Activation and Function

of T and B lymphocyte
Fairus Hassim, PhD
PPSA, UMT
09-6683701
What will you learn?
CD4+ T cells activation
Interaction between antigen presenting cells (APCs) and CD4 + T cells
Function of costimulatory pairs
CD4+ T subsetting by cytokine
CD4+ T cell memory
CD8+ T cell function
Elimination of targeted cell by cytotoxic T cells
Superantigen
Activation of B cells and its function
T and B cooperation
Carrier effect
T-independent immune response
T and B cell activation
Activation and Maturation of B cells
Activation and Maturation of B cells
Another mode of B cell activation and
maturation
 How B and T cells being activated at
molecular level?

1. Presented MHC interacted with

TCR
T cell Interaction via TCR with
MHC alone fail to:
i. produce cytokines
ii. Sustain proliferation
iii.Often undergo apoptosis
iv.Non responsive to subsequent
stimulation
 How B and T cells being activated at
molecular level?

1. Signal for full activation

1st signal: Presented MHC interacted
with TCR
2nd signal: Co-stimulation
What is co-stimulation?
independent of the antigen receptor

critical to allow full activation,

sustain cell proliferation,

prevent anergy and/or apoptosis,

induce differentiation to effector and memory status, and

allow cell-cell cooperation.

Costimulation is in turn regulated by the expression of inhibitory

receptors upon lymphocyte activation.
 What is/are the stimulant in the co-
stimulation?
Cytokines (soluble factor) was thought to be the co-
stimulants
Such as Interleukin-1, IL-2, IL-4 etc. enhance activation of
B and T cells.

Latest finding, critical interaction between

receptor-ligand pairs of cell surface molecules on
the responder lymphocyte and an accessory cell.
an antigen-presenting cell (APC), T cell activation

or a helper T cell for B cell activation

 What is/are the stimulant in the co-
stimulation?
Cytokines (soluble factor) was thought to be the co-
stimulants
Such as Interleukin-1, IL-2, IL-4 etc. enhance activation of
B and T cells.

Latest finding, critical interaction between

receptor-ligand pairs of cell surface molecules on
the responder lymphocyte and an accessory cell.
an antigen-presenting cell (APC), T cell activation

or a helper T cell for B cell activation

How T cell subset occurs?
How CD4+ T cell memory being generated?

1. After the nave T cell (N) encounters an antigen it

becomes activated and begins to proliferate into many
clones or daughter cells.
2. Some of the T cell clones will differentiate into
effector T cells (E) that will perform the function of
that cell (e.g. produce cytokines in the case of
helper T cells or invoke cell killing in the case of
cytotoxic T cells).
3. Some of the cells will form memory T cells (M) that
will survive in an inactive state in the host for a long
period of time until they re-encounter the same
antigen and reactivate. (wikipedia)
How CD4+ T cell memory being generated?
CD4+ T cell subpopulation?

Propose model for memory T cell development by Restifo

(2014)
CD8+ T cell
 How bacteria manipulate T cell activation?
SEC
Superantigen: a toxin produce
by bacteria SEB
Non-specific activation of T
cells resulting in polyclonal
activation of T cells and
massive release of cytokines.
Normal antigen T response:
0.0001-0.001% T cells MHCII
activated but with
superantigen T cell activation
increase up to 20%.
Carrier effect

Usually: A primary humoral immune response requires the cooperation

of three cell types, an ANTIGEN-PRESENTING CELL (APC, typically a
dendritic cell or macrophage), a T-HELPER CELL (TH2), and a B-CELL.
The APC/T-CELL interaction involves the recognition of MHC Class II-
bound peptide by the T-cell receptor, and the participation of the
accessory molecule CD4.
Carrier Effect: The same principles apply to secondary humoral
responses, except that the B-cell can also take on the role of APC,
presenting processed antigen to memory T-cells; thus, only two cells (B-
cell and memory T-cell) need participate in this interaction.
 A n tig e n
b o u n d b y Ig B (V ) - C ELL T - c e ll h e l p :
r e c e p to r s IL -4

Carrier effect
( " C " = c a r r ie r d e te r m in a n t ,
" H " = h a p te n d e te r m in a n t) D iffe r e n tia tio n
to A F C
A N T I G E N P R E S E N T A T I O N B Y M A C R O P H A G E T O TH (V ) - C E L L

A n t ig e n p h a g o c y t o s e d b y m a c r o p h a g e A g - p r e s e n ta tio n
( A g / C la s s I I +
H
C H

H C H
C H
C

c o s ti m u l a tio n )
H
C H
H
H
A n tig e n
" p r o c e s s in g " A g - p r e s e n ta tio n : H
C H
C H ( A g / C la s s II +
H
c o s tim u la tio n ) H

APC 7 7 28
II
C 28
A n tig e n
CD
A n tig e n " p r o c e s s in g "
C H 4 C
T H (M ) - C E L L
H
C H
T H ( V )- C E L L b o u n d b y Ig II
H C

H
H
r e c e p to r s B (M ) -C E L L C D 4

A n tig e n
b o u n d b y Ig B (V ) -C E L L T - c e ll h e l p :
r e c e p to r s IL -4
D i f f e r e n t i a ti o n
( " C " = c a r r ie r d e t e r m in a n t, to A F C T - c e ll h e lp :
D i f f e r e n t i a ti o n
" H " = h a p te n d e te r m in a n t )
to A F C IL -4
A N T I G E N P R E S E N T A T I O N B Y M A C R O P H A G E T O TH (V ) - C E L L
A N T I G E N P R E S E N T A T I O N B Y B ( M ) - C E L L T O TH ( M ) - C E L L
A g - p r e s e n ta tio n
C H
( A g / C la s s I I +
H
C H
c o s tim u l a tio n )

C E L L IN T E R A C T IO N S IN H U M O R A L IM M U N IT Y
H
C H

7 28
 References

http://www.nature.com/nri/journal/v12/n1/fig_tab/nri3128_F1.html
Frauwirth, Kenneth A., and Craig B. Thompson. Activation and Inhibition of Lymphocytes by
Costimulation. The Journal of Clinical Investigation 109, no. 3 (February 1, 2002): 29599.
doi:10.1172/JCI14941.
Restifo, Nicholas P. Big Bang Theory of Stem-like T Cells Confirmed. Blood 124, no. 4 (July 24, 2014):
47677. doi:10.1182/blood-2014-06-578989.