Biology of the T cell Flashcards

Question

adhesion molecule info

Answer 1

may also play a role in facilitating TCR-MHC interactions by slowing their migration through the lymphatic tissues to allow for the potential interaction. Some of the well characterized adhesion molecules include CD2 which binds to CD58(LFA-3) on APCs (i.e. macrophages); CD11aCD18 (LFA-1) which binds to CD54(ICAM-1) on APCs and endothelial cells plus some other ligands; CD50 (ICAM-3) which binds to LFA-1 on APCs.

Answer 2

play an important role in facilitating TCR-MHC interaction as well as mobilizing the T cells post activation to other tissues in the body. CD62L (L-selectin) functions as a “homing receptor” with adhesion properties for T cells and other lymphocytes enabling their passage through the high endothelial venules, by binding to CD34, to the secondary lymphoid tissues. These events in combination with integrins (i.e. LFA-1 family) and chemokine receptors (i.e. CCR7)

Answer 3

a congenital autosomal recessive immunodeficiency involving a defect in LFA-1 synthesis and or expression on the cell surface and thus expression in select leukocytes. This results in an inability of the leukocytes to migrate to affected tissues

Answer 4

When the γδ TCR is expressed on the cell surface it is associated with CD3 and the zeta molecules. These T cells typically don’t express co-receptors CD4 or CD8 with exception in the intestine where a subset has been identified as CD8+. Similar to the a,b TCR, the γδ TCR is composed of 2 chains each containing a globular variable chain and globular constant chain in which the variable regions have the capacity to undergo some rearrangement. Since the genes that code for the γδ variable regions are fewer, the potential number of combinations for the γδ TCR binding sites are more limited.

Answer 5

phospholipid antigens, tend to have a more rapid response rate to select pathogens such as, mycobacterium, cytomegalovirus and plasmodium falciparum

Answer 6

IFN-γ and TNF

Answer 7

BD, Type I diabetes, rheumatoid arthritis, multiple sclerosis

Answer 8

and J segments similar to the Ig light chains.

Answer 9

V, D and J chains similar to the Ig heavy chains.

Answer 10

1. secrete cytokines (i.e IL-7) to aid in maintaining cell survival and inducing proliferation 2. thymocyte selection

Answer 11

dendritic cells and macrophages

Answer 12

thymic epithelial cells fail to develop and thus an absence in a thymus. Since T cell differentiation cannot take place, these individuals are severely immunocompromised

Answer 13

thymic epithelial cells fail to develop and thus an absence in a thymus. Since T cell differentiation cannot take place, these individuals are severely immunocompromised

Answer 14

the common lymphoid precursor cell differentiates into a precursor pre -thymic cell that enters at the cortico medullary junction to start is migration through the cortex. At this point, there are no discernable classic T cell surface molecules on its surface and thus it classified as a DN thymocyte. The gene for the TCR undergo rearrangement and the rest of the previously described steps to yield either a pre-T cell expressing only the β chain or γδ thymocyte. If the γδ TCR is expressed on the thymocyte, it exits out of the thymus to become γδ T cells. So, these cells are only transiently in the thymus. The thymocyte pre-T cell expressing the β chain remains in the thymus migrates through the cortex then to the medulla. During the migration the α chain is synthesized and co-expressed to form the complete TCR. In addition, both the CD4 and CD8 co-receptors are upregulated in their expression on the cell surface of the thymocyte (i.e. ab+, CD3+, CD4+, CD8+) with the thymocyte classified as a DP (double positive CD4 and CD8) thymocyte, for short. In fact, the majority of thymocytes in the thymus in a pre-pubic host are DP thymocytes. The DP thymocytes migrate through the cortex into the medulla during which these cells undergo a series of tests to determine if each will be a functional T cell and that it won’t overly react to self-MHC a process known as thymic selection. If it passes thymic selection, the thymocyte exits the thymus as a single positive (SP), CD4+ T cell or CD8+ T cell.

Answer 15

During migration through the cortex, the DP thymocyte encounters thymic epithelial cells that present linear peptide self-antigens via MHC Class I and MHC Class II molecules. The primary test by the epithelial cells is to determine whether the DP thymocyte has a functional TCR and which MHC molecule it will recognize as self. This step is called positive selection. This is the stage of selection in which the thymocyte commits to recognizing linear Ag through only one MHC molecule directed in part by the co-receptor CD4 or CD8. The term self-MHC restriction of T cell responses commemorates this relationship. Note, not all thymocytes recognize the peptides and/or can bind to MHC. These cells are induced to undergo apoptosis. If the DP thymocyte passes this test, it down regulates one of its 2 co-receptors and migrates to the cortico-medullary junction where it encounters either a thymic dendritic cell or medullary epithelial cell for its final test

Answer 16

, the thymocytes entering the cortico-medullary junction have already committed to being either being CD4 or CD8. They encounter either a thymic dendritic cell or medullary epithelial cell which present on their surface both MHC class I and MHC class II molecules expressing linear peptides. The purpose of this selection is to ascertain whether affinity of the thymocyte for its specific self-MHC is intermediate and is called negative selection. If the binding affinity is too high, this could infer that the thymocyte has an autoreactivity to self-antigen. If this were to occur, the thymocyte would be induced to die via apoptosis. T cell differentiation through the thymus is believed to take a few weeks. As one can see, T cell differentiation is highly regulated. If the thymocyte passes negative selection, it can stay in the thymus for a few days after which guided by adhesion molecules and chemokine receptors it migrates out of the thymus to circulate through the secondary lymphoid organs in search of its cognate linear peptide Ag. Once a naïve T cell recognizes its cognate linear Ag peptide presented by MHC, it clonally expands into effector T cells and memory cells. The effector T cells are activated to combat the antigen response and will continue until the antigen response abates then will likely be induced to die via apoptosis. Memory cells are already primed to the antigen and remain in sort of a “cell cold storage” until activated

Answer 17

subset of T cells that express a TCR and cell surface protein NK1.1. NKT cells recognized glycolipids complexed through CD1d and not MHC. The TCR of the NKT cells is generated via one V gene and a limited number of V genes it usage is referred to as semi-variant and thus believed to respond to a limited number of antigens. The current belief is that these cells display both innate and adaptive function

Answer 18

subset of CD4+ T cells (10% of the population) denoted by cell surface protein CD25 and transcription factor Foxp3. They have a major role in peripheral tolerance

Answer 19

lymphocytes that fall under the innate immunity umbrella. Most of these cells originate from the bone marrow. Based on the literature a small subset can differentiate in the thymus (duration unknown) as DN cells. Regardless, they emigrate out before TCR gene rearrangement occurs. NK cells express cell surface molecules CD16 and CD56.

Answer 20

lymphocytes that fall under the innate immunity umbrella. Most of these cells originate from the bone marrow. Based on the literature a small subset can differentiate in the thymus (duration unknown) as DN cells. Regardless, they emigrate out before TCR gene rearrangement occurs. NK cells express cell surface molecules CD16 and CD56.