Immuno 7

Question 1

What is a T cell?

Answer 1

it is a lymphocyte that develops in the thymus and that bears many copies of the same antigen-specific receptor (called a T cell receptor) on its surface. T cells are one of the two cell types (along with B cells) that comprise the acquired immune system.

Question 2

Remember that all immune cells are initially generated in the _____.

Answer 2

bone marrow (one of the two primary lymphoid organs), but T cells actually develop in the other primary lymphoid organ: the thymus. 
Once T cells develop in the thymus, they enter the circulation and are transported to the many secondary lymphoid tissues around the body where they will reside in the T cell zones of those tissues.

Question 3

How are T cells different from B cells?

Answer 3

One of these ways is that T cells only recognize peptide antigens. A peptide is a short fragment of a protein. B cells can recognize peptide determinants, but B cells can also recognize whole proteins, carbohydrates, nucleic acids, lipids, etc. B cells can also recognize soluble or particulate antigens. T cells, on the other hand, can only recognize peptides, and they can only recognize them once they have bound to an MHC molecule. T cells are “MHC restricted”.

T cells serve several important roles in acquired immune responses. One type of T cell recognizes and kills cells that are infected with intracellular pathogens such as viruses or intracellular bacteria. The other type of T cell modulates the activities of other immune cells, primarily via their expression of cytokines and chemokines; these T cells are known as helper T cells.

Unlike B cells, T cells do not secrete any immunoglobulin molecules. The immunoglobulins produced by T cells are anchored into their cytoplasmic membrane where they serve as the antigen-specific receptor component of the T cell receptor, but they are never secreted. Therefore, T cell immunoglobulins cannot serve as effector molecules.

Question 4

There are two distinct lineages of T cells that are known as either ___ or ___.

Answer 4

alpha/ beta (or α/β) T cells or gamma/delta (γ/δ) T cells.

The immunoglobulin component of the TCR is a heterodimer composed of proteins encoded by the TCR alpha chain and TCR beta chain genes, or from proteins encoded by the TCR gamma chain and delta chain genes. These two lineages of T cells have very different roles in the immune response

Question 5

Describe the composition of T cell immunoglobulin molecules

Answer 5

Both chains (either alpha and beta or gamma and delta) have a variable region and a constant region extending from the cell surface. Each of these four regions have carbohydrates attached. A ‘stalk’ region extends from the C region of each chain and these are connected by disulfide chains. Both chains are then anchored into the cytoplasmic membrane of the T cell via a transmembrane domain and each have a small cytosolic tail

The T cell receptor immunoglobulin is analogous in most ways to a Fab region of an antibody molecule

Question 6

T or F. Gamma/delta T cells are not a component of the acquired immune response.

Answer 6

T

Question 7

Why are gamma/delta T cells not considered a component of the acquired immune response?

Answer 7

They are believed to be a primitive cell type and they appear to not be MHC-restricted. They do not recognize peptide determinants, but instead appear to recognize lipid antigens, primarily.

These cells mature extrathymically, which makes them very different from alpha/beta T cells that do mature in the thymus

One other feature of gamma/delta T cells, that distinguishes them from the more- abundant alpha/beta T cells, is that they are usually double-negative cells (CD4- and CD8-).

Keep in mind that they are very similar structurally despite these many differences

Question 8

Where are gamma/delta T cells primarily found?

Answer 8

primarily in the mucosal epithelial layers of the gut.

Question 9

What is CD3?

Answer 9

n important surface marker that is expressed by all T cells. It is the protein complex that initiates signaling to the cell nucleus when the T cell immunoglobulin binds to its cognate determinant. Therefore, CD3 is referred to as the signal transduction unit of the T cell receptor.

Question 10

Describe the composition of CD3

Answer 10

The CD3 complex is composed of 6 protein chains. There are two copies of what is known as the epsilon chain, two copies of what is called the zeta chain (which are almost entirely cytoplasmic), and one copy each of a delta chain and a gamma chain (these are different from the gamma and delta chains that make up the immunoglobulin component of gamma/ delta T cells).

Can you draw this?

