the gastrointestinal or

respiratory tracts pass through

M (microfold) cells over Peyer s patches, which contain APCs

Copyright 2010 Pearson Education, Inc. Figure 17.9a

M Cells on Peyer s Patch

Copyright 2010 Pearson Education, Inc. Figure 17.9b

M Cells


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T Helper Cells

CD4+ orTH cells TCRs recognize Ags and MHC II on APC TLRs are a costimulatory signal on APC and TH TH cells produce cytokines and differentiate into

-TH1-TH2-Memory cells


T Helper Cells

TH1 produces IFN- which activates cells relatedto cell-mediated immunity, macrophages, and

Abs

TH2 activate eosinophils and B cells to produceIgE


Activation of CD4+ T Helper Cells

Figure 17.13


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Activation of CD4+ T Helper Cells

Figure 17.10


T Cytotoxic Cells

CD8+orTC cells Target cells are self carrying endogenous

antigens

Activated into cytotoxic T lymphocytes (CTLs) CTLs recognize Ag + MHC I Induce apoptosis in target cell

CTL releases perforin and granzymes


T Cytotoxic Cells

Figure 17.11


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Apoptosis

Figure 17.12


T Regulatory Cells

Treg cells CD4 and CD25 on surface

Suppress T cells against self


Antigen-Presenting Cells

Digest antigenAg fragments on APC surface with MHC

B cells Dendritic cells Activated macrophages


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A Dendritic Cell

Figure 17.13


Activated Macrophages

Figure 17.14


Granular leukocytes destroy cells that dontexpress MHC I

Kill virus-infected and tumor cellsAttack parasites

Natural Killer (NK) Cells


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Duality of the Immune System


Cytokines

Chemical messengers Overproduction leads to cytokine storm


Cells Communicate via Cytokines

Cytokine Representative Activity

Interleukin-1 (IL-1) Stimulates TH cells in presence ofantigens; attracts phagocytes

Interleukin-2 (IL-2) Proliferation of antigen-stimulatedCD4+ T helper cells, proliferation

and differentiation of B cells;

activation of CD8+ T cells and NK

cells

Interleukin-12(IL-12) Inhibits humoral immunity;activates TH1 cellular immunity


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Cells Communicate via Cytokines

Cytokine Representative ActivityChemokines Induce the migration of leukocytes

TNF- Promotes inflammation

Hematopoieticcytokines

Influence differentiation of bloodstem cells

IFN-and IFN- Response to viral infection;interfere with protein synthesisIFN- Stimulates macrophage activity


Immunological Memory

Antibody titeris the amount of Ab in serum Primary response occurs after initial contact

with Ag

Secondary (memory oranamnestic)response occurs after second exposure


Immune Responses to an Antigen

Figure 17.16


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Types of Adaptive Immunity

Naturally acquired active immunity Resulting from infection

Naturally acquired passive immunity Transplacental or via colostrum

Artificially acquired active immunity Injection of Ag (vaccination)

Artificially acquired passive immunity Injection of Ab



Figure 17.1


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Terminology of Adaptive Immunity

Serology: The study of reactions betweenantibodies and antigens

Antiserum: The generic term for serum because itcontains Ab

Globulins: Serum proteins Immunoglobulins: Antibodies Gamma ( ) globulin: Serum fraction containing Ab

Copyright 2010 Pearson Education, Inc.Lectures prepared by Christine L. Case

Chapter 18

Practical

Applications of

Immunology


Vaccines


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History of Vaccines

Variolation: Inoculation of smallpox into skin(18th century)

Vaccination: Inoculation of cowpox virus into skin (Jenner) Inoculation with rabies virus (Pasteur)


Measles in the United States, 19602007

Clinical Focus, p. 505


Measles Worldwide

Kills 600 children per day

Clinical Focus, p.505


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Vaccines Used to Prevent BacterialDiseases

Disease Vaccine

Diphtheria Purified diphtheria toxoid

Meningococcalmeningitis

Purified polysaccharide fromNeisseria meningitidis

Pertussis (whoopingcough)

Killed whole or acellular fragmentsofBordetella pertussis

Pneumococcalpneumonia

Purified polysaccharide from 7strains ofStreptococcus

pneumoniae

Tetanus Purified tetanus toxoid

Haemophilus influenzaetype b meningitis

Polysaccharide from Haemophilusinfluenzae type b conjugated with

protein to enhance effectiveness


Disease Vaccine

Influenza Injected vaccine, inactivated virus(nasally administered: attenuated

virus)

Measles Attenuated virus

Mumps Attenuated virus

Rubella Attenuated virus

Chickenpox Attenuated virus

Poliomyelitis Killed virus



Disease Vaccine

Rabies Killed virus

Hepatitis B Antigenic fragments of virus

Hepatitis A Inactivated virus

Smallpox Live vaccinia virus

Herpes zoster Attenuated virus

Human papillomavirusAntigenic fragments of virus



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Vaccines for Persons Aged 06 Years

Hepatitis B Rotavirus DTP Haemophilus

influenzae b

Pneumococcal

Inactivated poliovirus Influenza MMR Varicella Hepatitis A Meningococcal

ANIMATION Vaccines: Function


Types of Vaccines

Attenuated whole-agent vaccines MMR

Inactivated whole-agent vaccines Salk polio

Toxoids Tetanus


Types of Vaccines

Subunit vaccinesAcellular pertussis Recombinant hepatitis B

Nucleic acid (DNA) vaccines West Nile (for horses)


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Copyright 2010 Pearson Education, Inc. Figure 18.1

Vaccine Development

Culture pathogen

Copyright 2010 Pearson Education, Inc. Figure 13.7

Culturing Viruses


New Vaccines

An ideal vaccine should:Be taken orallyGive lifelong immunity

Remain stable withoutrefrigeration

Be cheap


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Safety of Vaccines

Therapeutic index = Risk vs. benefit

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Ch17 - Adaptive ImmunityA