Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
29 Cards in this Set
- Front
- Back
Signals for T Lymphocyte Effector Functions |
Only require Ag:MHC (Signal 1) Does not require costimulatory molecules once activated. |
|
What signal draws activated T cells out of lymph node? |
CXCR5 and Sphingosine 1 phosphate (S1P). Once exit lymph node, T cells stop expressing CCR7 chemokine receptor. Blocked by the drug FTY720, which inhibits T cell responses and transplantation rejection. |
|
How are naive T and B cells drawn into reactive lymph node? |
T cell lymph node homing receptors: CCR7 binds to CCL19 and CCL21. LFA1 binds to ICAM. L-selectin binds to L-selectin ligand. |
|
T cell lymph node honing - chemokines |
T cells have chemokine receptor CCR7 on surface, which is drawn to chemokines CCL19/21 from lymph node. B cells have chemokine receptor CXCR5 on surface, which is drawn to chemokines CXCL13 from lymph node. |
|
How are effector T and B cells targeted to site of injury? |
Change chemokine receptors and integrins expressed so that they are attracted to chemokines released at site of injury. L-selectin changes to E- and P-selectin ligand. LFA-1 changes to LFA-1 (I-CAM1) or VLA-4 (VCAM-1) CCR3 changes to CXCR3 (CXCL10) |
|
From which vessels do lymphocytes enter and exit lymph node? |
Enter via blood stream Exit via efferent lymphatic vessel, to thoracic duct and then to blood stream and periphery. |
|
How long does adaptive immune response take to kick in? |
Bout a week or so |
|
Signals for T and B cell directions and duties |
Selectin - Rolling/tethering. Slows down T cell. Chemokine - Stimulate/signaling. Signals that there is an inflammatory response nearby. Integrin - Firm adhesion. Chemokine signal converts integrin from low- to high-affinity state. Finally leads to diapedesis. |
|
Effector function of CD8+ T cell |
Sense intracellular pathogen (mycobacteria, listeria, cryptococcus, rickettsia). Do not require signal 2. Induce apoptosis and cell death. Also induce cytokine secretion (IFNy) leading to inflammation. |
|
CD8 T cell activation and effector phase |
Activation - Forms granules with perforins (pore-forming) and granzymes (serine proteases). Requires costimulation with CD28 (or else, anergy). Effector - Granule exocytosis, does not require costimulation. |
|
CD4 T cell help of CD8 T cells. |
APC can activate both CD4+ and CD8+ T cell at same time (cross-presentation) CD4 T cells "help" T cells through both binding to the APC. Uses "DC Licensing" - CD40L (CD4+) binding to CD40 (APC) licenses the dendritic cell to induce a proper CD8+ response via CD27 (CD8+) binding to CD70 (APC) Patients with hyper-IgM (faulty CD40) also have decreased CD8+ function because CD4+ cannot help CD8+. |
|
Mechanisms of cell-mediated immunity by CD8 cells. |
1. Perforins form pore in target cells, allowing granzymes (serine proteases) to enter. Granzymes activate caspases to induce apoptosis. 2. T cells upregulate Fas-L on surface. Can bind Fas on target cell. Induces apoptosis in target cell via caspase activation. |
|
Perforin homology |
Perforin is structurally homologous to complement C9, part of MAC. |
|
Is perforin sufficient to produce apoptosis? |
Mammalian cells can protect themselves from perforin-induced pores. Perforins and granzymes together is sufficient to induce caspase cascade and cell death. |
|
Perforin deficiency |
HLH (hemophagocytic lymphohistiocytosis) Fever, splenomegaly, hemophagocytosis, high levels of inflammatory cytokines (IFNy, TNFa) T cells can make granules but are unable to kill target. Release cytokines including IFNy. Leads to high levels of macrophage activation. |
|
Chediak-Higashi syndrome |
Deficiency in granule exocytosis. Causes inflammatory signals and HLH-like presentation because cannot secrete perforins on to target. |
|
Treatment for HLH |
Anti-IFNy antibody. Macrophages are not activated so inflammatory cytokines are not secreted, mass phagocytosis and clinical presentation is prevented. Increases survival of mice. |
|
Can one CTL kill multiple targets? |
Yes |
|
What cytokines do different helper T cells secrete? What cell types do they signal to? |
Th1 - IFNy, TNFa, lymphotoxin - signal to monocytes/macrophages Th2 - IL-4, IL-5, IL-13, IL-25, Amphiregulin, IL-10 - signal to eosinophils Th17 - IL-17, IL-21, IL-22 - signal to neutrophils Treg - TGFb, IL-10 - suppress T cell |
|
What is signal 3 for T cell activatoin? |
Cytokines present during primary T cell activation. If T cell exposed to IFNy or IL-12 during activation -> Th1 If T cell exposed to IL-4 during activation -> Th2 If T cell exposed to TGFb, IL-6, or IL-21 during activation -> Th17 If T cell exposed to TGFb or IL-10 during activation -> Treg |
|
Downstream functions of Th1, Th2, and Th17 |
Th1 - Intracellular pathogens Th2 - Extracellular parasites, allergy/asthma Th17 - Extracellular pathogens, fungi, autoimmunity |
|
What transcription factors promote development of helper T cell into each subtype? |
TFs open up domains of chromatin associates with genes necessary for subtype Th1 - T-bet Th2 - GATA-3 Th17 - RORyt Treg - FOXP3 |
|
Th1 function |
Detects typical intracellular pathogens - viruses, mycobacteria, listeria, cryptococcus, rickettsia. Signals via IFNy to monocytes and macrophages to phagocytose. |
|
Activation of macrophages by TH1 cells |
Called Delayed Type (IV) Hypersensitivity IFNy hyperactivates macrophages leading to phagocytosis, secretion of cytokines, and inflammatory response. |
|
Th2 function |
Secrete IL-4 and IL-5 to drive immune response to typical extracellular pathogens - staphyloococcus, helminths, clostridium. Driven by eosinophils. Also stimulates allergic response, driven by mast cell histamine relase. |
|
Th17 function |
Secrete IL17 and stimulate (a) neutrophil response and (b) epithelial cell antimicrobial peptide production. |
|
Job's Syndrome |
Also called Hyper-IgE syndrome Inherited mutations in STAT3, intermediate signalling in cytokine receptor leading to secretion of RORyt, IL-17, IL-22. In absence of STAT3, no IL-17 function. Presents with recurrent staphylococcus (extracellular bacteria) and fungal infections (candida). Unknown how loss of Th17 leads to hyper-IgE. |
|
Memory cells |
Associated iwth more rapid and larger response for both B and T cells. i.e. Memory T cells secrete IFNy within 6 hours rather than 7 days. |
|
Lymphocyte response to HHV-3 |
Overtime, lose frequency of T cells for HHV, even if had chicken pox as child (although antibody responses are still good). Can develop shingles. |