Transcript Antibody production

T cell and B cell activation
For Ab production against
Antigens
B cell activation
 Antibody responses to protein antigens
require Th cells
 Antibody responses to nonprotein antigens
don’t require Th cells
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
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
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
T cell activation
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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
T cell activation
 Earliest detectable responses of T cells to Ag recognition is the
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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
CD40 – CD40L
 Stimulates B cell proliferation and differentiation
 Mutation in CD40L gene results in X-linked hyper IgM
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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
Ab response to proteins
1)Isotype switching
2) Affinity maturation
3)Memory cell production
4)Prolonged immunity
5)More Ab production
T cell and B cell interaction
T cell and APC interaction
Adhesion
Recognition
Activation
Costimulation
Coreceptor
T cell and B cell interaction
CMI Lab. Diagnosis
T cell count
Skin test
- Tuberculin, PPD
-LTT (Lymphocyte transformation test)
MLR (Mixed lymphocyte reaction),
Lymphokine production
Lymph node biopsy
PC
HMI Lab. Diagnosis
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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,
phagocytosis/killing microorganizing
antitumor activity
PC
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
The Lymphocyte Transformation
test
 Chronic mucocutaneous candidiasis,
 · Congenital or acquired immunodeficiency
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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
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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 molecules
 CTLA-4 :Ig
Rheumatoid arthritis
Transplant rejection
Psoriasis
Crohn’s disease