1. Humoral Immune Response Terry Kotrla, MS, MT(ASCP)BB Fall 2006

2. 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.

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

4. 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.

5. 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

6. Humoral Immune Response

7. Dynamics of Antibody Production

8. 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

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

10. Basic Antibody Structure Two identical light chains  Kappa OR  Lambda

11. Basic Antibody Structure

12. Basic Structure of Immunoglobulins

13. 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.

14. Papain Cleavage

15. 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

16. Papain and Pepsin Cleavage

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

18. 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

19. IgG

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

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

22. Secretory IgA

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

24. 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.

25. IgM

26. 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

27. IgE

28. 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.

29. Cellular Immune Response Important in defending against: fungi, parasites, bacteria. Responsible for hypersensitivity, transplant rejection, tumor surveillance. Thymus derived (T) lymphocytes

30. Cell Mediated Reaction Helper T cells – turn on immune response Suppressor T cells – turn off immune response Cytotoxic T cells directly attack antigen

31. Cell Mediated Immunity

32. Lymphokines

33. Summary http://www.biology.arizona.edu/immunology/tutorials/immunology/page2.html

34. 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