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Transcript
17
Adaptive
Immunity:
Specific
Defenses
of the Host
SLOs
Differentiate between innate and adaptive immunity, and humoral and cellular immunity.
Define antigen, epitope, and hapten.
Explain the function of antibodies and describe their structural and chemical
characteristics. Name one function for each of the five classes of antibodies.
Compare and contrast T-dependent antigens and T-independent antigens.
Differentiate between plasma cell and memory cell.
Describe clonal selection.
Describe how a human can produce different antibodies.
Describe four outcomes of an antigen-antibody reaction.
Differentiate between helper T and cytotoxic T
Define apoptosis.
Define antigen-presenting cell.
Describe the role of antibodies and natural killer cells in antibody-dependent cellmediated cytotoxicity.
Identify at least one function of each of the following: cytokines, interleukins, interferons.
Distinguish a primary from a secondary immune response.
Contrast the four types of adaptive immunity.
Copyright © 2010 Pearson Education, Inc.
Immune System Overview
Innate immunity: An individual’s genetically
predetermined resistance to certain diseases.
Adaptive immunity: Ability of the body to react to
specific microbial infection.
Adaptive immunity
 is antigen specific, has memory
 is made up of two branches
Humoral Immunity (B cell mediated)
Cellular Immunity (T cell mediated)
 collaborates with innate immunity
 has ability to ignore healthy “self” molecules
(tolerance)
Copyright © 2010 Pearson Education, Inc.
Vocabulary
 Antigen (Ag): A substance that causes the body to
produce specific antibodies or sensitized T cells.
 Antibody (Ab): Proteins made in response to an Ag;
can combine with that Ag.
 Serology: The study of reactions between
antibodies and antigens.
 Antiserum: A generic term for serum because it
contains Ab.
 Globulins: Serum proteins
 Immunoglobulins (= Gamma () globulins): Serum
antibodies
 Complement:
Copyright © 2010 Pearson Education, Inc.
Serum Proteins
Fig 17.18
Copyright © 2010 Pearson Education, Inc.
The Nature of Antigens
Antigens and
antigenic
Determinants
Antibodies
recognize and
react with
antigenic
determinants or
epitopes on an
antigen
Copyright © 2010 Pearson Education, Inc.
Fig 17.1
Haptens
Fig 17.2
Definition: Small separable part of an antigen that
reacts specifically with an antibody but is incapable
of stimulating antibody production except in
combination with a carrier protein molecule
Copyright © 2010 Pearson Education, Inc.
The Nature of Antibodies
Immunoglobulin Structure: 4 polypeptide chains (2
heavy and 2 light)
 Variable regions
 Constant regions
Copyright © 2010 Pearson Education, Inc.
Fig 17.3
Fig 17.3
IgG antibodies
 Monomer
 80% of serum antibodies
 Activate complement
 In blood, lymph, and intestine
 Cross placenta
 Enhance phagocytosis; neutralize
toxins and viruses; protects fetus
and newborn
 Half-life = 23 days
Copyright © 2010 Pearson Education, Inc.
IgM Antibodies
 Pentamer
 5-10% of serum
antibodies
 Fix complement
 In blood, lymph, and on
B cells
 Agglutinates microbes;
first Ab produced in
response to infection
 Half-life = 5 days
Copyright © 2010 Pearson Education, Inc.
IgA Antibodies
 Dimer
 10-15% of serum
antibodies
 In secretions
 Mucosal protection
 Half-life = 6 days
Copyright © 2010 Pearson Education, Inc.
IgD Antibodies
IgE Antibodies
 Monomer
 Monomer
 0.2% of serum
antibodies
 0.002% of serum
antibodies
 In blood, lymph, and on
B cells
 On mast cells,
basophils, and in blood
 On B cells, initiate
immune response
 Allergic reactions; lysis
of parasitic worms
 Half-life = 3 days
 Half-life = 2 days
Copyright © 2010 Pearson Education, Inc.
B cells and Humoral Immunity
Effective against free antigen (toxins, bacterial
surface structures, viruses in between cells)
B cell receptors (mostly IgM and IgD)
Activated B-cells go through clonal expansion
leading to
1.Plasma cells (effector cell for
antibody production) and
2.Memory cells
Copyright © 2010 Pearson Education, Inc.
Clonal Selection
Fig 17.5
ANIMATION Humoral Immunity: Clonal Selection and Expansion
Response to T – dependent antigens
B cells require help of T cells for most protein
antigens (T-dependent ag)
B cells internalize antigen and present it to Thelper cell in combination with MHC class II
molecules
If T cell recognizes antigen it
activates B cell  clonal expansion
 plasma cells and memory cells
Review
Fig 17.4
Copyright © 2010 Pearson Education, Inc.
Antigen
Presentation by
B-cell
Compare to Fig. 17.4
Response to T – Independent Antigens
No T-helper cells involved
Polysaccharides (bacterial capsules) and LPS
Weak response
with no memory
cells
Young children
react poorly
Fig 17.6
Copyright © 2010 Pearson Education, Inc.
