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Objectives 8
A.
Characteristics of Immune Responses
Every immune response has these characteristics:
1.
It is antigen specific
2.
It is systemic in scope
3.
It has memory
Objective 9
Cell Mediated and Humoral Immunity
There are two interacting mechanisms in the immune response:
Humoral Immunty
(Antibody Mediated)
Cells Involved
B lymphocytes and
plasma cells
Mechanism
 plasma cells secrete
antibodies into body fluids
 antibody is transported in
body fluids to the site of
infection
 antibodies form complexes
with antigens and may
activate complement,
neutralize the antigen or
immobilize the antigen by
precipitation or agglutination
But first a word about antigens!
Examples of antigens:
• Bacteria
• Viruses
• Transplanted cells
• Cancer cells
• Incompatible blood transfusion
• Pollen (for some of us)
Neutralization: the antibody combines with the antigen
and blocks an active site, preventing antigen binding to
receptors on tissue cells
Agglutination: antibodies are divalent (have more than one
binding site); they can bind to more than one antigen at
a time, forming cross linked clumps of antigen/antibody
complexes
Precipitation: same as
agglutination, but the
antigen is a soluble
molecule; clumping
causes the soluble
antigen to fall out of
solution
Precipitation
Aggultination
Neutralization
All the ways antibodies work in immunity:
Remember PLAN OP
Precipitate
Lyse (via complement)
Agglutinate
Neutralize
Opsonization
Phagocytosis
Cell Mediated
Immunity
Cells Involved
Mechanism
T lymphocytes
T lymphocytes travel
directly to the site of
infection and act directly to
lyse the invader or indirectly
by secreting chemicals which
activate other immune
mechanisms
Objective 10
Cells of the Adaptive IS
Antigen Presenting Cells: include dendritic cells,
macrophages, B lymphocytes
APCs engulf antigens and present fragments of the engulfed
antigens to B cells and/or T cells
Objective 16
(page 4.42)
MHC
Major histocompatibility (MHC) antigens are self antigens
that are tolerated by the host, but not by other
genetically different individuals. There are two classes of
MHC surface markers, MHC class I and MHC class II
MHC Class I:
Location:
All cells except RBCs ( all nucleated cells)
Recognized by:
cytotoxic T cells (CD8)
Function
activate cytotoxic T cells if body cells
are infected with intracellular parasites
such as viruses, if body cells become
malignant, or by non-self antigens
(eg, transplants)
MHC Class I antigens allow activated
cytotoxic T cells to interact with
the target cell
How MHC Class I and Endogenous Peptides are
displayed on all cells (except RBCs)
MHC Class II:
Location:
Dendritic cells, macrophages,
B cells (all APCs)
Recognized by:
CD 4 cells (T cell subtype)
present antigens to helper
T cells
Function:
How MHC Class II and peptide derived from
extracellular antigen is displayed on an APC surface
MHC Class I
MHC Class II
All nucleated cells
Antigen presenting
cells
Binds endogenous
Binds exogenous
antigens synthesized in
antigens
a cell
Presents antigen to
cytotoxic T cells
(CD8)
Presents antigen to
helper T cells (CD 4)
The MHC Class I antigens of a donor will stimulate a recipient to reject a
transplanted tissue causing tissue incompatibility; it is the class I proteins
that are typed and matched prior to transfusion
autograft
: tissue is grafted from an individual back to himself
isograft
: tissue is transplanted between genetically identical
individuals
allograft
xenograft
: tissue is transplanted between two members of the same
species (not genetically identical)
: tissue is transplanted from a member of one species to
a member of another species
A young female soccer player tears her ACL during
practice and decides to have it replaced with a graft.
She is given several surgical options – decide which
category each graft below falls in to:
a. A porcine (pig) derived ligament (Z-lig)
xenograft
b. A section of the patient’s own patellar tendon:
autograft
c. A section of hamstring from a cadaver (not a
relative):
allograft
Back to objective 10 page 4.30
Cells of specific immunity: B Lymphocytes and T Lymphocytes
The overall plan
Birth
Education
Job Search
Job interview
A job!
B Lymphocytes
Are born and develop
immunocompetence in bone marrow
Acquire B cell receptor (surface
antibody) to a specific antigen
They then travel to lymph nodes and
other lymphoid tissues

