Transcript Help to T cells

T cells
Jan Novák
The immune system
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Protection against infectious agents
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Clearance of dying, damaged and
dangerous cells
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Regulation of the immune responses
The immune system
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Non-specific defence mechanisms
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Innate immune system
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Adaptive immune system
The adaptive immune system
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T cells - cellular
immune responses
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B cells – humoral
immune responses
T cells
Central role in the immune system
 Coordination of the immune response
 Cytotoxic functions
 Suppression of the immune responses
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T cells versus B cells
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Minimal morphological
differences
Differentiation based on
the detection of surface
markers
B cells: CD19, B220,
T cells: TCR, CD3, CD4,
CD5, CD8 etc.
T cell receptor (TCR)
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Antigen recognition (ab +
CD4/8 – MHC class I/II)
Signalization (CD3
transmembrane complex)
defosforilations
Proliferation,
differentiation, effector
functions
Phenotype of T cells
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T cell receptor (TCR)
Other receptors involved in the antigen
recognition and signalization (CD4, CD8, CD3)
Receptors and molecules involved in the
migration of T cells
Receptors for cytokines
Activation markers (CD25, CD28, CD69)
T cells
 ab
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- T cells
CD4 helpers
Th1
 Th2
 Th3
 Th17
 CD4+CD25+
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CD8 cytotoxic T cells
 iNKT (CD4+CD8- a CD4-CD8-)
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 gd
T cells
The pathway of T cell development
10
Thymus
Today
Thursday
12
TCR development
The development of infinite repertoire of
TCRs
 Each TCR of each T cell can recognize
one antigen
 The repertoire of all TCR has the capacity
to recognize any antigen
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Formation of TCR repertoire
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Organization of genes coding for TCR is similar to the
genes coding for immunoglobulins
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Gene complexes TCRa (TCRg)  gene complex for IgH
Gene complexes TCRb (TCRd)  gene complex for IgL
TCR development
TCR is encoded by several gene
segments
 V - variability
 D - diversity
 J - joining
 C - constant
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TCR development
Random rearrangement of V,D,J and C
segments
 Recombination of gene segments (D-J, VD)
 Recombination controlled by RAG
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TCR development
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Rearrangement of gene
segments for b chains
Expression of pre-TCR
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b chain
CD3 complex
pre-a chain
Rearrangement of gene
segments for a chains
Formation of definitive
TCR
Central education/deletion
The maintenance of T cell
tolerance
T cells
 ab
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- T cells
CD4 helpers
Th1
 Th2
 Th3
 Th17
 CD4+CD25+
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CD8 cytotoxic T cells
 iNKT (CD4+CD8- a CD4-CD8-)
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 gd
T cells
CD4+ T cell activation
MHC class II – TCR-CD4 interaction
CD4+
T cell
APC
Costimulation
CD80/86-CD28
CD4+ T cells – T helpers
Th1
IL-12
Th0
Naive Th0
cell
Th0
APC
TCR – MHC interaction
Engagement of
costimulation pathways
IL-4
Th2
TGF-b
Cytokine milie
Th3
Th1 cells
Inflammatory cells
 Production of cytokines:
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(IFN) – g
 interleukin (IL) – 2
 tumor necrosis factor (TNF) - a
 interferon
Th1 cells
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Help to
macrophages (M)
Activation of M
(IFN–g)
Stimulation of their
killing activities
Elimination of
intracellular agents
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Help to T cells
Differentiate into Th1
profile (due to the IL12 production by
APC)
Secretion of
autocrinne growth
factor of T cells IL-2
Th1 cells
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Involved in the clearance of
intracellular pathogens
Involved in the delayed type
of hypersensitivity
Involved in some
autoimmune diseases
Th2 cells
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Production of cytokines
 IL-4
 IL-5
 IL-6
 IL-13
Th2 cells
Help to B cells
 Antibody production by B cells is
dependent on the help of T cells (Th2)
 Cytokine dependent help: IL-4
 Cell contact dependent help: CD40 (B cell)
- CD154 (T cell) interaction
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Th3
Th2 cells
Specific (direct) help
T
APC
Nonspecific (bystander) help
T
APC
B
B
Th3
Th2 cells
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Participation in the
defense against
extracellular agents
Participation in the
allergic reactions
Th3
Th1 – Th2 competition
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Th1 cytokines inhibit the development of
Th2 responses
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Th2 cytokines inhibit the development of
Th1 responses
Th3
Th3 cells
Develop in the presence of TGF-b, IL-10
and IL-4
 Secretion of TGF-b and IL-10
 Induced after oral administration of
antigens, play a role in the induction of
oral tolerance
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Th3
Cytotoxic CD8+ T cells
Elimination of dangerous cells
 Direct elimination of cells infected by
intracellular pathogens
 Elimination of stressed cells (tumors,
damaged cells)
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Activation of CD8+ T cells
Recognition, activation
CD8
MHC class I - TCR
Somatic
cell
CD4 help CD4
CD8
APC
APC activation
Killing by CD8+ T cells
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CD8
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Somatic
cell
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Perforin-granzyme system
(degranulation, perforation,
apoptotic death)
Fas-FasL interaction
(apoptotic death)
Cytokine dependent lymphotoxin (apoptotic
death)
Killing by CD8+ T cells –
Perforin-granzyme system
Killing by CD8+ T cells –
Fas – dependent killing
CD8+ T cells in immune reactions
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Clearance of infected
cells – viruses,
bacteria, parasites)
Elimination of tumor
cells in cooperation
with NK cells
Elimination of dying
and damaged cells
Literature
Immunobiology – The immune system in
health and disease: Charles A. Janeway
Jr., Garland Publishing, 2001
 The autoimmune diseases: Noel A. Rose,
Academic Press – Third edition, 1998
 Medical Immunology: Tristam G. Parslow,
Lange – Tenth edition, 2001
 Nature Reviews Immunology
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