ch17 - adaptive immunitya
TRANSCRIPT
-
7/31/2019 Ch17 - Adaptive ImmunityA
1/27
3/30/11
1
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
Copyright 2010 Pearson Education, Inc.
The Adaptive Immune System
-
7/31/2019 Ch17 - Adaptive ImmunityA
2/27
3/30/11
2
Copyright 2010 Pearson Education, Inc.
Immunity
Innate immunity: Defenses against any pathogen Adaptive immunity: Induced resistance to a
specific pathogen
Copyright 2010 Pearson Education, Inc.
Dual Nature of Adaptive Immunity
Figure 17.8
Copyright 2010 Pearson Education, Inc.
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
3/27
3/30/11
3
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
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
Anatomy of the Lymphoid System
Copyright 2010 Pearson Education, Inc.
Secondary lymphoid organs Sites where lymphocytes gather to encounter antigens Organs include
-Lymph nodes-Spleen-Tonsils-Adenoids-Appendix
Anatomy of the Lymphoid System
-
7/31/2019 Ch17 - Adaptive ImmunityA
4/27
3/30/11
4
Copyright 2010 Pearson Education, Inc.
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
Anatomy of the Lymphoid System
Copyright 2010 Pearson Education, Inc.
Antigens and Antibodies
Copyright 2010 Pearson Education, Inc.
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
5/27
3/30/11
5
Copyright 2010 Pearson Education, Inc.
Antigens
Figure 17.1
Copyright 2010 Pearson Education, Inc.
Haptens
Figure 17.2
Copyright 2010 Pearson Education, Inc.
The Nature of Antibodies
Globular proteins called immunoglobulins The number ofantigen-binding sites determines
valence
-
7/31/2019 Ch17 - Adaptive ImmunityA
6/27
3/30/11
6
Copyright 2010 Pearson Education, Inc.
Antibodies
Figure 17.3a,b
Copyright 2010 Pearson Education, Inc.
Antibodies
Figure 17.3c
Copyright 2010 Pearson Education, Inc.
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
7/27
3/30/11
7
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
IgA Antibodies
Dimer 1015% of serum Abs In secretions Mucosal protection Half-life = 6 days
Copyright 2010 Pearson Education, Inc.
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
8/27
3/30/11
8
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
B Cells and Humoral Immunity
Copyright 2010 Pearson Education, Inc.
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
9/27
3/30/11
9
Copyright 2010 Pearson Education, Inc.
Activation of B Cells
Figure 17.4
Copyright 2010 Pearson Education, Inc.
Activation of B Cells
Figure 17.6
Copyright 2010 Pearson Education, Inc.
Clonal Selection
Figure 17.5
-
7/31/2019 Ch17 - Adaptive ImmunityA
10/27
3/30/11
10
Copyright 2010 Pearson Education, Inc.
Activation of B Cells
B cells differentiate intoAntibody-producing plasma cells Memory cells
Clonal deletion eliminates harmful B cells
Copyright 2010 Pearson Education, Inc.
The Results of Ag-Ab Binding
Figure 17.7
Copyright 2010 Pearson Education, Inc.
Agglutination
Figure 17.7
-
7/31/2019 Ch17 - Adaptive ImmunityA
11/27
3/30/11
11
Copyright 2010 Pearson Education, Inc.
Opsonization
Figure 17.7
Copyright 2010 Pearson Education, Inc.
Neutralization
Figure 17.7
ANIMATION Humoral Immunity: Antibody Function
Copyright 2010 Pearson Education, Inc.
Complement Fixation
Figure 17.7
-
7/31/2019 Ch17 - Adaptive ImmunityA
12/27
3/30/11
12
Copyright 2010 Pearson Education, Inc.
Antibody-Dependent Cell-MediatedImmunity
Figure 17.7
Copyright 2010 Pearson Education, Inc.
ADCC
Antibody-dependent cell-mediated cytotoxicity
Figure 17.15b
Copyright 2010 Pearson Education, Inc.
ADCC
Figure 17.15a
-
7/31/2019 Ch17 - Adaptive ImmunityA
13/27
3/30/11
13
Copyright 2010 Pearson Education, Inc.
T Cells and Cellular Immunity
Copyright 2010 Pearson Education, Inc.
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
T Cells and Cellular Immunity
Copyright 2010 Pearson Education, Inc.
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
T Cells and Cellular Immunity
-
7/31/2019 Ch17 - Adaptive ImmunityA
14/27
3/30/11
14
Copyright 2010 Pearson Education, Inc.
