Thymus-Derived Cells (T Cells) Flashcards
(134 cards)
1
Q
What is the lifespan of a T cell?
A
6 months to over 20 years.
2
Q
T cells constitute up to ___ of the recirculating pool of small lymphocytes.
A
80%
3
Q
What do developing T cells acquire in the thymus?
A
Antigen-specific receptors and other functional and phenotypic characteristics that mark it as a mature T cell.
4
Q
What are the functions of mature T cells’ surface proteins?
A
Antigen recognition, signal transduction, and adhesion to APCs + target cells.
5
Q
Activation of a cell surface receptor requires binding to its specific ____, which may be a ____-_____ on another cell or soluble protein.
A
ligand; counter-receptor.
6
Q
What are some of the accessory molecules’ functions on T cells?
A
- Adhesion molecules.
- Deliver signals to the T cell that functions, in concert with signals from the TCR-CD3/zz complex, to fully activate the T cell.
7
Q
Generally speaking, what do CD4 and CD8 molecules do?
A
They promote the adhesion of T cells to APCs and target cells and also play a role in signal transduction, thereby potentiating T cell activation.
8
Q
Where is CD4 (TCR co-receptor) found?
A
On helper T cells [present on monocytes and macrophages of some species].
9
Q
What does CD4 bind to?
A
It binds to the B2 domain of the class 2 MHC molecules on the surface of professional APCs.
10
Q
Where is CD8 (TCR co-receptor) found?
A
On cytotoxic T cells.
11
Q
What does CD8 bind to and what is its function?
A
Its function is the recognition of the a3 domain of class 1 MHC molecules, enabling cytotoxic T cells to bind to target cells.
12
Q
Generally speaking, what is the function of lymphocyte adherence molecules?
A
They strengthen interactions between helper T cells and professional APCs or cytotoxic T cells and target cells (e.g., virus-infected cells).
13
Q
What is CD11aCD18? What does it bind to? What is its function?
A
It is lymphocyte function-associated antigen-1, LFA-1); it binds T cells to CD54 molecules (ICAM-1,2,3) on APCs and target cells; it promotes the binding of T cells to endothelial cells during T cell extravasation.
14
Q
What is CD2? Where is it found? What does it bind to? What is its function?
A
CD2 is LFA-2; CD2 molecules are found on mature T cells; CD2 binds to a protein called CD58 (LFA-3) present on APCs and target cells; CD2 functions both as an intracellular adhesion molecule and as a T cell signal transducer [contributes to optimal T cell activation].
15
Q
What is CD28? Where is it expressed? What are its ligands? Where are these ligands expressed?
A
- CD28 is a constitutively expressed membrane receptor for co-stimulatory signals (signal 2).
- Its ligands are B7-1 (CD80) and B7-2 (CD86) cell surface proteins that are expressed on professional APCs.
- NOTE: IL-6 and IL-1 can help function as B7 proteins if you do not have any B-7s, but they are not as potent.
16
Q
What does signal 2 function with? What do these two signals do?
A
- Signal 2 functions with signal 1 (delivered by the TCR complex) to activate naive T cells.
- Signal 2 is when the T cell is exposed to co-stimulating molecules such as cytokines and cell membrane proteins produced by the APC.
17
Q
What does the TCR complex consist of?
A
- T cell receptor (TCR).
- CD3 Complex.
- z (zeta) proteins.
18
Q
What kind of protein is the TCR?
A
A disulfide-linked heterodimer glycoprotein.
19
Q
What does the TCR enable T cells to do?
A
The TCR enables T cells to recognize processed antigens presented in association with MHC molecules.
20
Q
What are the two identified types of TCRs?
A
TCRaB and TCRgd
21
Q
Explain the construction of TCRaB.
A
The aB chains are integral membrane proteins with an extracellular domain, a transmembrane domain, and a short cytoplasmic tail. The extracellular domains consist of variable (N-terminal), constant and hinge regions.
22
Q
What are hyper-variable regions?
A
- Complementarity-determining regions (CDRs), which reside in the variable regions; they consist of unique amino acid sequences that form the antigen-binding site of the TCR.
- BOTH CHAINS POSSESS 3 CDRs (1,2,3) JUXTAPOSED TO ONE ANOTHER.