Self reactive B cells are deleted in bone marrow or are
inactivated in peripheral lymphoid tissues (anergy)
B lymphocyte activation
Activation occurs
when antigens bind
Clonal proliferation
means that many
copies of this cell
are produced
Maturation
Plasma Cell:
antibody secreting cell that is a descendant of an activated
B lymphocyte
Memory Cell
descendant of a B lymphocyte that is programmed to
respond quickly to the same subsequent encounters with
the same antigen
T Lymphocyte:

lymphocyte that has differentiated in the thymus gland where it
acquires a T cell receptor (TCR)

It later travels to lymph nodes and other lymphoid tissues
T cells must acquire two properties while in the thymus gland:
1. Must be able to bind to MHC class 1 antigens
found on the surfaces of nucleated body cells (positive
selection)
2. Must not react to self antigens bound to MHC
class 1 molecules on the surface of nucleated body cells
T cells that fail to meet these criteria are removed from the pool
of developing T cells via apoptosis
Helper T Cells:
Specific Glycoprotein:
Activating Cell:
CD 4
APC presentation of antigen
Requires MHC class II antigen
and processed antigen
Functions:
Generally, they activate
macrophages, attract WBCs,
assist in B cell and T cell
activation and stimulate B
cell and T cell division
TH1 subset
TH2 subset
Is involved in
stimulating
inflammation,
activating
macrophages, and
promoting
cytotoxic T cell
activation
Is involved in
eosinophil
recruitment ;
stimulates B cell
division and
antibody
production
activation
Cytotoxic T Cells
Specific Glycoprotein: CD8
Activating Cell:
APC presentation of antigen
Functions:
Directly attack and kill body cells
infected with virus or other
intracellular parasites, cancer cells and
transplanted tissue cells
Cytotoxic T cells kill their targets by:
1.
Inducing apoptosis
2. Releasing cytokines
Regulatory T Cells
Specific glycoprotein:
CD8
Function: Regulate the immune response by releasing
inhibitory cytokines (IL 10, transforming growth factor ,
 interferon)
Objective 11
Antigens (Immunogens)
A. Immunogens (antigens) are substances which evoke
immune responses


Typically, antigens are:
1.
Large, complex molecules – the larger and
more complex the more immunogenic they are
2.
Natural or man-made substances
3.
Are non-self (normally)
Chemically (in order of highly to less immunogenic)
1. Proteins
2. Polysaccharides
3. Nucleic acids
4. Lipids
Examples of antigens:
1. Pathogens
2. Toxins
3. Foreign RBCs
4. Pollen
5. Food
6. Transplants
7. Fungus
A complete antigen has two properties:
Immunogenicity
can activate B cells and/or T cells
Reactivity
can react with activated T cells or antibodies
Immunogenicity
Reactivity

An incomplete antigen (hapten) is a molecule that is too small by
itself to be immunogenic; it can become immunogenic if it attaches
to a larger carrier protein and becomes part of a larger complex

