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Cell-Mediated Immunity
Cell Mediated Immunity
 Involves
specialized set of lymphocytes called T cells
that recognize foreign antigens on the surface of cells,
organisms, or tissues.
T
cells regulate proliferation and activity of other cells
of the immune system: B cells, macrophages,
neutrophils, etc.
 Defense
against:

Bacteria and viruses that are inside host cells and are
inaccessible to antibodies ( intracellular pathogens).

Fungi, protozoa, and helminths

Cancer cells
 Involved
in harmful effects of delayed hypersensitivity
reactions included in transplant rejections, contact
dermatitis, skin tests, and granuloma formation.
Cell Mediated Immunity is Carried Out by T
Lymphocytes
T Cells and Cell Mediated Immunity
Antigens that stimulate this response are mainly
intracellular.
Unlike humoral immunity, cell mediated
immunity is not transferred to the fetus.
Cytokines: Chemical messengers of immune cells.
 Over
100 have been identified.
 Stimulate and/or regulate immune responses.
 Interleukins: Communication between WBCs.
 Interferons: Protect against viral infections.
 Chemokines: Attract WBCs to infected areas.
T Cells and Cell Mediated Immunity
Antigen processing and presentation:
 T cells have an antigen receptor that recognizes
and reacts to a specific antigen (TCR).
 T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on
the surface of cells.
 MHC
Class I: Found on all cells.
 MHC Class II: Found on phagocytes.
 Clonal
selection increases number of T cells
recognizing a specific antigen.
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
Ag processing and presentation by APCs
MHC Class II
MHC Class I
Antigen Presenting Cell (APC)
MHC Class II + peptide
MHC Class I + peptide
Antigen Presenting Cell (APC)
CD8 T cell
CD4 T cell
T cell receptor (TCR)
TCR
Class II
Class I
Antigen Presenting Cell (APC)
Association of peptide with an MHC II (exogenous Ag)
Ag)
Association of peptide with an MHC I(endogenous
T Cells and Cell Mediated Immunity
Types of T cells
1. T Helper (TH) Cells: Central role in
immune response.
are CD4+
 Recognize antigen associated with MHCII on
the surface of antigen presenting cells (e.g.:
macrophage, denteritic cells, and B cells).
 Activate macrophages
 Induce formation of cytotoxic T cells
 Stimulate B cells to produce antibodies.
 They
Central Role of Helper T Cells
Types of T cells (Continued)
2. Cytotoxic T (Tc) Cells: Destroy target cells.
are CD8 positive & (CD4 -).
 Recognize antigens associated with MHC I on
the surface of all cells:
• Kill host cells that are infected with viruses
or bacteria.
• Recognize and kill cancer cells.
• Recognize and destroy transplanted tissue.
 Release protein called perforin which forms a
pore in target cell, causing lysis of infected
cells.
 Undergo apoptosis when stimulating antigen is
gone.
 They
Cytotoxic T Cells Lyse Infected Cells
Nonspecific Cellular Components
1. Activated Macrophages:
They are stimulated
phagocytes.
 Stimulated by ingestion of
antigen or by cytokines.
 Larger and more effective
phagocytes.
 Enhanced ability to
eliminate intracellular
bacteria, virus-infected
and cancerous cells.
Nonspecific Cellular Components -cont.
2. Natural Killer (NK)
Cells:
 Lymphocytes that
destroy virus infected
and tumor cells.
 Not specific. Don’t
require antigen
stimulation.
 Not MHC restricted.
 Not phagocytic, but must
contact cell in order to
lyse it.
Relationship Between Cell-Mediated and
Humoral Immunity
1. Antibody Production
T- Dependent Antigens:




Antibody production requires assistance from T helper cells.
A macrophage cells ingest antigen and presents it to TH cell.
TH cell stimulates B cells specific for antigen to become plasma
cells.
Antigens are mainly proteins on viruses, bacteria, foreign red
blood cells, and hapten-carrier molecules.
T- Independent Antigens:



Antibody production does not require assistance from T cells.
Antigens are mainly polysaccharides or lipopolysaccharides with
repeating subunits (bacterial capsules).
Weaker immune response than for T-dependent antigens.
Humoral Response to T Dependent Antigens
Relationship Between Cell-Mediated and
Humoral Immunity
2. Antibody Dependent Cell Mediated Cytotoxicity
 Target
cell is covered with antibodies, leaving Fc
portion sticking outwards.
 Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
 Target organism is lysed by substances secreted by
attacking cells.
 Used to destroy large organisms that cannot be
phagocytosed.
Destruction of Large Parasites by ADCC
Phases of T cell responses


Ag processing and presentation by APCs
Activation of T lymphocytes requires
 Recognition
of Ag displayed on APCs
 Costimulators: increase the strength of adhesion
between APCs and T cells
 Cytokines produced by APCs (IL-1,TNF-α , IL-12)
and by T cells themselves (IL-2, INF-γ, LT)
 Clonal expansion: proliferation and differention of T
cells to effector T cells: in response to autocrine
growth factor IL-2

