Humoral Immunity

1. Humoral Immunity AjithSominanda 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) • Globular proteins in the serum are immunoglobulins • Typical immunoglobulin molecule consists of • 2 heavy chains (450-600 a.acids) • 2 light chains (230 a.acids) • These are cross linked by disulphide bonds

8. Immunoglobulin molecule has Two functional regions • 1. Variable region (‘V’ region) • For antigen binding • 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. Specific B cell produces specific antibodies against a specific antigen Process of Somatic recombination in B cell nucleus produces this Antibody diversity

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 • Neutralization • Opsonization • Complement activation

18. 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. Signaling that occurs during cell-cell interaction: comparison between ‘APC-T cell’ and ‘B cell-T cell’ For T cells second signal is delivered by a professional antigen-presenting cell such as dendritic cell. For B cells (right panel), the second signal is usually delivered by an activated T cell.

21. 2. B cells proliferation and differentiation 1st signalling through Ag-BCR 2ndsignalling through CD40-CD40L IL4 drives B cells to proliferate

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

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

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 SecondaryImmune Responses Memory B cell Activated B cell Plasma cell

28. Primary and Secondary Immune Responses

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

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

31. Just before the END

32. 4. IgA A. is present in the secretions of mouth and intestinal tractB. is a pentavalent antibodyC. can activate the classical complement cascadeD. both a and c 1. IgG A. is the major type of antibody in serumB. is a multivalent antibodyC. can activate the complement cascadeD. can cross the placenta2. IgM A. is a divalent antibodyB. is the first antibody synthesized in a primary infectionC. Found on surface of B cellD. activates complements3. IgE A. is at high concentrations in the bloodB. is found on mast cellsC. plays a role in allergic responsesD. produced in parasitic infestation

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 • BCR • TCR • CD3 • CD19 CD40L CD40

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

37. The end