Immunodeficiencies Flashcards
What is the difference between priamry and secondary immunodeficiencies
- Primary is congenital
- Secondary is acquired through infections, nutritional abnormalities, and medical treatments
What is X-linked SCID?
Primary Immunodefiency, where there is a defect in lymphocyte maturation.
- only males affected.
- mutation in gene coding gamma C signaling subunit (normally on IL receptors)
- there is an absence of T cells and NK cells
Which cytokines require gamma C for signaling?
IL
In X-linked SCID, what is the cause for very few or no T cells?
Lack of production of IL-7 due to mutation in gamma C subunit of IL-7 receptor (normally leads to JAK/STAT pathway)
The NK cell deficiency of X-linked SCID is a result of which cytokine receptor missing its gammaC subunit?
IL-15 receptor which would normally be responding to IL-15 and type I IFNs, activating NK cells which will secrete IFN gamma and help control viral infection/replication
Would you expect antibody response to be normal in an X-linked SCID patient?
No, antibody production of B-cells relies on classswitching and activation by T-cells, since there is no T-cell activation telling the what antibody to be produced, you would not get normal levels of antibodies and most of them would be IgM
What are the nine characterisitcs that would implicate immunodeficiencies as an underlying disease?
- 8 or more new ear infections in 1 year
- 2 or more serious sinus infections in 1 year
- 2 or more months on antibiotics w/ little effect
- Two or more pneumonias within 1 year.
- failure of an infant to gain weight or grow normally.
- recurrent, deep skin or organ abscesses
- persistent thrush in mouth or elsewhere on skin, after age 1
- Need for IV antibiotics to clear infections
- Two or more deep-seated infections
- A family history of primary immunodeficiency.
What are the 3 sites of mutations in Autosomal SCID?
- Mutation in the purine salvage pathway (Adenosine Deaminase ADA most common) or mutation in purine nucleoside phorylase (PNP)
-leads to build up of purine metabolites that are toxic to T cells causing them to die
- Mutation in JAK3 (required for gamma c signaling)
- Mutation in RAG1/2 (a mutation in RAG genes that result in reduced RAG protein expression is Omenn Syndrome)
What would a reduced expression of RAG proteins lead to?
Omenn Syndrome is reduced expression of RAG genes
Which cell types are missing in a patient lacking RAG1 expression?
They would be missing T cells and B cells because RAG1 expression is responsible for production of TCRs and BCRs
In addition to multiple infections, what is a common clinical manifestation in Omenn Syndrome?
Autoimmunity (reasoning is not completely understood)
What is the underlying mutation responsible for X-linked aggamglobulinemia? What would be lost as a result?
Mutation in BTK (Bruton Tyrosine Kinase) leads to loss of mature B cells, loss of serum Igs, and Autoimmunity
Most states, Kansas is in the process of doing so, have implemented screening for newborn SCIDs. What test is used?
TREC assay (T cell receptor excision circle)
What would be the clinical findings for a SCID?
- decreaed TRECs
- absence of Thymic shadow on chest x-ray]
- absence of germinal centers on lymph node biopsy
- and absence of T cells on flow cytometry
What are the presentation and treatment for SCID?
failure to thrive, chronic diarrhea, thrush, recurrent infections
-treatment is bone marrow transplant (no concern for rejection in this case because there is no production of antibodies)