Effector functions of T cells
T cell Recognition of Antigen on an APC
Antigen
Endocytosis
CD4+
T cell
T Cell
Receptor
APC
Peptide
MHC II
T cell Activation by an Activated APC
IL-1
IL-6
IL-12
IL-12 Receptor
CD28
“Signal 3”
B7
CD4+
T cell
LPS
T Cell
Receptor
“Signal 2”
TLR4
“Signal 1”
Peptide
MHC II
Antigen Presenting Cell (APC)
Signal 1: Specificity
Signal 2: Activation
Signal 3: Cytokines& differentiation
APC and T cell Interactions
( Costimulatory signals)
CTLA-4
B7 (CD80/86)
B7 (CD80/86)
CD28
Activation
Recognition
TCR
MHC II
Activation
APC
CD58 (LFA-3)
Activation
CD40
CD2
Adhesion
CD40L
CD4+
T Cell
Clonal Selection and expansion
Only those lymphocytes whose receptor recognizes th
antigen become activated, and then proliferate.
CD4 T cell cytokine effects
IL2,IFNγ
Macrophag
Activation
Th1
IL12
Th0
IL4
IL2,IL4,IL12,
IL13, IFN-λ
IL4,IL13
Th2
B Cell
Activation
Effector Functions of TH1 CD4+ T Cells
(Cell-Mediated Immunity)
Effector Functions of TH2 CD4+ T Cells
(Humoral Immunity)
The Control of Activated CD4+ T Cells by Regulatory
T cells
CD4+CD25+ cells
Apoptosis
peptide/APC
(- )
TH1 CD4+ cells
IL-12/
IFN-g
(- )
IL-10
IL-4
Resting CD4 T cells
IFN-g
(- )
Activated CD4 T cells
(- )
TH2 CD4+ cells
Regulatory immunity
CD4/CD8 interactions
CD8 or CD4
CD8 or CD4 suppressor
suppressor effector
precursor
L. Chess 2002
Overview of the Immune Response
 The
body's second line of defense
against infections is _____.
 active
immunity
 inflammatory response
 passive immunity
 cell-mediated immunity
 humoral immunity
 Tissue
 begin
macrophages
their lives as neutrophils
 have short life spans because they self-destruct
after engulfing foreign invaders
 originate from monocytes that leave the
circulation and enter the tissues
 do not attack microorganisms directly; instead,
they destroy virus-infected body cells
 Which
of the following types of cells
initiate a secondary immune response?
 natural
killer cells
 immature white blood cells
 memory cells
 effector cells
 plasma cells

The biggest difference between cell-mediated
immunity and humoral immunity is _____.
 how
long their protection lasts
 whether a subsequent secondary immune
response can occur
 whether clonal selection occurs
 how they respond to and dispose of invaders
 how fast they can respond to an invader
 Helper
T cells are part of
 cell-mediated
immune response
 the first line of defense
 the complement system
 a group of phagocytic white blood cells
 The
role of cytotoxic T cells is to attack
_____
 body
cells that have been infected
 antibodies
 proteins circulating in the body fluids
 specific viruses and bacteria
 complements
 Viruses
and bacteria in body fluids are
attacked by _____.
 antibodies
from B cells
 cytotoxic T cells
 complement proteins
 helper T cells
 antigens
 The
role of cytotoxic T cells is the
secretion of _____, which plays a role in
the _____ immune response.
 antibodies
... antibody-mediated
 antibodies ... humoral
 perforin ... cell-mediated
 perforin ... humoral
 interleukin-2 ... humoral
A
T cell recognizes Ag in association
with MHC molecule, causes the APC
to secrete:
 IL-1
 IL-2
 1L-4
 IL-6
 All
the following are true about CMI
except:
 Characterized
by mononuclear cell infiltration
 Can be transferred to non immune individual by
serum
 Delayed in time compared to humoral immunity
 Initiated by intracellular Ags
 B7
surface molecule on the APC can
bind to ...... on Th:
 CD28




CTLA4
LFA-1
a&b
b&c
A
cytolytic T cell (Tc) may be able to
kill a virally-infected antigen presenting
cell (APC)
True
False
 True

Explanation
All nucleated cells express class I MHC molecules.
Cells infected with virus have some viral peptides
associate with class I MHC molecules which are
then expressed on the cell surface where they can be
recognized by a cytolytic T cell and be killed.
Therefore an antigen presenting cell (APC), which
expresses both class I and class II MHC molecules
and is infected by virus, is susceptible to killing by a
cytolytic T cell.
 Antigen
presenting cells (APC) process
superantigens
True
False
False
 Explanation
By definition, antigen processing involves the
internal cellular fragmentation of proteins into
peptides that can associate with class I or class II
MHC molecules and then be presented on the cell
surface to a T cell. Superantigens are not processed,
but rather exert their effect externally by binding as
an intact (non-fragmented) molecule to T cell
receptor (TCR) molecule and to some portion of a
class II MHC molecule on an antigen presenting cell

 Th1
and Th2 cells are capable of
interfering with each other's effector
pathways
True
False
True
 Explanation
Th1 cells produce interferon-gamma that interferes
with the Th2 pathway, and Interleukin-10 (IL-10)
produced in the Th2 pathway interferes with the Th1
pathway
