Objectives Mention the types of T cells List the Types of T helper cell (CD4+) Discuss the Activation of T cells Define Interleukins Distinguish the Super Ag from ordinary Ag Show the action T Cytotoxic cells (CD 8+)
T lymphocytes
-They constitute 60-80% of total lymphocytes -They differentiated into ; -T helper Th (CD4+ cells) kills the target Ag in association with class II MHC by secreting of Interleukins (IL) that regulate the immune reactions -Th 17 (CD4+ cells) -T reg. CD4+ &CD25+ (T helper 3) -T cytotoxic Tc CD8+ kills the target Ag in association with class I MHC -Memory cell (CD4+ OR CD8+)T cell markers ( Receptors & Molecules)
Antigen receptor ; (TCR) heterodimer non identical polypeptide chain linked by disulphide bond divided intoTCR1 α,β while TCR2 γ,δ chains TCR varies in their a.a. as the variable region of IgFc receptor for IgG & IgMReceptor for sheep RBCs (E-Roseate) T cellSheep RBC
MOL. Of T Lymphocytes
CD2 (LFA)adhesion Mol. Present in all T cells CD3 polypeptide chains near TCR for signal transduction . Present in all T cells CD4 only on Th cells react with class II MHC to control Th cell activation (immune restriction) CD8 on Tc cells react with class I MHC to control Tc cell activation (immune restriction) CD 28 on Th cells react with B7 mol.(Co-stimulatory signal)Types of T helper cells T Helper (TH) Cells: Central role in immune response. (Th1) CD4+ ,Recognize antigen on the surface of antigen presenting cells (e.g.: macrophage) in the groove of class II MHC Function :Activate macrophages ,NK cells, Th & cytotoxic T cells. (Th2) CD4+ Activate & regulate B cells Recognize antigen on the surface of antigen presenting cells (Usually B Lymphocytes) in the groove of class II MHC
T helper
Th1(IL 12) Intracellular Ag presented by macrophage & Dendritic cells Secrete TNF, IL2, IL3 gamma IFN Regulate cellular ImmunityTh2(IL4) Extracellular Ag Presented by B lymphocyte Secrete IL4,IL5, IL6 IL 10 Regulate humoral immunity
Th3Suppress Th1 cell Secrete TGFβ&IL 10 which inhibitIL12 So anti-inflammatory cell
Activation of T helper Lymphocyte
T h cells can not recognize & react with an Ag unless presented by APC in association with class II MHC for activation of Th (CD4+) cells Class II presented only on the surface of APC So APC focus & engulf the Ag,( usually Exogenous) slice it through lysozomal enz. With preservation of its epitops which will be coupled with class II through the endocystic pathway then distributed on the surface of APCAPC
IL2
Th cells regulate the proliferation and activity of other cells of the immune system: TC, NK cells, macrophages, neutrophils, etc. through Th1 (Cellular immunity) And regulate B lymphocyte through Th2 (Humoral immunity)
Th cells regulate the immune system by Interleukins
CytokinesCytokines: They are soluble mediators with hormonal like action secreted by various cells & act on many target cells & play an important role in the regulation of the immune response so they are Chemical messengers of immune cells. Over 100 have been identified. Stimulate and/or regulate immune responses. Interleukins: Communication between WBCs. Interferons: Protect against viral infections. Chemokines: Attract WBCs to infected areas
Different from hormonesAct locally Autocrine or paracrine while the hormones are endocrinesIL they have a lower conc. Than hormones & secreted only on need not continuous as the HormonesIL either pro inflammatory as IL2,6, 17 , TNF,gamma IFNOr anti inflammatory as IL 10 TGFβ
Super Ag
Potent T cell Mitogen trigger mitosis of CD4+ cells in the absence of Ag processing . It is able to activate a large population of T h cells up to 20% of all peripheral blood Th cells, so realizing a large quantity of cytokines as TNF Toxic shock syndrome(Staph. Toxin) (toxins, Mycoplasma some viruses). Cytotoxic T (Tc) Cells: Destroy target cells. They are CD4 negative (CD4 -) but CD8 positive (CD8+) Recognize antigens on the surface of all nucleated cells: Kill host cells that are infected with viruses Recognize and kill cancer cells. Recognize and destroy transplanted tissue. Release protein called perforin which forms a pore in target cell, causing lysis of infected cells. Release TNF & Granzymes
Cytotoxic T cell Tc=CD8 It lyses the target cell on viral infected cell & get rid of foreign cell (tumor cell) that exposure non self Ag associated With class 1 Ag Mode Of killing = hit & run 1-Releasing preforin protein =pore memb. 2-TNF Inhibit prot. Synthesis & produce toxin free radicals 3-granzyme
Esterase degrade protein cell memb.
Nuclease degrade Nucleic acid