Cell cooperation in immune response.
Dr Laila Hamed Damanhouri
Any immune mechanisms depend on the interaction among the cellular components
comprising the immune system. The interaction depend on two important specific
mechanisms: - a) direct contact between cell, b) soluble molecules that released by the
immune cells and bind to specific receptors on responding cells.
Interaction of cells of the immune cells.
Several cells of the immune system must interact, and communicate with each other
in order to generate an effective immune response. Basically these cells are antigen
presenting cells (APCs), T cells and B cells. In addition to the activity of other cells
such as monocytes, macrophages and granulocytes which is also influenced by
cellular communication.
A. ِgeneration of stimulated B and T-cells.
APCs display peptide fragments of protein antigen on their surface MHC class II
molecules to facilitate antigen recognition by T helper cells via the T cell surface
receptors. This interaction initiate T cell activation, which is amplified by further
interaction between other molecules known as costimulatory molecules present on
both T cells and APC surface. Once T cells are activated by this interaction, they
communicates with other cells resulting in producing a variety of cytokines, which
have a wide ranging biological function, particularly in immune response.
Additionally APCs must also provide a variety of costimulatory signal to T cells.
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The most important co-stimulatory signal is originated by binding of:1. CD40 L on CD4 + T cell with CD40 on surface of APcS.
2. CD28 on CD4 + T cell with CD80 (B7) on surface of APcS.
3. LFA-1 on CD4 + T cell with ICAM-1 on surface of APcS.
Cooperation between B & T lymphocytes.
The Cooperation between B & T lymphocytes is well organized. T cells are activated
when they recognize antigen on the cell surface of APCs in association with MHC
molecules.
Binding of antigen to membrane-bound immunoglobulin (usually IgM, IgD) on B-cell
activate the B-cell and increase the level of expression of membrane molecules that
results in cell to cell contact with T cells. The contact of T-helper cells provides signal
needed for B-cell activation. The major molecules that involved in B-T cells
interaction includes
A)MHC II on the surface of B-cell bind with TCR on the T cells..
B) ICAM-1 on the B-cell bind with LFA-1 on T-cells.
C) CD40 on B-cell bind with CD40L on T-cells.
D) CD80 and CD86 (B7-1,B7-2) on B cell bind with CD28 and CTLA-4 on the T
cell.
The initial interaction between APCs, T and B cell result in the production of
different soluble molecules known as cytokines. These molecules regulate
communication between different cells of the immune system. Cytokines are secreted
from activated immune cells and have a number of different biologic functions in both
humoral and cell mediated immune responses.
During the T-B cell interaction, T cells secrete a number of cytokines that have a
powerful effect on B cells. These include interlukin 2 (IL-2) which act as growth
Factor for both T and B cell, Interlukin 4 (IL-4) which acts early in B cell activation
and proliferation, interlukin 6 (IL-6) which is a strong signal for B cell differentiation.
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The response of the B-cell depend on cytokines that secreted from T-helper cell.
When the T-helper cell secrete IL-4 and IL-5 this will results in activation and help in
antibody production especially IgG1 and IgE. On other hand if the T-helper cell
secrete IL-2 and IFN gamma, this will help the B cells to produce IgG2 and will
activate the delayed type hypersensitivity response.
Differentiation of TH cell
Important of accessory molecules.
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Interaction at TCR or membrane immunoglobulin alone can not mediate activation
signal for T or B cells. A number of interactions are involved in the activation of both
T and B cells.
T cell activation of B-cells depend on two signals. The first one is specific and
depend on recognition of antigen by the B-cell through the B cell surface receptor.
This signal alone is not enough to activate the B-cell. It is need to the second signal
which is mediated by co-stimulatory signal which is usually provided by T-helper
cells. The most important co-stimulatory signal involves direct cell-cell contact
between the B cell and the T-helper cell. CD40 on the surface of B-cell bind to CD40
ligand. on the T-cell. The interaction between these two molecules is very important
on B-cell activation. genetic defect on one or both of these molecules results in the
defect of B-cell response and failure in the production of antibody .
Once the B-cell is activated, they express new proteins on their surfaces such as IL-2
receptor that interact with IL-2 (secrete from the T-helper cell). IL-2 is a growth
factor for B-cell and is stimulate the B-cell to proliferate.
In the absence of second signal which provided by costimiulatory molecule, the cell
became un responding (energized)
Signal(1)
2nd signal for T cell activation
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