Term
| What happens when naïve T cell encounters its specific antigen for the first time and is stimulated to differentiate into an effector cell? |
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Definition
| T-cell activation or T-cell priming |
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Term
Upon infection, the immune system quickly recruits the small number of naïve T cells that are specific to the pathogen --> make contact with antigens derived from the pathogen.
Recruitment involves secondary lymphoid tissues |
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Definition
-Antigen is brought in from outlying tissues via lymph.
-Antigen encounters the T cells brought in via blood. |
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Term
| Interaction of a naïve T cell with antigen presented by cells other than P-APCs leads to: |
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Definition
| inactivation rather than activation of T cells(becomes anergic) |
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Term
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Definition
only known function is the triggering T-cell responses --> highly specialized and effective.
-Far superior to macrophages in stimulating naïve T cells.
-Reason, dendritic cells are migratory cells --> carry load of antigen from infection site to nearest secondary lymphoid tissues. |
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Term
| In tissues, dendritic cells are active in the capture, uptake and processing of antigen – called |
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Definition
immature dendritic cells.
-In secondary lymphoid tissues, dendritic cells gain the capacity to interact with T cells – called mature or activated dendritic cells.
-Mature dendritic cells have finger-like processes called dendrites that contact T cells in the cortex of lymph node |
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Term
| Macrophages stop pathogens from entering the bloodsream. If pathogen makes it to blood potentially: |
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Definition
| systemic release of TNF-alpha (leads to death) |
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Term
| nearest lymph node to infection will become: |
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Definition
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Term
| Dendritic cells tell MHC plus peptide to move to |
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Definition
| secondary lymphoid tisue (drainage lymph) through HEVs to resent to Tcells |
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Term
-Skin and peripheral tissue infection =
-Blood infections =
-Respiratory mucosa infection =
-Gastrointestinal infections = |
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Definition
-T cell response in draining lymph nodes.
-antigen enter the spleen
-tonsils or other bronchial-associated lymphoid tissue (BALT).
-Peyers patches, appendix or gut-associated lymphoid tissues (GALT)
Similar sequence of events in each case |
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Term
| On reaching a lymph node “mature” dendritic cells begins |
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Definition
| antigen presentation to T-cells, stimulating the T cells instead of uptaking and processing antigen. |
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Term
| Naïve T cells enter lymphoid tissues via |
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Definition
| blood capillaries or from the afferent lymph. |
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Term
| When the T cell encounters a peptide:MHC complex that it can bind to |
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Definition
| the T cell is retained in the lymph node and is activated, then proliferates and differentiates into a clone of effector T cells. |
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Term
Naïve T cells (blue & green) recirculate through secondary lymphoid organs, such as the lymph node.
These leave the blood through HEVs and enter the lymph node cortex, where they mingle with professional APCs (mainly dendritic cell and macrophages).
T cells that do not encounter their specific cells and antigen |
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Definition
leave the lymph node in the efferent lymph and eventually rejoin the bloodstream.
T cells that encounter antigen (blue) on antigen-presenting cells are activated to proliferate and to differentiate into effector cells.
These effector T cells can also leave the lymph node in the efferent lymph and enter the circulation. |
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Term
| Most T cells that enter a lymph node |
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Definition
| do not encounter a specific antigen and will recirculate for many years |
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Term
| Once an antigen-specific T cell is trapped in the lymph node by an APC and activated |
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Definition
it takes several days for the activated T cell to proliferate and differentiate into effector T cells .