23
Q
Where is CDR3 located? How diverse is it? And what does it interact with?
A
CDR3 is located in the center of the CDRs; it displays the most diversity; and directly interacts with the antigenic peptide.
24
Q
What does CDR1 interact with?
A
CDR1 interacts with both peptide and the MHC.
25
What does CDR2 interact with?
CDR2 interacts with the MHC.
26
What part of the TCRaB contains a 4th hyper-variable region? What does this 4th region do?
The B-chain and the V-domain contains a 4th hyper-variable region, which is the binding site for microbial products called superantigens.
27
How many TCRs does a single T cell possess?
About 50,000.
28
Each TCR is ______, ie, will recognize only a single epitope bound to an MHC protein.
Clonotypic.
29
In humans and nonruminants, ____-____% of T cells carry aB receptors.
90-99%.
30
T or F?
TCR is produced in secreted form, and therefore performs effector functions on its own.
FALSE.
Unlike BCR, TCR is not produced in secreted form, hence it does not perform effector functions on its own.
31
T or F?
TCRs can respond to as many different foregin antigens as possible, but not to self-antigens.
TRUE.
32
What controls the genetic expression of TCRs?
Allelic exclusion. It occurs when only one of the parental alleles that code for the TCR is functional, rendering each T cell responsive to only a single epitope.
33
T or F?
The genes encoding the a chain and B chain are found on the same chromosome.
FALSE.
The genes encoding the a-chain and B chain are found on SEPARATE chromosomes.
34
What regulates the rearrangement of TCR gene segments and BCR gene segments?
Several enzymes collectively called recombinases.
35
What are RAG-1 and RAG-2? Where are they found? Where are they active?
RAG-1 and RAG-2 are recombination-activating genes 1 and 2. They are only found on T and B lymphocytes; however, they are active only in developing lymphocytes.
36
TCR and BCR rearrangements DO NOT continue in mature T and B cells that have completed gene rearrangements... why?
Because RAG-1 and RAG-2 are only active in developing lymphocytes.
37
What do RAG proteins cleave?
DNA at recombination sequences which are located adjacent to the V, D, or J coding sequence.
38
T or F?
Individuals or animals lacking RAG genes fail to produce both BCR and TCR proteins and manifest severe combined immunodeficiency, SCID.
TRUE.
39
T or F?
Like RAG proteins, DNA repair enzymes are expressed in only a few cell types.
FALSE.
UNLIKE RAG proteins, DNA repair enzymes are expressed in MANY cell types.
40
What is DNA repair enzymes role in TCR and immunoglobulin (BCR) gene recombination?
To repair the double-stranded breaks introduced by the RAG proteins.
41
T or F?
Lacking DNA repair enzymes will also result in SCID.
TRUE.
42
What is the purpose of TCR gene rearrangements?
Deletion of unwanted genes.
43
Describe the two general steps of TCR gene rearrangements.
1) Cells initially loop out unwanted genes and then excise them.
2) The cut ends are joined by DNA ligase.
44
What is the first chain genes of the TCR that rearranges before the others?
The B chain genes, followed by the a chain genes.
45
What are the three region genes that occur at the TCRB locus?
- Multiple variable (Vn) region genes.
- Diversity (Dn) region genes.
- Joining (Jn) region genes.
46
What are the three steps of the B chain gene rearrangement?
First, DB gene segments rearrange and join to JB gene segments, followed by VB to the DJB gene rearrangement, and then to a CB gene.
47
Where are the multiple variable (Vn) region genes and joining (Jn) region genes occur at in a-chain gene rearrangement?
At the TCRa locus.
48
T or F?
During the rearrangement of a-chain genes, a randomly selected V gene is jointed to a J gene and the exon is transcribed, combined with a constant (Ca) regeion gene, and translated.
True.
49
What does multiple germ-line genes; gene rearrangements; and junctional diversity account for?
The diversity of TCRaB.
50
Removal of a few bases from the broken ends of the coding sequences by endonucleases is called...?
Base deletions.
51
How does base deletions affect diversity in the TCRaB?
Base deletions will affect the which precise nucleotide at which V, D, and J genes can join, resulting in greater diversity.
