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Flashcards in Immuno 7 Deck (81)
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1

What is a T cell?

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.

2

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

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.

3

How are T cells different from B cells?

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.

4

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

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

5

Describe the composition of T cell immunoglobulin molecules

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

6

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

T

7

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

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

8

Where are gamma/delta T cells primarily found?

primarily in the mucosal epithelial layers of the gut.

9

What is CD3?

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.

10

Describe the composition of CD3

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?

11

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

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.

12

What are CD4 and CD8 molecules?

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.

13

CD4 has affinity for MHC class __ molecules,

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

14

Describe the composition of CD4 molecules

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?

15

CD8 has affinity for MHC class _ molecules,

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

16

Describe the composition of CD8 molecules

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

17

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

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?

18

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

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?

19

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

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

20

What is CD-28?

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).

21

What is Fas ligand?

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.

22

What are adhesion molecules?

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.

23

What is CTLA-4?

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.

24

What is PD-1?

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.

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.

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.

26

What are the two primary regions of the thymus?

the cortex and the medulla.

27

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

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.

28

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

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

29

The macrophages in the cortex are termed ____.

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).

30

T or F. Thymocytes interact with thymic epithelial cells

T.