= delay between onset of infection and appearance of primary adaptive immune response |
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Term
| Passage of naïve T cell out of the bloodstream, through HEV to the lymph node cortex is controlled by |
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Definition
cell-surface molecules on the T cells and endothelial cells
-These contacts are initiated by adhesion molecules on the T cell which bind to complementary molecules on other cells |
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Term
| Adhesion molecules of the immune system comprise four structural classes |
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Definition
1. Selectins – are carbohydrate-binding lectins
2. Vascular addressins - contain carbohydrate groups to which selectins bind
3. Integrins
4. Proteins in the immunoglobulin superfamily |
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Term
| Receptors on Tcell that recognize chemokines |
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Definition
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Term
Movement of naïve T cells into secondary lymphoid tissues
Homing |
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Definition
| determined by T-cell surface selectin (L-selectin) interacting with two vascular addressins on surface of HEV venules (CD34 & GlyCAM-1) |
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Term
| L-selectin on naïve T cells (and naïve B cells) binds to |
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Definition
| sulfated carbohydrate sialyl-Lewisx moieties of vascular addressins CD34 and GlyCAM-1 on the high endothelial cells of lymph venules |
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Term
Lymphocytes bind to the endothelium in the lymph node through interaction of L-selectin with vascular addressins.
Chemokines, which are also bound to the endothelium, activate the |
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Definition
the integrin LFA-1 on the lymphocyte surface enabling it to bind tightly to ICAM-1 on the endothelial cell.
Establishment of tight binding allows the lymphocyte to squeeze between two endothelial cells, leaving the lumen of the blood vessel and entering the lymph node
The T-cells will migrate toward the high concentrations of CCL21 and CCL19 within the lymph node |
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Term
As naïve T cells move through the cortex of the lymph node, these will bind transiently to APCs.
The initial encounter of T cells with antigen-presenting dendritic cells involves |
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Definition
integrins and members of the immunoglobulin superfamily:
-The T cell’s LFA-1 binds to ICAM-1 or ICAM-2 on the APC
-The APC’s LFA-1 binds to ICAM-3 on the T cell |
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Term
Adhesion is strengthened by:
(These transitory interactions allow the T cell to screen the peptide:MHC complexes on the APCs) |
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Definition
-CD2 on the T cell binding to LFA-3 on the APC.
-ICAM-3 on the T cell and the lectin DC-SIGN on activated dendritic cell. |
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Term
| When activated transient adhesive interactions need: |
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Definition
| confirmational change in LFA-1 to get tighter binding (gives high affinity to ICAMs) |
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Term
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Definition
| direct Tcells out of lymph and back into circulation in Tcell doesnt meet its antigen. If it is meet--> pulling in of S1P receptors so Tcell doesnt leave lymph node |
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Term
| Initial intracellular signal generated by TCR:peptide:MHC complex = necessary for naïve T cell activation but… |
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Definition
Not sufficient…..a second co-stimulatory signal is required.
Co-stimulatory signals delivered by APC.
Both the antigen-specific stimulation and the co-stimulation must be delivered by ligands on the same APC. |
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Term
| Binding of the T-cell receptor and its co-receptor CD4 to the peptide:MHC class II complex on the dendritic cell delivers a signal 1. |
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Definition
This signal induces clonal expansion of T cells only when the co-stimulatory signal 2 is also given by the binding of CD28 (on the T cell ) to B7 (on the APC).
Both CD28 and B7 are members of the immunoglobulin superfamily.
(2 clases of B7) |
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Term
B7 exression is
(B7 along with CD28 Also known to as co-stimulatory molecules or co-stimulator molecules) |
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Definition
| direct consequence of infection, induced by interaction of a potential APC with microbial products via cell-surface receptors that contribute to innate immune response |
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Term
| CD28 is the receptor for activation and when binds to B7 will express another B7 receptor called |
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Definition
| CTLA-4 (binds B7 twentyfold more strongly than does CD28 and functions as an antagonist) -limits cell proliferation |
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Term
The characteristic that distinguishes professional antigen-presenting cells (APCs) from other antigen-presenting cells is the presence of B7 co-stimulatory molecules on their surface
The three kind of professional APCs are: |
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Definition
the dendritic cell, the macrophage and the B cell.
All three types are present in secondary lymphoid tissues but at different locations. |
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Term
Dendritic cells are where in the lymph node?
Macrophages?
Bcells? |
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Definition
-Cortical Tcell areas
-Throughout the lymphnode (by afferent and efferent lymphn, Tcell area to activte Tcells, Bcell area to tell Bcells to die by apoptosis if not activated)
-Lymphoid follicles in the cortex (germinal centers) |
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Term
Immature dendritic cells phagocytose microbial antigens using DEC 205 receptors (among others)
Antigens can also be taken up nonspecifically by |
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Definition
macropinocytosis in which a cell engulfs extracellular fluid (ECF).
