Term
| Describe the role of antigen presenting cells in T cell activation |
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Definition
Dendritic cells, macrophages, B cells
Present antigenic peptide via MHC I&II
Express co-stimulatory molecules, secrete cytokines |
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Term
Describe a dendritic cell as antigen-presenting cells
-routes of antigen processing and presentation
-location in lymph node
-Ag uptake
-MHC expression
-co-stimulator delivery
-Ag presented
-Location in body |
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Definition
They initiate adaptive immune responses in lymph nodes
In the spleen they initiate adaptive immune responses against blood borne pathogens
Receptor-mediated endocytosis: EC bacteria, MHCII, CD4 T cells
Macro-pinocytosis: EC bacteria/soluble Ag/virus particles, MHCII, CD4 T cells
Viral infxn: viruses, MHCI, CD8 T cells
Cross-presentation after phagocytic or micropinocytic: viruses, MHCI, CD8 T cells
T-cell areas
macropinocytosis & phagocytosis by tissue dendritic cells; viral infxn
low on tissue dendritic cells
high on dendritic cells in lymphoid tissue
constitutive by mature, nonphagocytic lymphoid dendritic cells
peptides, viral antigens, allergens
ubiquitous throughout body |
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Term
Describe macrophages as antigen-presenting cells
-location in lymph node
-Ag uptake
-MHC expression
-co-stimulator delivery
-Ag presented
-Location in body |
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Definition
found throughout lymph node
phagocytosis
inducible by bacteria and cytokines
inducible
particulate Ag; IC & EC pathogens
lymphoid tissue, connective tissue, body cavities |
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Term
Describe B cells as antigen-presenting cells
-location in lymph node
-Ag uptake
-MHC expression
-co-stimulator delivery
-Ag presented
-Location in body |
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Definition
follicle
Ag-specific receptor (Ig)
Constitutive, increases on activation
Inducible
Soluble Ag, toxins, viruses
Lymphoid tissue, peripheral blood |
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Term
| Describe how different routes of antigen processing and presentation result in activation of different subset of T cells |
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Definition
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Term
| Describe the steps in T cell activation, including TCR, co-receptor (CD4 or CD8), adhesion molecules, and co-stimulatory signals |
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Definition
T cells enter lymph nodes from the lymph & blood
-L-selectin binds GlyCAM-1 and CD34, allows rolling interaction
-LFA-1 binds ICAM-1
-diapedesis: lymphocyte leaves blood & enters lymph node
Naive T cell activation req's 2 signals:
-binding of TCR & co-R CD4 to peptide:MHCII on dendritic cell
-ligand C28 recognizes Ag, binds co-stim molec B7
-pathogens induce expression of co-stim molec on APC
-adjuvants administered with protein vaccines also induce expression of these cells
Induction of TCR signaling
-CD3 molec & zeta chains contain ITAM, are responsible for signaling once TCR binds peptide/MHC
-Zap-70 is imp
Once activated, T cells make IL-2, induces proliferation - clonal expansion |
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Term
| Describe peripheral tolerance of T cells |
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Definition
Activation of T cell requires co-stim signal and specific signal
Signal 1 comes from TCR
Signal 2 comes from co-R
specific signal only -> anergic
co-stim signal only -> no effect (T cell becomes non-responsive)
T cell tolerance to Ag expressed on non-professional APC results from Ag recognition w/o co-stimulation |
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Term
State the characteristics of Th1, Th2, and Th17 cell subsets, and their importance in immunity (function) and disease
how does the circulating cytokine milieu influence the differentiation of a naive CD4 T cell? |
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Definition
Th1:
-IL-2, IFN-gamma, LT
-imp in cell immunity, inducing production of opsonizing Ab
-tuberculoid leprosy, low infectivity
-activate macrophages to kill intravesicular bacteria (IFN-gamma, CD40L)
-kills chronically infected macrophages (Fas ligand or LT)
-induces T cell proliferation (IL-2)
-induces macrophage differentiation in BM (IL-3 + GM-CSF)
-activates endothelium to induce macrophage adhesion & exit from BV (TNF-alpha + LT)
-causes macrophages to accumulate (CXCL2)
Th2:
-IL-4, IL-5, IL-10
-general activation of B cells to make Ab
-lepromatous leprosy, high infectivity
Th17: can mobilize neutrophils
TGF-beta -> FoxP3, TGF-beta, IL-10 -> Treg cells
IL-12, IFN-gamma -> T-bet, IL-2, IFN-g -> Th1 cells
IL-4 -> GATA-3, IL-4, IL-5 -> Th2 cells |
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Term
| Discuss how CD8 T cells become activated, and why co-stimulation is not required for activated CD8 T cells to perform effector functions |
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Definition
requirements are very stringent!
Dendritic cells express hi B7, activate naive CD8 T cells -> makes IL-2, driving its own proliferation
APC stimulates effector CD4 T cell, activates APC -> expresses B7, co-stimulates naive CD8 T cell
APC activates CD4 T cell to make IL-2 & naive CD8 T cell to express IL-2 R -> IL-2 secreted by activated CD4 T cell is bound by CD8 T cell
Once stimulated, T cells don't require co-stim to perform effector functions
-activation of naive T cells req's T cell to recognize both specific Ag and a B7 co-stim on APC
-proliferation & differentiation produces effector T cells that can respond to cells have specific Ag on their surface but no B7 (which most cell types never express) |
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Term
| List and describe the two major mechanisms that cytotoxic T cells utilize to kill cells |
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Definition
Kills cells through the release of lytic granules
-cytoplasmic granules containing perforin, granzyme B
-perforin forms pore in target cell membrane
-granzyme B enters cell through pore, induces apoptosis
Kills cells via FAS ligand:FAS interactions b/t cytotoxic T cells:target cell, induces apoptosis |
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Term
State the difference between naïve, effector, and memory cells
-cell surface PT
-how memory & effector cells are different from naive T cells |
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Definition
Naive: L-selectin, +(LFA-1, CD2, CD4, TCR, CD44, CD45RA)
-L-selectin keeps them coming back to lymph nodes, allows them to get in
Activated: +VLA-4, ++(LFA-1, CD2), +(CD4, TCR), ++CD44, +CD45RO
M&E cells: circulate through tissue other than secondary lymph nodes (go to site of infxn); reduced need for co-stim to become activated & perform effector functions |
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Term
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Definition
Expressed on activated T cells
Binds to B7 with higher affinity than CD28 - out-competes CD28
Dampens activation of T cells
Limits T cell proliferation
Imp for shutting down T cell responses |
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Term
| Stages of CD4 T cell activation |
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Definition
| Naive CD4 -> proliferating T cell -> immature effector T cell -> TH1 or TH2 |
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Term
| Effector molecules made by T cells |
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Definition
CD8:
-cytotoxins: perforin, granzymes, granulysin
-cytokines: IFN-gamma, LT
Th1:
cytokines: IFN-gamma, GM-CSF, TNF-alpha, LT, IL-3
Th2:
cytokines: IL-4, IL-5, IL-10, IL-13, TGF-beta |
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Term
| Autoimmune lymphoproliferative syndrome (ALPS) |
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Definition
Patients lack Fas
Fas/FasL interactions are imp for removing extra, self-reactive, or unwanted lymphocytes
big swollen lymph nodes, lots of extra T cells and lymphocytes - CD8 T cells can't kill virally infected cells |
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