Immunodeficiency Flashcards
What is immunodeficiency?
One of more components of the immune system are defective, resulting in an impaired or absent response to infection
What is primary immunodeficiency?
Rare, caused by inherited mutations in genes that are involved in, or control, immune responses. Classified on the basis of the immune system components involved but because of the integration of many aspects of immune defence, defects in one component can impact the function of others. Provide insight into the normal pathway of defence against infectious diseases
What is secondary immunodeficiency?
Common, acquired as a consequence of other diseases or arises due to environmental factors such as starvation or as a side effect of medical intervention
What causes immunodeficiency?
Defects in T cell and B cell development, can be caused by mutations in genes in the thymic epithelium that impair thymic development and hence T cell development
What is an X-linked SCID?
Most common form of SCID due to mutations in the IL2RG gene, an IL-2R common γ chain, gc, on the X chromosome, defects in signalling in receptors of the IL-2 cytokine family (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), T cell and NK cell development abnormal, normal B cell development, abnormal function due to absence of T cell help, mutation in JAK3
What causes abnormal development of T and NK cells?
Defects in IL-7 and IL-15 signalling. Targeted mutations in IL-15 or a chain of IL-15 receptor have no NK cells but relatively normal T cell development, maintenance of memory CD8 T cells is defective.
How does SCID occur?
Defects in antigen receptor gene rearrangement of the RAG gene. Mutations in either the RAG1 or RAG2 gene, whose products are essential for gene rearrangement. No T or B cells, NK cell development not impaired. Hypomorphic RAG mutations, including patients with Omenn syndrome, develop multiple opportunistic infections and symptoms similar to graft-verus-host disease. Mutations in either gene that result in non-functional proteins cause lymphocyte development arrest at the pro-to-pre T and B cell transition because of failure of V(D)J recombination. This results in no B cells and autoreactive T cells
What causes graft-versus-host disease?
An attack on the tissues of a recipient by mature T cells in a bone marrow graft from a non-identical donor. Normal or increased numbers of activated T cells due to low levels of RAG activity allowing some limited TCR gene rearrangements. patients have no B cells
What is RS-SCID?
Radiation-sensitive SCID. Patients have very few B and T cells due to failure of antigen receptor gene rearrangement. Defects in ubiquitous DNA repair proteins involved in repairing DNA double-strand breaks, which are generated not only during antigen receptor gene rearrangement but also by ionising radiation.
What is WAS?
Wiskott-Aldrich syndrome. Defect in the WAS gene on X chromosome that encodes WAS protein (WASp). Characterised by reduced T cell numbers, defective NK cell cytotoxicity and a failure of antibody responses.
