L7-Exam 2

Question 1

The ___ is an absolute requirement for the maturation and differentiation of mature T cells

Answer 1

Thymus

Question 2

Children born without a thymus (DiGeorge’s Syndrome) do not have ______

Answer 2

mature T cells

Question 3

T cell differentiation occurs throughout life , but will tapper off subsequent to ___ as the thymus decreases in size (known as: thymic involution)

Answer 3

puberty

Question 4

The___ is the site of education of a T cell and is the primary lymphoid organ for development of T cells; it is analogous to the bone marrow as the primary organs for development of B cells

Answer 4

The thymus

Question 5

What three things occurs to a T cell when it is in the thymus?

Answer 5

1) Acquires T cell antigen receptor (TCR) - antigen specificity
2) Learns tolerance of self
3) Learns self-HLA restriction (recognition of foreign peptide only in association with self HLA molecules)

Question 6

True or False: A common lymphoid progenitor stem cell leaves the bone marrow, without any T cell features. It could not be distinguished from a pro-B cell.

Answer 6

True

Question 7

True or False: when T lymphocytes are in the bone marrow, they contain chemokine receptors on their surface

Answer 7

True

Question 8

The precursor stem cells enter the thymus at the cortical-medullary junction and then migrate to the cortex. At this time, they are called ______ cells.

Answer 8

Double Negative Cells

Question 9

True or False: Double negative cells expressed both CD4+ and CD8+

Answer 9

False - double negative cells express neither CD4+ nor CD8+

Question 10

The decision whether to be an alpha-beta or gamma-delta T cell occurs at the ___ stage

Answer 10

Double Negative

Question 11

Shortly after becoming DN cells, the cells begin expressing the genes for ___ and ___

Answer 11

RAG-1 and RAG-2

Question 12

What is the function of RAG-1 and RAG-2?

Answer 12

Responsible for randomly rearranging genes that encode the delta/gamma and alpha/beta chains of the T cell antigen receptor (TCR)

Question 13

The DN cells that become delta-gamma T cells express what three proteins on their cell surface?

Answer 13

CD3+
TCR gamma
TCR delta

Question 14

True or False: The DN cells that become γδ T cells leave the thymus and migrate to epithelial sites around the body

Answer 14

True

Question 15

If a DN cell does not become a delta-gamma T cell, it will be come a ____, which expresses what four proteins on its cell surface?

Answer 15

Pre-aßT cell (pre-T cell)
1. CD3+
2. Pre-Ta
3. TCRß
4. Zeta

Question 16

True or False: γδ T cells continue to differentiate within the thymic cortex

Answer 16

False -Pre-aßT cell (pre-T cell) continue to differentiate within the thymic cortex

Question 17

The functioning of the pre-T cell receptor results in ___ signals that stop further re-arrangement of the __ chain and initiates rearrangement of the __ chain

Answer 17

intracellular; beta; alpha

Question 18

What five proteins do double positive cells of the thymus cortex express on their surface?

Answer 18

1) CD3+
2) CD4+
3) CD8+
4) TCRa
5) TCRβ

Question 19

As maturing double positive thymocytes filter through the thymic cortex, they must pass through a mesh of stromal cells, known as:
1)
2)

Answer 19

1) thymic epithelial cells
2) interdigitating thymic dendritic cells

Question 20

Double positive CD4+ and CD8+ thymocytes undergo selection, which is mediated by interactions with HLA molecules on ___ cells and CD4 and CD8 molecules on ___

Answer 20

stromal cells; thymocytes

Question 21

_____ are among the few cells the express both class of HLA molecules (class I and II) constitutively

Answer 21

Thymic epithelium

Question 22

During ___ selection, thymocytes must bind with a certain critical affinity to HLA molecules on the thymic epithelium.

Answer 22

positive

Question 23

Once a cell completes positive selection, the cells are now educated to self HLA molecules, meaning they will only responds to….?

And the are considered to be ___-restricted

Answer 23

Self HLA + processed antigen (self or foreign)

HLA-restricted

Question 24

____ selection occurs during transition from thymic cortex to thymic medulla, when encounter interdigitating dendritic cells at CM junction and later when they interact with medullary epithelial cells

Answer 24

Negative selection

Question 25

Since T cells that survive positive selection are potentially able to respond to peptides derived from both self and foreign molecules loaded into the MHC, allowing those cells to leave the thymus and enter the circulation could result in ___

Answer 25

autoimmunity

Question 26

If developing T cells responds to MHC + self peptide at the stage of negative selection, the cells die via ______

Answer 26

central tolerance mechanisms

Question 27

The process of negative selection weeds out self-reactive cells via ___ or by inducing ___. The surviving cells are said to be ____

Answer 27

apoptosis; inducing T cell anergy self-tolerant

Question 28

____ immature thymocytes must bind HLA Class I and II on thymic epithelial cells with "just the right affinity." If they don't, they undergo apoptosis and die

Answer 28

CD4+/CD8+

Question 29

Tolerance learned during ontogeny is called ____

Answer 29

central tolerance

Question 30

Antigens present in the thymus are almost always ___ antigens

Answer 30

self

Question 31

True or False: In Central T Lymphocyte tolerance, strong recognition to antigens results in apoptosis

Answer 31

True

Question 32

Central T Lymphocyte Tolerance involves immature, ____ T cells

Answer 32

Double positive

Question 33

True or False: The cells that survive both positive and negative selection become either CD8+ or CD4+

Answer 33

True

Question 34

What are four features of cells that have survived positive and negative selection?

