Activation of lymphocyte

Initiating event of adaptive immune response

• Interaction between naive T cell and an antigen-presenting cell

• Signal 1 – provided by antigen-specific TCR engagement

• Signal 2 – provided by contact with costimulatory ligand expressed by APC
• Example - CD28
• Signal 3 - cytokines
T cell Activation
• Initiated by TCR-CD3 complex with processed antigen on MHC
molecule
• CD8+ cells with Class I
• CD4+ cells with Class II
• Initiates cascade of biochemical events
• Inducing resting T cell to enter cell cycle, proliferate, differentiate into memory and
effector T cells
T cell Activation
• Cascade of biochemical events leading to gene expression:
• Interaction of signal and molecule (example: TCR + MHC and antigen)
• Generation of “second messenger” that diffuses to other areas of cell
• Protein kinases and protein phosphatases are activated or inhibited
• Signals are amplified by enzyme cascades
ACTIVATION of T LYMPHOCYTE
• Naive T lymphocytes home to secondary lymphoid organs, where
they may encounter antigens presented by mature dendritic cells on
class I or class II MHC molecules and thus become activated.
• This results in the expansion of the antigen-specific lymphocyte pool
and the differentiation of these cells into effector and memory
lymphocytes
• Antigens that enter the circulation may be captured by dendritic cells
in the blood and in the spleen.
• the dendritic cells are activated and induced to express costimulators
on the cell surface.
• Dendritic cells that have encountered microbes and internalized their
antigens begin to mature and migrate to the T cell zones of secondary
lymphoid organs such as the lymph nodes.
• When they reach these T cell areas, the dendritic cells present antigens on
MHC molecules and also express costimulators that can provide second
signals to naive T cells
• Antigen-stimulated T cells that have received both "signal one" through the
antigen receptor and "second signals" via costimulatory receptors may be
induced to secrete cytokines and to express cytokine receptors.
• Some of these activated T cells leave the lymphoid organ where activation
occurred and enter the circulation.
• Other activated CD4+ T cells remain in the lymphoid organ, where they
help B lymphocytes to differentiate into antibody-secreting plasma cells
Effector T cells
• Effector T cells recognize antigens in lymphoid organs or in peripheral
nonlymphoid tissues and are activated to perform their effector functions
• Effector T cells are able to migrate to any site of infection or inflammation
• Here the cells again encounter the antigen for which they are specific and
respond in ways that serve to eliminate the source of the antigen.
• Effector T cells of the CD4+helper subset express membrane molecules and
secrete cytokines that activate (help) macrophages to kill phagocytosed microbes.
Some CD4+ helper T cells remain in lymphoid organs and help B cells to
differentiate into cells that secrete antibodies that bind to the antigens
• CD8+cytotoxic T lymphocytes (CTLs), the effector cells of the CD8 subset, kill
infected cells and tumor.
• Antigen-stimulated T cells that have received both "signal one" through the
antigen receptor and "second signals" via costimulatory receptors may be
induced to secrete cytokines and to express cytokine receptors.
• T cell responses decline after the antigen is eliminated by effector
cells
• It decline is important for returning the immune system to a state of
rest, or homeostasis.
• T cell responses decline mainly because the majority of antigen-
activated T cells die by apoptosis.
• It is estimated that more than 95% of the antigen-specific CD8+T cells
that arise by clonal expansion die by apoptosis as the antigen is
cleared.
ACTIVATION OF CD4+ T LYMPHOCYTES

• The differentiation of naive CD4 T lymphocytes into effector cells of

cell-mediated immunity (CMI) requires antigen recognition and
costimulation.
• The initiation of cell-mediated immune responses requires that naive
CD4+ T cells and the antigens.
• Naive T cells migrate from the blood into lymphoid organs, from one
lymphoid organ to another, and back into the blood, until they
encounter the antigen for which they express specific receptors.
• Antigen is delivered to lymph nodes by lymphatic drainage, and to the
spleen by the blood.
• Dendritic cells play an important role in taking up antigens at sites of
infection.
• migrating through lymphatic vessels to draining lymph nodes.
• the migration to the lymph nodes, dendritic cells mature and become
efficient antigen presenting cells (APCs)
Activation of naive CD4+ T cells
• Activation of naive CD4 T cells requires antigen presentation by
dendritic cells.
• CD4+ T cell mediated immune reactions are elicited by protein
antigens of extracellular microbes that are ingested by dendritic cells,
• The microbial or soluble antigens are internalized into vesicles by the
dendritic cells and presented in association with class II MHC
molecules
• Some chemicals introduced through the skin also elicit T cell
reactions, called contact sensitivity reactions.
ACTIVATION OF CD8+T CELLS
• 1-The activation of naive CD8+T cells also requires antigen recognition
and second signals.
• stimulated to proliferate and differentiate into effector CTLs, naive
CD8+T cells must recognize class I-associated peptide antigens and
also encounter costimulators on APCs or signals provided by helper T
cells.
• 2-Dendritic cells play an essential role in activating naive CD8 T cells.
 CD8+T cell responses are elicited by microbial peptides that are present in
the cytosol of infected cells and are displayed by class I MHC molecules.
CD8+ T cells may respond to some phagocytosed bacteria and viruses if
these microbes or their protein antigens are transported out of phagosomes
into the cytosol
Dendritic cells that express these cytosolic antigens are able to activate naive
CD8+T cells, much like the way dendritic cells initiate CD4+T cell responses.
Dendritic cells have a special ability to capture and ingest virus-infected or
tumor cells, and present the viral or tumor antigens to naive CD8+T cells,
.
Helper T cell
• The full activation of naive CD8+ T cells and their differentiation into
functional CTLs may require the participation ofCD4+ helper cells
• helper T cells can provide "second signals" for CD8+T cells.
• The requirement for helper cells may vary according to the type of
antigen exposure.
B-Cell Activation
• Antigen-driven activation and clonal selection of naive B cells leads to
generation of plasma cells and memory B cells.
• B-cell activation proceeds by two different routes, one dependent
upon TH cells,the other not
• The B-cell response to thymus-dependent (TD) antigens requires direct
contact with TH cells, not simply exposure to TH-derived cytokines.
• Antigens that can activate B cells in the absence of this kind of direct
participation by TH cells are known as thymus-independent (TI) antigens.
• TI antigens are divided into types 1 and 2
• TI-1 Ags Bacterial cell wall components, LPS
• act as polyclonal B cell activators or B cell mitogens
• LPS can also bind to TLR4 to activate most B cell
• TI-2 Ags Repeating epitopes that induce cross-linking