Severe Combined Immunodeficiency (SCID) – Primary Immunodeficiency

by Peter Delves, PhD

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    00:01 The worst type of primary immunodeficiency is SCID (severe combined immunodeficiency).

    00:10 The title tells it all, doesn’t it really? It’s severe and it’s combined because it affects not only T-cells but also B-cells.

    00:18 It’s due to mutations in one of a number of different genes involved in controlling cytokine signaling, or T-cell receptor signaling, or VDJ recombination of the immunoglobulin and T-cell receptor genes, or in metabolism.

    00:34 There is a complete and total failure of T-cell development.

    00:41 It affects approximately one child in every 80,000 live births.

    00:50 There are severe defects in both cellular and humoral immunity.

    00:56 The result is severe and recurrent viral, bacterial and fungal opportunistic infections.

    01:04 And unfortunately without treatment, this condition is fatal within the first year of life.

    01:09 Although there are a number of treatments that are available.

    01:13 And the key thing about SCID is that there is a complete absence of T-cells.

    01:19 There are a number of different genes that can cause SCID, and the particular genes that are involved will determine exactly which cell types are absent in the immune response.

    01:30 But the common theme is there is always a absence of T-cells.

    01:33 So if there’s a gene defect in the γC component of the interleukin receptors or in JAK3, the result is that there are no T-cells.

    01:46 There are B-cells present, but there are no NK cells.

    01:51 So this is referred to as T negative, B positive, NK negative SCID.

    01:57 In contrast, if there is mutation in those other genes that you can see listed there, RAG1, RAG2 and so forth, then the result is T negative, B negative, NK positive SCID.

    02:12 In other words, those children will totally lack T-cells and B-cells, but they do have NK cells.

    02:19 The third group of genes that you can see there, the interleukin-7 receptor α-chain, CD3δ and so forth; defects in those genes will result in the T negative, B positive, NK positive phenotype of SCID.

    02:35 In other words, there are no T-cells, but there are B-cells and NK cells.

    02:39 And then the most severe of the severe immunodeficiency is the ADA and AK2 gene defects.

    02:49 So defects in those two genes, will result in an absence of T-cells, an absence of B-cells and an absence of NK cells.

    03:01 The γC defect and JAK3 defects, account for approximately 50% of SCID cases.

    03:17 This results in an inability to signal through six different interleukin receptors, because those receptors all use the γC-chain of the interleukin receptors; it’s called γC, the C stands for Common, it’s common to six different interleukin receptors.

    03:39 And they all use JAK3 as a signaling molecule.

    03:44 And these six receptors are the interleukin-2 receptor, the interleukin-4 receptor, the interleukin-7 receptor, the interleukin-9 receptor, interleukin-15 receptor, and finally the interleukin-21 receptor.

    04:03 All six using both the γC common chain of the receptor, and JAK3 signaling molecule.

    04:11 So there’s no signaling from any of these six different cytokines, and that leads to this severe combined immunodeficiency.

    About the Lecture

    The lecture Severe Combined Immunodeficiency (SCID) – Primary Immunodeficiency by Peter Delves, PhD is from the course Immunodeficiency and Immune Deficiency Diseases.

    Author of lecture Severe Combined Immunodeficiency (SCID) – Primary Immunodeficiency

     Peter Delves, PhD

    Peter Delves, PhD

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