Question 11

What are immunoreceptor tyrosine-based activation motifs (or ITAMS)?

Answer 11

They are located on the cytoplasmic domains of each of the 6 protein chains of CD3. These regions of the CD3 chains are critical for initiation of the signaling cascade that occurs when the TCR engages its cognate determinant.

I do not care if you memorize what ITAMS stands for, but I want you to know that all six of the protein subunits of the CD3 complex are involved in intracellular signaling when the TCR is engaged with its cognate determinant.

Question 12

What are CD4 and CD8 molecules?

Answer 12

These are the TCR co-receptors that promote peptide sampling by the two primary types of alpha/beta T cells (these two cell types are referred to as CD4+ T cells and CD8+ T cells). Each mature alpha/beta T cell expresses either CD4 or CD8 (but not both) on their surface.

Question 13

CD4 has affinity for MHC class __ molecules,

Answer 13

II. And that affinity enables CD4+ T cells to sample peptides bound to MHC class II molecules.

Question 14

Describe the composition of CD4 molecules

Answer 14

has a small cytoplasmic domain and then extends from the T cell surface as a series of immunoglobin-like domains named (from closest to the cell surface to farthest): D4, D3, D2, and D1

can you draw this?

Question 15

CD8 has affinity for MHC class _ molecules,

Answer 15

I. And that affinity enables CD8+ T cells to sample peptides bound to MHC class I molecules.

Question 16

Describe the composition of CD8 molecules

Answer 16

CD8 is a heterodimeric protein that is composed of an alpha and a beta chain that extend from the cell surface and attach to each other near the cell surface. They have small cytosolic tails

Question 17

How do CD4 molecules interact with MHC class II molecules on ABCs?

Answer 17

The D2 and D1 proteins on the CD4 molecule attach to the B1 and B2 subunits (respectively) of the MHC class II molecule on the surface of the ABC

Can you draw this?

Question 18

How do CD8 molecules interact with MHC class I molecules on ABCs?

Answer 18

The alpha and beta chains of the CD8 molecule cross (in some way) and connect with the alpha2 and alpha3 subunits on the MHC class I molecule

Can you draw this?

Question 19

What are some other important surface markers expressed by T cells?

Answer 19

CD-28, Fas ligand, Adhesion molecules, CTLA-4, and PD-1

Question 20

What is CD-28?

Answer 20

this is a molecule that binds to the co-stimulator molecules (known as B7) that are expressed by antigen presenting cells that have encountered pathogens (based on their recognition of PAMPs via their PRRs).

Question 21

What is Fas ligand?

Answer 21

Fas ligand is a homotrimeric molecule that can bind to three copies of Fas on target cells, resulting in signaling that can initiate programmed cell death of the target cell.

Question 22

What are adhesion molecules?

Answer 22

there are a number of adhesion molecules that facilitate the interactions between T cells and antigen presenting cells, vascular endothelial cells, and potential target cells. All cell-to-cell interactions involving immune cells are initiated by adhesion molecules.

Question 23

What is CTLA-4?

Answer 23

a surface marker that is very similar to CD28 and that binds to B7 molecules. In fact, CTLA-4 has a 20-fold higher affinity for B7 molecules than does CD28. CTLA-4 is not expressed on resting T cells, but is expressed once a T cell becomes activated. When CTLA-4 binds to B7 molecules, signaling occurs that interferes with T cell activation and proliferation.

Question 24

What is PD-1?

Answer 24

another surface marker of T cells whose role is to down-regulate T cell activation. PD-1 has two ligands that are expressed by the three professional antigen presenting cell types (dendritic cells, macrophages, and B cells) as well as a number of other cell types. When PD-1 binds to either PD-L1 or PD-L2, signaling occurs that interferes with T cell activation/proliferation. The function of this surface marker is critical for preventing activation of self-reactive T cells, but it also has repercussions with respect to tumor development.

Question 25

T cells (actually, precursors to T cells known as thymocytes) are derived from the common lymphoid progenitor cell in the bone marrow. Once the thymocytes are produced, they enter the circulation and travel to the thymus. Most of the developmental steps of T cells occurs during thymic development.

