T cell and B cell activation For Ab production against Antigens.
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Transcript of T cell and B cell activation For Ab production against Antigens.
T cell and B cell activationT cell and B cell activationFor Ab production against For Ab production against
AntigensAntigens
B cell activationB cell activation
Antibody responses to protein antigens Antibody responses to protein antigens require Th cellsrequire Th cells
Antibody responses to nonprotein antigens Antibody responses to nonprotein antigens don’t require Th cellsdon’t require Th cells
Th dependent Ab responses to Th dependent Ab responses to proteinsproteins
Require recognition of the Ag by Th cells and Require recognition of the Ag by Th cells and cooperation between Ag specific T and B cellscooperation between Ag specific T and B cells
1)Ag induced activation of the two cells1)Ag induced activation of the two cells
2)Physical contact between the cells2)Physical contact between the cells
3)Ag presentation by B cells to differentiated Th3)Ag presentation by B cells to differentiated Th
4) Expression of membrane and secreted 4) Expression of membrane and secreted molecules by the Th cells that bind to and molecules by the Th cells that bind to and activate the B cellsactivate the B cells
B cell activationB cell activation
Activation of B cells initiated by binding of Ag to Activation of B cells initiated by binding of Ag to BCR as a first signal.BCR as a first signal.
Second signal: Signaling by CR2Second signal: Signaling by CR2 B cell receptor serves two key roles in B cell B cell receptor serves two key roles in B cell
activation:activation:1)antigen-induced clustering of receptors deliver 1)antigen-induced clustering of receptors deliver
biochemical signals to the B cells that initiate the biochemical signals to the B cells that initiate the process of activationprocess of activation
2)The receptor bind Ag and internalizes it into 2)The receptor bind Ag and internalizes it into endosomal vesicles for processing and endosomal vesicles for processing and presentationpresentation
Functional responses of B cells to Functional responses of B cells to Ag recognitionAg recognition
Ag recognition stimulates the entry of Ag recognition stimulates the entry of resting cells into G1 stage of cell cycleresting cells into G1 stage of cell cycle
Activated B cells express more MHC-II Activated B cells express more MHC-II and B7 and also cytokine receptorsand B7 and also cytokine receptors
T cell activationT cell activation
Naïve T cells recognize peptide –MHC and are activated in Naïve T cells recognize peptide –MHC and are activated in peripheral lymphoid organs ,resulting in the proliferation and peripheral lymphoid organs ,resulting in the proliferation and differentiation of these cells in to effector and memory cellsdifferentiation of these cells in to effector and memory cells
Effector helper cells recognize Ag in lymphoid organs or other Effector helper cells recognize Ag in lymphoid organs or other tissues and are activated to perform their effector functionstissues and are activated to perform their effector functions
They secrete cytokines that activate macrophages and help B cells They secrete cytokines that activate macrophages and help B cells The activation of T cells requires:The activation of T cells requires:
1)1) Recognition of peptide –MHC complex Recognition of peptide –MHC complex
2)2) CostimulatorCostimulator
3)3) Cytokines produce by APC and by the T cells themselvesCytokines produce by APC and by the T cells themselves
T cell activationT cell activation
Earliest detectable responses of T cells to Ag recognition is the Earliest detectable responses of T cells to Ag recognition is the secretion of cytokinessecretion of cytokines
Increase their expression of cytokine receptorsIncrease their expression of cytokine receptors CD69 (bind to sphingosine1 –phosphate r.)CD69 (bind to sphingosine1 –phosphate r.) CD25CD25 CD40L(24-48)CD40L(24-48) CTLA-4(24-48)CTLA-4(24-48) CCR7CCR7 CD44CD44
CD40 – CD40LCD40 – CD40L
Stimulates B cell proliferation and differentiationStimulates B cell proliferation and differentiation Mutation in CD40L gene results in X-linked hyper IgM Mutation in CD40L gene results in X-linked hyper IgM
syndromesyndrome Enhance expression of B7 molecules on B cells causing Enhance expression of B7 molecules on B cells causing
more T cell activationmore T cell activation Activated Th cells secrete cytokines that act in concert Activated Th cells secrete cytokines that act in concert
with CD40L to stimulate B cell proliferation and with CD40L to stimulate B cell proliferation and production of different Ab isotypesproduction of different Ab isotypes
Cytokines serve two principle functions in Ab response:B Cytokines serve two principle functions in Ab response:B cell proliferation and differentiation and switching to cell proliferation and differentiation and switching to different isotypesdifferent isotypes
Induce affinity maturationInduce affinity maturation
Ab response to proteinsAb response to proteins
1)Isotype switching1)Isotype switching
2) Affinity maturation2) Affinity maturation
3)Memory cell production3)Memory cell production
4)Prolonged immunity4)Prolonged immunity
5)More Ab production5)More Ab production
T cell and B cell interactionT cell and B cell interaction
T cell and APC interactionT cell and APC interaction
Adhesion
Recognition
Activation
Costimulation
Coreceptor
T cell and B cell interactionT cell and B cell interaction
CMI Lab. Diagnosis T cell countSkin test - Tuberculin, PPD -LTT (Lymphocyte transformation test)MLR (Mixed lymphocyte reaction), Lymphokine productionLymph node biopsy
PC
HMI Lab. Diagnosis
Serum Ig B cell count Specific Ab Plaque forming assay
PC
WBC Function Tests
Phagocytic function Chemotactic factors CMI : - LTT, LMC, ADCC - Skin tests HMI - Vaccination - Plaque forming test CBC Ig, ‘C3, CH50
PC
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, phagocytosi
s/killing microorganizing antitumor activity
PC
Lab. Evaluation
1. Initial screening test : CBC/Ig/CH50,C3/Skin test2. 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
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.
Why LTT?
to assess the ability of the lymphocytes to proliferate and to recognize and respond to antigens
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
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)
Fusion moleculesFusion molecules
CTLA-4 :IgCTLA-4 :Ig
Rheumatoid arthritisRheumatoid arthritis
Transplant rejectionTransplant rejection
PsoriasisPsoriasis
Crohn’s diseaseCrohn’s disease