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chapter7- Flashcards

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1
Q

lymphopoiesis

A

differentiation of lymphoid cells for a common lymphoid progenitor

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2
Q

central lymphoid tissues

A

the sites of lymphocyte development, in humans these are the bone marrow (B cells) and thymus (T cells). Also called the primary lymphoid organs

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3
Q

peripheral lymphoid tissues

A

the lymph nodes, spleen, mucosal-associated lympoid tissues, in which immune responses are induced as opposed to the central lymphoid tissues, where the lymphocytes develop

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4
Q

positive selection

A

a process occurring in the thymus in which only those developing T cells whose receptors can recognize antigens presented by self MHC molecules can mature

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5
Q

negative selection

A

the process by which self-reactive thymocytes are deleted from the repertoire during T cell development in the thymus. Autoreactive B cells undergo a similar process in bone marrow

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6
Q

homeostasis

A

the state of physiological normality. In the case of the immune system, homeostasis refers to its state (for example the numbers and proportions of lymphocytes) in an uninfected individual

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7
Q

stromal cells

A

the nonlymphoid cells in central and peripheral lymphoid organs that provide soluble and cell bound signals required for lymphocyte development, survival, and migration

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8
Q

multipotent progenitor cells

A

bone marrow cells that can give rise to both lymphoid and myeloid cells but are no longer self renewing stem cells

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9
Q

common lymphoid progenitor

A

stem cells that can give rise to all the types of lymphocytes

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10
Q

immature B cells

A

b cells that have rearranged a heavy and light chain v region gene and express surface IgM, but have not yet matured to express surface IgD

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11
Q

mature B cells

A

b cells that expresses IgM and IgD on its surface and has become able to respond to antigen

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12
Q

early pro-B cells

A

a stgage in B lymphocyte development in which cells are undergoing heavy chain D-J rearrangement, not light chain rearrangement yet. Express surface marker proteins but not BCR

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13
Q

late pro-B cells

A

Stage in B lymphocyte development where cells are undergoing V-DJ rearrangement on heavy chain.

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14
Q

large pre-B cells

A

After heavy chain rearrangement in pro-B cells, Test heavy chain on cell surface to see if functional. If functional, the cell proliferates.

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15
Q

small pre-B cells

A

try to rearrange V-J on kappa chains and then the lambda rearrangement. If successful, light chain expressed with heavy chain on cell surface.

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16
Q

pre-B-cell receptor

A

receptor produced by pre-B cells that includes an Ig heavy chain as well as other proteins, and which induces the Pre-B cells to enter the cell cycle., to turn of RAG genes, to degrade RAG proteins and to proliferate

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17
Q

VpreB

A

one of the proteins in the surrogate light chain found in large pre-B cells that pairs with the heavy chain and allows it to move to cell surface.

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18
Q

allelic exclusion

A

restriction of expression of the individual chains of the antigen receptor genes, so that each individual lymphocyte produces immunoglobulin or T cell receptors of a single antigen specificity. Both heavy and light chains. If rearrangement on one chromosome is unsuccessful then rearrangement tried on other chromosome, only genes from one successful

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19
Q

isotypic exclusion

A

production of light chain from only one of the two light chain loci.

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20
Q

central tolerance

A

immunological tolerance of self antigens that is established while lymphocytes are developing in central lymphoid organs.

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21
Q

peripheral tolerance

A

the tolerance acquired by mature lymphocytes in the peripheral tissues.

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22
Q

clonal deletion

A

the elimination of immature lymphocytes when they bind to self antigens, which produces tolerance to self as required by the clonal selection theory of adaptive immunity.

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23
Q

receptor editing

A

the replacement of a light or heavy chain of a self reactive antigen receptor on immature B cells with a chain that does not confer autoreactivity.

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24
Q

anergy

A

a state of nonresponsiveness to an antigen. T an B cells don’t respond to their specific antigen under optimal conditions of stimulation