Answer 34

1) alpha/beta TCR+, CD3+, and CD4+ (or: alpha/beta TCR+, CD3+, and CD8+) 2) self-HLA restricted 3) self-tolerant 4) foreign antigen specific (HLA + foreign peptide specific)

Question 35

If they survive the positive and negative selection process in the thymus, a mature, naiive T cell will leave the thymus and enter the circulation via the ____ and ____

Answer 35

blood; secondary lymphoid organs

Question 36

What population of T cells leave the thymus for epithelial sites without undergoing positive and negative selection?

Answer 36

T cells that have the γδ TCR

Question 37

Stem cells migrating to the thymus express this/these molecules on their surface A. CD3 B. CD3, CD4, and CD8 C. CD4 and CD8 D. Chemokine receptors E. Chemokine receptors and CD3

Answer 37

D. Chemokine receptors

Question 38

True or False: Recirculation increases the change that a lymphocytes will encounter its antigen

Answer 38

True

Question 39

Specific receptor-ligand interactions between ____ and _____cells occurs that mediate ___ and homing of the lymphocyte

Answer 39

lymphocytes and endothelial cells; recirculation

Question 40

If, while filtering through a lymph node, a T cell encounter an APC (dendritic cell or B cell) expressing HLA+foreign peptide, it may respond (___) or not responds (___)

Answer 40

respond = activation not respond = tolerance

Question 41

T lymphocytes respond only to processed protein antigens derived from what three pathways?

Answer 41

-Endosomal -Phagosomal -Cytosolic (exogenous and endogenous)

Question 42

B cells differentiate into ___ cells, which produce antibodies to deal with ___ antigens

Answer 42

plasma cells; extracellular antigens

Question 43

Are T cells designed to deal with extracellular or intracellular cellular-associated antigens?

Answer 43

Intracellular antigens (cell-associated antigens)

Question 44

What are the two possible outcomes due to T cell activation by antigen?

Answer 44

1) Production of cytokines, which signal other cells of immune system to become activated (helper T cells) 2) Killing cell possessing or expressing foreign antigen (cytoxic T cells)

Question 45

T cells become activated with the immunological synapse is formed between an ___ and a ___ cell

Answer 45

APC (dendritic cell) and a T cell

Question 46

___: a disulfide linked heterodimer glycoprotein belonging to the Ig superfamily of molecules

Answer 46

TCR (T-Cell Receptor)

Question 47

True or False: Each member of the Ig Supergene Family is involved in binding or recognition of foreign antigens (HLA, Ig, TCR, etc.)

Answer 47

True

Question 48

Like Ig receptors in B cells, the TCR is clonally distributed, which means that?

Answer 48

Each T cell clone bears a unique TCR that determines its antigen specificity

Question 49

The majority of T cells have a ___ heterodimer composed of _ and _ chains and mature in the ___

Answer 49

TCR heterodimer; alpha/beta; thymus

Question 50

True or False: A smaller population of T cells posses gamma and delta chains (gamma/delta TCR+) and mature without a requirement for the thymus

Answer 50

True

Question 51

TCR's have variable region domains in the alpha and beta chains (_ and _)

Answer 51

Va and Vβ

Question 52

In the Va and Vβ regions of the TCR, the two polypeptide chains come together to form a ____ site (similar to antibody hypervariable region) - this is where antigen binds

Answer 52

terminal antigen binding

Question 53

True or False: CD3 is composed of gamma, epsilon and delta chains

Answer 53

True

Question 54

True or False: CD3+ is a complex found on all mature T lymphocytes

Answer 54

True

Question 55

___ is a chaperone for TCR and is a critical signaling molecule

Answer 55

CD3+

Question 56

Which is a member of the Ig superfamily gene: TCR or CD3?

Answer 56

TCR

Question 57

True or False: TCR has conserved and variable domains AND recognizes antigens and HLA on APC

Answer 57

True

Question 58

Which molecules contain signaling molecules known as zeta chains (CD247) ?

