The maturation of B cells involves two phases: an antigen-independent phase and an antigen-dependent phase. In the antigen-independent phase, B cells are activated by T-independent antigens through signals from antigen binding. In the antigen-dependent phase, activation of B cells requires two signals - antigen binding and T cell help through interactions such as CD40 ligand/CD40. Activated B cells differentiate into plasma cells that produce antibodies or memory B cells. Cytokines produced by lymphocytes and other immune cells mediate and regulate immune responses by activating and directing immune cells.

1. Activation and proliferating of B cell
The maturation of B cells into antibody producing
plasma cells can be divided into two phases. An
antigen independent phase followed by an antigen
dependent phase.
1.Antigen independent phase of B cell activation:
T- independent ag do not require T-cell help when
these antigen bind to the surface receptor(Ig) of B
cells both signal 1 and 2 come from the binding by
polymeric structure and the B cell transfer into
plasma cell for producing antibodies. These antigen
cant activate mature B cell but only naïve or
immature B cells.

2. 2.T- dependent antigen mediated B cell activation:
•B cell activation requires two signals and the help of
CD4 T-cells in case of T-dependent antigens.
•T cell and B cell contact with surface and only then
activation and proliferation of B cell occurs.
•The mechanism of B cell acivation and proliferation is
rather complex than that of T cell independent
antigen.
•At first T-dependent antigen binds to the surface Ig of
B cells.
•After binding,the B cell membrane engulf the bound T
dependent antigen by endocytosis mechanism.
•After internalization of antigen and binding antibody,B
cell enzymes degrade the T dependent antigen into
several peptides.

3. •After that MHC II proteins starts to synthesize and at the
same time,the expression of co-stimulatory protein B7 is
also enhanced.
•After this MHC II peptide complex is expressed on the
membrane as antigen presentation.
•The circulating CD4 T cell recognized the antigen
presentation by MHC II molecule on B cell surface.
•And then the CD28 molecule on the T helper cell binds to
the B7 molecule of B cell.
•The binding of B7-CD28 provides a co-stimulatory signal
for T cells to synthesize CD40 ligand which binds with the
CD40 of B cell and this interlinks provides signal-2 for the
activation of B cells.
•All these bindings brings B and T cells very close and
membrane contact and B cell then starts to produce
surface receptors for various cytokines.

4. •The T cells then synthesizes various types of cytokines
that brings various changes to B cells,and these changes
transform B cell into plasma cell,formation of memory B
cell and class switching of B cell.

5. Cytokines
It is a soluble protein which is secreted by the
monocytes,activated lymphocytes,fibroblast which functions
as mediators for immune and inflammatory reactions.
In innate immunity, cytokines are produced by the
macrophages and NK cells and in adaptive immunity
cytokines are produced by T lymphocytes.
Some of cytokines are as follows:
 Interleukins:Synthesized by T lymphocytes and leucocytes.
Interleukins 1:produced by activated macrophages,
Interleukins 2:Produced by activated CD4 T cells which
converts naïve T cells into Th1 and also produced by
macrophages.
Interleukin 4-produced by activated CD4 T cells which
converts naïve T cell into TH2.

6.  Interferon: It is specific to viral infection and are of two
types:
Type I interferon(IFN-α ,IFN-ß):It increases expression of
class I MHC and activates NK cells.
Type II(IFN-ƴ):It activates the macrophages.
 Tumor necrosis factor:It is a cytokine produced by
activated macrophages that functions to recruitment
the neutrophils and monocytes to the site of infection
and destroy the microbes.
 Chemokines: Low molecular weight cytokines that
stimulates the movement of leucocytes and regulate
migration of leucocytes from blood to
tissue(chemotaxis activation).

7. T cells: During the immune response, T cells have
extremely important role of creating cellular immunity.
There are two types of T cells
I. Helper T cells(CD4 cells)which serve as helper cells for
other lymphocytes,phagocytes and natural killer cells.
II. The cytotoxic T cells (CD8 T cells) which specialize in
identifying and killing tumor cells and cells infected with
viruses or other micro organisms.
Activation of CD4 T cells: The activation of CD4 T cells
occurs also in the secondary lymphoid tissues.This is
accomplished when a complex consisting of a class II
MHC protein carrying a peptide of foreign antigen which
are expressed on the surface of APC.

9. 1. Fragmentation of antigen and presentation by class II
MHC molecule: Exogenous antigens such as pathogenic
micro organisms when enter the secondary lymphoid
tissue or carried to the tissue by macrophages, Peptides
fragments which are engulfed and digest binds to a cleft
in a MHC II.
2. Recognition of MHC II molecules bound with ag by CD4
T cells: When the TCR recognizes the class II MHC-
peptides complex,the CD4 molecules binds to MHC II
molecules.
• The cell surface protein(co-stimulatory signals)
provided by interaction of CD28 on the T-cell and B7 on
the APC,activates the CD4 T cells.
• CD4 cells can be divided into two major types:type
1(Th-1) and type 2(Th-2) helper cells.

10. •The naïve CD4 T cells is initially termed as Th-0 cell which
has the potential to develop into Th-1 cell or Th-2 cell
depending upon the cytokine present.
•If a Th-0 cell is exposed to IFN-ƴ from NK cells and IL-2
produced by macrophages,the Th-0 become Th-1 cell, the
activator of cell mediated immunity.
•The Th-1 cell stimulates itself to secrete IL-2 and IL-2 can
also activate the cytotoxic T cells.
•In addition,Th-1 cell produce the cytokine IFN-ƴ which
enhances the ability of APC to increase the expression of
class II MHC and B7 proteins.This results in the
presentation of increasing numbers of antigen peptides to
CD4 T cells, thus enhancing the immune response and
become memory cells which can be rapidly activated to
secondary immune response.

11. •If Th-0 cells are exposed to IL-4 produced by specialized
subset of CD4 T cells,the Th-0 cells become TH-2 cells.
•TH-2 cells express a cell surface protein,CD-40 ligand and
secrete IL-4,5,6.These proteins are required to activate B
cells which eventually become antibody producing plasma
cell, leading to humoral immunity.

13. Activation of CD8 T cells:
•The activation of CD8 T cells enhances when the peptide
is presented by MHC class I molecules on APC and results
in the generation of cytotoxic T-cells which participate in
killing foreign cells.
•Activated CD8 T cells produce IFN-ƴ, tumor necrosis
factor and additional cytokines (IL-2).
•When antigen peptides bind to MHC I molecules and
are presented to surface of the infected cells then CD8 T
cell with appropriate TCR recognizes antigen fragments
class I MHC complex on surface.
•The co stimulatory signal necessary for full activation of
the cytotoxic T cell is either IL-2 secreted by TH-1 cell or
the interaction of CD28 present on T cell with B7 present
on APC cell.

14. The activated CD8 T cells (cytotoxic T cell) kill target cell
by:
•Induction of osmotic lysis: Cytotoxic substances
produced during CD8 T cell activation are released on the
surface of target cells by exocytosis. Substances include
perforins which forms channels and high concentraion of
perforins cause influx of water and leakage of cell
contents leading to death of cell.
•Induction of apoptosis: Here cytotoxic T cell makes the
target cell “commit suicide”by degrading its DNA.This is
accomplished by low concentration of perforins that form
a limited number of pores through which proteases
(Granzymes)can pass. These enzymes induce the target
cells own apoptotic pathway.Granzymes are responsible
for DNA fragmentation.