Title: A1258150756nHySP
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3Natural 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. Â More closely related to innate
immune response.
4Natural 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-?).
5Acquired 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. Â Specificity- the mechanisms of
acquired immunity are always highly specific to
the immunogen. Â Â
6Acquired 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. Â Disc
rimination between 'self' and 'non-self'- most
important feature of acquired immunity is the
ability to distinguish between host and foreign
molecules.
7Binding Antigens by B- and T-Lymphocytes
Bind antigens by means of specialized antigen
receptors, and they do collaborate in the immune
response. Â B-cell antigen receptor is an
immunoglobulin (Ig) molecule. Â T-cell antigen
receptor is a related molecule of different
structure called the T-cell receptor
(TcR). Â B-cells can use their Ig receptors to
recognize native antigenic molecules. Â T-cells
recognize only peptide fragments of antigens
prepared by antigen-presenting cells
(macrophage-monocyte lineages and the B-cells
themselves).
8Binding 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. Â Antigen
receptors are synthesized and expressed prior to
encounters with antigens. Â --immune systems
pre-arms itself with a vast array of antigen
receptor specificity's.
9Binding 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.
10The 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. Â 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. Â 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. Â --MHC class I are found in
virtually all nucleated cells.
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13Antigen Recognition by T-Cells
T-cells do not recognize intact proteins as
antigens. Â --T-cell receptor on T-cells
recognizes foreign particle in the groove of MHC
class I and II molecules. Â Class I MHC
molecules are expressed by virtually all cells.
 --T-cells that express CD8 interact with
class I MHC. Â
14Antigen Recognition by T-Cells (contd)
In contrast, class II MHC molecules are
constitutively expressed on a limited number of
cell types. Â --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.
15Presentation 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). Â Class I
restricted CD8 T-cells exert primarily a
cytotoxic function against virally infected or
neoplastic cells. Â Antigenic peptide associated
with the class I molecule is produced by the
antigen presenting cell itself.
16Presentation 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.
17T-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) ? ? Â 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
18T-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) ? ? Â act as a brake on
TH release cytolytic lymphocytes substances
such a perforin directly onto
target cells
19Need 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. Â B-cell
growth factors from T-cells interferon-g, IL-2,
IL-4.
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