Download CELL MEDIATED IMMUNITY (T * CELL)

CELL MEDIATED IMMUNITY
(CMI)
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CELL MEDIATED IMMUNITY
Pathogen that escapes Ab detection can enter and infect
cells,Cytotoxic cells kill infected cell and one has kind of
receptor
Cell-mediated immunity is an immune response that does
not involve antibodies or complement but rather
involves the activation of
• macrophages,
• natural killer cells (NK),
• antigen-specific cytotoxic T-lymphocytes, and the
• release of various cytokines in response to an
antigen.
Activating antigen-specific cytotoxic T-lymphocytes that
are able to induce apoptosis in body cells displaying
epitopes of foreign antigen on their surface, such as
virus-infected cells, cells with intracellular bacteria, and
cancer cells displaying tumor antigens;
Types of T cells (Lymphocytes)
There are various types T cells
Cytotoxic T cells (Tc) or Killer Cell(Tk)
Helper T cells (Th)
 Memory T cells sub types
 Suppressor T Cells sub types
These are main players T lymphocytes the rest are small
and regulatory
The T cells look alike but can be differentiated by their
functions
Types of T cells (T Lymphocytes)
• Cytotoxic T (Tc)-Killer T cells
• They attack and destroy cells bearing foreign antigen or
misbehaving
• ie Virus,bacterial infected or cancellous cells etc.
How: They have chemical (Perforin )in their storage vacoule
as they perforates cell membrane so allows water and
salt into the cell leading to eventual burst hence cell
death
Therefore T cells are responsible for CMI characterized by
destruction of Ags bearing cells
Types of T cells (T Lymphocytes)
Cont.
• Helper T (Th) cells they regulate immunity by enhancing
the response of immune cells.
• How: In response to Ag they enlarge and secrete
Cytokines (Interferon and interleukins)
Cytokines are stimulatory molecules that cause Th cells to
clone and other immune cells to perform their functions
 They stimulate Macrophages to phagocytize Ags and B
cells to manufacture Abs
 Example: HIV infection: the virus attacks Th cells hence
inactivate the immune response.
 Cytokines that stimulate B cell to produce Abs are called
Interleukin -4
CELL MEDIATED IMMUNITY
(T – CELL)
The T cells develop in the thymus gland.
Briefly, the stem cells in the thymus undergo differentiations
that form two major groups of T cells, the Killer T cell (Tc or
Tk) and the Helper T Cells (Th).
Each Tk and Th cell responds only to a unique epitope.
T cells that react with self antigens die off during the early
stages of differentiation.
The T cell clones migrate throughout the lymphatic system.
When a T cell encounters its coresponding antigen (epitope)
it goes through a series of changes that convert it into its
final immunological defense posture.
Types of T cells (T Lymphocytes) Cont.
• When activated Th devides, the clone contains
suppressor T (Ts) cells and memory T (Tm) cells sub types
• Once there is a sufficient number of TS cells the immune
response ceases but a population Tm cells persist which
are capable of secreting Cytokines in turn stimulation of
macrophages and B cells whenever an Ag of the same
nature attacks again in the future
Activation of Cytotoxic and Helper Cells
• T cells have unique receptors like B cells the difference
they don’t recognize the Ags in the plasma or blood till
when Ags presented by APC such as macrophage.
• APC enzymatically digests the Ags into peptide fragments
which are antigenic
• The fragments are linked to Major Histocompatibility
Complex(MHC) protein and together are displayed to a T
cell at cell membrane
• MHC proteins contribute to specificity at tissue hence
difficult to transplant incompatible individuals unless
immunosuppressed
Activation of Cytotoxic and Helper Cells cont..
• There two types of MHCs(I&II)
• Most of the body cells display MHC type I protein and
only immune cells display MHC type II ie: Macrophages,B
cell and some T cells
• Th express a protein in the CD family known CD4 on their
surface
• TC express protein called CD8 therefore CD4 are helper
proteins and CD8 are killer protein
• T cells recognize peptide fragments which are displayed
by specialized molecules(MHC) on the surface of APCs
• MHC type I are found on healthy nucleated cell in the
body and they display peptides antigens that are found
within cytoplasm of the cells.
Activation of Cytotoxic and Helper Cells cont.
• ie: If a cell is infected by the virus that particular cell will
display the Viral peptides on the surface which normally
are recognized by CD8+ cytotoxic T cells which are better
than CD4+ in responding to viral infection.