*Important for initiation of T-cell viral responses
-Dendritic cells acquire viral antigens via infection or by taking up virus particles from the ECF or other infected cells . |
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Term
| Activated dendritic cells not only express B7 and class II MHC molecules but also express |
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Definition
high levels of adhesion molecules (i.e. DC-SIGN) and secrete the chemokine CCL18 to attract naïve T-cells.
DC-SIGN binds to ICAM-3 on the T-cell |
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Term
| Once a Tcell is told to become anergic, |
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Definition
| can never be activated again |
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Term
Immature DC (dendritic cell):
DEC205 facilitates |
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Definition
| phagocytosis and pinocytosis of antigens |
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Term
| Mature DC: Increase expression of |
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Definition
| B7 co-stimulators, MHC molecules and adhesions molecules like DC-SIGN |
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Term
Macrophages are found throughout the lymph node tissue and have several different functions:
Are phagocytic cells that take up microbes and particles from the extracellular environment |
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Definition
-Degrade microorganism in phagolysosomes that are loaded with hydrolytic enzymes.
-Trap and degrade pathogens this enables macrophages to process and present antigen to naïve T cells and prevents infection from reaching blood.
-Prevents noninfectious particulates from lymph nodes from entering blood and blocking small blood vessels.
-Remove and degrade lymphocytes that die in secondary lymphoid tissues. |
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Term
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Definition
| activation of mature naive Tcells by antigen presented to them by prof. APCs |
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Term
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Definition
| stimulation of mature naive Tcells by antigen presented to them by prof. APCs --> leads to their proliferation an differentiation into effector T cells |
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Term
| In the absence of infection, macrophages do not express B7 co-stimulators but have receptors that recognize |
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Definition
| bacterial components that are part of the innate immune recognition response: mannose receptor, scavenger receptors, complement receptors and Toll-like receptors. (When these receptors are engaged signals transmitted to the macrophage induce expression of B7 and increase expression MHC molecules) |
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Term
| Activation of naïve T cells leads to |
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Definition
| CD28 binding to B7 along with peptide:MHC complexes binding to TCR and co-receptor binding. |
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Term
| B cell Ig binds specific antigen from extracellular environment |
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Definition
| Ag:Ig complex --> internalized by receptor-mediated endocytosis -> transported to endocytic vesicles degraded into peptides -> peptides bind MHC class II molecules ->peptide:MHC class II complex -> transported to cell surface |
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Term
| In the primary immune response, the naïve B-cells are activated by |
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Definition
effector T-cells that were activated in the same secondary lymphoid tissue.
They don’t typically activate naïve T-cells in the primary immune response. |
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Term
| CD3 cytoplasmic tails contain sequences called ITAMS which |
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Definition
associate with cytoplasmic protein tyrosine kinases.
Kinases are activated by receptor clustering and phosphorylate ITAM tyrosine residues.
Enzymes and other signaling molecules bind to the phosphorylated tyrosine residues and become activated.
Pathways of intracellular signaling are initiated to effect alterations in gene expression. |
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Term
| Signaling pathways initiated by the T-cell receptor complex, its CD4 co-receptor and CD28 |
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Definition
| Naive Tcell interacts w DC presenting its antigen--> activation of kinase Zap-70 ->activation of PLC-gamma which cleaves PIP2 -> makes DAG and IP3-----> eventually NFkappaB, NFAT and AP-1 change the pattern of gene expression Transcription factors)->leads to prolif. and diff. to effector Tcells |
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Term
| One of the most important genes to be transcribed codes for the cytokine IL-2. Activation of T cell by professional APC initiates a program of differentiation controlled by |
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Definition
the cytokine IL-2.
A burst cell division
Acquisition of effector function
IL-2 is synthesized and secreted by activated T cells.
