Immunology Flashcards
when do primary immune deficiencies (PIDs) clinically manifest? why?
first years of life (≥ 5-6 months) because maternal IgG stops at this time
-immune deficiencies are not detected in the newborn
what immune deficiency presents with recurrent infections with encapsulated bacteria?
B cell deficiency
humoral immune deficiency (B cell deficiencies) results from what?
impaired antibody production
- often severe upper and lower resp tract infections with encapsulated bacteria (e.g., strep pneumoniae, haemophilus influenzae)
- present with recurrent otitis media, sinusitis, and pneumonia
- uncomplicated viral infections
- chronic infections by intestine pathogens (e.g., giardia, salmonella, etc.)
- autoimmune disorders are common
all of these may present as what type of immune deficiency?
B cell deficiency
pts with suspected antibody deficiency should have measurement of what?
total serum IgG, IgA, and IgM
if a progenitor cell cannot mature into a pro-B cell, there is a deficiency in what?
ADA (adenosine deaminase)
-ADA deficiency inhibits progenitor»_space; pro-B cell
the ability of pro-B cells to mature into pre-B cells is inhibited with mutations in what? (3)
RAG1, RAG2, Artemis mutation
the maturation of a pre-B cell into an immature B cell is inhibited if there are mutations in what? (5)
BTK BLNK Ig-alpha chain mu chain gamma-5 chain
CD19 mutations inhibit what?
CD19 mutations inhibit the conversion of mature/activated B cells into plasma cells or memory cells
TQ
vaccination with live oral polio vaccines is contraindicated in pts with what?
agammaglobulinemias (e.g., BTK)
i.e., don’t give polio vaccine to pts with B cell deficiency
X-linked agammaglobulinemia (XLA) is assoc with a mutation in what enzyme’s gene? what two B lineage cells are involved?
- X-linked agammaglobulinemia (XLA) is assoc with a mutation in BTK (Bruton’s tyrosine kinase)
- pre-B cell cannot become an immature B cell
classical XLA have < 1% positive lymphocytes with what 2 CD markers?
CD19- or CD20-
i.e., no B cells
TQ
-X-linked
-mutations in BTK gene ***
-diagnosed at 5-6 months old
-caused by defect in rearrangement of the Ig heavy chain genes
-early B cell development is stopped at the pre-B cell stage»_space; absent or low # of circulating B cells
-low or totally absent IgG, IgA, and IgM *
[ T+ B– NK+ ] *
X-linked agammaglobulinemia
Bruton disease
the only difference between X-linked and autosomal recessive agammaglobulinemia is what?
the genetic defects AR agammaglobulinemia has mutations in: mu Ig-alpha gamma-5 BLNK
CVID involves the impaired ability to produce what 2 cells?
plasma cells
B memory cells
TQ
-impaired B cell differentiation with defective Ig production
-poor or absent response to immunization ** (never have B memory cells)
-recurrent bacterial infections with encapsulated bacteria *
-low IgG and IgA **
-normal or low IgM **
[ T+ B+(70%) NK+ ] **
common variable immune deficiency (CVID)
TQ
-recurrent respiratory and GI infections **
-low IgA **
-normal IgG and IgM ***
-often remain asymptomatic and undiagnosed
-may cause anaphylactic shock in pts with Abs against IgA (anti-IgA IgE) in blood transfusions
[ T+ B+ NK+ ]
IgA deficiency
TQ -high IgM with low IgG and IgA *** -impaired Ig class switching -low memory B cells -CD40L mutation *** (expressed on CD4+ T helper cells) [ T+ B+ NK+ ]
IFN(gamma) favors:
IL-4 favors:
TGF-ß favors:
hyper IgM syndrome (HIGM)
IFN(gamma) favors IgG subclasses
IL-4 favors IgE
TGF-ß favors IgA
- low IgG and IgA
- low or normal IgM
- intrinsic Ig production is delayed for up to 36 months (normalize between 2 and 4 years of age)
transient hypogammaglobulinemia of infancy
TQ -low IgM -normal IgG -elevated IgA and IgE -selective depletion of circulating mature B cells -decrease # and function of T cells -impaired chemotaxis of phagocytic cells -defective Ab responses to some vaccine antigens * [ T low B low NK+ ] ***
characterized by:
- thrombocytopenia *
- small platelets *
- platelet dysfunction
- eczema *
- susceptible to infections
Wiskott-Aldrich syndrome (WAS)
hypogammaglobulinemia M
what immunodeficiency may present with lymphopenia within hours of birth?
combined T and B cell deficiency
(severe combined immunodeficiency)
cannot use vaccines on these pts
TQ
-MC form of SCID
-X-linked recessive trait (only males)
-gene encodes gamma-chain shared by T cell growth factor receptor (IL-2Rgamma) *
-low IgG, IgA, and IgE *
-no functional B cells, plasma cells, or memory cells
[ T– B+ NK– ] *
- opportunistic fungal infections
- chronic diarrhea
- skin, mouth and throat lesions
common gamma chain deficiency
gamma-c or IL-2Rgamma
TQ -mutations in ADA gene -autosomal recessive -2nd MC form of SCID -low IgM, IgG, and IgA * [ T– B– NK– ] *
-live vaccines may be fatal *
adenosine deaminase deficiency (ADA deficiency)
TQ -SCID caused by mutation in a gene on Chr. 19 that encodes Janus kinase 3 (Jak3) -defect in IL-2 receptor signaling ** -both and girls affected (AR) -low IgG, IgA, and IgE * [ T– B+ NK– ] *
-opportunistic infections (same as gamma-c)
Deficiency of Jak3
TQ
- defective development of the pharyngeal pouch system **
- T cell deficits
- most pts have mild defects, but severe form imitates SCID
- deletion of 22q11
- hypocalcemia ***
- neonatal hypocalcemia may present as tetany and seizures
Dx:
- facial abnormalities
- major outflow tract defect of the heart
- h/o recurrent infections
-susceptible to opportunistic infections
DiGeorge syndrome (DGS)
