Unit 3 Flashcards
T Cell Development (93 cards)
1
Q
Positive Selection
A
Selection for those cells whose Tcell receptors respond to self-MHC
resulting in MHC restriction
2
Q
Negative Selection
A
Selection against those cells whose Tcell receptors react strongly to self-peptide/MHC combinations
Resulting in Self-Tolerance
3
Q
Lineage Commitment
A
Commitment of thymocytes to effector cell lineages, including CD4+ helper or CD8+ Cytotoxic populations
4
Q
Notch
A
regulates the decision of a lymphoid precursor to becoming a T vs B lymphocyte
5
Q
When Notch 1 is overexpressed in hematopoietic cells, which cells develop in the bone marrow
A
T Cells develop
6
Q
When Notch 1 is knocked out among hematopoietic precursors, Which cells develop in the bone marrow?
A
B Cells Develop
7
Q
Double-Negative cells
A
T cells which
8
Q
DN1 Genotype
A
Ckit(Cd117)++
CD44+
CD25-
9
Q
DN1 Location & Description
A
BoneMarrow to Thymus (Migration to thymus)
10
Q
DN2 Genotype
A
Ckit (CD 117)++ CD44+ CD25+
11
Q
DN2 Location & Description
A
Subcapsular cortex
TCr gamma, Delta and Beta chain rearrangement
T-Cell Lineage commitment
12
Q
Which DN stage has t-Cell Lineage commitment
A
DN2
13
Q
DN3 Genotype
A
Ckit CD117+ CD44- CD25+
14
Q
DN3 Location and Description
A
Subcapsular Cortex
Expression of Pre-TCR
Beta Selection
15
Q
DN4 Genotype
A
CKIT CD117 Low/- CD44- CD25-
16
Q
DN4 Location and Description
A
Subcapsular Cortex to Cortex
Proliferation, allelic exclusion of Beta Chain
Lics Alpha CHain locus rearrangement begins
Becomes DP Thymocyte
17
Q
CKIT CD117
A
The receptor for stem cell growth factor
18
Q
CD44
A
An Adhesion molecule
19
Q
CD25
A
Alpha chain of the IL2 Receptor
20
Q
DN1 Thymocytes
A
First to enter the thymus and capable of giving rise to multiple cell types. They express only Ckit and CD44, but once they encounter the thymic environment, they proliferate and express CD25, becoming DN2 Cells
21
Q
DN2 Thymocytes
A
Genes for TCR Gamma, Delta, and Beta chains begin to rearrange (NOT ALPHA). Precursors fully commit to T-Cell lineage
22
Q
DN3 Thymocytes
A
Continue rearrangement of the TCR beta, Delta, and Gamma chains and make their first major decision in D-Cell development: whether to join Alpha-Beta or Gamma-Delta.
23
Q
DN4 Thymocytes
A
Those DN3 cells which successfully rearrange their beta chain and commit to the TCR Alpha-Beta T-Cell lineage lose expression of CD25, halt proliferation and enter DN4 stages, which mature into Double Positive thymocytes
24
Q
Which cells develop into Double-Positive Thymocytes
A
DN4
25
How likely is a T Cell to become Alpha-Beta vs Gamma Delta? Why?