Answer 25

T cells (actually, precursors to T cells known as thymocytes) are derived from the common lymphoid progenitor cell in the bone marrow. Once the thymocytes are produced, they enter the circulation and travel to the thymus. Most of the developmental steps of T cells occurs during thymic development.

Question 26

What are the two primary regions of the thymus?

Answer 26

the cortex and the medulla.

Question 27

The cortex of the thymus is populated with what three primary cell types?

Answer 27

1) cortical epithelial cells: these cells play a very important role in T cell development,
2) thymocytes, that migrate from the bone marrow and then begin proliferating when they reach the thymic cortex, and
3) macrophages.

Question 28

The medullary portion (medulla) of the thymus is populated with what kinds of cell types?

Answer 28

1) dendritic cells,
2) macrophages,
3) developing (near mature) thymocytes, and
4) a specialized cell called the Hassall’s corpuscle.

The junction between the cortex and the medulla of the thymus is referred to as the corticomedullary junction

Question 29

The macrophages in the cortex are termed ____.

Answer 29

tinglible body macrophages because their primary role is to phagocytose and remove dead thymocytes. Because they take up some much chromatin from these cells, they have a very distinct staining pattern

many of the thymocytes populating the thymic cortex will die via programmed cell death (or apoptosis).

Question 30

T or F. Thymocytes interact with thymic epithelial cells

Answer 30

T.

Question 31

One of the critical processes that occurs during T cell development is positive and then negative selection of the T cell repertoire.

Answer 31

These combined selections enrich the T cell repertoire for T cells that have potentially functional T cell receptors, and it removes most of the T cells in the repertoire that have specificity for self determinants. Removal of self- reactive T cells is one of the most important processes that occurs in the immune system because if self-reactive T cells become activated, they will attack and damage tissues of the host, often causing severe to fatal autoimmune disease.

Question 32

Describe the early steps of T cell development

Answer 32

Thymocytes come from the bone marrow and enter the thymus via the bloodstream. When they arrive, the begin to proliferate (divide rapidly, giving rise to many additional thymocytes). They then begin to express their T cell receptor (immunoglobulin gene rearrangement occurs at this time). The cells begin to express their TCR, CD3, and BOTH CD4 and CD8 (termed double positive T cells). This all occurs early during cortical development of the thymocytes.

Once they express all of those surface markers just mentioned, the developing thymocytes undergo positive selection. In a nutshell, positive selection allows for thymocytes that express T cell receptors that can interact well with either MHC class I or MHC class II molecules to continue to develop. If they do not, they will not receive survival signals from the cortical epithelial cells and they will undergo programmed cell death. This process positively selects thymocytes that have the potential to be functional T cells and leave those that would never be able to sample peptide determinants bound to MHC molecules to die. Again, this process occurs entirely within the thymic cortex

Question 33

What happens to thermocytes that receive positive signaling?

Answer 33

Thymocytes that receive positive signaling and continue their development eventually reach the corticomedullary junction. By this time, they are either CD4+ CD8- thymocytes or they are CD8+ CD4- thymocytes. They begin to undergo negative selection in the corticomedullary junction, but the bulk of that process occurs in the thymic medulla. Any developing thymocyte that binds too tightly to any MHC:peptide complex will be recognized as a self-reactive T cell, and it will receive signals that result in it undergoing programmed cell death.

The bulk of the negative selection takes place in the medulla of the thymus. The developing thymocytes that are not detected as self-reactive will now become mature naïve T cells and will move into the circulation, routing them to the various secondary lymphoid tissues around the body.

Question 34

What happens when thymocytes enter the thymus (via the bloodstream from the bone marrow)?

Answer 34

they soon begin to rearrange their immunoglobulin genes. Initially, the beta, gamma, and delta chains begin to rearrange

If either gamma or delta chain gene are first to rearrange successfully, the developing thymocyte is destined to become a gamma/delta T cell..

Question 35

What happens if beta chain rearrangement is the first to be successful?

