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Cell mediated immune response
1. Immune Response II
DR. SUFI H. Z. RAHMAN
MBBS, MD (IMMUNOLOGY)
LECTURER, MEDICAL FACULTY, AUCMS
2. Objectives
◆Role of antigen presenting cells in cellular
immune response
◆Role of lymphocytes in cellular immune
response
◆Mechanisms involved in cellular immune
response
◆Types cytokines and their role in cellular
immune response
◆Interaction between the components of the
immune system in regulating immune
response
3. Cell Mediated Immunity
◆Provided by T lymphocytes
◆Provides immunity to (i) intracellular bacteria
(ii) viruses, (iii) fungi, (iv) protozoa and (v)
tumours
◆T cells can recognize antigen only when it is
presented on the surface of Antigen presenting
cells (APCs) by self MHC molecules
◆This self MHC restriction results from positive
selection during maturation of T cells in the
thymus
4. Antigen Presenting Cells
◆Cells that present antigens to T lymphocytes and activate
them
◆Express both Class I and Class II MHC molecules on
surface
◆Also express B7 (B7.1 and B7.2) molecules
◆Present antigens by Class I MHC molecules to CD8+ T
cells and by Class II MHC molecules to CD4+ T cells
◆Professional APCs are Dendritic cells, Macrophages and B
6. Antigen Presentation
APCs process and present
antigens in two pathways
1. Exogenous or Endocytic
pathway: Phagocytosed
microorganisms are degraded
in the phagosomes and
peptides are presented in this
pathway by Classs II MHC
molecules
2. Endogenous or Cytosolic
pathway: Intracellular
microorganisms synthesize
protein in the cytoplasm that
are presented in this pathway
by Class I MHC molecules
8. ◆Derived from bone marrow by haematopoiesis
◆Progenitor T (Pro- T) cells migrate to thymus
◆Maturation occurs in the thymus
• Rearrange TCR gene segments and acquire TCR
• Undergo two selection process
Positive selection: Self MHC restriction
Negative selection: Self tolerance
• Acquire surface CD molecules e.g. CD3, CD4/
CD8
◆Two population of T cells are released to the
circulation:
• CD4+ or helper T (TH) cells
• CD8+ or Cytotoxic T (TC) cells
T lymphocytes
Maturation
11. Mechanism of CMI
APCs present antigens by Class I MHC molecules to CD8+ (TC)
cells and by Class II MHC molecules to CD4+ T (TH) cells
TC
B7 CD28
Antigen recognition by T cells
12. ◆T cells recognize specific
antigens presented with
MHC molecules on the
surface of APCs by TCR
◆Each T cell has 105 TCRs
on its surface all of which
recognize a one antigen
(or epitope)
◆1010 clones of T cells will
recognize 1010 antigens
Antigen recognition by T cells
Mechanism of CMI
13. ◆Antigen recognition by
TCR provides Stimulatory
signal (Signal 1) to the T
cell
◆Binding of B7 molecule
on APC with CD28
molecule on T cell
provides Co-stimulatory
signal (Signal 2) to the T
cell
Antigen recognition by T cells
Mechanism of CMI
14. ◆When T cells receive
both Stimulatory (Signal
1) and Co-stimulatory
(Signal 2) signals they
are activated (clonal
activation)
◆If the T cells receive only
the Stimulatory signal
without Co-stimulatory
signal, they are
permanently inactivated
(clonal anergy)
Stimulatory signal+ Costimulatory signal= Activation
Stimulatory signal without Costimulatory signal= Anergy
T cell
T cell
T cell activation
Mechanism of CMI
15. ◆Activated T cells start to
proliferate, synthesize and
secrete IL-2 and express IL-
2 receptors on cell surface
◆After several divisions they
differentiate to effector
and memory T cell
populations
◆Memory T cells have long
life span (20- 30 years)
and provide immunity if
the person is re-exposed
to the same antigen
T cell differentiation
Mechanism of CMI
16. Effector T cells are short-lived (few days to
weeks) cells and carry out specialized
functions e.g.