IL-2 binds IL-2 receptors of T cell to drive clonal expansion of the activated cell
IL-2 is one of a number of cytokines produced by activated and effector T cells to control the development differentiation of cells in the immune response. |
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Term
| IL-2 production requires both the signal delivered through the TCR:co-receptor complex and the co-stimulatory signal delivered through CD28. Signals through the TCR:CD3 complex activate |
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Definition
NFAT -> activate transcription of the IL-2 gene (IL-2 mRNA is inherently unstable).
Co-stimulation (CD28:B7) stabilizes the IL-2 mRNA which causes an increase in the synthesis of IL-2 by T cells (X 20-30).
Co-stimulation also activates other transcription factors that stimulate the transcription of the IL-2 gene (3X).
Principal effect of co-stimulation is to increase synthesis of IL-2 by 100 fold. |
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Term
| IL-2 binds to the IL-2 receptor producing |
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Definition
| an intracellular signal that promotes T-cell proliferation |
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Term
| When a TCR on a mature naïve T cell binds to a peptide:MHC complex on an APC that does not express the co-stimulatory molecule B7 |
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Definition
| B7 the T cell becomes nonresponsive or anergic and cannot be activated with subsequent antigen encounter |
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Term
Some mature naïve T cells may be specific for self-proteins expressed by cells not found in the thymus.
These T cells will not be activated because |
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Definition
because the cells expressing these self antigens will not express the co-stimulatory molecule, B7.
A mature, naïve T cell that binds a self-peptide:MHC complex on a cell without B7 does not receive a co-stimulatory signal and undergoes anergy.
Anergic T-cells don’t make IL-2 -> no proliferation or differentiation
Anergic T cells can never be stimulated to proliferate or differentiate.
This process induces tolerance in the mature T cell repertoire. |
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Term
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Definition
| more effective vaccines than highly purified Ag molecules |
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Term
Towards the end of the proliferative phase, T cells acquire the capacity to synthesize the proteins they need to perform their specialized functions.
The main cytokines secreted by TH1 cells |
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Definition
| cells (INF-gamma and IL-2) lead to macrophages activation, inflammation and production of opsonizing antibodies to enhance phagocytosis of pathogens. IL-2 & INFgamma produce IL-2 and INF-gamma |
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Term
| The main cytokines secreted by TH2 cells |
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Definition
(IL-4 and 5) lead to B-cell differentiation and production of neutralizing antibody.
IL-4 produces IL-4 |
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Term
| Only type of cell with high enough concn of B7 to activate CD8s?? |
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Definition
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Term
| A response biased towards TH1 cells is |
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Definition
| called cell-mediated immunity because the response is mediated by effector cells. |
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Term
| A response biased toward TH2 cells is called |
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Definition
| humoral immunity because the response is dominated by the production of antibodies |
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Term
| CD8 T cells stimulated by antigen and co-stimulation will synthesize IL-2 and the high affinity IL-2 receptor, which induces |
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Definition
their proliferation and differentiation.
Under conditions of suboptimal co-stimulation, CD4 T cells can help activated naïve CD8 T cells.
CD4 and CD8 T cells must recognize the their specific antigen on the same APC, then the CD4 T cells will secrete cytokines that upregulate co-stimulation on the APC, which then activates the CD8 T cell. |
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Term
Activated effector T cell VERSUS Resting naïve T cells
How are they different? |
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Definition
1. Types of cell surface molecules expressed
2. Abundance of these cell surface molecules |
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Term
| L-selectin in naive (resting) lymphocytes |
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Definition
| hel gain access (allows rolling adhesion to allow tight binding) thru HEVs (attahed to HEVs) |
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Term
| LFA-1 and CD2 upgrade from resting phase to activated phase |
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Definition
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Term
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Definition
| makes Tcell more sensitive to presentation |
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Term
| Effector T cells can respond to their specific antigen without the need for co-stimulation via B7-CD28 interaction |
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Definition
Effector T cells can respond to antigen presented on cells other than professional antigen-presenting cells.
What’s the benefit of these relaxed activation requirements for effector T cells?
