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    • 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 IL-12 IL-4 TGF-  Th1 Th2 Th3 Th0 APC Th0 TGF-  IL-6 Th17
    • Th1 cells
      • Inflammatory cells
      • Help to macrophages
        • Activation , s timulation of their killing activities
        •  Elimination of intracellular agents
      • Help to T cells
        • Proliferation, Th1 differentiation
      • Production of cytokines (IFN-   TNF-   IL-2)
    • Th1 cells
      • C learance of intracellular pathogens
      • D elayed type of hypersensitivity
      • A utoimmune 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
      • D efense 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 tol er a n ce
      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 Klebsiell a 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
      • E limination of cells infected by intracellular pathogens
      • Elimination of stressed cells (tumors, damaged cells)
    • Killing by CD8+ T cells
      • Perforin-granzyme system (degranulation, perforation, apopt o tic death)
      • Fas-FasL interaction (apopt o tic death)
      • Cytokine dependent -lymphotoxin (apoptotic death)
    • CD8+ T cells in immune reactions
      • Clearance of infect ion
      • 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 inh i bitory 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, candid ia sis, 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 - as s ociated 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