52
What does the enzyme terminal deoxynucleotidyl transferase (TdT) do?
It adds up to 10 nucleotides to the cut ends of the V/J (a-chain) and V/D/J (B-chain) coding sequences in a process called N-REGION NUCLEOTIDE ADDITION.
53
What are P-nucleotides?
When a gene is cleaved asymmetrically, the shorter strand is usually extended with nucleotides complementary to the longer strand before the two are ligated. The added nucleotides at the V/D/J and V/J sections are called P-nucleotides.
54
Which nucleotides in the TCRaB are "nongermline nucleotides"?
The N-region nucleotide additions and the P-nucleotides.
55
T or F?
Once rearranged in the thymus, the coding sequence of each TCR remains changed and displays somatic hypermutation as with B cell-derived B cell receptors (BCRs).
FALSE.
Once rearranged in the thymus, the coding sequence of each TCR remains UNCHANGED and does not display somatic hypermutation as with the BCRs.
56
It is estimated that the total TCR repertoire may be in the order of ____.
1 X 10^16.
57
What are CD3 and zz proteins?
They are accessory molecules that noncovalently associate with the T cell receptor.
58
This complex consists of a 4 invariant polypeptide chains (gamma, delta, 2 epsilon chains)...
The CD3 complex.
59
T or F?
The two zz chains are the same on all T cells.
TRUE.
60
T or F?
The T cell response does not necessarily need a signal sent to the T cell nucleus when a TCR binds to an antigen.
FALSE.
When a TCR binds an antigen, a signal must be sent to the T cell nucleus in order to initiate its response.
61
T or F?
The cytoplasmic tail of the TCR transduces signals.
FALSE.
The cytoplasmic tail of the TCR is TOO SMALL to transduce signals.
62
Biochemical signals for T cell activation DO NOT come from the _____, but, rather, from the ____ ____ and the ______ (collectively referred to as ______ ______).
TCR; CD3 complex; zz chains; signal transducers.
63
T or F?
The CD3 complex also functions in stabilizing cell surface expression of TCR.
TRUE.
64
T or F?
Mutations in the CD3 genes effectively prevent T cell expression of TCRs.
TRUE.
65
What are "forbidden clones"?
Thymocytes whose TCRs bind strongly to self peptides.
66
What are the two thymocyte critical selection processes during T cell development?
The two critical selection processes result in self-MHC restriction of TCRs and the elimination of forbidden clones.
67
What part of the organ does thymocyte selection take place? What cells carry this out?
The cortex; thymic stromal cells (cortical epithelial cells, macrophages, and dendritic cells).
68
T or F?
Thymic stromal cells express MHC class 1 molecules only.
FALSE.
Thymic stromal cells express both MHC class 1 and MHC class 2 molecules.
69
Thymocytes whose TCRs have moderate affinity for self-MHC molecules are rescued from cell death are ______ selected.
Positively.
70
What does positive selection of thymocytes ensure?
It ensures that mature T cells are self-MHC restricted, ie, CD4+ T cells interact with peptide-MHC II complexes, whereas, CD8+ T cells interact with peptide-MHC I complexes.
71
Thymocytes whose TCRs have low affinity OR high affinity for self-MHC molecules are eliminated by apoptosis in a process called ______ selection.
Negative.
72
T or F?
Death by apoptosis elicits an inflammatory response and triggers host defense mechanisms.
FALSE.
Death by apoptosis does NOT elicit an inflammatory response NOR triggers host defense mechanisms.
73
Which WBC takes up cellular debris resulting from negative selection apoptosis?
Macrophages.
74
Thymocytes that express TCRs with high affinity for self-antigen presented by self-MHC molecules are eliminated, contributing to the maintenance of ____-_____.
Self-tolerance.
75
Where are TCRgd receptors expressed?
On a subset of T cells that are found mostly in epithelial locations, so-called intraepithelial lymphocytes.
76
What does TCRgd recognize?
A native antigen rather than peptide-MHC complex.
77
T or F?
TCRgd displays limited antigenic diversity.
TRUE.
78
What does Helper T cell (TH; CD4+) do?
It helps B cells produce antibodies to protein antigens.
