Mutations Affecting T-cell Maturation

00:01 So those are a number of different primary immunodeficiencies that affect the innate response.

00:08 Let’s now look at some of the immunodeficiencies that affect the adaptive immune response.

00:13 Here we can see a common lymphoid progenitor that is going to develop into T-cells.

00:20 So listed here are a number of genes that if they’re not functioning, the product of those genes is not produced, and therefore you can’t progress from this common lymphoid progenitor to a pro-T cell.

00:36 So the gamma C-chain which is a component of six interleukin receptors, the IL-7 receptor α-chain, the IL-2 receptor α-chain, JAK3, ADA, PNP, can all result in this inability to produce pro-T cells; a block in the differentiation pathway.

00:57 A number of other genes which you can see listed here, if they’re not functioning, there will be a block in the progression from pro-T to pre-T cell development within the thymus.

01:10 And eventually in a normal situation, these pre-T cells will develop into double positive T-cells and then into single positive, either CD4 or CD8 T-cells.

01:22 And again there are a number of gene defects that you can see listed here that will result either in a total absence of both CD4 and CD8 T-cells, or in some cases the CD4 T-cells will be blocked or the CD8 T-cells will be blocked.

01:41 What about B-cell maturation? Well again we have a situation where a common lymphoid progenitor is going to develop into B-cells.

01:51 Mutations in the gene for adenosine deaminase or purine nucleoside phosphorylase (PNP) will result in an inability to produce pro-B cells.

02:06 A very large number of mutations will lead in a block that the pro-B cell cannot reach the pre-B cell stage.