Immunodeficiencies Flashcards
(30 cards)
Severe Combined Immune Deficiency (SCID)
Caused By?
Lymphocytes impacted?
Immunoglobins?
Characterizations
ADA Deficiency | ARTEMIS Deficiency
Converting deoxyadenosine to deoxyinosine | repairing double strand breaks in VDJ recomb
ADA: T-B-NK-
ARTEMIS: T-B-NK+
Low IgG, IgA, IgM
Severe Lymphopenia, severe opportunistic infections, chronic diarrhea, FTT
Avoid Live Viral Vaccines
ADA Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
Autosomal Recessive
T-, B-, NK-
Low IgG, IgA, IgM
Accumulation of deoxyadenosine
HSCT
Avoid Live Viral Vacccines
Purine Nucleoside Phosphorylase (PNP) Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations?
Treatment?
Autosomal Recessive
T-, B+, NK+/-
Normal IgG, IgA, IgM
Accumulation of intracellular dGTP
Decrease in peripheral T-cells
Early Onset Neurological Abnormalities
Autoimmune Disorders
HSCT Treatment
Avoid Live Viral Vacccines
ARTEMIS Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
Autosomal Recessive Radiosensitive
T-, B-, NK+
Low IgG, IgA, IgM
Diarrhea, candidiasis, pneumonia
T/B cell decreased
HSCT
Avoid Live Viral Vaccines
RAG1/RAG2 Def
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
Autosomal Recessive
T-, B-, NK+
Low IgG, IgA, IgM
Causes impaired VDJ Recombination, defective pre-TCR/BCR
Diarrhea, candidiasis, pneumonia
Leaky RAGs = Omenn Syndrome
HSCT
Avoid live viral vaccines
Omenn Syndrome
Similar to Rag1/Rag2 Def.
Characterized by:
severe erythroderma, splenomegaly, eosinophilia, high IgE
Avoid live viral vaccines
Jak3 Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
Autosomal Recessive
T-, B+, NK+
Very low IgG, IgA, IgM
Caused by mutation in Jak3 gene
Causes defect in IL-2 signalling
HSCT Possible treatment
Avoid Live Viral Vaccines
Agammaglobulinemia
Characterizations
Mostly X-linked trait, but Autosomal Recessive also exists
Early B-cell development arrested
Pre-B cells are normally absent or in very low numbers
X-Linked Btk Kinase Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
X-linked disorder
B-, T+, NK+
No IgG, IgA, IgM
Mutation in tyrosine kinase
Caused by defect in rearrangement of Ig heavy chain genes
Presents in 5-6 month infants
HSCT
Isolated IgG Subclass Deficiencies
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
B+, T+, NK+
Low IgG, normal IgM, IgA, IgE
Decrease of one or more IgG subclasses
Caused by defects in several genes
Normally asympotmatic, sometimes recurrent infections in respiratory tract
Low IgG2, varying IgG4
IgA Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
B+, T+, NK+
No IgA, normal IgG, IgM
Higher prevalence in males, diagnosed by recurrent infections w/ encapsulated bacteria
Mostly asymptomatic
Development of autoimmune diseases
May have anti-IgA IgG in response to anaphylaxis
Digeorge Syndrome (DGS)
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
T-, B+, NK+
Normal IgG, IgA, IgM
Results from microdeletion of 22q11.2 region (35 genes)
Classic triad: Cardiac anomaly, hypocalcemia, hypoplastic thymus
Humoral Immunity intact
Live Viral Vaccines given to CD > 300
Hyper IgM Syndromes (HIGM)
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
B+, T+, NK+
High TgM, low IgG, IgA
Impaired class switching & somatic hypermutation
Normal peripheral B cells, but low CD27 positive memory cells
Increased bacterial infections
X-linked HIGM: Mutations in CD40L gene
HSCT
CD40L/CD40 Deficiency
X-Linked: Happens only in males, 2/3 of all HIGM cases
Autosomal CD40 def: Male and Female, 1/3 of all HIGM
Transient Hypogammaglobulinemia of Infancy
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
B+, T+, NK+
Low IgG, IgA, Normal or Low IgM
Maternal IgG disappears 6 months after birth
Ig production delayed for up to 36 months
Increased susceptibility to sinopulmonary infections
Normalizes between 2-4 years
Common Variable Immune Deficiency (CVID)
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
Autosomal
B-/+, T+, NK+
Low IgG, IgA, sometimes low IgM
Defect in Ab production
immature B cells fail to differentiate into plasma cells or mature into B cells
Based on history of recurrent sinopulm infections, autoimmune disease, lymphomas
Onset 4-5 yoa, but diagnosed at 20-30
HSCT
Common y-Chain Deficiency (yC or IL-2Ry)
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
X-Linked Recessive
T-, B+, NK-
Very low IgG, IgA, IgM
Most common SCID (45%)
No functional B-cells
FTT, severe thrush, opportunistic infections, chronic diarrhea
HSCT
Avoid Live viral vaccines
IL-7R Alpha Chain Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
Autosomal Recessive (SCID)
T-, B+, NK+
Very low IgG, IgA, IgM
Il-7 is involved in early T-cell development
Ig low/absent even with presence of B-cells
Patients present with classic SCID
Sequencing IL-7R gene confirms diagnosis
HSCT
avoid live viral vaccines
Bare Lymphocyte Syndrome Type 2 (BLS II)
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment
Autosomal Recessive
CD4-, CD8+, B+, NK+ Variable hypogammaglobulinaemia (IgA and IgG2)
Mutation in gene encoding transcription factors regulating MHC II expression
Reccurent GI/Urinary infections, death in early childhood
HSCT
MHC I Deficiency
Lymphocytes impacted?
Immunoglobins?
Characterizations
CD4+, CD8-, B+, NK+
Normal DTH and Ab
Caused by mutation in TAP1
Can’t transplant HSCT, won’t solve problem
CD3 Complex Deficiencies
Lymphocytes impacted?
Immunoglobins?
Characterizations
Treatment?
Autosomal Recess
T-, B+, NK+
Low IgG, IgA, IgM
Presents in lymphopenia and decreased T cell numbers, FTT, opportunistic
Specific Antibody responses decreased
HSCT
IFN-y-IL-12 Axis Defect
Characteristics
Mutations in IL-12 or IL12R genes resulting in susceptibility to nontuberculous mycobacteria
IFN-y
Patients do not produce Th1 cytokine IFN-y
Selective susceptibility to intracellular pathogens
Also have defects in formation of IL-17 –> Th17
Th17 Deficiency
Characteristics
Unusual susceptibility to chronic mucocutaneous candidiasis
Mutations in genes encoding: IL-17, IL-17R
Or Transcription Factors: STAT1, STAT3, AIRE
Immunodysregulation, Polyendocrinopathy
, and enteropathy, X-linked Syndrome (IPEX)
Self Reactive T Effector cells not inhibited
Mutation in FOXP3 —> loss of inhibition of CD4, CD25, Treg
HSCT
