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From what I understand, T-cells are constantly traveling in the body, inspecting cells by looking for antigens. If they're self antigens, then the T-cell doesn't attack, whereas if they're non-self, they attack. My question is how does a T-cell know when it just inspected a cell? Does the T-cell leave something behind on the cell to mark it as checked or does the cell itself present something on its surface to indicate that it has just been checked? If there is no such system, then what prevents the T-cells from being stuck in a loop, and just inspecting the same cell over and over?

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    $\begingroup$ As answered on Reddit, where you asked the identical question, it's because there's extensive movement even in the relatively calm environment of the lymph nodes, so that once the T cell disengages from its target the natural movement makes it unlikely to bump into the same cell. See the references and videos on Reddit. $\endgroup$ – iayork May 23 '16 at 11:57
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    $\begingroup$ Here is the Reddit link for anyone who's interested. $\endgroup$ – MattDMo May 23 '16 at 13:06
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    $\begingroup$ I've edited your title and removed anthropomorphic 'know'. $\endgroup$ – David May 23 '16 at 13:35
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Your question spans two activities of T-cells that are related to each other: migration and activation. T-cells that usually stay in lymphoid organs migrate to non-lymphoid organs with different mechanisms for each T-cell subtype. When migrated to non-lymphoid organ, the T-cells move through the organ looking for infected cells.

Migration

As you can see in the image below, there are many mechanisms for moving T-cells across the endothelial layer.

Migration of T-cells through the endothelial layer depends on the type of T-cell and the organ the endothelial layer is situated in.

The main idea for all three mechanisms is that the tethering of the T-cell to the endothelial layer is weak. Because of the weak interaction, the blood flow causes the T-cell to move across the endothelial layer while still being attached to the endothelial layer. This is known as rolling. Other stimuli (usually chemokines) such as CCL21, CCL25, or ICAM 1 are needed to induce T-cell to migrate across the endothelial layer. This is important because these chemokines are expressed where there is inflammation. For example, there is a correlation between CCL25 level in the gut and inflammation in the area.

T-cells express α4β7 integrin or CCR7 that bind T-cell to the endothelial layer. Central memory T-cells and naive T-cells express CCR7 and CD62L and thus reside preferentially within the secondary lymphoid organs. Effector memory T-cells bind to gut endothelium with α4β7 integrin, CCR9, and LFA-1.

CCL21 is expressed by both stromal cells of lymph node paracortex and endothelium of lymphatic vessels to assist migration of activated dendritic cells and naive and central memory T-cells to lymph node respectively. Dendritic cells are professional antigen-presenting cells (APCs) that migrate to lymph node where it can interact with T-cells more efficiently.

T-cell activation

One important concept to take away from T-cell activation is that there needs to be direct contact between MHC complex and T-cell receptor (TCR).

T-cells that have moved into the lymph node interact with dendritic cells, which have high MHC complex concentration on their cell surface. This leads to subsequent activation of the T-cell leading to release of cytokines such as IL-2 leading to proliferation of activated T-cells.

The activated T-cells now are able to freely move across the endothelial layer of non-lymphoid organs to infiltrate and look for infected sites. (Naive T-cells enter endothelial layer of non-lymphoid organs as well but this is chemokine independent nad thus not a reaction to inflammation).

Sources:

Difference between naive T-cells and memory T-cells: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782715/

Dendritic cell's role in immune response: http://lab.rockefeller.edu/steinman/dendritic_intro/immuneResponse

Memory vs naive T-cell migration: http://www.nature.com/icb/journal/v86/n3/full/7100132a.html

Dendritic cell and role of CCL21: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078419/

Naive T-cell non-lymphoid organ infiltration: http://onlinelibrary.wiley.com/doi/10.1002/eji.200535539/full

CCL25 and inflammation relation: http://www.sciencedirect.com/science/article/pii/S0896841116300014

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  • $\begingroup$ Please add a citation to your answer (like the process of a T-cell inspecting a cell, there are no such markers ever discovered, etc.) $\endgroup$ – another 'Homo sapien' May 22 '16 at 9:49
  • $\begingroup$ Sorry, I meant there's no marker that is well known to have that function. Several literature searches yielded no results, so I simply have written "none commonly known". $\endgroup$ – Kenny Kim May 22 '16 at 10:10
  • $\begingroup$ Its all right. You should just have a back-up claim if someone asks you about the correctness of your answer. $\endgroup$ – another 'Homo sapien' May 22 '16 at 10:13
  • $\begingroup$ @John It was hard to find in other literatures whether T cell bind to MHC or antigen first. However, that doesn't matter in this case because you cannot have one without the other! MHC and antigen go together. If the cell wasn't antigen presenting cell, it wouldn't have MHC to bind in the first place! $\endgroup$ – Kenny Kim May 22 '16 at 16:19
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    $\begingroup$ The more effector T cells respond to antigen, the more inhibitory receptors it starts expressing that lead to death of that particular T cell. At that, the longer it takes for the T cell to die, it starts to enter progressively more severe stages of exhaustion. So really the T cells regulate their own persistence (in part). It would be useful to cover this as well. $\endgroup$ – CKM May 22 '16 at 22:43
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T-cell does not inspect any cell until the cell shows a piece of the "non-self" antigen on it by the MHC.

The helper T-cell connects with the antigen which is on the cell's surface. The T-cell sorts the cytokines that activate the cytotoxic T-cell to divide and form a colony of cytotoxic cells. The colony of cytotoxic cells then attack the "non-self" antigen expressing cell.

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