Answer 35

gamma and delta chain rearrangements cease and the alpha chain genes begin to rearrange. While the alpha chains are rearranging, the expressed beta chain associates with a protein chain that is known as the pTalpha chain.

Question 36

What is the pTalpha chain?

Answer 36

The pTalpha chain is an invariant chain that serves as a surrogate alpha chain so that a pre-T cell receptor complex can form (complete with the CD3 complex). Once TCR alpha chain gene rearrangement is successful, the expressed alpha chain will then associate with the beta chain, resulting in the final TCR complex.

Question 37

Why is it critical that a beta-chain associate with a pT alpha chain while the alpha chain is rearranging?

Answer 37

because the beta chain is not very stable unless is it paired with either a copy of the alpha chain or a copy of the pTalpha chain.

Mice that have a deficiency of pTalpha expression produce increased numbers of gamma/delta T cells, significantly fewer alpha/beta T cells, and exhibit increased susceptibility to almost all pathogens (severe combined immunodeficiency, or SCID).

It is also important for you to understand that each T cell bears many identical copies of the T cell receptor on its surface.

Question 38

Once thymocytes enter the ____ and begin to proliferate, the daughter cells begin to rearrange their gamma, delta, and beta chain genes.

Answer 38

thymic cortex

Question 39

Describe the pre-T receptor complex.

Answer 39

Once thymocytes enter the thymic cortex and begin to proliferate, the daughter cells begin to rearrange their gamma, delta, and beta chain genes.

Can you draw this?

Pre-T cell receptor complex is formed once the beta chain genes (but not the alpha chain genes) have successfully rearranged and the beta chain is being expressed. The developing thymocyte also expresses all 6 of the chains of the CD3 complex and the surrogate alpha chain, known as pTalpha. The beta chain is stabilized and limited signaling via the T cell receptor (that is required for continued development and for turning off gamma and delta chain rearrangements) can occur once the pTalpha chain is paired with the TCR beta chain.

The next step is for the TCR alpha chain genes to begin rearranging.

Question 40

What happens if the alpha chain rearrangement is successful?

Answer 40

Once alpha chain rearrangement has been successful and the alpha chain is being expressed, the final complete TCR is expressed on the developing thymocyte. The TCR is now capable of “complete” signaling.

Question 41

What happens following expression of the complete TCR on the developing thermocyte?

Answer 41

At this point, the developing thymocyte begins to undergo positive selection in the CORTEX

Question 42

What is positive selection and where does it occur?

Answer 42

In a nutshell, positive selection allows for thymocytes that express T cell receptors that can interact well with either MHC class I or MHC class II molecules to continue to develop. If they do not, they will not receive survival signals from the cortical epithelial cells and they will undergo programmed cell death. This process positively selects thymocytes that have the potential to be functional T cells and leave those that would never be able to sample peptide determinants bound to MHC molecules to die. Again, this process occurs entirely within the thymic CORTEX

Question 43

Thymocytes enter the thymus from the circulation after they are produced and released from the bone marrow.

T or F. The venules that they enter through may be in the medulla, or in the cortex.

Answer 43

T. Regardless, the immature thymocyte begins to proliferate and the daughter cells migrate into the CORTEX

Be aware that at this stage the thymocyte has not yet rearranged its immunoglobulin genes and, therefore, does not yet express a T cell receptor. It also does not express either CD4 or CD8 at this point (double-negative refers to CD4/CD8 expression).

As the thymocytes proliferate, they begin to rearrange their immunoglobulin genes. Initially, the beta, gamma, and delta chain genes begin to rearrange

Question 44

What happens if the gamma or delta chain genes are the first to rearrange productively?

Answer 44

the thymocyte will be destined to become a gamma/delta T cell, and once its immunoglobulin chain gene rearrangements are complete, it will leave the thymus and mature extrathymically.

Question 45

What happens if the beta chain gene rearrangement is the first to be completed?

Answer 45

gamma and delta chain gene rearrangements will cease and alpha chain gene rearrangement will begin. This marks the 1st checkpoint in TCR expression and the pre-T cell receptor will feature the surrogate pTalpha chain pairing with the beta chain.