Antibody Diversity
1015 different B-cell receptors
How many genes in human genome?
Mechanism of antibody diversity:
somatic recombination
Susumu Tonegawa
Nobel Prize 1987
(during embryonic development)
Primarily through Gene rearrangement (mix
and match)
Copyright © 2010 Pearson Education, Inc.
Antigen—Antibody Binding and its Results
 Affinity: Strength of bond between Ag and Ag.
 Specificity: Ab recognizes a specific epitope.
Antibody function:
1. agglutinate and precipitate
2. opsonize
3. neutralize (immobilize and prevent adherence)
4. activate complement
5. Antibody-Dependent Cell-mediated Cytotoxicity
(ADCC) via NK cells and eosinophils
Protective outcome  disposal of antigen
(based on antigen-antibody binding)
Copyright © 2010 Pearson Education, Inc.
The Results
of Ag-Ab
Binding
Fig 17.7
Copyright © 2010 Pearson Education, Inc.
T Cells and Cellular Immunity
T cells have TCR on
surface.
TCR does not recognize
free antigen. Ag must
be presented in
association with MHC
on an antigenpresenting cell (APC).
Antigens are processed
by APC and
positioned on the
surface of the APC.
Copyright © 2010 Pearson Education, Inc.
Compare to
Fig 17.10
APCs
 Digest antigen
 Ag fragments on APC
surface with MHC-II
 B cells
 Dendritic Cells
 Macrophages
 Activated macrophages:
Macrophages stimulated
by ingesting Ag or by
cytokines.
ANIMATION Cell-Mediated Immunity: Helper T Cells
Classes of T cells
Helper T Cells (CD4, TH)
 are activated by antigen presented by MHC class II.
After binding to Ag presented by APC, CD4 cells
secrete cytokines activating other T cells and B cells
 TH1 cells activate cells involved in cellular immunity
 TH2 stimulate production of eosinophils, IgM, and IgE
( associated with allergic reactions and parasitic
infections)
Cytotoxic T cells (CD8, TC, CTL)
 activated by endogenous antigens and MHC class I
 When activated transform into CTLs and memory cells
 CTLs lyse target cell or induce apoptosis
Copyright © 2010 Pearson Education, Inc.
MHC Class I on all
nucleated cells
Antigen
Recognition by
T Cells
MHC Class II on
surface of APCs
(Macrophages, Bcells, dendritic
cells)
Mechanism of
Action of CTL
Destruction of cells
displaying MHC-I-Ag
complexes
Perforin molecules
create protein channels
in target cell membrane
Granzymes enter and trigger
apoptosis in target cell
Copyright © 2010 Pearson
Compare
toEducation,
Fig. Inc.
17.11
Similar but different
from MAC !!
Natural Killer (NK) Cells
Granular leukocytes.
Not immunologically specific.
Lyse virus-infected and tumor cells.
Kill target cell in absence of MHC-I (early stages of
virus infection and tumor cells)
Similar mechanism to CTLs
In Antibody-Dependent Cell Mediated
Cytotoxicity (ADCC) NK cells and macrophages
lyse antibody-coated cells (protozoans and
helminths)
Fig 17.15
Copyright © 2010 Pearson Education, Inc.
Immunological Memory
 Amount of antibody in serum is called the antibody titer.
 1 response: Response of the body to the first contact
with an antigen. Mostly IgM
 2 response: any subsequent contact with the same
antigen. Rapidly very high antibody titer. Mostly IgG
Fig 17.16
Copyright © 2010 Pearson Education, Inc.
Self Tolerance: Negative Selection
Goal: eliminate B and T cells, recognizing “self”
molecules
Clonal deletion of B cells taking place in bone
marrow  apoptosis
Negative selection of T cells in thymus
Failure results in auto-antibodies and
autoimmune disease
Copyright © 2010 Pearson Education, Inc.
Types of Specific Immunity
Active immunity
Protection via introduction of antigen into
responsive host, e.g.:
 Naturally acquired via
infection or
 Artificially acquired via
vaccination
Copyright © 2010 Pearson Education, Inc.
Passive Immunity
Protection via transfer of antibodies or
immune cells into a non-immune host, e.g.:
 Naturally acquired:
Fetus receives mothers
antibodies via placenta
 Artificially acquired via
vaccination injection of
immune serum after
exposure (snake bite,
Rh+ child with Rhmother etc.)
Copyright © 2010 Pearson Education, Inc.
Compare to
Fig 17.17
Cellular Immunity Review
T-cells specific surface receptors (TCRs)
TCR cannot bind free ag. Ag must be
presented by APCs
Activated T-cells go through clonal expansion
 effector and memory T cells.
CTLs directly kill virus infected and tumor
cells
T-helper cells help the humoral and cellular
immunity
Copyright © 2010 Pearson Education, Inc.