Antigenic determinants (epitopes):
the portions of the antigen that are actually
immunogenic, the portion to which antibodies or
T cells bind
Objective 14 (page4.39)
Antibodies (Immunoglobulins)
Antibodies (immuoglobulins) are glycoproteins secreted by plasma
cells. They are located in interstitial fluid, plasma (gamma globulins)
and in body secretions
 Four polypeptide chains (two
heavy, two light)
 Chains are held together by
covalent disulfide bonds (S=S)
Antibody Structure
 each heavy and light chain has two functional areas:
Variable region
consists of highly variable amino acid sequences and
forms the basis of antigen specificity; antigen
binds here
Constant region
more conserved amino acid sequences, which
define the 5 antibody classes: IgA, IgD, IgE, IgG,
IgM
each class has its own effector functions
B. Antibody Classes:
Class Structure
IgD
IgM
IgG
Think “GAMED”
Location(s)
Attached to B cell
surfaces antigen
receptor
Pentamer is found in
IF and plasma
Monomer is attached
to B cell surfaces
Function(s)
B cell activation
First antibody released during a
primary infection; potent
agglutinator; activates compliment
Monomer is involved in B cell
activation
Plasma and IF
IgA
Effective against bacteria,
extracellular viruses and toxins;
activates complement and crosses
the placenta
Body Secretions
Protects body surfaces and
prevents the attachment of
pathogens
IgE
Attached to mast cell
and basophil surfaces
(75-85 %)
(0.1%)
Triggers the release of histamine
and other mediators of inflammation
during allergic reactions
What do antibodies do?
Think “PLAN OP”
Objective 12 (page 4.34)
Humoral Response To Antigen
1.
Activation: antigen binds
to B cell receptor
2. Clonal expansion: binding
of the antigen to the B
cell receptor induces
proliferation of identical
B cells
3. Effector cells: B cells
become antibody
secreting plasma cells
Note: co-stimulation by IL-2,
secreted by T helper cells is
required
4. Memory B cells: increased
number of antigen
specific B cells ready for
next encounter with the
specific antigen
Objective 13
Acquired Immunity
Immunity can be innate or acquired through exposure to antigens:
Active Immunity
generated when an individuals B cells encounter antigen and manufacture
antibodies as part of an immune response (IR); long lasting protection is
generated
Passive Immunity
generated when an individual receives antibodies produced by another
organism (human or animal donor); shorter duration because no memory is
generated
Naturally Acquired Immunity
Immunity that is acquired as a result of a natural process
(e.g., infection, placental transfer of antibody)
Artificially Acquired Immunity
Immunity that is acquired when the antigen is introduced
as part of a clinical process (e.g., vaccination)
Acquired Immunity specifically obtained through the
transfer of serum from one individual to another
individual in order to fight a disease is an example of:
Immunity that is passive and artificial
Objective 15: The Cell
Mediated Response
T lymphocytes are the cells
(helper T and cytotoxic T)
Cell-mediated immune
response is effective against:
•Virus infected cells
•Tumor cells
•Grafted tissues
•Fungi
•Intracellular parasites
•Some intracellular
bacteria (slow growing e.g.
tuberculosis)
Antigens are
presented to T
cells by
1.APC cells with
MHC class II
protein complexed
with foreign
antigen
2.Infected body
cells with MHC
class I protein
complexed with
foreign antigen
What are the steps in activating cell mediated immunity ?
This diagram illustrates
the activation of T
helper cells.
What is different in the
process of activating
cytotoxic T cells?
What do activated helper
T cells do?
1. Stimulate cytotoxic T
cells via secretion of
interleukin 2 (IL-2)
2. Stimulate B cells via IL2, IL4, IL-5, IL-6
3. Activate macrophages
4. Stimulate helper T cells
via IL-2
5. And remember….
TH1 subset
TH2 subset
Is involved in
stimulating
inflammation,
activating
macrophages, and
promoting
cytotoxic T cell
activation
Is involved in
eosinophil
recruitment ;
stimulates B cell
division and
antibody
production
activation
What do activated cytotoxic T
cells do?
Destroy:
1. virus infected cells
2. cancerous cells
3. intracellular
parasites
4. some bacterial
infected cells
5. non-self cells
Cytotoxic T cells kill target cells by binding to the
target cell and releasing:
1. Perforin which causes pore formation
2. Granzymes which stimulate target cell apoptosis
Cytotoxic T cells also:
1. Bind to Fas receptor on target cell which
induces apoptosis in target cell
2. Release the cytokines tumor necrosis factor
beta and gamma interferon which stimulate
macrophages