• CD8+ effector T cells: Induce apoptosis of
virus infected and tumour cells (Cytotoxic
killing)
• CD4+ effector T cells: Secrete cytokines
that cause macrophage activation to kill
intracellular pathogens and to help TC cell
and B cell activation
T cells differentiation
Mechanism of CMI
17. Antigen Elimination by CMI
Cytotoxic T cells induce
apoptosis of infected cells
bearing antigen on the
surface
CD8+ Effector T cells
18. Antigen Elimination by CMI
◆ With influence of cytokines
e.g. IL- 12 from APCs, TH
cells differentiate to TH1 cells
◆ TH1 cells release cytokines
e.g. interferon- g (IFN- g)
◆ IFN-g activates macrophages
that phagocytose and
eliminate intracellular
pathogens
CD4+ Effector T cells
19. Antigen Elimination by CMI
Activated macrophages have more phagocytic and killing
activity and they phagocytose and kill intracellular pathogens
effectively
CD4+ Effector T cells
20. Naïve cytotoxic T cells (cytotoxic T cell precursor) require
cytokines from TH cells for activation
TH cells help TC cell activation
Regulatory role of TH cells
21. Activation of naïve B cells
require
◆Direct interaction with TH cells
by
• Antigen in Class II MHC and
TCR
• CD40 and CD40L
• B7 and CD28
◆Cytokines from TH cells
TH cells help B cells
TH cells help B cells to induce humoral immune response
Regulatory role of TH cells
22. Regulatory Role of TH cells
◆ Cytokines from TH1 cells also
help TC cell activation
◆ Thus TH1 cells regulate CMI
◆ With the influence of IL-4
(from mast cells?) TH cells
differentiate to TH2 cells
◆ Cytokines from TH2 cells
help B cell activation
◆ Thus TH2 cells regulate
humoral immunity
23. 4a. Activated T cells differentiate to
effector T cells and memory T cells
(macrophages)
Interaction between the components of the immune system
CD4+ T (TH) cells regulate the function of both TC and B cells
24. TH cell activation by Superantigens
◆Superantigens are viral or
bacterial proteins that bind
simultaneously to the Vb
domain of a TCR and to the a
chain of class II MHC
molecule
◆They bind outside of the TCR
antigen binding cleft
◆Any T cell expressing a
particular Vb sequence will be
activated by a corresponding
superantigen
25. ◆Hence, the activation of TH cells by
superantigens is polyclonal and can affect a
huge number TH cells
◆It results in overproduction of cytokines from
TH cells (e.g. IL-2) and from macrophages
(e.g. IL-1, TNF)
◆Huge amount of cytokines produce toxic
systemic effects e.g. shock, vomiting,
diarrhoea, organ failure etc. rather than
providing immunity
◆Super antigens are usually soluble proteins
secreted by bacteria (exogenous) but may
TH cell activation by Superantigens
26. Superantigen Disease
Enterotoxin of Staphylococcus aureus Food poisoning
Toxic shock syndrome toxin (TSS1) of
Staphylococcus aureus
Toxic shock syndrome
Exfoliative dermatitis toxin of
Staphylococcus aureus
Scalded skin syndrome
Erythrogenic toxin of Streptococcus
pyogenes
Scarlet fever
Pyrogenic toxin of Streptococcus
pyogenes
Streptococcal Toxic shock
syndrome
Mycoplasma arthritidis supernatant Arthritis, Shock
TH cell activation by Superantigens
27. Cytokines
◆ Protein molecules secreted by
cells that regulate function of
that cell or other cells
◆ The name denotes their role in
cell to cell communication
◆ Development of an effective
immune response involves
lymphocytes and other
leukocytes
◆ Cytokines play key role in the
complex interaction between
cells of the Immune system
28. Cytokines
◆ Autocrine: Acts on the same
cell that secretes it
◆ Paracrine: Acts on adjacent
cells
◆ Endocrine: Carried by the
blood or body fluid to a
distant site and acts on
distant cells
29. Cytokines
◆ One cytokine may act on various cells and
produce various effects
◆ Many cytokines may act on the same cell
and produce same effect
◆ One cytokine may increase action of the
other
◆ One cytokine may inhibit action of the others
30.
31. Cytokines
◆ Cytokines secreted by some leukocytes and
acting on other leukocytes are called
interleukins
◆ Cytokine secreted by lymphocytes are called
lymphokines
◆ Cytokines secreted by monocytes and
macrophages are sometimes called
monokines
◆ Cytokines that cause chemotaxis of
leukocytes are called chemokines