Unit 1 Nature of the Immune ResponsePart 5 Humoral 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 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.

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.

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

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

Basic Antibody Structure

Two identical heavy chainsGammaDeltaAlphaMuEpsilon

Basic Antibody Structure

Two identical light chains Kappa ORLambda

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

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

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.

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

Cell Mediated Immunity

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 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.

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