79
In most species, what is the ratio of TH cells to TC cells?
2:1
80
What does the Cytotoxic T cell (TC; CD8+) cause?
It causes the lysis of antigen-bearing target cells.
81
T or F?
TH cells play a major role in promoting adaptive immune responses only.
FALSE.
TH cells play a major role in promoting innate AND adaptive immune responses.
82
How do TH cells promote innate and adaptive immune responses?
By releasing soluble helper factors (cytokines) that affect the activities of several cell types.
83
Helper T cells respond only to ______ ______ when it is presented by professional APCs in association with self-MHC class II molecules.
Processed antigen.
84
T or F?
Interaction with an APC involves multiple TH cell membrane proteins that recognize different ligands on the APC.
TRUE.
85
Naive TH cell activation requires how many signals?
2
86
What constitutes the first signal in naive TH cell activation?
TCR complex and CD4 recognition of peptide-MHC complexes on the APC.
87
What constitutes the second signal in Naive TH cell activation?
co-stimulation.
88
What are the most potent activators of naive TH cells of the professional APCs? Why?
Mature dendritic cells because they constitutively express MHC molecules and co-stimulators.
89
Name some B7 proteins.
B7-1, CD80; B7-2, CD86.
90
What do B7 proteins do?
They are best characterized as co-stimulators for naive TH cells.
91
T or F?
B7 proteins are absent or expressed at low levels on resting APCs.
TRUE.
92
What can enhance the expression of B7 proteins on APCs?
When APCs are stimulated by endotoxin (LPS), interferon-g, and binding of T cell CD40L to CD40 on the APC.
93
What is CD28? What does it do?
CD28 is a T cell receptor for B7 proteins. It enhances several TH cell responses to antigen, including the production of cytokines such as IL-2 and differentiation of naive T cell into effector cells and memory cells.
94
T or F?
Interleukin-1 is a major co-stimulator of TH1 cells.
FALSE.
IL-1 is a major co-stimulator of TH2 cells (TH1 cells lack IL-1 receptors and do not respond to IL-1).
95
IL- 6 promotes ___, ___ and ___.
IL-2; IL-2 receptor production; and T cell proliferation.
96
T or F?
Antigen recognition by helper T cells induces the expression of CD40L.
TRUE.
97
What does CD40L do?
CD40L binds to CD40 on the APC and stimulates the expression of B7 molecules (which bind to CD28 on helper T cells) and the secretion of cytokines that activate the helper T cell.
98
Antigen-activated naive TH cells synthesize ____ and ____ ____.
IL-2 and IL-2 receptors (IL-2Rs).
99
What is T cell autocrine growth factor?
IL-2.
100
What happens when IL-2Rs are bound by IL-2?
If IL-2Rs are bound by IL-2 (T cell autocrine growth factor), the cell undergoes clonal expansion (proliferation of the antigen-specific clone).
101
What do most of the daughter cells of naive helper T cells differentiate into?
Effector cells.
102
What does a smaller fraction of the naive helper T daughter cells differentiate into?
Antigen-specific memory cells.
103
T or F?
The terminally differentiated effector TH cells enter the circulation and are carried to the peripheral tissues (lymphatic only).
FALSE.
The terminally differentiated effector TH cells enter the circulation and are carried to the peripheral tissues (LYMPHATIC AND NONLYMPHATIC).
104
What happens once the terminally differentiated effecter TH cells reach the peripheral tissues?
There, they are triggered to effector function by encountering MHC-peptide complexes on APCs.
105
T or F?
In contrast to naive Th cells that require 2 signals for activation, effector TH cells are more sensitive to TCR/CD4 recognition of peptide-MHC complexes (signal 1) and, therefore, have no need for co-stimulation (signal 2).
TRUE.
106
T or F?
Effector TH cells are able to respond to peptide-MHC complexes displayed on APCs that lack the co-stimulatory B7 molecule because they have no need for co-stimulation (signal 2).
TRUE.
107
What is the result of effector TH cell activation?
The synthesis of various membrane bound (eg, CD40L) or secreted (eg, cytokines) effector molecules.
108
What does CD40L do?
It binds to CD40 on macrophages and B cells and activates them (see page 97).