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25
immunological ignorance
a form of self tolerance in which reactive lymphocytes and their target antigen are both detectable within an individual, yet no autoimmune attack occurs. Unlikely to come into contact with antigen
26
thymic stroma
the epithelial cells (express MHCI and MHCII) and connective tissue of the thymus that form the essential microenvironment for T cell development.
27
thymic medulla
central area of the thymic lobe, rich in bone marrow development APCs (Macrophages and DCs). Macrophages help clean up discarded T cells.
28
thymic cortex
host thymic stroma (cortical epithelial cells), early stages of T cell development.
29
double negative thymocytes
immature T cells in teh thymus that lack expression of the two co-receptors CD4 and CD8. In a normal thymus, these represent 5% of thymocytes
30
DN1
in T cell development. CD44+/CD25- on cell surface. No rearrangement
31
DN2
in T cell development. CD44+/CD25+ on cell surface. D-J Beta chain rearrangement.
32
DN3
in T cell development. CD44 low/CD25+ and CD3+. V-DJ Beta rearrangement. Beta chain expressed on cell surface with a surrogate alpha chain (pTalpha) (checkpoint 1).
33
DN4
in T cell development. CD44-/CD25-. Proliferation of cells at this stage.
34
pTalpha
surrogate alpha chain that pairs with TCR-beta chains produced in DN2 and DN3 that allows expression on T cell surface, checks that heavy chains are functional
35
pre T-cell receptor
consists of TCR beta and pTalpha chains on T cell surface. Expressed in DN3, DN4 and large DP.
36
double positive thymocytes
immature T cells in the thymus that are characterized by expression of both CD4 and CD8 co-receptor proteins. Represent the majority of thymocytes. Large DP are CD4+/CD8+ and express preTCR. Small DP have VJ recombination on small chain and then expression of full TCR and CD4+/CD8+
37
single-positive thymocytes
a mature T cell that expresses either the CD4 or CD8 co-receptor but both.
38
natural regulatory T cells
regulatory CD4 T cells that are specified in the thymus. Express FoxP3 and bear the markers of CD25 and CD4 on cell sruface
39
activation induced cell death
the normal process by which all immune responses end in the death of most of the responding cells, leaving only a small number of resting memory cells
40
signal transduction
process by which a cell transforms one type of signal for example antigen binding to a lymphocyte antigen receptor into the intracellular events that signal the cell to make a particular type or response
41
protein kinases
enzymes that add phosphate groups to proteins at particular amino acid residues (tyrosine, threonine, or serine)
42
protein phosphorylation
the covalent addition of a phosphate group to a specific site on a protein. Phosphorylation can alter the activity of a protein and also provides new binding sites for other proteins to interact with it
43
tyrosine protein kinases
enzymes that specifically phosporylate tyrosine reisdes in proteins. They are critical in the signaling pathways that lead to T and B cell activation.
44
receptor tyrosine kinases
receptors that have an intrinsic tyrosine kinase activity in their cytoplasmic tails
45
nonreceptor kinases
cytoplasmic protein kinases that associate with the intracellular tails of signaling receptors and help generate the signal but are not an intrinsic part of the receptor itself.
46
protein phosphatases
enzymes that remove phosphate groups from proteins phosphorylated on tyrosine, threonine, or serine residues by protein kinases
47
SH2 domainns
part of Src family tyrosine kinases. SH2 domain binds phosphotyrosine residues.
48
Small G proteins
single subunit G proteins, such as Ras, that act as intracellular signaling molecules downstream of many transmembrane signaling events.
49
scaffolds
adaptor-type proteins with multiple binding sites, which bring together specific proteins int a functional signaling complex
50
adaptors
nonenzymatic proteins that form physical links between members of a signaling pathway, particularly between a receptor and other signaling pathways. They recruit members of the signaling pathway into functional protein complexes.
51
Ras
A small GTPase with important roles in intracellular signaling pathways, including those from lymphocytes antigen receptors.
52
GEFs
proteins that can remove the bound GDP from G proteins, thus allowing GTP to bind and activate the G protein
53
GAPs
Regulatory proteins that accelerate the intrinsice GTPase activity of G proteins and thus facilitate the conversion of G proteins from the active (GTP bound) state to the inactive (GDP bound) state
54
phosphotidylinositol kinase
PI 3-kinase. Enzyme involved in the intracellular signaling pathways. It phosphorylates the membrane lipid PIP2 to form PIP3, which can recruit signaling proteins to the membrane
55
PIP2
a membrane associated phospholipid that is cleaved by phospholipase C-gamma to give the signaling molecules diacylglycerol (DAG) and inositol trisphosphate(IP3)
56
PIP3
a membrane associated phospholipid that can recruit intracellular signaling molecules to the membrane
57
ubiquitin
a small protein that can be attached to other proteins to target them for degredation in the proteosome.
58
second messangers
small molecules or ions (such as Ca 2+) that are produced in response to a signal; they act to amplify the signal and carry it to the next stage within the cell
59
CD3 complex
the invariant proteins CD3 gamma, epsilon, delta, and zeta chains which form the signaling complex of the T cell receptor
60
Zeta chain
one of the signaling chains associated with the T cell receptor. Phosphorylated by Fyn or Lck, allowing Zap70 to bind
61
ITAMs
sequence mottifs present in signaling chains of receptors, including those associated with teh antigen receptors on lymphocytes, that are the site of tyrosine phosphorylation after activation of the receptor by ligand binding. The phosphorylated tyrosines then recruit other signaling proteins.
62
Lck
