بنام خدا

1. بنام خدا

2. T cell and B cell activation For Ab production against Antigens

3. B cell activation • Antibody responses to protein antigens require Th cells • Antibody responses to nonprotein antigens don’t require Th cells

4. Th dependent Ab responses to proteins • Require recognition of the Ag by Th cells and cooperation between Ag specific T and B cells 1)Ag induced activation of the two cells 2)Physical contact between the cells 3)Ag presentation by B cells to differentiated Th 4) Expression of membrane and secreted molecules by the Th cells that bind to and activate the B cells

5. B cell activation • Activation of B cells initiated by binding of Ag to BCR as a first signal. • Second signal: Signaling by CR2 • B cell receptor serves two key roles in B cell activation: 1)antigen-induced clustering of receptors deliver biochemical signals to the B cells that initiate the process of activation 2)The receptor bind Ag and internalizes it into endosomal vesicles for processing and presentation

6. Functional responses of B cells to Ag recognition • Ag recognition stimulates the entry of resting cells into G1 stage of cell cycle • Activated B cells express more MHC-II and B7 and also cytokine receptors

7. T cell activation • Naïve T cells recognize peptide –MHC and are activated in peripheral lymphoid organs ,resulting in the proliferation and differentiation of these cells in to effector and memory cells • Effector helper cells recognize Ag in lymphoid organs or other tissues and are activated to perform their effector functions • They secrete cytokines that activate macrophages and help B cells • The activation of T cells requires: • Recognition of peptide –MHC complex • Costimulator • Cytokines produce by APC and by the T cells themselves

8. T cell activation • Earliest detectable responses of T cells to Ag recognition is the secretion of cytokines • Increase their expression of cytokine receptors • CD69 (bind to sphingosine1 –phosphate r.) • CD25 • CD40L(24-48) • CTLA-4(24-48) • CCR7 • CD44

9. CD40 – CD40L • Stimulates B cell proliferation and differentiation • Mutation in CD40L gene results in X-linked hyper IgM syndrome • Enhance expression of B7 molecules on B cells causing more T cell activation • Activated Th cells secrete cytokines that act in concert with CD40L to stimulate B cell proliferation and production of different Ab isotypes • Cytokines serve two principle functions in Ab response:B cell proliferation and differentiation and switching to different isotypes • Induce affinity maturation

10. Ab response to proteins 1)Isotype switching 2) Affinity maturation 3)Memory cell production 4)Prolonged immunity 5)More Ab production

17. T cell and B cell interaction

18. T cell and APC interaction Adhesion Recognition Activation Costimulation Coreceptor

19. T cell and B cell interaction

22. CMI Lab. Diagnosis T cell count Skin test - Tuberculin, PPD -LTT (Lymphocyte transformation test) MLR (Mixed lymphocyte reaction), Lymphokine production Lymph node biopsy PC

23. HMI Lab. Diagnosis Serum Ig B cell count Specific Ab Plaque forming assay PC

24. WBC Function Tests Phagocytic function Chemotactic factors CMI : - LTT, LMC, ADCC - Skin tests HMI - Vaccination - Plaque forming test CBC Ig, ‘C3, CH50 PC

25. The Phagocytic Function Defects of PMN function - Defects in the migration cascade - Defects in the killing function - Defects in both cascades Defects of macrophage function - Defects in immune response, phagocytosis/killing microorganizing antitumor activity PC

26. Lab. Evaluation 1. Initial screening test : CBC/Ig/CH50,C3/Skin test 2. Specific neutrophil function assay Rebuck skin window Molecular assay (CD11/CD18 glycoprotein def.) Chemotaxis assay Oxygen burst activity Phagocytosis/Intracellular killing Degranulation assay Neutrophil-mediated antibody dependent cellular cytotoxicity (ADCC) PC

27. The Lymphocyte Transformation test • Chronic mucocutaneous candidiasis, • · Congenital or acquired immunodeficiency disorders; • · To study the integrity of lymphokine production, • · Monitor immunosuppressive or immunoenhancing therapy, • · Severe combined immune deficiency, • · To predict allograft compatibility in the transplantation setting, • · DiGeorge anomaly, • · Nezelof syndrome.

28. Why LTT? • to assess the ability of the lymphocytes to proliferate and to recognize and respond to antigens

29. Types? mitogens assay • using nonspecific plant lectins • evaluates the mitotic response of T and B lymphocytes to a foreign antigen. • lymphocytes from the patient is incubated with a nonspecific mitogen for 72 hours. • The culture is labeled with tritiated thymidine • measured by a liquid scintillation spectrophotometer in counts per minute, antigen assay *uses specific antigens such as PPD, Candida, mumps, tetanus toxoid and streptokinase *After incubation of 4 ½ to 7 days *transformation is measured by the same method

34. T cell count Skin test - Tuberculin, PPD -LTT (Lymphocyte transformation test) MLR (Mixed lymphocyte reaction), Plaque forming assay Phagocytic function Specific neutrophil function assay Neutrophil-mediated antibody dependent cellular cytotoxicity (ADCC)

35. Fusion molecules CTLA-4 :Ig Rheumatoid arthritis Transplant rejection Psoriasis Crohn’s disease