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Cellular Interactions in the Immune Response - T-cell activation

Cellular Interactions in the Immune Response - T-cell activation

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BIO/MI 494 Fall 2008 Cellular Interactions in the Immune Response T-cell Activation I. Introduction 1. Overview of T-cell activation II. Review of TCR/CD3 complex 1. αβ T-cells a. Signaling components b. Immunoreceptor tyrosine based activation motifs (ITAM) 2. Comparison of properties of TCR and BCR III. Molecules involved in T-cell activation 1. Antigen recognition a. TCR 2. Accessory molecules a. Signal transduction b. Adhesion IV. Co-receptor molecules 1. CD4 and CD8 molecules a. Presence of T-cell subsets b. Structure c. Function i. Adhesion ii. Signal transduction V. Costimulatory molecules 1. Two signal model of T-cell activation 2. Requirement for costimulatory molecules a. CD28 interaction with B7 or APC b. Importance of costimulatory signals 3. Induction of CTLA-4 on activated T-cells 4. Regulation of costimulatory molecules on APC VI. Interleukin-2 (IL-2) and IL-2 receptor (IL-2R) 1. Introduction 2. IL-2 mechanism of Action 3. IL-2 receptor a. Affinities of IL-2R
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I Site of infection I Activation of effector T cells at site of infection; Activation of naive T cells in lymph node, eradication of development of effector' cells microbe FIGURE 9-1 Activation of naive and effector T cells by antigen. Antigens that are transported by dendritic cells to lymph nodes are recognIzed by naive T lymphocytes that recirculate through these lymph nodes. The T cells are activated to differentiate into effector and memory cells. which may remain in the lymphoid organs or migrate to nonlymphoid tissues. At sites of infection. the effector cells are again activated by antigens and perform their various functions. such as macrophage activation.
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Antigen recognition ~ Effector functions '======'-----~ .. ~>~E'·ffe·ctor=t> :~~~~~~~~~~, I B cells, other cells CD4+ '-----------' T cell '~~ CD4+ Tcell .'" ,.,,=+ ~o~ '- , CD8'Tcell "~~~ Killing of infected "target cells:'; macrophage activation '-- Lymphoid organs CD8+ Peripheral tissues . __-.1 Differentiation =====::-'::=====-=----_._-. ====.~ ~. ~ L:"'J,. ........ - '''1> ~~IL~2R ~~ b 0: -O-tl'----"Cytokines (e.g., IL-2) Figure 8-2 Phases of T cell responses. Antigen recognition by T cells induces cytokine (e.g., IL-2) secretion, clonal expansion as a result of IL-2-induced autocrine cell proliferation, and differentiation of the T cells into effector cells or memory cells. In the effector phase of the response, the effector CD4+ T cells respond to antigen by producing cytokines that have several actions, such as the activation of macrophages and B lympho- cytes, and CDS' CTLs respond by killing other cells. APC, antigen-presenting cell; CTL, cytolytic T lymphocyte. .----------.-.---. . ----.-. "'-1 r----------------· TCR I i . CI. ~ ; Extracellular space Plasma Figure 6-6 Components of membrane the TCR compleJ(. The TCR complex of MHC- restricted T cells consists of the Ci~ TCR noncovalently linked to the CD3 and 1;, proteins. One pos- sible stoichiometric combination \ Cytoplasm is shown, but this may vary. The associations of these proteins are mediated by charged residues in their transmembrane regions, L ..
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Cellular Interactions in the Immune Response - T-cell activation

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