an Src family tyrosine kinase that associates with the cytoplasmic tails of CD4 and CD8 and phosphorylates the cytoplasmic tails of the T cell receptor signaling chains, thus helping to activate signaling from the T cell receptor complex once antigen has bound
63
CD45
a transmembrane tyrosine phosphatase found on all leukocytes. It is expressed in different isoforms on different cell types, including the different subtypes of T cells.
64
ZAP-70
a cytoplasmic tyrosine kinase found in T cells that binds to the phosphorylated zeta chain of the T cell receptor. The main cellular substrate of Zap-70 is a large adapter protein called LAT.
65
LAT
linker of activation in T cells. A cytoplasmic adapter protein with several tyrosines taht become phosphorylated by the tyrosine kinases Zap-70. It helps to coordinate downstream signaling events in T cell activation
66
SLP-76
a scaffold protein involved in the antigen receptor signaling pathway in lymphocytes.
67
phospholipase C-gamma
PLC-gamma. Key enzyme involved in the intracellular signaling pathways leading from many different receptors. It is activated indirectly by receptor ligation and cleaves membrane inositol phospholipids into inostiol trisphosphate (IP3) and diacylglycerol (DAG)
68
Co-stimulation
additional signals required for the activation of naive lymphocytes in addition to the signals generated by the binding of antigen to the antigen receptors
69
DAG
a lipid intracellular signaling molecule formed from membrane inositol phospholipids by the action of PLC-gamma after the activation of many different receptors. The DAG stays in the membrane and activates protein kinase C, which further propagates the signal
70
IP3
a soluble second messanger produced by the cleavage of membrane inositol phospholipids by PLC-gamma. It acts on receptors in the ER membrane, resulting in the release of stored Ca 2+ into the cytosol
71
NFAT
transcription factor composed of NFATc and Fos/Jun dimer AP-1. It is activated in response to signaling from the antigen receptor in lymphocytes
72
calmodulin
calcium binding protein that is activated by binding calcium ion. It is then able to bind to and regulate the activity of a wide variety of enzymes.
73
calcineurin
a cytosolic serine/threonine phosphatase with a crucial role in signaling via the T cell receptor. The immunosuppressive drugs cycolsporin A and tacrolimus inactivate calcineruin, suppressing T cell responses
74
protein-kinase-theta
a serine-threonine kinase that is activatd by DAG and calcium as part of the signaling pathways from the antigen receptor in lymphocytes.
75
MAPK
a series of protein kinases that become phosphorylated and activated on cellular stimulation by a variety of ligands and lead to new gene expression by phosphorylating key transcription factors. The MAPKs are part of many signaling pathways, especially those leading to cell proliferation.
76
transciption factor
a protein involved in promoting the expression of certain genes
77
CD28
an activating receptor on T cells for the B7 co-stimulatory molecules present on specialized antigen-presenting cells, such as DCs
78
B7.1 and B7.2
cell surface proteins on specialized antigen-presenting cells such as DCs, which are the major co-stimulatory molecules for T cells. B7.1 and B7.2 are closely related members of the Ig superfamily and both bind to CD28 on Tcells
79
costimulatory molecules
cell-surface proteins on antigen-presenting cells that deliver co-stimulatory signals to naive T cells. Examples are the B7s on DCs, which are ligands for CD28 on naive T cells.
80
Syk
a cytoplasmic tyrosine kinase found in B cells that acts in the signaling pathway from the B-cell antigen receptor.
81
B-cell coreceptor
a transmembrane signaling receptor on the B-cell surface composed of the proteins CD19, CD81, and CD21. Binds complement fragments on bacterial antigens also bound by the BCR. Co-ligation of this complex with the B-cell receptor increases responsiveness to antigen by 100 fold
82
CTLA-4
a high affinity inhibitory receptor on T cells for B7 molecules; its binding blocks T cell activation
83
Fc receptors
type of cell surface receptor on macrophages and other cells in the immune system that binds the Fc portions of immunoglobulins. There are different Fc receptors for different isotypes.
84
ITIM
sequence of motifs present in the cytoplasmic tails of some inhbitory receptors. Phosphorylated tyrosines in thees motifs recruit phosphatases to the signaling pathway, which remove phosphate groups added by tyrosine kinases.
85
SHIP
an SH2 containing inositol phosphatase that removes the phosphate from PIP3 to give PIP2
86
STATs
signal transducers and activators of transcription
87
Janus Kinase family
enzymes of the JAK-STAT intracellular signaling pathways that link many cytokine receptors with gene transcription in the nucleus. The kinases phosphorylate STAT proteins in the cytosol, which then move to the nucleus and activate a variety of genes.
88
apoptosis
a form of cell death common in the immune system, in which the cell activates an internal death program.
89
caspases
a family of cystein proteases in some receptor tails that can dimerize with other CARD-domain contain proteins, including caspases, thus recruiting them into signaling pathways.
90
Fas
a member of the TNF receptor family that makes cells on which it is expressed susceptible to killing by cells bearing Fas ligand, a cell-surface member of the TNF family of cytokines. Binding of Fas ligand to Fas triggers apoptosis in the Fas-bearing cell
91
Bcl-2 family
family of intracellular proteins that includes members that promote apoptosis (Bac, Bak, and Bok) and members that inhibit apoptosis (Bcl-2, Bcl-W, and Bcl-X)
92
positive/negative selection
checkpoint 2 in TCR development. After small DP produces TCR, TCR must bind to self-MHc and self-antigen to pass but not have too high affinity. If either doesn't bind at all or has too high affinity, the cell is discarded

mbio4883 (5 decks)

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