Mar27 M3-Adaptive Immunodeficiency

Question 1

when to suspect PID (primary immunodef)

Answer 1

• infections that are frequent, severe or unusual

- unexplained prolonged diarrhea or FTT (failure to thrive)

Question 2

recurrent infections with encapsulated bacteria suggest what type of PID

Answer 2

• think Ab deficiency

- (other lecture says C5-C9 complement deficit get these also)

Question 3

name of an antibody replacement treatment + when it is used

Answer 3

IVIG (IV Ig, intravenous immunoglobulin)

• PIDs
• autoimmune disease
• got transplant

Question 4

SCID prognosis and treatment

Answer 4

• ONLY thing you can do is bone marrow transplantation

- otherwise, die before 1 year of age

Question 5

2 PIs in boys

Answer 5

• XLA (X-linked agammaglobulinemia)

- XL-SCID (X-linked SCID)

Question 6

cause of XLA (XLA is a primary B cell deficiency. SCID and X-linked SCID (a form of SCID) are not related)

Answer 6

• mutation in btk gene (Bruton tyrosine kinase)
• arrest of B cell development at pre-B cell stage
• absent circulating mature B cells
• absence of all major Ig classes (G, M, A, etc.)

Question 7

function of btk gene

Answer 7

• important in signaling cascade needed for B cell class switching from M to G, A, E.
• important for B cell dev

Question 8

symptoms of XLA

Answer 8

• infections that begin at 4-6 months after mom Abs gone
• bacteremia, meningitis, septic arthritis, sino-oto-pulm infections with encapsulated bacteria
• enteroviruses

Question 9

most common form of SCID

Answer 9

X-linked SCID (where the gamma common chain (ALSO KNOWN AS CD132 OR IL-2R) is absent and you get problems in IL signaling. no T cells)

Question 10

what happens in X-linked SCID

Answer 10

IL signalling problem because mutation in a chain of the IL-2R (gamma common chain, common to other IL Rs) and it’s absent. you get no T cells
*problem in IL signaling, big problem bc IL-2 signaling is crucial

Question 11

symtpoms of SCID in general (includes X-linked SCID)

Answer 11

• severe T cell defect, +- B cells and NK cells.
• lymphopenia and Ab deficiency
• high susceptibility to infection
• FTT, protracted (long lasting) diarrhea

Question 12

other example of primary B cell deficiency

Answer 12

hyper IgM immunodeficiency (HIGMS) where CD40L of T cells is mutated so B cells stay in IgM mode, don’t class switch and are not functional.

Question 13

2 most common SCIDs after X-linked SCID

Answer 13

• ADA deficiency

- RAG 1,2, Artemis

Question 14

what happens in ADA deficiency SCID

Answer 14

• ADA = enzyme that detoxifies products of adenosine
• ADA deficiency = metabolites accumulate and are toxic to lymphocytes
• lymphopenic at birth = SCID

Question 15

what happens in RAG1,2 and Artemis mutation SCID

Answer 15

• RAG1,2 and Artemis = recombination molecules needed to make TCRs and B cell Igs in GC (for B)
• SCID bc don’t get TCR and BCR diversity