The second checkpoint for TCR expression is reached once alpha chain gene rearrangement is complete. At this stage, the thymocyte will now express a complete TCR.

Now that the thymocyte expresses a complete TCR, it becomes a double-positive cell (it now expresses both CD4 and CD8 on its surface).

Question 46

T or F. Once the thymocyte becomes a double-positive TCR-expressing cell, it begins to undergo positive selection.

Answer 46

T. Only then, and this occurs in the thymic cortex

Question 47

Double-positive TCR expressing T cells interact very closely with what cells in the cortex?

This is part of the process of positive selection

Answer 47

cortical epithelial cells that populate the thymic cortex. That these cells express both MHC class I and MHC class II (although all nucleated cells express class I molecules, these are the only cells other that the professional antigen presenting cells that express significant quantities of MHC class II on their surface)

Question 48

As the developing thymocytes interact with the cortical epithelial cells, those that can best interact with those cells will receive what?

This is part of the process of positive selection

Answer 48

survival signals and will continue to develop. Those that cannot compete as well for binding to the cortical epithelial cell will not receive the survival signals and will undergo apoptotic death. The cells that receive survival signals are those whose TCRs can bind with highest affinity to MHC class I or MHC class II molecules expressed on the surface of the cortical epithelial cells. This is very important, because if the TCR cannot bind to MHC class I or MHC class II, it would never be able to adequately sample peptides bound to MHC molecules, and would therefore be a non-functional T cell.

This positive selection process ensures that most of the T cells in our repertoire have the potential to be functional T cells.

Question 49

Where do developing thermocytes go once positively selected for?

Answer 49

the corticomedullary junction

Question 50

What happens by the time a developing thymocyte that has been positively selected reaches the corticomedullary junction?

Answer 50

it will be either a CD4+/CD8- or CD4-/CD8+ cell. If the thymocyte binds best to MHC class II molecules through its TCR, it will upregulate expression of CD4 and downregulate its expression of CD8. On the other hand, if the thymocyte binds best to MHC class I molecules through its TCR, it will upregulate expression of CD8 and downregulate its expression of CD4.

These single positive thymocytes will now move into the medullary region of the thymus and will undergo negative selection there.

Question 51

T or F. By the time the developing thymocyte has reached the corticomedullary junction, what will have happened?

Answer 51

it will have upregulated expression of either CD4 or CD8 and downregulated the expression of the other marker. (and have been positively selected for)

Question 52

If a developing thymocyte’s TCR interacts well with MHC class I molecules, it will upregulate its expression of ____.

Answer 52

CD8 and down-regulate expression of CD4.

Likewise, if a developing thymocyte’s TCR has affinity for MHC class II molecules, it will upregulate expression of CD4 and downregulate expression of CD8. This thymocyte is destined to become a CD4+ T cell.

Question 53

T or F. Self-reactive T cells are even more likely to receive positive selection during thymic development than T cells that are not self-reactive.

Answer 53

T. This makes negative selection a very important process.

Sometimes the binding of thermocyte TCRs with MHC molecules is very strong because the TCR on the developing thymocyte specifically recognizes the peptide that is bound in the binding groove of the MHC molecule that it has affinity for. This means that the thymocyte expresses a self-reactive TCR and it should be removed from the repertoire.

However, that does not occur until the cell reaches the MEDULLA of the thymus.

Question 54

Once developing thymocytes reach the medulla of the thymus as single-positive cells, they begin to undergo negative selection. How?

Answer 54

Any developing T cell that binds too tightly to an MHC:peptide complex will be signaled to undergo programmed cell death (apoptosis).
The affinity of the interaction that results in negative selection is typically much higher than that that occurs between developing thymocytes as they undergo positive selection in the cortex, because in this case the T cell is recognizing a specific peptide determinant bound to an MHC molecule.*

Because under normal circumstances almost every peptide presented on MHC molecules in the thymic medulla are self-derived peptides, any T cell that recognizes one of those peptides is a self-reactive T cell that should be removed from the repertoire.

