Immunodeficiency Flashcards
X-linked SCID
MOST COMMON
gamma chain receptor mutation
dec. T cell maturation - no IL-7 signal
B cells fine , but dec. IgG bc no T helper
NK deficient - no IL-15 signal
AR SCID due to ADA deficiency
Dec T, B, IgG
accumulation toxic metabolites in lymph - dATP
AR SCID due to PNP deficiency
Dec T cells
B and IgG normal
accumulation of toxic metabolites - dGTP
AR SCID due to other causes
Dec T, B, IgG
defect/mutation in IL-7R signaling : missing JAK3
RAG gene mutation
How is SCID treated?
Treat early
Stem cell transplant - ideal. Compatible donor needed
Gene therapy - Success with ADA def
Gene therapy in x-linked SCID
Normal gamma gene introduced in BM stem cell – then back into patient
Bruton’s agammaglobulinemia X-linked (XLA)
Maturation defect of B cells
- BTK mutation
cant go from pre to mature B
mom- carrier, MALES get it
diagnosed at 5-6 mo bc maternal Ig present until then
Repeated bacterial infections due to virtual absence of all Ig classes
treat with gamma globulin injections
XLA - infants develop reccurent what
otitis media
pneumonia
sinusitis
S. pneumo, H. flu (extracellular encapsulated bacteria, staph)
XLA - missing what in peripheral blood? serum Ig levels?
State of germinal centers? Plasma cells? T cells? increase is seen in what?
CD19 decreased Underdeveloped germinal centers no plasma cells normal t cell reactions increased autoimmune disease
DiGeorge Syndrome
3rd and 4th pharyngeal pouches - dysmorphogenesis
hypoplasia/aplasia of thymus/parathyroid with facial and heart abnormalities
What are two main presentations of DiGeorge?
Neonatal tetany
Absent thymic shadow
Whats normal/abnormal in DiGeorge?
dec T cell count, absent Ab resp, LN - depletion of paracortical areas
thymic tissue contains hassall’s corpuscles, normal thymocyte density, corticomedullary distinction present
some physical features in children with DiGeorge?
small jaw, cleft lip/palate, low set ears, underdeveloped parathyroid, learning difficulties, cardiac malformation
Whats deleted in DiGeorge?
22q11 deletion
q11.2 on long arm of chromosome 22
required for dev of brachial arch and great vessels
X-linked hyper IgM syndrom is defect in what?
lymphocyte activation
What is the mutation seen in X-linked hyper IgM syndrome?
Mutation in CD40L gene on X chromosome - T cell/CD4+
no class switching of Ig bc help needed from T cell–> elevated levels of IgM
Defects in CMI (DTH)
Selective IgA deficiency
most Common primary deficiency
low serum IgA - other isotypes normal
asymptomatic or recurrent sinopulmonary infections + diarrhea
Common Variable immunodeficiency
failure in maturation of B cells into plasma cells
Low IgG and IgA
normal to low IgM
mature B cells present, just plasma cells absent
major problems with Common Variable Immunodef
Respiratory and GI infections with PYOgenic bacteria
Wiskott-Aldrich Syndrome
X-linked
Triad:
- low platelet count - thrombocytopenia
- skin rashes (eczema)
- Recurrent bacterial infections
Can’t respond to bacterial polysaccharides
LOW IgM
treat with gene therapy
Ataxia Telagiectasia
Not an immunodeficiency
MULTISYSTEM disorder
- staggering gate
- abnormal vessel dilation - spider veins
- affects BOTH T and B cells
low IgA, IgG
CANT RESPOND to SKIN tests
reduced T cells
What do you see with defects in innate immunity
Recurrent intracellular bacterial and fungal infections
Leukocyte adhesion deficiency
no adhesion of leukocyte to vasc. endothelium
limits recruitment to site of infl
Defects on Leukocyte :
- selectin ligand
- beta chain of integrin
NO PUS formation
Bacterial infections
Chediak-Higashi syndrome
Giant cytoplasmic granules in phagocytes
granules dysfunctional
CANT kill bacteria
