Is there an immunity training school in our bodies ?

In my previous post we talked about how dendritic cells get activated and march to lymph nodes along the concentration gradient of one of the chemokines (CCL21). How they pass the baton to the next series of cells in line of defence is equally remarkable, but before we dive into detail lets introduce our combat soldiers.

T cells or T lymphocytes are the combat soldiers of the immune system, they belong to a group of white blood cells known as lymphocytes.They are called T cells because they mature in the thymus. T cells play a key role in cell-mediated immunity. They can be distinguished from other lymphocytes by the presence of a T cell receptor (TCR) on their surface.

There are several subsets of T cells, each with a distinct function. Just like many other blood cells, T cells originate from haematopoietic stem cells in the bone marrow. So they share a common bloodline with dendritic cells.

Precursor T cells leave bone marrow and migrate to thymus where they undergo maturation and differentiation to take their specialised combat roles. T cell maturation is an important step towards building body’s defence mechanisms. It takes place in thymus gland which acts as the immune training school for T cells.

Thymus produces thymosin, a hormone necessary for T cell development and maturation.

Before T cells can be deployed as combat soldiers they require rigorous training regime to make sure they are fit to fight. So where does this training take place?

Well….our body houses a full fleshed training academy hidden in our thymus.

It is the thymus where T cells learn to differentiate between body’s own antigens and foreign substances. T cells are allowed to leave thymus only if they are mature enough to tackle the real threats. In order to be successful in their business T cells must be able to strongly bind to MHC complex of antigen presenting cells so that they can identify the antigens.

The T cells contain many receptors on their surface, T cell receptor (TCR) is however the key receptor that achieves binding with antigen presenting cells (APC’s). TCR has two binding sites, one that binds to the MHC complex on APC and the second one binds to the antigen presented by APC. The T cells maturation process assures the binding ability is fully developed before cells are allowed to graduate from the thymus training school.

The TCR itself does not have a significant intracellular protein domain. Instead, it is associated with CD3 molecules that contain intracellular signaling domains. So it is the TCR/CD3 complex that activates the downstream signaling machinery when TCR binds to MHC complex on antigen presenting cells.

When T cells enter the training school it has two kinds of MHC-receptors, CD4 and CD8. In the thymus T cells are exposed to variety of peptides including MHC I and II. The process is called positive selection. The cells that can bind to MHC I protein are called CD4 cells the ones that bind to MHC II are called CD8 cells.

In order to pass positive selection T cells must be able to bind with at least one kind of protein available in thymus cortex.

Depending on the type of binding, T cells differentiate into one of the two types. If CD4 receptors participate in binding during positive selection, their CD8 receptors degenerate and cell acquires the characteristics of a Helper T cell.

If CD8 receptor binds then the T cell stops making CD4 receptors anymore and it becomes a cytotoxic T cell.

Precursor T cells are designed to self destruct after a while so they must receive a survival signal in order to survive. Only the cells that bind to MHC protein receive the survival signal, other eventually self destruct.

MHC binding test is to make sure they are able to communicate the language of antigen presenting cells and able decode the enigma to initiate immune response. The ones that fail this task are of no use, so they are sacrificed in the interest of the colony and their relics used for other purposes.

In the thymus apart from MHC I and MHC II proteins, cells are also exposed to variety of other proteins that normally exist in the body, the cells that show strong affinity with body proteins are also signaled to self destruct This is referred to as negative selection.

If this mechanism somehow fails the immune system starts an attack on itself and body develops an autoimmune disease.

Once T cells graduate from the thymus training school they are ready to march to the control centre in lymph nodes where they receive their combat instruction via a process called T cell activation. I will leave the T cell activation for a subsequent post.

Originally published at scriptgrandeur.wordpress.com on May 23, 2015.