A1258150756nHySP

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Natural Killer (NK) Cells
A group of cells that are classified neither as
B- or T-cells, are considered "null cells". NK
cells are the biggest of this group   --they
lack receptors for antigen recognition --they
can not participate in acquired immunity   Large
granular lymphocytes, but since they lack many of
the receptors of B- and T-cells, they can not
function directly in the acquired immune
response.   More closely related to innate
immune response.
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Natural Killer (NK) Cells (contd)
 What makes NK a cell unique is their
spontaneous ability to kill tumor cells and
virus-infected cells, which produce large
quantities of ?-interferon (IFN-?).
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Acquired Immunity
Protection by the crude mechanism of innate
immunity is augmented by "acquired" or "adaptive"
immunity   Prior exposure- acquired immunity
requires prior exposure to the inducing agent for
full expression contact with the immunogen is
immunization.   Specificity- the mechanisms of
acquired immunity are always highly specific to
the immunogen.   
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Acquired Immunity (contd)
Memory- primary response to immunization is
short-lived with generation of specific memory
lymphocytes. Secondary exposure leads to a rapid
substantial response. --memory is the
rationale for the practice of vaccination.   Disc
rimination between 'self' and 'non-self'- most
important feature of acquired immunity is the
ability to distinguish between host and foreign
molecules.
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Binding Antigens by B- and T-Lymphocytes
Bind antigens by means of specialized antigen
receptors, and they do collaborate in the immune
response.   B-cell antigen receptor is an
immunoglobulin (Ig) molecule.   T-cell antigen
receptor is a related molecule of different
structure called the T-cell receptor
(TcR).   B-cells can use their Ig receptors to
recognize native antigenic molecules.   T-cells
recognize only peptide fragments of antigens
prepared by antigen-presenting cells
(macrophage-monocyte lineages and the B-cells
themselves).
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Binding Antigens by B- and T-Lymphocytes (contd)
Common features that characterize mode of antigen
recognition   Cell surface receptors (thousands
of them per cell) expressed by an individual T-
or B-cell are identical   --confers
specificity to respond to a single antigen, and
to have limited cross-reactivity.   Antigen
receptors are synthesized and expressed prior to
encounters with antigens.   --immune systems
pre-arms itself with a vast array of antigen
receptor specificity's.
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Binding Antigens by B- and T-Lymphocytes (contd)
On encounter with an antigen, a T- or B-cell
proliferates and differentiates into mature
effector cells. --leads to expansion of clones
and an effective immune response. Alternatively,
antigen encounter can lead to cell inactivation
or immune cell death. --result is specific
immune tolerance (that is, "self"). --formulated
on theoretical grounds as the clonal selection
theory, now supported by experimental evidence.
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The Antigen-Presenting Cell (APC)
Many short fragments (peptides, carbohydrates)
from these antigens are then bound to major
histocompatibility complex (MHC) molecules and
incorporated into the cell membrane.   If the
antigen is of exogenous origin, that is, it came
from outside the body, it will bind to class II
MHC molecules   --MHC class II are found in
APC's.   If the antigen is of endogenous origin,
that is, it was produced from inside the infected
cell, it will bind readily to class I MHC
molecules and move to the cell membrane of the
infected cell.   --MHC class I are found in
virtually all nucleated cells.
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Antigen Recognition by T-Cells
T-cells do not recognize intact proteins as
antigens.   --T-cell receptor on T-cells
recognizes foreign particle in the groove of MHC
class I and II molecules.   Class I MHC
molecules are expressed by virtually all cells.
  --T-cells that express CD8 interact with
class I MHC.  
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Antigen Recognition by T-Cells (contd)
In contrast, class II MHC molecules are
constitutively expressed on a limited number of
cell types.   --T-cells that express CD4
interact with class II MHC. Class II
MHC-containing cells have a well-developed
lysosomal apparatus, and cause phagocytosis of
antigens   -macrophage-monocytes -Langerhans
cells -dendritic cells and -B-cells are
also antigen- presenting cells.
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Presentation of Antigen in Class I MHC
There are several differences in the mode of
antigen presentation by MHC class I restricted
CD8 T-cells   Class I molecules are expressed
by virtually all cell types (therefore, any
nucleated cell is a potential APC).   Class I
restricted CD8 T-cells exert primarily a
cytotoxic function against virally infected or
neoplastic cells.   Antigenic peptide associated
with the class I molecule is produced by the
antigen presenting cell itself.
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Presentation of Antigen in Class I MHC (contd)
The cell that serves the function of
antigen-presenting cell, cytoplasmic proteins are
degraded by proteosomes --multimeric proteases
of which are encoded in the MHC complex of
genes. --these peptides are then transported
to the ER lumen, bind class I molecules and
transported to the cell surface.
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T-Lymphocyte Subsets (contd)
CD4 bind MHC Class II-peptides on target APC
cells. ("CD" stands for Cluster of
Differentiation)
 Two subsets of CD4 T-lymphocytes (65 of
peripheral blood T-cells are CD4) ? ?   T-h
elper lymphocytes (TH) T-delayed-type
hyper- sensitivity (TDTH) ? ? help
and induce activation secrete chemotactic of
B-lymphocytes factors for macrophages ? sec
rete IL-2, interferon-gamma act as growth
factors
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T-Lymphocyte Subsets (contd)
CD8 bind MHC Class I-peptides on target cells.
  Two subsets of CD8 T-lymphocytes ? ? su
ppressor T-lymphocytes cytotoxic
T-lymphocytes (TS)
(TC) ? ?   act as a brake on
TH release cytolytic lymphocytes substances
such a perforin directly onto
target cells
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Need for T- and B-cells for the Humoral Response
An efficient humoral response does not occur in
the absence of T-cell because they provide the
help needed to promote B-cell proliferation and
differentiation into plasma cells.   B-cell
growth factors from T-cells interferon-g, IL-2,
IL-4.
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