Immuno Lec 7 - T cells and the T cell receptor Flashcards
acquired immune response; arms
-antibody mediated immune response (B cells)
-cell mediated immune response (T cells)
three potential pathways for antigen processing
- Endogenous antigen processing pathway:
‐intracellular proteins (e.g., from viruses; abnormal cells like cancer cells) are loaded onto MHC class I and presented on surface
-MHC class 1 only presents epitopes to CD8+ cytotoxic cells - Exogenous antigen processing pathway:
‐used to present peptides from endocytosed extracellular proteins (e.g., from bacteria)
‐peptides from degraded proteins get loaded onto MHC class II
-MHC class II only presents epitopes to CD4+ helper T cells - Cross‐presentation pathway:
-A phenomenon whereby “endogenous” antigens from other cells can be taken up from the extracellular environment by an antigen‐presenting cell (i.e., dendritic cell) and cross‐presented in the context of MHC class I (instead of MHC class II)
importancce of antigen cross presentation
- Influenza and herpes simplex viruses are examples of viruses that directly infect DCs without killing them, allowing CD8+ T cell responses to be initiated via the endogenous antigen processing pathway
- The cross‐presentation pathway is
essential for viruses (and other intracellular pathogens) that infect cells other than DCs
why are they called T cells
they mature in the thymus
surface receptors of T cells, their ligands and functions
IL2 - a critical cytokine for T cell survival
CH58 - expressed on target cells and antigen presenting cells (allows cell-cell contact)
antigen receptor complex - this is how a T cell sees its target. co-stimulation is involved
- CD4 or CD8 depending if cytotoxic cell or helper cell
- CD3; needed for T cell receptor signalling
-epitope
(three above points are involved in the antigen receptor complex)
surface molecues on blood T cells
TCRy/o (gamma/omega) and WC1 are highlighted and they are expressed on the same cell type
WC1 is completely unique to vet species
WC1
- Unique to veterinary immunology
(this marker is not expressed in mice or humans) - Expressed exclusively on γ/δ T cells
- WC1 +γ/δ+ T cells are predominantly in skin and at mucosal surfaces
- Ligand for WC1 is unknown
- Probably binds to macrophages and dendritic cells to receive a co‐stimulation signal
CD4; how its unique to dogs
- CD4 is only expressed on “helper” T cells in all species except dogs
- Canine neutrophils and macrophages (but not monocytes) also express this marker
- Why should a veterinarian care?
- Diagnostics (e.g., phenotyping leukemias; myeloid vs. lymphoid)
immunological synapse (T cells)
- The “tri‐molecular complex” is required for activation of T cells (T cell receptor – antigen – MHC [class I or II])
- Two signals are required for T cell activation:
1. formation of the tri‐molecular complex
2. co‐stimulation - The cytokine milieu is often called a third signal; it influences the qualitative nature of the response (e.g., whether a CD4+ T cells adopt a T helper1 or T helper2 phenotype)
Note: sometimes signal 3 (cytokines) can serve the role of signal 2 (e.g., during antigen cross‐presentation to T cells or activation of B cells)
T cell receptor
- Gene rearrangements (in thymus) create the receptor
- 2 chains bind to form complete receptor (α/β or γ/δ)
CDR = complementarity determining region
* it is the hypervariable region of the TCR and is formed by the junction of the V + J (α and γ chains) or V + D + J (β and δ) genes
T cell receptor diversity
- There are sufficient “V”, “D” and “J” genes and variations in their recombination to facilitate detection of the antigenic universe
- # of possible gene combinations: 5 x 1015 for the α/β receptor
- TCRs recognize short peptides derived from target proteins (i.e., antigens); these are known as epitopes
T cell subsets
Role of CD4 and CD8 in promoting T cell responses. These molecules link the T cell to the antigen‐ presenting cell, binding the two cells together and ensuring that an effective signal is transmitted between them. CD4 and CD8 bind to MHC class II and MHC class I molecules, respectively
(image on slide 14 of lecture 7 if need visual)
CD4+ T cells
- Recognize epitopes presented by MHC class II
- Usually don’t have direct effector functions
- Rather, support activation of other effector mechanisms via cytokine secretion
- Hence their designation as “helper” T cells
- Promote responses against both intracellular (e.g., most viruses; TH1 cells) and extracellular pathogens (e.g., bacteria ; TH2 cells)
CD4+ T cell activation
Resting APCs, which have not been exposed to microbes or adjuvants, may present peptide antigens, but they do not express costimulators and are unable to activate naïve T cells. T cells that recognize epitopes from antigens without costimulation may become unresponsive to subsequent exposure to antigen (called T cell anergy). Microbes, and cytokines produced during innate immune responses to microbes, induce the expression of costimulators, such as B7 molecules, on the APCs. The B7 costimulators are recognized by the CD28 receptors on naïve T cells, providing “signal 2”; in conjunction with epitope recognition (“signal 1”), this recognition initiates T cell responses. APC, antigen‐presenting cell; IL, interleukin
details about CD4+ helper T cell subsets
- Th1 cells: Stimulated by interleukin (IL)‐12 and secrete interferon (IFN)‐γ in response. They generally promote cell‐mediated responses, including
antibody types that are effective against viruses in their extracellular phase. - Th2 cells: Stimulated by IL‐1 and secrete IL‐4, 1L‐13, and IL‐10. They generally promote antibody responses against extracellular pathogens.
- Th17 cells: Development is stimulated by IL‐6, tumor growth factor (TGF)‐β, and IL‐23. They secrete IL‐17 and promote neutrophil mediated inflammation.
- Tregs: These are often self‐reactive T cells that are directed in the thymic microenvironment to become immunosuppressive (to prevent autoimmunity; e.g., secrete suppressive cytokines like IL‐10 and TGF‐β)
