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20130415 Lecture 8
Biochem Activation of T lymphocytes
| Question | Answer |
|---|---|
| CD4 helper T cells can activate ____, macrophages, NK cells, and help _____ cells to class switch? | CD8 T cells; B |
| The ability of the CD4 T cell to ______ is essential to mobilizing the immune response? | self-replicate |
| CD8 T cells require _____ from CD4 T cells to replicate? | IL-2 |
| Clonal selection of naive CD4 and CD8 T cells requires a ____ APC? | dendritic |
| CD4 and CD8 T cells require ____ bound to ____ for antigen recognition? | peptide; MHC |
| T/F CD4 and CD8 T cells can recognize only protein antigens. | True |
| Besides peptide-MHC, ____ molecules and _____ molecules are also required to fully activate T cells? | co-stimulatory; adhesion |
| Naive T cells are only activated by dendritic cells. Why? | because dendritic cells possess all of the necessary co-stimulatory activity |
| Signal 1 is the peptide-MC presenting to the ____? | TCR |
| Signal 2 is _____? | co-stimulation |
| T/F Either Signal 1 or Signal 2 is needed for T cell activation-but not both. | False-both are needed |
| What can a lack of co-stimulation lead to? | anergy (opposite of energy) or production of T regulatory cells |
| T/F Lack of co-stimulation can act as a protective mechanism. | True-preventing self-reactive T cells that have escaped thymic deletion from attacking self |
| A self-reactive T cell that encounters sel-antigen, w/out co-stimulation, will be _____? | turned off (peripheral tolerance) |
| B7/CD28 are the best characterized _____? | co-stimulatory molecules |
| B7-1 and B7-2 are expressed on activated ____ and bind to the _____ receptor on T cells? | APCs; CD28 |
| T/F B7 is at high levels on inactivated APCs. | False-B7 is expressed mostly on activated dendritic cells, macrophages, and B lymphocytes (all can be activated APCs) BUT at low levels on unactivated APCs |
| B7-1 on an activated APC binding to CD28 receptor on T cell is this? (hint: a step) | Signal 2 required for lymphocyte activation |
| CD28 can activate PI-3 kinase the net result is enhanced secretion of ____ and differentiation of cells into ___ and ____ T cells? | IL-2; effector; memory |
| T/F Previously activated effector and memory cells are less dependent on co-stimulation than naive T cells. | True |
| T/F CD8 T cell replication and development into CTLs is dependent on co-stimulation. | True |
| Can CTLs kill w/out co-stimulation? | Yes |
| How can CD28 be inhibited? | Via inhibitory CD28-like receptors like CTLA-4 and PD-1. |
| How does CTLA-4 inhibit CD28 effects? | By binding to B7-1 and B7-2 because CTLA-4 has a higher affinity for the B-7s than does CD28 |
| What would happen if co-stimulation was blocked? | would turn off immune response |
| CD40 ligand (CD40L) on T cells binds to CD40 on APC eventually leading to T cell activation is the _____ activation route? | slow |
| Abatacept and Belatacept are drugs used for autoimmune diseases, they block ____ from binding _____ and inhibit co-stimulation of ___ cells. | B7; CD28; T |
| Does CTLA-4 inhibit or excite? | It is inhibitory by blocking B7 which turns off immune response from T cell |
| Ipililumab, for melanoma, is a monoclonal antibody that blocks ____ and prevents CTLA-4 from _____ T cells (causes T cell activation)? | CTLA-4; inhibiting |
| What causes T cell to remain in lymph node for replication and contact w/ other APCs? (This occurs after T cell has been activated). | CD69 binds to S1PR1 |
| W/in 24-48 hours after activation of T cell, ____ ligand increases on the cell surface allowing reciprocal activation of APCs? | CD40 |
| After 24-48 hours CTLA-4 increases and this will start to ____ T cell activation? | inhibit |
| After activation of T cells, there are sequenced alterations in T cell surface proteins that correspond to T cell function: Retention in lymph node? | CD69 |
| After activation of T cells, there are sequenced alterations in T cell surface proteins that correspond to T cell function: Proliferation? | IL-2R (CD25) |
| After activation of T cells, there are sequenced alterations in T cell surface proteins that correspond to T cell function: Amplification of effector functions? | CD40L (slow way) |
| After activation of T cells, there are sequenced alterations in T cell surface proteins that correspond to T cell function: Control of response? | CTLA-4 starts to outnumber |
| ___ is an early and critical growth (proliferation), survival and differentiation factor for T cells? | IL-2 |
| T/F IL-2 can increase proliferation of the same cell that makes it (producing clones) or adjacent cells. | True |
| IL-2 production goes up w/in ___ of T cell activation, peaks at ___ hours, and declines by ___ hours. | 2-3; 12; 24 |
| What do regulatory T cells do? | help suppress the immune response |
| Is IL-2 necessary for the survival and function of regulatory T cells? | Yes |
| T cells that recognize antigen produce ___ and respond to IL-2 because they make ____? This proliferation is called ____? | IL-2; IL-2R; clonal expansion |
| What are the T helper cell subsets that are critical for host defense? | Th1, Th2, Th17 |
| How do the same CD4 T cells elicit different responses to different pathogens? | different CD4 T cells subsets polarize or shift depending on the signals (cytokines) they get from APCs |
| Th1 cells secrete _____ and activate cell-mediated immunity effective against _____? | IFN-gamma; viruses and Mycobacterial infections |
| Th2 cells secrete ___, ____, ____, and activate _____ production effective against helminthes? | IL-4; IL-5; IL-13; IgE |
| Th17 cells secrete ____, ____, and activate ______ and _____, effective against bacteria? | IL-17; IL-22; neutrophils; macrophages |
| Each subset of T helper cells produces _____ that promote its own subtype and suppress the other subtypes. T regulatory cells may be able to _____ all 3 subsets of T helper T cells? | suppress |
| All viruses stimulate ____ response? | Th1 |
| CD8 and NK rely upon ____ response to turn them into killing cells? | Th1 |
| Humans w/out _____ are susceptible to Mycobacterial infections? | IFN-gamma |
| IFN-gamma inhibits the Th2 and ____ subsets and promotes further polarization towards _____? | Th17; Th1 |
| Th2 cells are stimulated by ___ in response to ____ and ____? | IL-4; helminths; allergies |
| Allergic responses can promote ____ development due to IL-4 and inhibit the ___ and ___ subsets? | Th2; Th1; Th17 |
| TGF-beta | made by Treg cells and suppresses Th1 and Th2 but does not suppress Th17 cells |
| Extracellular bacteria killing experts? | Th17 --> Neutrophils, monocytic inflammation |
| How do CD4 T cells help CD8 T cells? | CD4 cells secrete cytokines that stimulate CD8 cells into CTLs. CD4 secretes more IL-2 which CD8 needs. CD4 has CD40L which can also stimulate CD8 T cells |
| Does your immune system ever forget an antigen? | Nope-immunity is forever |
| T/F The number of memory T cells is smaller than the number of naive T cells for a particular antigen after the first exposure. | False-the number of memory T cells is larger |
| IL-7 | the key cytokine for maintenance of CD4 and CD8 memory T cells |
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