Transcript T cells
T cells.
Phenotype, function,
fallacies.
Jan Novák
T cells
Central role in the immune system
Recognition of antigens
Direct effect on the antigens
Coordination of the immune response
Suppression of the immune responses
T cells versus B cells
Minimal morphological
differences
Differentiation based on the
detection of surface markers
B cells: CD19, B220,
T cells: TCR, CD3, CD4,
CD5, CD8 etc.
Phenotype of T cells
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)
Groups of T cells
T cells
T-helpers (CD4+)
Th1
Th2
Th3
Cytotoxic T cells (CD8+)
NKT cells
Regulatory T cells (CD4+CD25+)
T cells
CD4+ T lymfocyty – T helpers
Th1
IL-12
Th0
Th0
APC
Th2
IL-4
TGF-
TGF- + IL-6
Th3
Th17
Th1 cells
Inflammatory cells
Help to macrophages
Activation, stimulation of their killing activities
Elimination of intracellular agents
Help to T cells
Proliferation, Th1 differentiation
Production of cytokines (IFN-, TNF-, IL-2)
Th1 cells
Clearance of
intracellular pathogens
Delayed type of
hypersensitivity
Autoimmune diseases
Th2 cells
Help to B cells
Development
Antibody production
Regulatory functions
Production of cytokines (IL-4,IL-5,IL-6,IL-13)
Th2 cells
Defense against
extracellular agents
Participation in
allergic reactions
Th3
Th3 cells
Develop in the presence of TGF-, IL-10 and IL-4
Secretion of TGF- and IL-10
Induced after oral administration of antigens, play a
role in the induction of oral tolerance
Th3
Th17
Development in the presence of TGF-b a IL-6,
IL-21, IL-23
Secretion of IL-17, IL-21, IL-22
Proinflammatory cytokines
Role in the immune defense against Klebsiella a
citrobacter
Contribution ion the pathogenesis of some
organ-specific autoimmune diseases in
experimental model
Th3
Cytotoxic CD8+ T cells
Elimination of dangerous cells of the body
Elimination of cells infected by intracellular
pathogens
Elimination of stressed cells (tumors,
damaged cells)
Killing by CD8+ T cells
Perforin-granzyme system (degranulation,
perforation, apoptotic death)
Fas-FasL interaction (apoptotic death)
Cytokine dependent -lymphotoxin (apoptotic
death)
CD8+ T cells in immune reactions
Clearance of infection
Onco-immunosurveillance
Regulatory T cells
CD8+ T cells are not supressors!!!
CD4+CD25+ T cells
Th3 T cells
T reg cells
NKT cells
T cells
Functions of regulatory T cells
Inhibition of the immune responses
Maintenance of immunological tolerance
Regulation of exagerated reaction against
infection
Supresssion of anti-tumor responses
Functions of regulatory T cells
Cell-contact dependent mechanisms
Secretion of cytokines (IL-4, IL-10, TGF-)
Killing of effector cells
NK cells
NK = natural killer
Large granular lymphocytes
Development in bone marrow
Immune reactions of NK cells
Functions antigen-non specific
Recognition of unknown structures on the
surface of target cells
Immune reactions of NK cells
The function of NK cells is a result of the
interaction of their inhibitory and activation
receptors
Activation: Fc receptor CD16
ADCC – antibody-dependent cellular
cytotoxicity
Inhibition – killer inhibitory receptors (Ly49,
CD94-NKG2)
Immune reactions of NK cells
Cytotoxicity – perforin-granzyme dependent
Immune reactions of NKT
cells
Natural Killer T cells
Phynotypic and functional features of both NK
and T cells
Immune reactions of NKT
cells
Natural Killer T cells
Phynotypic and functional features of both NK
and T cells
Restriction by MHC class I like molecule
CD1d presenting glycolipids and lipids
Phenotype of NKT cells
Expression of TCR, CD3, CD4
Expression of markers of NK lineage
Biased TCR repertoire
Recognition of conserved glycolipid structure
presented by CD1d
Functions of NKT cells
Secretion of both, Th1 and Th2 cytokines
Impact on Th1/Th2 differentiation of naive T cells
Activation of B cells
Activation of NK cells
Activation of dendritic and other ather antigen
presenting cells
Cytotoxic functions
Regulatory functions
T cells in the development of
diseases
Defence against infection -
immunodeficiencies
Allergic reactions
Autoimmunity
Oncological diseases
Immunodeficiencies
Primary (SCID, RAG, common chain)
Secondary (HIV, tumors, metabolic disorders,
malnutrition, sepsis)
Immunodeficiencies clinical features
Life-threatening – asymptomatic relapsing
infections (viruses, fungi, intracellular
bacterias)
Human immunodeficiency virus
Retrovirus, RNA virus
Targets selectively
CD4+ T cells,
macrophages and
dendritic cells
HIV infection
1. 3-12 weeks after infection: Flu-like
syndrom
2. Asymptomatic period, decrease of
CD4+ T cells, production of anti-HIV
antibodies
HIV infection
3. AIDS related
complex:
generalized
lymphadenopaty,
diarrhoe,
candidiasis, fever
HIV infection
4. AIDS: infekce
oportunními patogeny
pneumocysty,
kryptokoky,
toxoplazmoza, CMV
retinitis, enteritidis,
pneumonitis, encefalitis,
maligní nádory Kaposhi sarkom,
primární lymfom mozku,
NHL B, HIV
encefalopatie
Allergic and hypersensitive reactions
Type 1 of immunopotahologic reactions
Pathological production of IgE antibodies
1.: binding of IgE on mast cells and bazofiles,
degranulation and histamine, bradykinine release
oedema
2.: eozinofiles, Th2 cells – secretion of leukotriens a
prostaglandines smooth muscle constriction
Participation of Th2 and NKT cells, production of IL-4,
IL-13.
Allergic and hypersensitive reactions
Evolutionary – reactions
against worms and
parazites
Allergic reactions –
orms, parazites, dust,
food antigens…
Autoimmunity
Reaction of the immune system against body-
own tissues
Failure of the immune system to eliminate
autoreactive T cells (central, peripheral
tolerance).
Autoimmune diseases
Th1 biase of autoreactive T cells
Prevention of the disease by Th2 switching
Participation of Th1 and CD8+ T cells in
tissue destruction by cytotoxic mechanisms
and cytokines
Autoimmunity
Decreased numbers and impaired function of
regulatory T cells in experimental animals and
patients suffering from autoimmune diseases
Oncoimmunology
The immune system has the
capacity to detect and to
destroy tumor cells
The animals deficient in T
cells develop tumors in
increased frequencies
Increased incidence of
tumor in immunosupprimed
patients
Why immune system does not
destroy all tumor cells?
The same HLA phenotype
Impaired antigen presentation by tumor cells
The selection of less immunogenic cells in
the tumor
Production of immunosuppressive factors by
tumor cells
Can we treat oncologic patients by the
manipulation of the immune system?
Detection of Tu-specific or Tu-associated
antigens
CEA, -fetoprotein, MAGE
Can we treat oncological patients by the
manipulation of the immune system?
Immunostimulation
Vaccines based on
the enhancement of
Tu presentation
In vitro expansion of
Tu Ag specific T
lymphocytes
Vaccines against oncological
disorders
Cancer of cervicis uteri
Vaccination against papilomaviruses
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