Answer 58

TCR

Question 59

Most exogenous exogenous antigens are processed by dendritic cells and presented to: A. CD4+ T Helper Cells B. CD8+ T Cytotoxic Cells

Answer 59

A. CD4+ T Helper Cells

Question 60

True or False: TCR is noncovalent but closely associated with a number of transmembrane polypeptides (signaling and accessory molecules)

Answer 60

True

Question 61

True or False: CD8+ is T cell specific

Answer 61

False: CD3 is T cell specific

Question 62

What are the two primary functions of CD3?

Answer 62

1) Chaperone for TCR - transports newly made TCR molecules to cell surface 2) Cellular signaling molecule via transmembrane cytoplasmic domains

Question 63

____ molecules are tightly associated with zeta chains, which are two identical polypeptides that are not T cell specific and are mostly intracellular

Answer 63

CD3

Question 64

When antigen is process and presented with HLA molecules, it can be recognized and subsequently bound by the antigen binding site of TCR - known as ____

Answer 64

Signal 1 - This relays a conformational change that, in turn, activates CD3 and zeta molecule associated tyrosine kinases, and sets of a "cascade of intracellular events" leading to activation of T cell

Question 65

Binding HLA and associated processed peptide to the TCR is stabilized by ____

Answer 65

CD4 and CD8

Question 66

CD4 facilitates binding of HLA Class ___ molecules to TCR

Answer 66

HLA Class II

Question 67

___ facilitates binding of HLA Class I molecules to TCR

Answer 67

CD8

Question 68

___ and ___ are mutually exclusive in mature T lymphocyte

Answer 68

CD4 and CD8

Question 69

CD4 and CD8 are ___molecules and also function in _____

Answer 69

adhesion; signal transduction

Question 70

True or False: Binding of accessory molecules can function to either positively or negatively impact T cell activation

Answer 70

TRue

Question 71

Positive, co-stimulatory interactions (signal 2) include: 1) 2)

Answer 71

1. Binding of accessory molecule B7 (CD80) on APC to CD28 on T cell 2. CD40 on APC to CD40L on T cell (CD154)

Question 72

True or False: Positive, co-stimulatory interactions (signal 2) are critical to initial activation of a naiive T cell, but are not required for activation of memory T cells

Answer 72

True

Question 73

Negative co-stimulatory interactions include: 1. 2.

Answer 73

1. Binding of accessory molecules PD-L1 on APC to PD-1 on T cell 2. Binding of B7 (CD80) on APC to CTLA-4 on T cell

Question 74

____ binding strongly inhibits T cells and induces Treg differentiation. Further, it is essential for maintaining peripheral tolerance and limiting immune response.

Answer 74

PDL1/PD-1

Question 75

Activation of a T Helper cell includes the transcription of ____ and ___ receptor genes

Answer 75

IL-2 and IL-2 receptor

Question 76

___: an autocrine growth factor for T cells that induces both proliferation (entering the cell cycle) and eventually a differentiation to effector cell function (production of cytokines)

Answer 76

IL-2

Question 77

IL-2 receptor is also known as ___

Answer 77

CD25

Question 78

True or False: Memory T cells have fewer activation requirements upon second encounter with antigen and, therefore, are more easily activated than naiive T cells

Answer 78

True

Question 79

Once activate in subsequent encounters with antigen, memory cells become either ___ or ___ cells

Answer 79

effector or memory cells

Question 80

What interaction is critical for T cell activation?

Answer 80

Accessory B7 molecule (on the APC) interacts with CD28 on the T cell

Question 81

When does peripheral tolerance of T cell occur?

Answer 81

In the lymph nodes, when T cells are stimulated (MHC/peptide-TCR) without secondary stimulation (B7-CD28)

Question 82

When the primary signal (MHC/peptide-TCR binding) happens without the "second signal" (ex: B7-CD28) it can result in functional inactivation of T cell, known as: ______

Answer 82

clonal anergy

Question 83

True or False: Once T cells become anergic, they can only be activated if they encounter their specific foreign peptide/MHC molecule

Answer 83

False - Once T cells become anergic, they CANNOT be activated, even encounter their specific foreign peptide/MHC molecule

Question 84

Repeated stimulation of activation T cells can cause the T cell to due by _____

Answer 84

apoptosis (clonal deletion)

Question 85

____ cells can inhibit activation of T cells by self-peptide/MHC

Answer 85

Regulatory T cells

Question 86

Secondary signal is needed to stabilize ___ mRNA

Answer 86

IL-2 mRNA

Question 87

Activation-induced cell death induces expression of ___ and ___, resulting in apoptosis

Answer 87

Fas and Fas ligand

Question 88

In activation-induced cell death, expression of pro-apoptotic proteins results in ___

Answer 88

apoptosis

Question 89

What are three examples of Regulatory T cells?

Answer 89

CD4+ CD25+ Fox P3+

Question 90

True or False: Regulatory T cells suppress/inhibit activation of other T cells, most likely due to production of inhibitory cytokines

Answer 90

True