3x more likely to become Alpha-Beta than gamma-Delta because B chain requires one frame arrangement, while Gamma-Delta requires two separate ones
26
Gamma -Delta T Cells can recognize which types of unconventional antigens
Lipids associated w unconventional MHC molecules
27
Pre-TCR Signaling events
1. Maturation to DN4
2. Rapid Proliferation in subcapsular cortex
3. Suppression of further rearrangement of TCR Beta chain genes, resulring in allelic exclusion of the BEta chain locus
4. Development to the CD4+ CD8+ (DP)
5. Cessation of Proliferation
6. Initiation of TCR Alpha Chain rearrangment
28
Allelic Exclusion
The rsult of inhibition of further rearrangment at the otther TCRB allele which must be fully rearrangeed to be expressed. Reducing RAG expression to stio rearrangment &chromatin repackaging can stop rearrangement
29
Percentage of DP Thymocytes that meet the selection criteria and exit the thymus as mature T Cells
2-5%
30
TCR Affinity for self if Affinity is too high
Negatively selected
Deleted
2-5%
31
TCR Affinity for self if Affinity too low
Fail to be positively selected
Death By neglect
90-96%
32
TCR Affinity for Self if Affinity is intermediate
Positively selected
Survive
2-5%
33
AIRE
Protein that allows cells to express, process, and present prteins that are ordinarily only found in specific organs
34
Superantigens
```
Viral or Bacterial prteins that bind simultaneously to the VB domain of a T-Cel receptor and to the Alpha chain of a class II MHC molecule (Outside peptide binding groove), can induce activatio of all T Cells that express that faimily of VB chains
They can induce the negative selection of all DP thymocytes in that target
```
35
Affinity Hypothesis
Asserts that differences in the strength of TCR-Mediated signals received by thymocytes undergoing positive and negatvie selection determine the outcoe of the interacion. DP cells w low-affinity signals would be postively selected and those w no signal would die by neglect
36
Kinetic Signaling Model for T-Cell Lineage Commitment
A Proposal that thymocytescommit to the CD4+ T Cell lineage if they receive a continuous signal in response to the TCR coreceptor engagement, but commit to CD8 if the TCR signal is interrupted
37
Instructive Model for T-Cell Lineage Commitment
TR/CD4 and TCR/CD8 coengagement generates unique signals that directly initiate distinct developmental programs
38
Stochastic Model for T-Cell Lineage Commitment
a positively selected thymocyte randomly down-regulates CD4 or CD8. Only those cells that express the correct coreceptor (engage w MHC w correct CTC ) generate a TCR strong enough to mature
39
Intraepithelial Lymphocytes (IEL)
*Mostly CD8+
| have features of innate immune cellsand patrol mucosal surfaces
40
NKT cells
include mature expressed CD4 cells and cells tht have lost CD4 and CD8
play a role in innate immunity
Express a TCR that include an invariant Alpha Chain
MHC Presents Glycolipids, not peptides
41
T Regulatory Cells
Can inhibit the proliferation of other T cell population in vitro, effectively suppressing autoreactive immune responses. They express CD4, CD25, and the Alpha chain of IL2 receptor. They must also have FOXP3, a transcriptional regulator
Develop in Thymus (alternative for autoreactive cells)
42
Recent Thymic Emigrants (RTEs)
Mature T cells that exit the Thymus
not as functionally mature as most naive T Cells in the periphery
Do not proliferate or secrete cytokines
43
What is an important source of mature T cells for lymphopenic people
RTEs
44
AIRE
A protein that regulates expression of tissue specific antigens in the thymus. It is expressed by a subset of medullary epithelial cells and regulates transcription
45
Anergy
Unresponsive to antigenic stimulus
46
Apoptosis
Energy-dependent programmed cell death
| Cells dismantle their contents without disrupting the membrane and have neighboring cells engulf them
47
Necrosis
Cell death rising from injury or toxicity
| Cells Swell and burst, triggering an inflammatory response
48
Morphologic changes associated with Apoptosis
```
Pronounced decrease in cell volume
Modification of the cytoskeleton
Membrane Blebbing
Condensation of chromatin
degradation of the DNA into fragments
```
49
Caspases
A family of cysteine proteases that cleave after an aspartate residue. This protease is important in the chain of reactions that lead to apoptosis
50
Initiator caspases
Activated by a death stimulus
| Activate effector caspases
51
Effector Caspases
Execute the death program by
cleaving critical targets necessary for survival
activating other enzymes that carry out dismantling of the cell
52
Peripheral Tolerance
Process by which self-reactive lymphocytes in the circulation are eliminated, rendered anergic, or otherwise inhibited from producing an immune response
53
How do regulatory T Cells inactivate traditional T Cells
Cytokine Deprivation
Inhibitory Cytokines (IL-10, TGF Beta)
Inhibiting Antigen Presenting Cells
Cytotoxicity
54
Naive T Cells
Mature, But have not encountered an antigen
| Recirculate every 12-24 hours
55
Avidity
The combined affinity of all cell-cell interactions
56
2 Signals required for Full T-Cell Activation
Signal 1 Provided by Antigen-Specific TCR Engagement
| Signal 2 Provided by contact w costimulatory ligand, which can only be expressed by a funtctional APC
57
What happens when the T cell gets both full signals
It will be activated to produce cytokines that enhance entry into the cell cycle and proliferation
58
Costimulatory Receptors
Receptors expressed on the surface of T Cells that deliver one of the two required signals for T Cell activation (signal 2).
