Transcript Nature of the Immune System The Immune Response

Nature of the Immune System
IV. The Immune Response
Terry Kotrla, MS, MT(ASCP)BB
Antigens and Antibodies

An antigen is any substance which is
recognized as foreign by the body and is
capable, under appropriate conditions, of
provoking a specific immune response.
It is capable of:
Stimulating the formation of antibody and
the development of cell-mediated immunity.
 Reacting specifically with the antibodies or T
lymphocytes produced.

Physical Nature of Antigens

Foreign nature




The immune system of an individual can normally
distinguish between body components ("self") and
foreign substances ("non-self").
The body is tolerant of its own components and
does not initiate immune response against these.
Under certain circumstances this natural tolerance
may be disturbed, permitting the individual to react
against himself, as is seen in autoimmune
disease.
The greater the “foreignness” or difference from
self, the greater the immune response.
Physical Nature of Antigens

Molecular size
The higher the molecular weight, the better
the molecule will function as an antigen.
 The larger the size, the greater the number
of antigenic sites and the greater the variety
and amount of antibody production.
 Molecules with a molecular weight of less
than 10,000 daltons have no or weak
antigenicity.

Physical Nature of Antigens

Molecular complexity and rigidity




The more complex an antigen is, the more effective it will be.
Complex proteins are better antigen than large repeating
polymers such as lipids, carbohydrates, and nucleic acids,
which are relatively poor antigens.
Specific regions of limited size function at antigenic sites, it’s
thought that 2 antigenic determinants per molecule are
required to stimulate antibody production.
Haptens are substances, usually of low molecular weight, that
can combine with antibody but cannot initiate an immune
response unless it is coupled to a larger carrier molecule.
Physical Nature of Antigens

Genetic factors
Not all individuals within a species will show
the same response to a substance - some
are responders and some nonresponders.
 There is also a wide variation between
species.

Physical Nature of Antigens

Route of administration and dose
Route of administration (oral, skin,
intramuscular, IV, peritoneal, etc.) for
stimulation of the immune response is very
important.
 Recognition may not occur if the dose is to
small.
 If the dose is too large it may cause
"immune paralysis" and also fail to elicit an
immune response.

Antigenic Determinants or Epitopes

Structures on antigens that are
recognized as foreign by the immune
system.
Number of antigenic determinants on a
molecule varies with molecular size.
 An immune response is directed against
specific determinants, and resultant
antibodies will specifically bind to them.

Antigen-Antibody Binding

Binding of antigenic determinant to the
antibody binding can be likened to a "lock and
key". Antibodies of different degrees of
specificity may be produced in the immune
response to a given antigen.
 "Poor fit" of an antigen with an antibody is in
response to the antigen reacting with an
antibody produced in response to an entirely
different antigen. This phenomenon is called
cross reactivity.
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.

Dynamics of Antibody Production

Primary immune response
Latent period
 Gradual rise in antibody production taking
days to weeks
 Plateau reached
 Antibody level declines

Dynamics of Antibody Production

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.

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

Humoral Immune Response
Primary versus Secondary
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

Basic Antibody Structure

Two identical heavy chains
Gamma
 Delta
 Alpha
 Mu
 Epsilon

Basic Antibody Structure

Two identical light chains
Kappa OR
 Lambda

Antibody Structure
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.

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

Cleavage of Antibodies by Enzymes
Papain and Pepsin Cleavage
IgG
Most abundant
 Single structural unit
 Gamma heavy chains
 Found intravascularly AND
extravascularly
 Coats organisms to enhance
phagocytosis (opsonization)

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

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

Secretory IgA
Exists as TWO basic structural units, a
DIMER
 Produced by cells lining the mucous
membranes.

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.

IgM







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
IgM
IgE





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


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.