Transcript Humoral Immune Response

Unit 1 Nature of the
Immune Response
Part 5 Humoral
Immune Response
Terry Kotrla, MS, MT(ASCP)BB
Antigens and Antibodies
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An antigen is any substance which is
recognized as foreign by the body AND is
capable of provoking a specific immune
response.
It is capable of stimulating the formation of
antibody and development of cell mediated
immunity.
Reacts specifically with antibodies or Tlymphocytes.
Physical Nature of Antigens
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Foreign nature
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Immune system must distinguish between
“self” and “non-self”.
Body is tolerant of its own components and
does not initiation immune response against
these.
If natural tolerance disturbed immune
reaction occurs against self, autoimmune
disease.
The greater the foreignness the greater the
immune response.
Physical Nature of Antigens
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Molecular size
Higher molecular weight (MW) is
better antigen.
 Large size AND higher number and
variety of antigenic sites stimulates
greater antibody production.
 MW less than 10,000 daltons little or
weak antigenicity.
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Physical Nature of Antigens
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Molecular complexity and rigidity
The more complex the better.
 Complex proteins better than large
repeating polymers.
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Physical Nature of Antigens
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Haptens are low molecular weight but if
coupled to large carrier molecule can elicit
antibody response.
Physical Nature of Antigens
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Genetic Factors
Not all individuals within a species will
show the same response to an
antigen.
 “Responders” and “Non-Responders”
 Also wide variation between species.
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Physical Nature of Antigens
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Route of Administration and Dose
Oral, skin, intramuscular, IV,
peritoneal – different administration
required for stimulation.
 Recognition may not occur if the dose
is too small.
 If dose is too large may cause
“immune paralysis”.
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Antigenic Determinants
Also known as “epitopes”
 Actual structure recognized as
foreign.
 Number of antigenic determinants
varies with molecular size.
 Immune response directed against
SPECIFIC determinant for antibody
binding.
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Antigen-Antibody Binding
“Lock and Key”
 “Poor fit” may result in an antibody
that won’t stay put OR an antibody
that may react with more than one
antigen – “cross-reactivity”.
 In serology cross-reactivity is a
limitation of many tests.
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Antigen-Antibody Binding
Humoral Immunity
Results in production of proteins
called “immunoglobulins” or
“antibodies”.
 Body exposed to “foreign” material
termed “antigen” which may be
harmful to body: virus, bacteria, etc.
 Antigen has bypassed other protective
mechanisms, ie, first and second line
of defense.
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Dynamics of Antibody
Production
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Primary immune response
Latent period
 Gradual rise in antibody production
taking days to weeks
 Plateau reached
 Antibody level declines
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Dynamics of Antibody
Production
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Antibody production
Initial antibody produced in IgM
 Lasts 10-12 days
 Followed by production of IgG
 Lasts 4-5 days
 Without continued antigenic challenge
antibody levels drop off, although IgG
may continue to be produced.
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Secondary Response
Second exposure to SAME antigen.
 Memory cells are a beautiful thing.
 Recognition of antigen is immediate.
 Results in immediate production of
protective antibody, mainly IgG but
may see some IgM
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Humoral Immune Response
Dynamics of Antibody
Production
Cellular Events
Antigen is “processed” by T
lymphocytes and macrophages.
 Possess special receptors on surface.
 Termed “antigen presenter cell” APC.
 Antigen presented to B cell
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Basic Antibody Structure
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Two identical heavy chains
Gamma
 Delta
 Alpha
 Mu
 Epsilon
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Basic Antibody Structure
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Two identical light chains
Kappa OR
 Lambda
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Basic Antibody Structure
Basic Structure of Immunoglobulins
Papain Cleavage
Breaks disulfide bonds at hinge region
 Results in 2 “fragment antigen
binding” (Fab) fragments.
 Contains variable region of antibody
molecule
 Variable region is part of antibody
molecule which binds to antigen.