109
What do the TH cell cytokines do?
They promote and regulate the effector phases of innate and adaptive immune responses.
110
T or F?
Effector cell responses increase following elimination of the antigen.
FALSE.
Effector cell responses decline following elimination of the antigen.
111
T or F?
The vast majority of antigen-activated T cells die by apoptosis within a few hours.
FALSE.
The vast majority of antigen-activated T cells die by apoptosis within a few DAYS.
112
The decline in effector response is significant because...?
It returns the immune system to a state of rest or homeostasis.
113
What are the three types of effector T cells are:
1 - TH1 cells.
2 - TH2 cells
3 - CD8 + T cells.
114
Where do effector T cells traffic to mostly?
Inflammatory sites.
115
Which lives longer: the Naive T cell, or, the effector T cell?
The Naive T cell.
116
T or F?
The naive T cell has effector function.
FALSE.
The naive T cell has NO effector function.
117
T or F?
The memory TH cells, unlike effector cells, are long-lived cells.
TRUE.
118
What does the expanded clone of antigen-specific memory TH cells account for?
The increased and accelerated secondary response on subsequent exposure to the same antigen.
119
Normally, Memory T Helper cells are functionally _____, until re-exposure to the antigen (presented by APCs), which induces them to undergo _____ _____.
inactive; clonal expansion.
120
What happens after Memory T Helper cells undergo clonal expansion?
They differentiate from daughter cells into effector and memory cells.
121
T or F?
Like effector TH cells, memory TH cells need B7-CD28 co-stimulatory interactions (signal 2) to induce full T cell activation.
FALSE.
Like effector TH cells, memory TH cells DO NOT need B7-CD28 co-stimulatory interactions (signal 2) to induce full T cell activation.
122
Where do effector and memory T cells preferentially travel to in the body? Why?
The prefer to travel to inflamed peripheral tissues where they are needed to eliminate antigens in the effector phase of adaptive immune responses.
123
T or F?
Effector T cells down-regulate the expression of L-selectin and CCR7 and upregulate the expression of the chemokine receptor CCR10 and adhesion molecules LFA-1 and VLA-4, allowing them to bind to ICAM-1 and VCAM-1, respectively, on peripheral vascular endothelium at sites of inflammation.
TRUE.
Does your brain hurt yet?
124
Newly differentiated effector T cells are directed to the site of infection in the _______ tissues.
Peripheral.
125
Helper T cells are subdivided into TH1 and TH2 cells on the basis of...?
... their production of and responses to specific cytokines.
126
T or F?
TH1 and TH2 subsets develop from different T lymphocytes in the peripheral lymphoid organs.
FALSE.
TH1 and TH2 subsets develop from the SAME naive CD4+ T lymphocytes (TH0), in the peripheral lymphoid organs.
127
What do cytokines produced in the innate immune response to microorganisms, or, early in adaptive immune responses influence?
They influence the differentiation of naive CD4+ T cells into TH1 or TH2 cells.
128
T or F?
IL-12 promotes the production of the TH1-promoting transcription factor, T-Bet.
TRUE.
129
IL-4 promotes the production of the TH2-promoting transcription factor, _____.
GATA-3.
130
What specific situations especially promote the differentiation of naive CD4+ cells into TH1 cells.
While many pathogens cause the differentiation of naive CD4+ cells into TH1 cells - intracellular bacteria and viruses that infect or activate macrophages and NK cells to produce interleukin-12 or interferon-g will potently do this.
131
What does interleukin-4 do? What is it produced in response to?
Interleukin-4 causes proliferating of CD4+ cells to differentiate into TH2 cells. Interleukin-4 is produced in response to helminth parasites and other pathogens.
132
What is cross-regulation in cytokines?
Cytokines produced by the TH1 and TH2 subsets exhibit cross-regulation, ie, cytokines from the TH1 cells can block the production and/or activity of the cytokines secreted by TH2 cells and vice versa.
133
T or F?
Each subset of T Helper cells amplifies itself and cross-regulates the other subset.
TRUE.
134
T or F?
The significance of Cross-regulation is than an immune response tends to settle into a TH1 type response or a TH2 type of response, but not both at the same time.
TRUE.
