unit 1 nature of the immune response part 5 humoral immune response terry kotrla, ms, mt(ascp)bb
TRANSCRIPT
Antigens and Antibodies
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 T-lymphocytes.
Physical Nature of Antigens
Foreign nature 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
Molecular sizeHigher 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.
Physical Nature of Antigens
Molecular complexity and rigidityThe more complex the better.Complex proteins better than large
repeating polymers.
Physical Nature of Antigens
Haptens are low molecular weight but if coupled to large carrier molecule can elicit antibody response.
Physical Nature of Antigens
Genetic FactorsNot all individuals within a species will
show the same response to an antigen.
“Responders” and “Non-Responders”Also wide variation between species.
Physical Nature of Antigens
Route of Administration and DoseOral, 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”.
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.
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.
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 responseLatent periodGradual rise in antibody production
taking days to weeksPlateau reached Antibody level declines
Dynamics of Antibody Production
Antibody productionInitial antibody produced in IgMLasts 10-12 daysFollowed by production of IgGLasts 4-5 daysWithout 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
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
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.
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
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
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.
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.
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
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.
Cellular Immune Response
Important in defending against: fungi, parasites, bacteria.
Responsible for hypersensitivity, transplant rejection, tumor surveillance.
Thymus derived (T) lymphocytes
Cell Mediated Reaction
Helper T cells – turn on immune response
Suppressor T cells – turn off immune response
Cytotoxic T cells directly attack antigen
Lymphokines
Mixed group of proteins Not identified chemically, classified based
on biological activity. 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.
Control of the Immune Response
Very complex Genetic control
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.
Control of the Immune Response
Cellular controlTwo 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.
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.
References and Resources
http://www.biology.arizona.edu/immunology/tutorials/immunology/page2.html
http://www.jdaross.cwc.net/humoral_immunity.htm http://academic.brooklyn.cuny.edu/biology/bio4fv/page/aviruses/cellular-immune.html
http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect23.htm