1 / 10

Primary Immunodeficiency Diseases

Primary Immunodeficiency Diseases. Primary immunodeficiencies are those in which the defect is intrinsic to the immune ​system, meaning it is genetically determined. Chronic Granulomatous Disease (CGD)

barr
Télécharger la présentation

Primary Immunodeficiency Diseases

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Primary Immunodeficiency Diseases

  2. Primary immunodeficiencies are those in which the defect is intrinsic to the immune ​system, meaning it is genetically determined.

  3. Chronic Granulomatous Disease (CGD) • CGD is a disorder in which polys and monocytes phagocytose but can’t kill bacteria and fungi ​once they’re ingested. This affects phagocyte-rich endothelial organs such as lung, ​liver, spleen, and lymph nodes.

  4. Patients are susceptible to all types of bacteria and fungi that are catalase positive and ​oxidase negative, and​therefore do not produce hydrogen peroxide. • Organisms that are catalase negative (pneumococcus, streptococci, H. influenzae) don’t cause ​particular trouble because they generate hydrogen peroxide.

  5. This occurs because phagocytic cells normally kill ingested microbes by using myeloperoxidase ​in the presence of hydrogen peroxide to fix iodide to the microbial surface. • This iodide ​fixation kills microbes. In normal phagocytes, myeloperoxidase and H2O2 are contained ​in lysosomes that fuse with phagocytes.

  6. In CGD, phagocytic cells can’t generate H2O2, and can’t kill microbes that don’t themselves ​generate peroxide (staph, E coli, aspergillus, candida). • Gene defects that cause peroxide dysfunction may be X-linked or autosomal recessive. Most ​commonly it is the X-linked enzyme Cytochrome b558 that is defective. But various ​genetic defects can cause the same clinical syndrome.

  7. Diagnosis is by NBT dye (only changes color in presence of H2O2), and direct measurement ​of H2O2 production. • Severe Combined Immunodeficiency (SCID) • There are multiple genetic forms of this disease. ADA deficiency is autosomal recessive. IL2 ​receptor deficiency is X-linked recessive. JAK3 and RAG2 deficiencies may also ​cause SCID.

  8. SCID is characterized by severe recurrent infections, since both B and T cells are defective. In IL2 receptor and JAK3 deficiencies, the T cells alone are defective, but this also prevents ​activation of B cells by T cells. • In ADA deficiency, the defect is intrinsic to B/T cells. Adenosine Deaminase (ADA) is part of ​the purine salvage pathway.

  9. When absent, deoxy ATP accumulates and poisons T cells. • Prenatal diagnosis of ADA deficiency is possible. Developmentally, costrochondral flaring of ​the ribs can be seen.

  10. It is now possible to provide enzyme replacement therapy to salvage T cells. We can also ​insert the gene into lymphocytes, and this is the first successful example of gene ​therapy for a genetic disorder.

More Related