Costimulation – Lymphocyte Activation

by Peter Delves, PhD

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    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. CD3
    4. CD4
    5. CD40
    1. Enhancing/stimulating T-cell response
    2. Reducing/inhibiting T-cell response
    3. Stimulates phagocytosis of pathogens
    4. Inhibits phagocytosis of pathogens
    5. Inhibits cytokine secretion by the T cells
    1. Upregulation of B7 and cytokine release
    2. Upregulation of major histocompatibility complex on T cells
    3. Inhibition of cytokine release by the T cells
    4. Downregulation of major histocompatibility complex on T cells
    5. Downregulation of other co-stimulatory receptors

    Author of lecture Costimulation – Lymphocyte Activation

     Peter Delves, PhD

    Peter Delves, PhD

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