• MHC type II are restricted to specialized cells
• MHC type II display antigens from microbes within the cell
vesicles
Steps in CMI Response
• The Process starts when APC (Macrophage) ingests an Ag
• Digests it and incorporates pieces of Ag peptides on the
surface of cell membrane
• Wherever macrophage travels in blood or plasma
presents the Ag to any T helper cells that it encounters
• Helper cells have receptors on their membrane(T cell
receptors), receptors are proteins with specific shape
• If Ag on the macrophage matches with T cell receptor
• The T cell becomes active
• There are different millions of T helper cells with specific
receptors , shapes so when antigen on the macrophage
matches with T receptor the process starts(Why
response takes longer time)
Steps in CMI Response cont…
• Once appropriate T helper is activated proceed to
stimulate other T cells
CELL MEDIATED IMMUNITY
Cellular immunity protects the body by:(Briefly)
• Activating macrophages and natural killer cells, enabling
them to destroy intracellular pathogens; and
• Stimulating cells to secrete a variety of cytokines that
influence the function of other cells involved in adaptive
immune responses and innate immune responses.
• Cell-mediated immunity is directed primarily at
microbes that survive in phagocytes and microbes that
infect non-phagocytic cells. It is most effective in
removing virus-infected cells, but also participates in
defending against fungi, protozoans, cancers, and
intracellular bacteria. It also plays a major role in
transplant rejection
CELL MEDIATED IMMUNITY
T- CELL
T- Helper Cells
• Assist other white blood cells in immunologic processes,
including:
- maturation of B-cell into plasma cell
- activation of cytotoxic T cells and microphage,
among other functions.
• These cells are also known as CD4+ T cells because they
express the CD4+ glycoprotein on their surface.
CELL MEDIATED IMMUNITY
T- CELL
• Helper T cells become activated when they are presented
with peptide ANTIGEN by MHC class II molecules that are
expressed on the surface of Antigen Presenting Cell(APC)
• Once activated, they divide rapidly and secrete small
proteins called cytokines that regulate or assist in the
active immune response.
• These cells can differentiate into one of several subtypes,
which secrete different cytokines to facilitate a different
types of immune response.
• The mechanism by which T cells are directed into a
particular subtype is poorly understood, though signalling
patterns from the APC are thought to play an important
role.
Cytotoxic T - cell (TC cells, or CTLs)
- destroy virally infected cells and tumor cells, and
are also implicated in transplant rejection.
- These cells are also known as CD8+ T cells since
they express the CD8+ glycoprotein at their
surface.
- These cells recognize their targets by binding to
antigen associated with MHC class I , which is
present on the surface of nearly every cell of the
body.
•
•
Activation of Th and B-cell
by Antigen
A macrophage engulfs a virus or bacterium &
breaks(digests) down their proteins. Antigenic
fragments of these proteins are presented on
the surface of the macrophage.
The few Th-cells, which contain receptors on
their surface that recognizes a particular
peptide presented foreign antigen, INTERACTS
WITH that unique-foreign antigen. This
interaction triggers a series of events that
ACTIVATES the Th-cell.
Activation of Th and B-cell
by Antigen
• The activated Th-cells are stimulated to
proliferate, producing a population of this class
of Th-cells (clonal selection).
• The population of activated Th-cells interact
physically (via ligand/receptor interactions) with
only those rare B-cells that make antibody that
recognizes the SAME antigen molecules that
have activated the Th-cell.
Activation of Th and B-cell
by Antigen
• During this interaction the Th- & B-cells recognize
each other by their common recognition of the
unique antigen. The B-cells do not require the
macrophage-processed antigen as they react with the
whole antigen molecule (e.g. the virus, bacteria,
pollen etc.)
• The B- and Th-cell interaction stimulates the Th-cells
to produce chemicals (cytokines) that, in turn,
stimulate the appropriate B-cells to proliferate (clonal
selection) and to differentiate into Ab-producing
plasma cells that produce the Ab that bind the
antigen that the Th-cell originally reacted to.
Therefore, the Th helper cell acts as a MASTER CONTROL
CELL of the immune system. It is REQUIRED for both the
humoral and cellular immune systems to function. When
Th cells are not present the host's fate is sealed because
the correct B-cells will not proliferate and the correct
antibody will not be produced. E,g. HIV infection
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exogenous
antigen e.g.
bacteria, virus
MHC II
peptide
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