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mediated Immunity
PTM 3015
2016/2017
Darlington M. Mwenya
Types of cell-mediated immunity
• There are two types of cell-mediated
immune reactions designed to eliminate
different types of intracellular microbes:
2
Cell-mediated immunity against intracellular microbes
3
Induction and effector phases of cell-mediated immunity
4
Migration of effector T lymphocytes
to sites of infection
• Effector T cells migrate to sites of infection
because:
– Chemokines (chemoattractant
cytokines).
9
Adhesion
• Chemokines produced by macrophages and
endothelial cells increase the affinity of T
lymphocyte integrins for their respective
ligands.
10
Motility
• Chemokines produced by macrophages
and endothelial cells
11
Migration of naïve and effector T lymphocytes
12
Homing of T cells to site of infection
• Homing of T cells to a site of infection is
independent of antigen recognition.
14
Antigen-independent homing of T cells to
site of infection
15
Effector functions of CD4+ T
lymphocytes
• TH1 lymphocytes activate macrophages to
have increased microbicidal activities that
kill the ingested microbes.
16
T cell-mediated macrophage
activation
• TH1 lymphocytes activate macrophages by
both:
17
T cell-mediated macrophage
activation
• Activated CD4+ T cells also secrete TNF
which facilitates homing of the leucocytes
to the site of infection.
18
Elimination of microbes by
activated macrophages
• Macrophage activation leads to the
expression of enzymes that catalyse the
production of microbicidal substances in
phagosomes and phagolysomes.
19
Elimination of microbes by
activated macrophages
• Cell-mediated immunity is critical to host
defence in two ways:
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Side effects of macrophage
microbicides
• Macrophage microbicides are toxic to host
tissue e.g.:
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Other effects of activated
macrophages
• Activated macrophage
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Interactions between T lymphocytes and macrophages
in cell-mediated immunity
25
Role of TH2 cells in cell-mediated
immunity
• The TH2 CD4+ lymphocytes produce IL-4,
IL-5, IL-10, and IL-13.
26
Role of TH2 celles in cell-mediated
immunity
• Studies indicate that some patients
infected with Mycobacterium leprae who
have
– Well activated TH1 cells develop a less
destructive form of disease called
tuberculoid leprosy, and
– Defective TH1 activation and a dominant
TH2 response develop a more
destructive lepromatous form.
27
A. TH1 and TH2 interaction
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B. TH1 and TH2 interaction
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Effector functions of CD8+ cytotoxic T
lymphocytes
• When effector CD8+ CTL encounter and
recognise a specific Ag they are activated
to release toxic granules to the area
surrounding the target cell.
30
Effector functions of CD8+ cytotoxic T
lymphocytes
• CTL granules also release other enzymes
called granzymes which activate target-
cell enzymes called caspases.
31
CD8+ CTL – mechanisms of killing infected cells
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Effector functions of CD8+ cytotoxic T
lymphocytes
• Activated CTL express a membrane
protein called Fas ligand which binds to
Fas (CD95) on target cells.
33
Effector functions of CD8+ cytotoxic T
lymphocytes
• Mechanisms that cause fragmentation of
target cell DNA, may also break down
DNA of microbes living in the target cells.
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End
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Resistance of pathogenic microbes to
cell-mediated immunity
• Different microbes have evolved diverse
mechanisms to resist T lymphocyte-
mediated host defence.
36
CD4+ T cells and CD8+ T cells cooperation in eradication
of intracellular microbes
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Mechanisms of cell-mediated
resistance by pathogenic microbes
• Mechanisms by which microbes resist T
lymphocyte-mediated host defence
include:
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Evasion of cell-mediated immunity by microbes
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Evasion of cell-mediated immunity by microbes
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Evasion of cell-mediated immunity by microbes
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