The Tantalizing Tale of T Cells Flashcards

1
Q

iNK T cells

A

separate population of alpha beta T cells that recognize glycolipids complexed in non-classical HLA molecules called CD1d, function through cytokines. develop prior to any VDJ rearrangments

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2
Q

gamma delta T cells

A

separate population of T cells with a unique receptor

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3
Q

order of recombination in alpha beta T cells

A

beta first: VDJ recombination, alpha locus second: VJ recombination

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4
Q

co-receptor molecules

A

either CD4 (class II MHC associations, function: suppress/help B cells) or CD8 (class I MHC associations - function: kill)

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5
Q

CD3 subunits

A

one gamme, one delta, two zeta: non-covalently associated with alpha-beta TCR dimer

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6
Q

the thymus

A

formed by epithelial cells, mesenchymal cells, and bone marrow derived hematopoietic cells that become thymocytes; has a few dendritic cells and macrophages but NO B CELLS; 3-d meshwork

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7
Q

3-d meshwork

A

of the thymus, lost in lymphopenic people, formed by the interaction of epithelial cells and the thymocytest

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8
Q

the TCR’s developmental fate

A

is determined by its weak interaction with a dendritic cell or epithelial cell’s peptide/MHC receptor (from alpha/beta T cell to the following, based on interaction – MHC II:CD4::MHC I:CD8::CD1d/glycolipid:NK)

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9
Q

double positive; single positive; double negative

A

both CD8 and CD4 receptors; either or; neither nor

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10
Q

Double Positive T cells

A

have both CD8 and CD4 molecules and are immature and are found in the thymus

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11
Q

Double Negative T cells

A

have neither receptor and are therefore B cells, found in lymph nodes

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12
Q

co-receptor development pattern

A

double negative to double positive to single positive

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13
Q

thymopoiesis

A

when double negative cells become double positive. require the cytokine IL-7 to do so.

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14
Q

beta chain rearrangements occur

A

in the double negative stage, unless a successful TCR beta locus (and pre-TCR) is expressed, the cell is arrested in the DN3 stage

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15
Q

alpha chain rearrangements

A

are initiated once the cell successfully leaves the DN3 stage, and re-expresses RAG1/2. during alpha locus rearrangements (VJ), the cell is double positive

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16
Q

3 life/death developmental fates of a alpha/beta expressing T cells

A
  1. death by neglect (what happens behin the scenes during positive selection) – when the T cell finds no HLA/peptide to interact with in the thymus 2. survival (positive selection) – when the T cell has a weak affinity to a self-HLA/self-peptide 3. death by negative selection – when the T has a strong affinity to a self-HLA/self-peptide
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17
Q

AIRE

A

a transcription factor that forces tissue specific antigens to be expressed in the thymus - mutations in AIRE cause autoimmunity

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18
Q

TRECs

A

T Cell Receptor Excision Circles: chromosomal DNA with deleted unused V and or D/J regions found in newly ‘generated’ T cells leaving the thymus, measured clinically to determine immunodeficiencies in newborns

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19
Q

FY720

A

immunosuppressive drug that blocks the movement of T cells into the blood via attachment to the S1P receptor (which usually binds to the high levels of S1P found in the blood

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20
Q

CD4 count

A

important for indicating an HIV infection - CD4 numbers less than 400 “are of immediate concern for opportunistic infections”

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21
Q

Spleen T vs. B cell count

A

T cells ~ 20 % (minority)

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22
Q

activation of what three parts of a T cell is necessary to generate a make it an “effector T cell”

A
  1. the TCR 2. a costimulatory molecule (CD28/ICOS) 3. cytokine receptor
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23
Q

effector T cells

A

no longer need three signals now that they are “committed memory T cells”

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24
Q

T cell and APC “velcro” is comprised of what

A

LFA-1, ICAM-1, VLA-4, CD2 (interactions occur in T cell enriched zones in the lymph node, the best APC is a dendritic cell)

