MICB 212 Chapter 9 Notes

Antigen-Presenting Cells and T Cell Activation

Dendritic Cells

-liaison between innate and adaptive immune responses

-found in all parts of body that immune system patrols

-antigen-present cell

Dendritic Cell Function

  • engulf (phagocytose) and break up (process) pathogens

  • transport pathogen’s remains to local lymph node

  • dendritic cell presents peptides derived from pathogen necessary for activation of T cells

-Langerhans cells

  • immature dendritic cells in skin

  • efficiently phagocytose antigens but can’t activate T cells until they migrate to lymph node and mature

-express same pattern recognition receptors (PRRs) as macrophages

  • when PRRs are engaged → induces dendritic cells to mature and migrate from tissue to local lymph node to present peptides derived from pathogen to T cells

-express both MHC class I proteins and MHC class II proteins

-during maturation

  • dendritic cells up-regulate MHC class I and MHC class II production so that when they reach lymph node they express high levels of both proteins and ready to present antigen right when T cells are encountered

  • when engaged → PRRs induce dendritic cells to upregulate expression of other surface proteins to promote interactions with T cells → activation of cell

Co-Stimulatory Properties of Antigen-Presenting Cells

-only professional antigen-presenting cells (dendritic cells) are able to present antigenic peptides complexed with MHC proteins and provide co-stimulatory signal necessary to completely activate naive T cells

-B7 set of cell-surface proteins on antigen-presenting cell that binds to CD28 protein on T cell to provide to co-stimulatory signal

-immature dendritic cells are phagocytic but don’t express homing receptors to lymph nodes or other peripheral lymphoid organs

  • upon phagocytosis of pathogen & subsequent interaction of PRRs with PAMPs

  • dendritic cell matures → expresses homing receptors and migrates to lymph nodes and other peripheral lymphoid organs

-mature dendritic cells express high levels of MHC and B7 proteins

  • powerful activators of T cells (no longer phagocytic)

-dendritic cells most potent activators of naive T cells

-resting macrophages express low levels of MHC class II proteins

  • don’t express B7 proteins → can’t activate naive T cells

-when macrophage is stimulated by phagocytosis of antigen → increases expression of both MHC class II & B7 proteins → may activate T cells

-resting B cells express low levels of MHC class

  • don’t express B7 proteins

-binding of antigen to B cell receptor activates a B cell

-B cell increases expression of MHC class II proteins and begins to express B7 proteins

  • also up-regulate expression of B7 if its TLRs interact with PAMPs

T Cell Activation

-T cells subdivided to 2 populations based on expression of CD4 or CD8 membrane proteins

-T cells that express CD4 have TCRs that recognize antigenic peptides presented by MHC class II proteins

  • CD4 T cells function as T helper cells

-T cells that express CD8 have TCRs hat recognize antigenic peptides presented by MHC class I proteins

  • CD8 T cells function as cytotoxic cells (CTLs)

-full activation of naive T cell requires at least 3 signals

  1. interaction of T cell’s TCR with MHC + peptide complex on antigen-presenting cell

    • binding of co-receptor CD4 or CD8 to a conserved region of MHC protein presenting peptide strengthens interaction

    • CD4 and CD8 proteins don’t influence antigen specificity of TCR

    • CD3 complex signals to nucleus that TCR has recognized MHC-peptide complex of antigen-presenting cell

  2. interaction of accessory protein (CD28) on T cell with co-stimulatory protein (B7) on antigen presenting cell

  3. cytokine signalling

    • cytokines secreted by antigen-presenting cell & T cell itself

    • when activated → T cell needs cytokine IL-2 before it proliferates

    • T helper cells make enough of their own IL-2 to proliferate but CTLs don’t make enough and depend on IL-2 made by T helper cells

    • antigen-presenting cell provides enough cytokines to differentiation of T cell into effector T cell

-only professional antigen-presenting cells can provide necessary co-stimulatory function to activate naive T cells

-if T cell receives only antigen signal and fails to receive co-stimulatory signal → T cell becomes non-responsive (clonal anergy)

Activation of T Helper Cells

-CD4 T cell are T helper cells

  • recognizes antigenic peptides presented by MHC class II proteins

-role of T helper cell in adaptive immune response provides help to other cells

  • in form of cytokines

-cytokines are proteins secreted by cells of immune system used to direct behaviour of other immune cells

-T helper cells may also help by providing activation interactions involving CD40 ligand (CD40L)

  • important surface molecule for activation of B cells & enhances dendritic cell activation

-after T helper cells are activated by antigen-presenting cell

  • CD4 T helper cell provides help with

    • antigen-activated B cells

      • proliferate and differentiate into antibody secreting plasma cells

    • macrophages that have an intracellular bacterial infection

      • to increase ability of macrophage to kill bacteria

    • cytotoxic T cells (CTLs)

      • to enhance proliferation and differentiate into effector CTLs that kill virus-infected cells

Activation of Cytotoxic T Cells

-activated CD8 T cells develop into cytotoxic T cells (CTLs)

-important for recognition and elimination of cells infected with viruses and some tumours

-involved in rejection of transplanted tissues

-CD8 T cell recognize antigenic peptides presented by MHC class I proteins

-naive CD8 T cell incapable of killing target cells

-full activation and proliferation of CTLs requires sufficient concentration of IL-2

  • some provided by T helper cells

Summary

-T cell activation requires 3 signals

  • TCR ligation with MHC-peptide complex

  • co-stimulation (B7, CD28)

  • cytokine signalling

*for proliferation and differentiation

  • IL-2 also required

-CTLs are killer T cels

  • express CD8

  • recognize MHC class I protein

-T helper cells help other immune cells

  • express CD4

  • recognizes MHC class II protein