Cytotoxic CD8 T cells must recognize many types of cells. |
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Term
| Once an effector Tcell no need for: |
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Definition
| L-selectin (and more LFA-1 made). VLA-4 put up instead which binds to VCAM-1 |
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Term
| VLA-4 enables Tcells to go to |
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Definition
| site of infection (surface proteins such as VCAM-1 ut on infected cells (i.e. endothelial cells) --> to attract VLA-4 |
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Term
| INF-gamma is the main cytokine |
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Definition
| that sets up Th1 bias--> Th1 secretes INF-gamma which activates macrophages |
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Term
Secreted cytokines and related membrane-bound proteins that act through cell-surface receptors generally to induce changes in gene expression within target cells.
Work locally and work over short period of time |
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Definition
Autocrines: act on the cell that produced them
Paracrines: act locally on another cell
Ex. INF alpha and beta as paracrine- but can ac as autocrine too |
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Term
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Definition
| JAKs and STATs to change expresion of genes |
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Term
CD8 cytokines:
CD4 TH1:
TH2: |
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Definition
-INFgamma
-INFgamma, TNFalpha and IL3
-IL4, IL5 |
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Term
CD8 T cells synthesize cytotoxins in inactive forms and package them into lytic granules when T cells are activated by specific antigen in the secondary lymphoid organs.
CD8 T cells then migrate to |
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Definition
sites of infection and will recognize specific peptides (made from proteins from infected cell) in the context of MHC class I molecules presented by the infected cell.
TCR binding signals the cytotoxic T cell to secrete the contents of lytic granules directly onto a small localized area on the surface of the infected target cell. |
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Term
| Specific recognition of peptide:MHC complex on an infected cell by a cytotoxic CD8 T cell (CTL) programs the infected cell to die and leaves healthy cells alone |
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Definition
| The CTL detaches from the first target cell (which dies), synthesizes a new set of lytic granules and then seeks out and kills another infected cell (new target). |
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Term
| In addition to cytotoxic functions, CD8 cells also contribute to the immune response by secreting cytokines |
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Definition
Secretion of interferon-gamma inhibits the replication of viruses in the infected cells
IFN-gamma also increases the processing and presentation of viral antigen by MHC class I molecules.
IFN-gamma activates macrophages in the vicinity of the cytotoxic T cells.
Activated macrophages then get rid of dying infected cells helping damaged tissue to repair |
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Term
| T cells induce apoptosis by two pathways (1) initiated by cytotoxins and (2) interactions with cell surface molecules |
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Definition
Perforin (protein that polymerizes to form transmembrane pores in cell membranes, Granulysin also perturbs the membrane and granzymes, a family of three serine proteases .
Perforin and granulysin make pores in the target cell membrane for the granzymes to enter and cleave certain cell proteins leading to the activation of nucleases and other enzymes to initiate apoptosis. |
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Term
| Second death pathway involves inducing apoptosis between cell surface molecules on the cytotoxic T cell and the target cells. |
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Definition
Activated T cells surface cytokine – Fas ligand (FasL), which binds to the Fas receptor molecule on the surface of the target cell.
Fas:FasL interaction sends a signal to the target cell to undergo apoptosis.
Main pathway to kill unwanted or excess lymphocytes. |
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Term
| Lymphadenopathy in autoimmune lymphoproliferation syndrome (ALPS |
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Definition
Individuals who lack functional Fas molecules cannot control the size of their lymphocyte population nor remove autoimmune cells
Secondary lymphoid organs become swollen in the absence of infection |
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Term
| Tcell binds to MHC (ITAMS in intracellular domain) |
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Definition
| ITAMS phosphorylated by (kinase)FYN --> Zap 70 binds to the phoshorylated areas, CD4 binds to LCK (kinase) which phosporylates ZAP 70 --> activates phospholipase C --> cleaves PIP2 to IP3 and DAG |
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Term
| I3 and DAG make transcription factors (that change gene expression) |
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Definition
| NFkappaB,NFAT, and AP-1 (make IL2 and alpha chain of IL2) |
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Term
| IL-3 plus GM-CSF tells bonemarrow to make |
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Definition
| macrophages and neutrophils |
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