Question 55

All T cells that make it to the negative selection phase of development should have a weak to moderate affinity for either MHC class I or MHC class II proteins (because they can bind to one of those proteins and receive positive selection signals in the cortex); developing T cells that have this characteristic are not negatively selected and will ultimately leave the thymus as mature naïve T cells. However, a self- reactive T cell will have a very high affinity for either MHC class I or MHC class II because it recognizes the peptide bound to either of those molecules with high specificity. These T cells will be signaled to undergo apoptotic death.

Answer 55

However, the negative selection process in the thymic medulla is not 100% efficient. Therefore, some self-reactive T cells are allowed to continue their development and leave the thymus as mature naïve T cells. If they become activated later, the patient will likely suffer from autoimmune disease.

Question 56

What is an autoimmune regulator (AIRE)?

Answer 56

A transcription factor known as the autoimmune regulator (AIRE) is expressed in the thymus. This transcription factor drives the expression of hundreds of genes that encode proteins that are abundantly expressed in the host, but that have no role in the function of the thymus. These host proteins are expressed in the thymus so that they can be used as a source of peptides for negative selection in the thymic medulla. The expression of this transcription factor helps to eliminate a large number of self-reactive T cells from the repertoire.

Genetic deficiency of AIRE expression results in widespread and devastating autoimmune diseases in patients that inherit this deficiency.

Question 57

What is an important immune role of Hassall’s corpuscles (found in the medulla)?

Answer 57

It MAY play a critical role in the development of a special subset of T cells known as T regulatory cells (or Tregs) via TSLP

Question 58

What are T regulatory cells (Tregs) and how do Hassall’s corpuscles help develop them?

Answer 58

Tregs have an important role in self-tolerance (meaning that they help to prevent the development of autoimmune disease)

Hassall’s corpuscles produce a cytokine known as TSLP that drives some SELF-REACTIVE CD4+ T cells (that are identified during negative selection) to differentiate into Treg cells instead of undergoing apoptotic death.

Tregs are effector CD4+ T cells that help to prevent activation of self-reactive T cells and are therefore important for peripheral tolerance.

Question 59

T or F. some self-reactive T cells will not die

Answer 59

TRUE. REMEMBER THIS. some self-reactive T cells will not die but instead will become T reg cells.

Question 60

Will all self-reactive T-cells die?

Answer 60

No. some self-reactive T cells will not die but instead will become T reg cells.

Question 61

What happens if a T cell successfully expresses its chains (i.e. undergoes rearrangements), passes positive selection in the cortex, and passes negative selection in the medulla?

Answer 61

Once T cells leave the thymus, they are considered mature naïve T cells. These cells now migrate to the various secondary lymphoid tissues scattered around the body where they take up residence in the T cell zone of that tissue.

While in this tissue, they will constantly sample MHC/peptide complexes, and If they receive activation stimuli, they will begin to proliferate and differentiate into effector T cells

Question 62

Is TCR immunoglobulin gene rearrangement similar to B cell immunoglobulin gene rearrangement?

Answer 62

Yes, All of the same enzymes are involved in these rearrangements.

Question 63

Beta chain rearrangement is analogous to ____ immunoglobulin gene rearrangement while alpha chain gene rearrangement is analogous to ____ rearrangement.

Answer 63

beta- heavy chain

alpha- light chain

Question 64

T or F. The potential diversity of the TCR immunoglobulins is several orders of magnitude higher than that of the B cell immunoglobulin genes…which is pretty remarkable.

Answer 64

T. The TRC Ig genes code for up to 10^18 different TCR molecules

Question 65

TCR alpha chain genes are located on what chromosome?

Answer 65

14

Question 66

TCR beta chain genes are located on what chromosome?

Answer 66

6

Question 67

Describe the organization of the a-chain gene on chromosome 14.

Answer 67

There are 70-80 Va chins (each with leaders) followed by 61Ja chains and then a single C chain

Question 68

Describe the organization of the b-chain gene on chromosome 6.

Answer 68

There are 52 Va chins (each with leaders) followed by a single DB1 chain (diversity), 6 JB1 chains, a single CB1 (constant) chain, and then

a DB2 chain, 7JB2 chains, and a single CB2 chain

Question 69

As was the case for somatic recombination of the B cell immunoglobulin genes, somatic recombination of the TCR Ig genes is catalyzed by which enzymes?

