Costimulation – Lymphocyte Activation

by Peter Delves, PhD

My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      05 Slides Lymphocyte Activation.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    00:01 In order to activate lymphocytes, stimulation through the antigen receptor alone is not sufficient.

    00:10 You need what is referred to as co-stimulation.

    00:16 So here we have a T-cell, that’s a naïve T-cell, it hasn’t encountered antigen before.

    00:22 Its T-cell receptor is recognizing peptide MHC on the surface of an antigen presenting cell, like a dendritic cell. So this APC (antigen presenting cell) is showing peptide together with MHC to the T-cell receptor on the naïve T-cell.

    00:38 But actually nothing’s happening, because that’s the only signal that the T-cell is getting.

    00:44 And the result, if there is stimulation only through the antigen receptor, will be that there is actually functional inactivation of the T-cell; a process that is referred to as anergy.

    00:56 So there’s no response and we have a form of immunological tolerance.

    01:02 And this process of inactivating T-cells is very useful in preventing unwanted reactivity against self antigens.

    01:13 However, in the context of infection, dendritic cells become activated by the Pathogen-Associated Molecular Patterns present on microbes.

    01:24 And part of that activation of the dendritic cell, causes them to increase the expression of co-stimulatory molecules like the B7 molecules and also to release co-stimulatory cytokines such as interleukin-12.

    01:40 So in the context of infection, dendritic cells up-regulate the co-stimulatory molecules and cytokines that are required for T-cell activation.

    01:51 This will cause T-cells to themselves produce cytokines such as interleukin-2, and this will feed back onto the interleukin-2 receptor which is also expressed on these T-cells.

    02:03 And you’ll get extensive proliferation following activation of these T-cells, the development of effector T-cells, T-cell survival, proliferation and differentiation.

    02:14 The CD80 and CD86 B7 molecules are not the only molecules that are involved in co-stimulation.

    02:21 So here we have an example of a dendritic cell that is expressing the molecule CD40 on its cell surface.

    02:31 When the T-cell is stimulated by the dendritic cell, one of the things that can happen is that CD40 ligand becomes expressed on the T-cell.

    02:47 And the CD40 ligand binds to the CD40 on the dendritic cell.

    02:53 And this can lead the dendritic cell to express higher levels of B7.

    02:59 So there’s a feedback loop whereby interaction of CD40 ligand on the T-cell with CD40 on the dendritic cell, causes the dendritic cell to increase its expression of the B7 molecule - CD80 and CD86; and also to release cytokines.

    03:17 So the activated dendritic cells stimulate T-cell proliferation and differentiation.

    03:23 They have on their cell surface all the molecules now required to do that.

    03:27 They have MHC and peptide that can stimulate the T-cell receptor.

    03:32 They have CD40 that stimulates through CD40 ligand.

    03:36 And crucially, they have those all important B7 molecules that can co-stimulate via the CD28 molecule on the surface of the T-lymphocyte.

    03:47 And also they’re producing cytokines that further aid in the activation.

    03:51 So you have enhanced T-cell proliferation and differentiation resulting from these co-stimulatory signals.

    About the Lecture

    The lecture Costimulation – Lymphocyte Activation by Peter Delves, PhD is from the course Adaptive Immune System.

    Included Quiz Questions

    1. CD28
    2. CD86
    3. B7.1
    4. B7.2
    5. CD40
    1. ...functional inactivation of the T cell following stimulation of the antigen receptor only.
    2. ...inactivation of T cell during clonal differentiation.
    3. ...functional inactivation of T cells by APCs following costimulation.
    4. ...apoptosis of a T cell due after response to self antigen.
    5. ...downregulation of cytokines that produce a costimulatory response.
    1. ...dendritic cells to upregulate expression of B7 and release cytokines.
    2. ...upregulation of CD40 in response to antigen.
    3. ...cytokine release from naive T cell.
    4. ...activation and differentiation of T cells.
    5. ...blockage of costimulation signals.

    Author of lecture Costimulation – Lymphocyte Activation

     Peter Delves, PhD

    Peter Delves, PhD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star