59
When are costimulatory receptors activated
When engaged by ligands, which are typically expressed by a professional APC.
60
What is the most common costimulatory receptor
CD28
61
Negative Costimulatory Receptors
Receptors expressed on the surface of some T Cells that send signals that inhibit T Cell Activation.
62
Common Negative Costimulatory Receptor
CTLA-4
63
CTLA 4
Common Negative Costimulatory Receptor which is expressed on some activated T Cells and helps to downregulate immune responses when the antigen is clear
64
CD 28 Costimulation
CD80
CD86
Expressed by professional APCs
Activates Naive T Cells
65
ICOS Costimulation
ICOS- Ligand
Expressed by B Cells, Some APCs, and T Cells
Mantains activity of differentiated T Cells, a feature of T-B Cell interactions
66
CTLA-4 Negative Costimulation
CD80
CD86
Expressed by Professional APCs
Negative regulation of the immune response, reducing inflammation
67
PD-1 Negative Costimulation
PD-L1
PD-L2
Expressed by Professional APCs, some tumor cells, T And B Cells
Negative regulation of the immune response, regulation of T-Reg Differentiation
68
BTLA Negative Costimulation
HVEM
Expressed by Some APCs, T and B Cells
Negative regulation of the immune response, regulation of T-reg Differentiation
69
3 Signals required for Activation of Naive T Cells
```
TCR Signaling (TCR/MHC-Peptide interaction)
Costimulatory Interaction (CD28 or ICOS)
Cytokine Signaling (IL2)
```
70
Exogenous Superantigens
Soluble Proteins secreted by bacteria
71
Exotoxins
```
Toxins secreted by Gam Positive bacteria such as staph enterotoxins, Toxic shock syndrome, exfoliative dermatitis
Binds to BB sequences in T Cell Receptors and Cross-Links the TCR to a class II MHC Molecule
```
72
Endogenous Superantigens
Cell Membrane proteins generated by specific viral genes that have integrated into mammalian genomes
73
How do T Helper Cells affect other cells
T Helper cells regulate activation and antibody production of B Cells, Enhance Phagocytic, antimicrobial, cytolytic, and antigen-presenting capacity of macrophages, and are required for the development of B ell and CD8+ T-Cell memory
74
Autocrine
Acting on the same cell that produced them
75
Paracrine
Acting on the cells in the vicinity
76
T Helper 1
secretes IL-2 IFN-Gamma, ad TNF-Beta
| and is responsible for many classic cell-mediated functions, including activation of T-C and Macrophages
77
T Helper 2
Secretes IL-4 IL-5 IL-6 IL-9 IL-10, and IL-13
| and regulates B-Cell activity and differentiation
78
Adjuvant
Exert their influence on the innate immune system by regulating the expression of costimulatory ligands and cytokines by ACsm events that ultimately shape the consequences of T-Cell Activation
79
TH1 Polarizing Cytokines
IL-12
IFN-GAMMA
IL-18
80
TH1 Master gene regulators and effector Cytokines
T-Bet
IFN-Gamma
RNF
81
TH1 Functions
Enhance APC activity
Enhance Cytotoxic T Actvation
Protect against intracellular pathogens
Involved in Delayed type herpersensitivity, Autoimmunity
82
TH2 Polarizing Cytokine
IL-4
83
TH2 MAster gene regulators and Effector Cytokine
GATA 2
IL-4
IL-5
IL-13
84
TH2 Function
Protect Against extracellular pathogens (IGE responses)
| Involved in Allergy
85
TH17 Polarizing Cytokine
TGF Beta
IL-6
IL-23
86
TH17 Master Gene regulator and effector cytokines
ROR Gamma
IL17A
IL17F
IL22
87
TH17 Function
Protects against some fungal and bacterial infections
| Contributes to inflammation, Autoimmunity
88
T-Reg Polarizing Cytokines
TGF-B
| IL-2
89
T-Reg Master Gene Regulator and Effector Cytokines
FOX P3
IL-10
TGF-B
90
T-Reg Function
Inhibits Inflammation
91
T-FH Polarizing Cytokines
Bcl-6
92
T-FH Master Gene Regulators and Effector Cytokines
IL-4
| IL-21
93
T-FH Functions
B Cell Help in Follicles and germinal centers