Answer 69

RAG enzymes (RAG-1 and RAG-2).

Question 70

How does alpha chain rearrangement occur (keep in mind it occurs after beta chain rearrangement is successful)?

Answer 70

One of the many V region gene segments is randomly selected to be joined with one of the J region gene segments on the germline DNA to create the coding region for the variable domain of the alpha chain. Via transcription and splicing, an mRNA transcript is made and translated to express the alpha chain of the TCR.

Question 71

How does beta chain rearrangement occur?

Answer 71

Rearrangement of the beta-chain genes is analogous to B cell heavy chain gene rearrangement because the first rearrangement involves the random recombination of a single D region gene segment with a single J region gene segment. A second recombination event then randomly selects one of the V region gene segments to recombine with the DJ junction to create the recombined germline coding region for the TCR beta chain. Notably, TdT is responsible for junctional diversity during beta chain gene rearrangements (analogous to what happens in B cell heavy chain rearrangement).

Please remember that beta chain rearrangements always occur first and the alpha chain rearrangement only occurs after beta chain rearrangement has been successful.

Question 72

RAG-1 and RAG-2 (the same enzymes that catalyze B cell immunoglobulin gene rearrangement) are required for TCR gene rearrangement. Genetic deficiency of one of both of these enzymes would result in an almost total lack of which cells?

Answer 72

B AND T cells. The patient would be highly susceptible to all pathogens and would be classified with severe combined immunodeficiency (SCID).

Question 73

What does terminal deoxynucleotidyl transferase (TdT) do?

Answer 73

catalyzes the addition of N-nucleotides between the rearranging gene segments during TRC beta chain (and B cell heavy chain) rearrangements. A deficiency of TdT will result in reduced diversity of both the T cell and B cell repertoire because there will be no junctional diversity of the beta and heavy chain, respectively.

However, it is unlikely that this would result in overly increased susceptibility to infections that would be recognized clinically.

Question 74

Be aware that a tumor cell will generally have the same surface phenotype as the initial cell that resulted from the neoplastic event that altered the cells growth characteristics. Based on the surface phenotype of the T cell tumors, it can be determined at what point in the development of the T cell that the neoplastic event took place.

Answer 74

be aware that a tumor cell will generally have the same surface phenotype as the initial cell that resulted from the neoplastic event that altered the cells growth characteristics. Based on the surface phenotype of the T cell tumors, it can be determined at what point in the development of the T cell that the neoplastic event took place.

Question 75

The neoplastic event for a common acute lymphoblastic leukemia (C-ALL or B-ALL) tumor type took place where?

Answer 75

in a lymphoid progenitor cell

Question 76

Lymphoid progenitor cells express what 3 surface markers?

Answer 76

CD10 (expressed on B cell precursors and bone marrow stromal cells),

CD19 and CD 20 (B cell surface markers)

Question 77

Thymomas arise from which cells?

Answer 77

these tumor cells arise from thymic stromal cells, therefore the do not express any lymphocyte-specific surface markers.

Question 78

Thymoma is often observed in patients that suffer from what?

Answer 78

myasthenia gravis (an autoimmune disease).

Question 79

The neoplastic event for an acute lymphoblastic leukemia (T-ALL) tumor type took place where?

Answer 79

neoplastic event took place in a thymocyte, as evidenced by its surface expression of CD1; CD1 is expressed on cortical epithelial cells.

Question 80

The neoplastic event for an Adult T cell leukemia; chronic lymphocytic leukemia (CLL); or T prolymphocytic leukemia (TPLL): tumor type took place where?

Answer 80

the neoplastic event took place in a T cell that was nearing or was a mature T cell. The cell already expresses a complete T cell receptor and is a single positive cell (expresses either CD4 or CD8, but not both).

Generally, the neoplastic event occurs in T cells that have left the thymus (peripheral T cells).

Question 81

What is CD34?

Answer 81

is a stem cell (hemopoietic progenitor cell) surface marker.