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25
T cells get from the thymus to secondary lymphoid organs via
HEVs, or high endothelial venules; interaction via T-cell expressed L selectin
26
T-cell/APC interactions
only requires 3-5 foreign agonist peptide/HLA complexes, forms the immunological synapse
27
T Cell receptor signal cascade
tyrosine phosphorylation --> increase in intracellular Ca2+ --> activation of calcineurin & transcriptional factors (NFAT, NF-kappaB) -- also the basis of the BCR/NK/Ig-receptor cell's signaling pathways
28
CD28
co-stimulatory molecule, responsible for signal 2; binds to B7-1/B7-2 (CD80/CD86) on APCs ---> downstream: B7-1/-2 tails are tyrosine phosphorylated --> PI3K --> NF-kappaB --> translocated into nucleus = combined with signal 1, causes gene transcription and the release of cytokine IL-2
29
cell surface proteins induced upon T cell activation
chemokine receptors, increased expression of the CD40 ligand, increased expression of SIP1, expression of high-affinity IL-2 receptor, CD25
30
IL-2
secreted by the CD4 T-cell, growth factor that promotes T cell division, helps CD8 expand, works in a paracrine manner
31
CD40L
up-regulated by CD4 T-cell, aids in T cell interaction with B cells and macrophages, one of the fundamental methods of B/T-cell interactions, and allows for isotype switching. mutations in CD40L do not allow for isotype switching (Hyper-IgM syndrome)
32
Signal 3, T cell
signals 1&2 allow for T cell expansion. Signal 3 "instructs the T cell how to behave". cytokine mediated - this cytokine is produced and secreted by the associated APC
33
NK T cells
express a TCR receptor, secrete cytokines, but very rapidly, within minutes or hours of stimulation
34
cytokine release
the type of pathogen determines the type of pathogen released, different pathogens stimulate different sets of cytokines, many cells release pathogens, dendritic cells are the main cells that release pathogens
35
IL-12
Th1 cell differentiation via transcription factor t-bet
36
IL-4
Th2 cell differentiation via transcription factor GATA3 -- linked to allergy and atopy
37
Th17
viral, fungal, bacterial infections. require IL-1, IL-6, TGF-beta. activation causes RORgammat activation ---> IL-17 production
38
Tregs
suppress the development and/or activation of potential auto-reactive T cells, regulate pathogen-induced inflammatory responses, control immune cell homeostasis, characterized by Foxp3 transcription factor expression, release IL-10 and TGF-beta, serve to maintain peripheral tolerance to self-proteins
39
CD4 Treg cells
defined by the expression of the Foxp3 transcription factor, dependent on IL-2 for development
40
Tfh
T follicular helper cell - concentrate in the germinal center and support B cell activation and somatic hypermutation, key role is the production of cytokines
41
toxoplasma
common infection from the parasite T. gondii, required CD4 Th1 cells to clear
42
Th1 cells
important for clearing intracellular bacteria, viruses, and parasites via the interferon pathway
43
gamma-IFN
IL-12 induces Th1/CD8/NK cells to release this interferon, which primes cell populations to contain and eliminate infection
44
Th2 helper cells
activated by signal 3 - IL-4, IL-25 --> secrete IL-4, IL-5, IL-13 near a B cell --> IL-4 causes the B cell to secrete immunoglobulins, IL-5/IL-13 cause the B cell isotype switching to IgE
45
IL-5/IL-13
also activate macrophages and eosinophils
46
IL-10
"suppressive" cytokine released by Tregs
47
CD8 cell MO
release cytolytic granules (perforin, granzyme), resulting membrane perforations result n infected target cell lysis
48
one of the key targets of cytokines released by macrophages
macrophages (in response up-regulate cell surface proteins and undergo a "respiratory burst" to generate
49
reactive oxygen species
generated with the NADPH oxidase complex (anti bacterial products: hydrogen peroxide, nitric oxide, hydroxyl ions, hypochlorite)
50
caseous granuloma
has neurotic tissue evident in the middle, made as a result of macrophages and Th1 cells surrounding and walling off mycobacterium tuberculosis, virtually pathognomonic for lung TB
51
TNF and interferon
usually coordinate changes in other organ systems, toxic in large amounts
52
of days it takes to generate a significant amount of CD8 cells
8-10 days
53
cytokines
can act in a autocrine or paracrine manner
54
the T cell undergoes
a number of time dependent genetic changes including up regulation of CTLA-1 and fas
54
main mechanisms to decrease levels of T cells
reduction in IL-2, up-regulation of fas, expression of inhibitory molecules, differentiation of some activated T cells into memory cells
55
CTLA-4
inhibits further TCR signaling (binds to B7-1 and B7-2 with higher affinity then CD28)
55
PD-1
limits further T cell activation
56
fas
binds to fasl and causes the cell to be killed
57
memory T cells
have the characteristics of 1. memory 2. specificity
58
CTLA-4
inhibits further TCR signaling (binds to B7-1 and B7-2 with higher affinity then CD28)
59
PD-1
limits further T cell activation
60
fas
binds to fasl and causes the cell to be killed
61
memory T cells
have the characteristics of 1. memory 2. specificity
62
ITIMs
class of proteins expressed on T, B, and NK cells that associate with protein tyrosine phosphatases. They de-phosphorylate from tyrosine residues and key signaling proteins in B and T cell activation. Examples are SHP-1, SHP-1, and SHIP
63
IVIG
exogenous source of human Ig, can work by acting as a source of Igs to fight foreign infection or by competing with the host Ig and increasing the catabolism of host Ig (high doses hypothetically up-regulate an inhibitory FC receptor on macrophages and monocytes