Unit 1 Nature of the Immune Response Part 5 Humoral Immune Response

1. Unit 1 Nature of the Immune ResponsePart 5 Humoral 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 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.

3. 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.

4. Physical Nature of Antigens • Molecular size • Higher 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.

5. Physical Nature of Antigens • Molecular complexity and rigidity • The more complex the better. • Complex proteins better than large repeating polymers.

6. Physical Nature of Antigens • Haptens are low molecular weight but if coupled to large carrier molecule can elicit antibody response.

7. Physical Nature of Antigens • Genetic Factors • Not all individuals within a species will show the same response to an antigen. • “Responders” and “Non-Responders” • Also wide variation between species.

8. Physical Nature of Antigens • Route of Administration and Dose • Oral, 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”.

9. 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.

10. 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.

11. Antigen-Antibody Binding

12. 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.

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

14. 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.

15. 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

16. Humoral Immune Response

17. Dynamics of Antibody Production

18. 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

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

20. Basic Antibody Structure • Two identical light chains • Kappa OR • Lambda

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. Papain and Pepsin Cleavage

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

28. 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

29. IgG

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

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

32. Secretory IgA

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

34. 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.

35. IgM

36. 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

37. IgE

38. 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.

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

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

41. Cell Mediated Immunity

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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