1. Nature of the Immune System IV. The Immune Response
Terry Kotrla, MS, MT(ASCP)BB

2. 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.

3. 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.

4. 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.

5. 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.

6. 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 non-responders.
There is also a wide variation between species.

7. 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.

8. 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.

9. 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.

10. 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.

11. Dynamics of Antibody Production
Primary immune response
Latent period
Gradual rise in antibody production taking days to weeks
Plateau reached
Antibody level declines

12. Dynamics of Antibody Production
Initial antibody produced in IgM
Lasts 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.

13. 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

14. Humoral Immune Response

15. Primary versus Secondary

16. Dynamics of Antibody Production

17. 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

18. Basic Antibody Structure
Two identical heavy chains
Gamma
Delta
Alpha Mu
Epsilon

19. Basic Antibody Structure
Two identical light chains
Kappa OR
Lambda

20. Antibody Structure

21. Basic Antibody Structure

22. Basic Structure of Immunoglobulins

23. 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.

24. Papain Cleavage

25. 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

26. Cleavage of Antibodies by Enzymes

27. Papain and Pepsin Cleavage

28. IgG Most abundant Single structural unit Gamma heavy chains
Found intravascularly AND extravascularly
Coats organisms to enhance phagocytosis (opsonization)

29. 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

30. IgG

31. IgA Alpha heavy chains Found in secretions Produced by lymphoid tissue
Important role in respiratory, urinary and bowel infections.
15-10% of Ig pool

32. Secretory IgA Exists as TWO basic structural units, a DIMER
Produced by cells lining the mucous membranes.

33. Secretory IgA

34. IgA Does NOT cross the placenta. Does NOT bind complement.
Present in LARGE quantities in breast milk which transfers across gut of infant.

35. 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.

36. IgM

37. IgM

38. 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

39. IgE

40. 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.