Immunodeficiencies Flashcards
(36 cards)
What is the most common class of immunodeficiency?
Humoral (B cell) - 50% > Combined (B and T cell) 20% > Phagocytic 18% > T Cell 10% > Complement 2%
When do PIDs usually manifest clinically?
Between 6-15 mo (after maternal IgG disappears in fetus)
How do you test for Phagocytic disorders?
Nitroblue tetrazolium test
Adenosine Deaminase (ADA) Deficiency
Immunophenotype: T- B- NK- Low Igs Autosomal Recessive Second most common SCID Tx: HSCT
-Accumulation of toxic metabolic byproduct deoxyadenosine
Purine Nucleotide Phosphorylase (PNP) Deficiency
Immunophenotype: T- B+ NK+/-
Normal Igs
Autosomal Recessive
Tx: HSCT
- Accumulation of intracellular deoxyguanosine triphosphate (dGTP) which is toxic to peripheral lymphocytes
- Autoimmune disorders such as hemolytic anemia, thyroid disease, arthritis, and lupus also common
Artemis Deficiency
Immunophenotype: T- B- NK+
Low Igs
Autosomal Recessive
Tx: HSCT
-Lack double strand break repair during VDJ recombination
- Opportunistic infections (candidiasis, Pneumocystis Jiroveci pneumonia) and diarrhea
- Increased risk of developing lymphoma
- Defining factor is RADIOSENSITIVITY (Same immunopheotype as RAG1/2 deficiency)
RAG 1/RAG 2 Deficiency
Immunophenotype: T- B- NK+
Low Igs
Autosomal Recessive
Tx: HSCT
-Impaired V(D)J recombination leads to defective expression of pre-TCR and pre-BCR
- -Opportunistic infections (candidiasis, Pneumocystis Jiroveci pneumonia) and diarrhea
- RAGs can have partial function leading to Omenn Syndrome which has specific skin manifestations (srythroderma, spelnomegaly, eosinophilia, and high IgE)
Jak 3 Deficiency
Immunophenotype: T- B+ NK-
Very low Igs
Autosomal Recessive
Tx: HSCT
Mutation in gene coding Jak3 (kinase) which causes defective IL-2 receptor signaling
-B cells present but functionally deficient
Agammaglobulinemia
Immunophenotype: T+ B- NK+
Absent or very low Igs
Most commonly X-linked but could be autosomal recessive
Tx: HSCT
Mutation in BTK (tyrosine kinase) which causes lack of survival, proliferation, and maturation
Isolated IgG Subclass Deficiencies
Immunophenotype: T+ B+ NK+
Some IgG subclasses low, normal IgM and IgA
Tx: None
Usually asymptomatic but could be associated with recurrent viral/bacterial respiratory infections
IgA Deficiency
Immunophenotype: T+ B+ NK+
No IgA, Normal IgG and IgM
More common in males
About 50% asymptomatic bc IgM can compensate, others have recurrent encapsulated bacterial infections, autoimmune diseases, and allergy
-IgA deficiency could lead to anti-IgA Abs causing non-IgE mediated anaphylaxis in response to IVIG transfusion
DiGeorge Syndrome
Immunophenotype: T- B+ NK+
Normal Igs
Remember CATCH-22
- Cardiac defects*
- Abnormal facies
- Thymic hypoplasia*
- Cleft palate
- Hypocalcemia*
- 22q11 deletion
- indicates classic DGS triad
Hyper IgM Syndromes (HIGM)
Immunophenotype: T+ B+ NK+
High IgM, low IgG and IgA
Two types:
- CD40L deficiency: X-linked in males only (most common)
- CD40 deficiency: autosomal recessive
No class switching or somatic hypermutation
Increased susceptibility to bacterial infections
Transient Hypogammaglobulinemia of Infancy
Immunophenotype: T+ B+ NK+
Low IgG/IgA, normal or low IgM
Delay of IgG production for up to 36 months - most patients IgG levels normalize between 2-4 y.o.
Increased susceptibility to sinopulmonary infections
Common Variable Immune Deficiency (CVID)
Immunophenotype: T+ B+/- NK+
Low IgG/IgA, normal or low IgM
Class of diseases characterized by defect in Ab production associated with hypogammaglobulinemia
B cells can’t differentiate into plasma cells
- increased risk of infections, autoimmune diseases, and malignancies (lymphomas)
- Diagnosed based on history of recurrent pyogenic sinopulmonary infections
Common Gamma Chain Deficiency
Immunophenotype: T- B+ NK-
Very low IgG, IgA, and IgM
X-linked recessive trait
Tx: HSCT
Most common form of SCID
- Dysfunction of IL-2Rgamma and other growth factor receptors causing non-functional IL-4, 7, 9, 15, & 21
- No functional B cells because no activation by T-cells
-Present with failure to thrive, severe thrush, opportunistic infections, and chronic diarrhea
IL-7R Alpha chain Deficiency
Immunophenotype: T- B+ NK+
Very low IgG, IgA, and IgM
Autosomal recessive
Tx: HSCT
Lack of T cell development so functional deficiency in B cells due to lack of activation
Present with candidiasis, chronic diarrhea, Pneumocystis jiroveci pneumonia, and severe viral infections
Bare Lymphocyte Syndrome II (BLS II)
Immunophenotype: T+ B+ NK+
Variable hypogammaglobulinaemia (IgG2 and IgA)
Autosomal recessive
Tx: HSCT
- HLA class-II deficiency on APCs so no functional CD4+ T cells
- Mutation in transcription factor for MHC class-II
- Recurrent respiratory, GI, and urinary tract infections
- Death in early childhood
MHC class-I Deficiency
Immunophenotype: T+ B+ NK-
Normal Igs
Tx: None
- Mutation in TAP1 so no transfer of peptides into ER
- Causes functional deficiency in CD8+ cells
Recurring viral infections
CD3 Complex Deficiencies
Immunophenotype: T- B+ NK+
Low Igs
Autosomal recessive
Tx: HSCT
Low Ab responses due to deficiency in CD3 subunits which causes functional deficiency in B cells
-Lymphopenia, failure to thrive, opportunistic infections, and chronic diarrhea
Defect in IFN-g–IL-12 axis
Usually a positive regulatory loop
T cells and NK cells release IFN-g after IL-12 stimulation
MO and DCs release IL-12 after IFN-g stimulation
- Mutations in the IL-12 receptor, IFN-g receptor, or subunits of IL-12
- No differentiation to Th1 or Th17
-increase susceptibility to nontuberculosis mycobacteria
Th17 deficiency
Impairment of development associated in mutations in genes for IL-17, IL-17R, STAT 1, STAT3, or AIRE
Unusually susceptible to chronic mucocutaneous candidiasis
-Severe atopic dermatitis, skin abscesses
Immunodysregulation, Polyendocrinopathy, and Enteropathy x-linked Syndrome (IPEX)
X-linked
Self reactive T effector cells are not inhibited
Mutated FOXp3 so loss of inhibition of Tregs
Autoimmune Lymphoproliferative Syndrome (ALPS)
Defects in Fas, FasL, caspace-8 or caspace-10
lack of apoptotic signal results in resistance of effector T cells to apoptosis prolonging T cell response