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Papain Cleavage
Pepsin
Breaks antibody above disulfide bond.
 Two F(ab’)2 molecules
 The rest fragments
 Has the ability to bind with antigen
and cause agglutination or
precipitation
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Papain and Pepsin
Cleavage
IgG
Most abundant
 Single structural unit
 Gamma heavy chains
 Found intravascularly AND
extravascularly
 Coats organisms to enhance
phagocytosis (opsonization)
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IgG
Crosses placenta – provides baby
with immunity for first few weeks of
infant’s life.
 Capable of binding complement which
will result in cell lysis
 FOUR subclasses – IgG1, IgG2, IgG3
and IgG4
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IgG
IgA
Alpha heavy chains
 Found in secretions
 Produced by lymphoid tissue
 Important role in respiratory, urinary
and bowel infections.
 15-10% of Ig pool
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Secretory IgA
Exists as TWO basic structural units,
a DIMER
 Produced by cells lining the mucous
membranes.
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Secretory IgA
IgA
Does NOT cross the placenta.
 Does NOT bind complement.
 Present in LARGE quantities in breast
milk which transfers across gut of
infant.
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IgM
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Mu heavy chains
Largest of all Ig – PENTAMER
10% of Ig pool
Due to large size restricted to intravascular
space.
FIXES COMPLEMENT.
Does NOT cross placenta.
Of greatest importance in primary immune
response.
IgM
IgE
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Epsilon heavy chains
Trace plasma protein
Single structural unit
Fc region binds strongly to mast cells.
Mediates release of histamines and
heparin>allergic reactions
Increased in allergies and parasitic
infections.
Does NOT fix complement
Does NOT cross the placenta
IgE
IgD
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Delta heavy chains.
Single structural unit.
Accounts for less than 1% of Ig pool.
Primarily a cell bound Ig found on the surface of B
lymphocytes.
Despite studies extending for more than 4 decades, a
specific role for serum IgD has not been defined while for
IgD bound to the membrane of many B lymphocytes,
several functions have been proposed.
Does NOT cross the placenta.
Does NOT fix complement.
Cellular Immune Response
Important in defending against: fungi,
parasites, bacteria.
 Responsible for hypersensitivity,
transplant rejection, tumor
surveillance.
 Thymus derived (T) lymphocytes
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Cell Mediated Reaction
Helper T cells – turn on immune
response
 Suppressor T cells – turn off immune
response
 Cytotoxic T cells directly attack
antigen
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Cell Mediated Immunity
Lymphokines
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Mixed group of proteins
Not identified chemically, classified based
on biological activity.
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Cause aggregation of macrophages at site
of infection
Chemotaxis
Activate macrophages to phagocytose.
End result is amplification of inflammatory
response and recruitment of immune cells
to the site.
Lymphokines
Contact between antigen and specific
sensitized T lymphocyte necessary for
lymphokine release.
 NOT antigen specific but immune
reaction against one antigen may
stimulate simultaneous protection
from a second microorganism.
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Control of the Immune
Response
Very complex
 Genetic control
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Within a species some genetic types
are good antibody producers while
others are not.
 Rabbits produce high levels of
antibodies to proteins while mice do
not.
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Control of the Immune
Response
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Cellular control
Two branches of immune response,
cellular and humoral.
 T and B cell cooperation necessary for
antibody production.
 T cells play important role in
regulating antibody production.
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Control of the Immune
Response
Helper T-cells interact with antigenic
molecule and release substances
which stimulate B-cells to produce
antibody.
 Suppressor T-cells are thought to
“turn off” B-cells.
 Very fine balance between the action
of helper and suppressor T-cells.
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References and Resources
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http://www.biology.arizona.edu/immunology/tutorials/immunology/page2.html
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http://www.jdaross.cwc.net/humoral_immunity.htm
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http://academic.brooklyn.cuny.edu/biology/bio4fv/page/aviruses/cellular-immune.html
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http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect23.htm