1. Humoral Immunity Ajith Sominanda Department of Anatomy

2. The need of a humoral immunity Microorganisms multiply in the fluid compartments i.e. ECF and blood, therefore needs a soluble agent to act on ! Antibodies stick to microorganisms in the fluid compartments of the body A magnet coated with iron dust A bacteria coated with antibodies

3. Components in the Humoral immunity Cellular component B cells Plasma cells T cells Macrophages Molecular component Immunoglobulins (Antibodies) Complement proteins

4. B cell B cells are lymphocytes and mature in the bone marrow. Express immunoglobulin receptor (IgM or IgD) on the cell surface called B cell receptor (BCR). Different types of B cells are found (Naïve, Activated, Memory) B cells secrete antigen specific immunoglobulins which circulate as antibodies. IgM or IgD

5. Plasma cell Fully differentiated B cells form Plasma cells and secrete antibodies Has a different morphology and adapted to Secretory function

6. Antibodies

7. Structure of a typical antibody (IgG molecule) 1.Globular proteins in the serum are immunoglobulins 2.Typical immunoglobulin molecule consists of a)2 heavy chains (450-600 a.acids) b)2 light chains (230 a.acids) 3.These are cross linked by disulphide bonds

8. Immunoglobulin molecule has Two functional regions 1. Variable region (V region) For antigen binding 2.Constant region (C region) For effector functions of antibodies Complement activation Fc receptor activation Placental transfer

10. Antigen binding site Antigen CDR Complementarity determinant Region

11. Specific B cell produces specific antibodies against a specific antigen

12. Process of Somatic recombination in B cell nucleus produces this Antibody diversity Specific B cell produces specific antibodies against a specific antigen

13. Types (Classes) of antibodies

15. Comparison of antibody classes

16. Humoral Immune Response (sequence of events in antibody mediated immunity)

17. Humoral Immune Response Antigen binding to BCR & B cell Activation Proliferation of B cells (clonal expansion) Antibody production by plasma cells Effector mechanisms of antibodies 1.Neutralization 2.Opsonization 3.Complement activation

18. 1.B cell activation Antigenic stimulation / Binding starts the B cell activation First signal is sent through BCR Second signals are sent through co- receptors (CD 40/40L)

19. Types of B cell activation T cell independent activation T cell dependent activation

20. For B cells (right panel), the second signal is usually delivered by an activated T cell. For T cells second signal is delivered by a professional antigen-presenting cell such as dendritic cell. Signaling that occurs during cell-cell interaction: comparison between APC-T cell and B cell-T cell

21. 2. B cells proliferation and differentiation 1.1st signalling through Ag-BCR 2.2 nd signalling through CD40-CD40L 3.IL4 drives B cells to proliferate

22. During B cell proliferation, mutations (somatic hyper mutation) generate many clones of B cells bearing surface BCRs with different affinities towards the same antigen 2. B cells proliferation and differentiation Cont..

23. In the lymph node germinal centers, high affinity B cells are selected and differentiated into plasma cells 2. B cells proliferation and differentiation Cont..

24. Primary Immune response Immune response which occurs by activation of naïve B cells by encountering the relevant antigen for the first time Takes some time to mount this immune response (7- 14 days) Produces IgM antibodies Disappears rapidly Produces memory B cells Indicates an acute infection

25. Initial Humoral Immune Response The Primary Immune Response Antigen binding to Naïve B cells B cell Activation Proliferation of B cells (clonal expansion) Antibody production by plasma cells

26. Secondary Immune response Subsequent encountering of the same antigen by memory B cells produces antibodies rapidly and in a larger quantity (titer) The type of antibody is IgG (class switching has occurred) Indicates the protective immunity May last a longer period

27. Primary Immune Responses Naïve B cell Activated B cell Plasma cell Memory B cell Activated B cell Plasma cell Secondary Immune Responses

28. Primary and Secondary Immune Responses

29. 1.Neutralization i.e. Toxines 2.Fc mediated phagocytosis i.e. activation of Macrophages and ploymorpho nuclear leukocytes 3.Complement activation 3. Effector Mechanisms of antigen bound Antibodies

30. Effector Function: Fc receptor activation by antigen-antibody complex Fc receptor

31. Just before the END

32. 1. IgG A. is the major type of antibody in serum B. is a multivalent antibody C. can activate the complement cascade D. can cross the placenta 2. IgM A. is a divalent antibody B. is the first antibody synthesized in a primary infection C. Found on surface of B cell D. activates complements 3. IgE A. is at high concentrations in the blood B. is found on mast cells C. plays a role in allergic responses D. produced in parasitic infestation 4. IgA A. is present in the secretions of mouth and intestinal tract B. is a pentavalent antibody C. can activate the classical complement cascade D. both a and c

33. Q:Discuss the following aspects in relation to routine childhood vaccination: 1. Antigens and adjuvents 2. Booseter doses

34. Good to know stuff

35. Comparison of B cell and T cell CD40 BCR CD19 TCR CD3 Antigen bindingyes Antigen binding receptorBCRTCR Co-stimulatory moleculesYesyes Co-stimulatory partnerT cellAPC Cell marker / identityCD19CD3 CD40L

36. Comparison of Antigen processing and presentation: B cell as an APC

37. The end