T Cells and Cellular Immunity
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
15/27
3/30/11
15
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
T Helper Cells
TH1 produces IFN- which activates cells relatedto cell-mediated immunity, macrophages, and
Abs
TH2 activate eosinophils and B cells to produceIgE
Copyright 2010 Pearson Education, Inc.
Activation of CD4+ T Helper Cells
Figure 17.13
-
7/31/2019 Ch17 - Adaptive ImmunityA
16/27
3/30/11
16
Copyright 2010 Pearson Education, Inc.
Activation of CD4+ T Helper Cells
Figure 17.10
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
T Cytotoxic Cells
Figure 17.11
-
7/31/2019 Ch17 - Adaptive ImmunityA
17/27
3/30/11
17
Copyright 2010 Pearson Education, Inc.
Apoptosis
Figure 17.12
Copyright 2010 Pearson Education, Inc.
T Regulatory Cells
Treg cells CD4 and CD25 on surface
Suppress T cells against self
Copyright 2010 Pearson Education, Inc.
Antigen-Presenting Cells
Digest antigenAg fragments on APC surface with MHC
B cells Dendritic cells Activated macrophages
-
7/31/2019 Ch17 - Adaptive ImmunityA
18/27
3/30/11
18
Copyright 2010 Pearson Education, Inc.
A Dendritic Cell
Figure 17.13
Copyright 2010 Pearson Education, Inc.
Activated Macrophages
Figure 17.14
Copyright 2010 Pearson Education, Inc.
Granular leukocytes destroy cells that dontexpress MHC I
Kill virus-infected and tumor cellsAttack parasites
Natural Killer (NK) Cells
-
7/31/2019 Ch17 - Adaptive ImmunityA
19/27
3/30/11
19
Copyright 2010 Pearson Education, Inc.
Duality of the Immune System
Copyright 2010 Pearson Education, Inc.
Cytokines
Chemical messengers Overproduction leads to cytokine storm
Copyright 2010 Pearson Education, Inc.
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
-
7/31/2019 Ch17 - Adaptive ImmunityA
20/27
3/30/11
20
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
Immune Responses to an Antigen
Figure 17.16
-
7/31/2019 Ch17 - Adaptive ImmunityA
21/27
3/30/11
21
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
Copyright 2010 Pearson Education, Inc.
Figure 17.1
-
7/31/2019 Ch17 - Adaptive ImmunityA
22/27
3/30/11
22
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
Vaccines
-
7/31/2019 Ch17 - Adaptive ImmunityA
23/27
3/30/11
23
Copyright 2010 Pearson Education, Inc.
History of Vaccines
Variolation: Inoculation of smallpox into skin(18th century)
Vaccination: Inoculation of cowpox virus into skin (Jenner) Inoculation with rabies virus (Pasteur)
Copyright 2010 Pearson Education, Inc.
Measles in the United States, 19602007
Clinical Focus, p. 505
Copyright 2010 Pearson Education, Inc.
Measles Worldwide
Kills 600 children per day
Clinical Focus, p.505
-
7/31/2019 Ch17 - Adaptive ImmunityA
24/27
3/30/11
24
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
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
Vaccines Used to Prevent BacterialDiseases
Copyright 2010 Pearson Education, Inc.
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
Vaccines Used to Prevent BacterialDiseases
-
7/31/2019 Ch17 - Adaptive ImmunityA
25/27
3/30/11
25
Copyright 2010 Pearson Education, Inc.
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
Copyright 2010 Pearson Education, Inc.
Types of Vaccines
Attenuated whole-agent vaccines MMR
Inactivated whole-agent vaccines Salk polio
Toxoids Tetanus
Copyright 2010 Pearson Education, Inc.
Types of Vaccines
Subunit vaccinesAcellular pertussis Recombinant hepatitis B
Nucleic acid (DNA) vaccines West Nile (for horses)
-
7/31/2019 Ch17 - Adaptive ImmunityA
26/27
3/30/11
26
Copyright 2010 Pearson Education, Inc. Figure 18.1
Vaccine Development
Culture pathogen
Copyright 2010 Pearson Education, Inc. Figure 13.7
Culturing Viruses
Copyright 2010 Pearson Education, Inc.
New Vaccines
An ideal vaccine should:Be taken orallyGive lifelong immunity
Remain stable withoutrefrigeration
Be cheap
-
7/31/2019 Ch17 - Adaptive ImmunityA
27/27
3/30/11
Copyright 2010 Pearson Education, Inc.
Safety of Vaccines
Therapeutic index = Risk vs. benefit