Primary Immunodeficiencies Flashcards
Unlike B cell and Innate immunodeficiency, T cell deficiencies are associated with all of the following except?
A. Pneumocytosis jiroveci B. Cancer C. Non-TB mycobacteria D. Pyogenic bacteria E. Fungi
Pyogenic bacteria
T/F: A fetus with SCID is at RISK of abortion due to inability to reject the maternal T cells that cross the placenta into the fetal circulation
True
Adenosine Deaminase (ADA) deficiency
- autosomal recessive
- 2nd most common cause of SCID
- leads to accumulation of deoxyadenosine which is toxic to lymphocytes
Purine Nucleoside Phosphorylase (PNP) Deficiency
- autosomal recessive
- accumulation of intracellular dGTP that decreases the amount of T cells in the periphery
Artemis deficiency
- autosomal recessive
- T and B cell numbers are decreased, with NK cell numbers normal
- RADIOSENSITIVITY
All of the following deficiency result in low or very low IgA, IgG, or IgM except?
A. ADA B. PNP C. ARTEMIS D. RAG1/2 E. Jak3
PNP
RAG1/RAG2 Deficiency vs Leaky RAG1/RAG2
RAG1/2 deficiency leads to defective pre-BCR and pre-TCR
Leaky RAG1/2 is associated with Omenn Syndrome
X-linked Btk Kinase Decificency
- No IgG, IgM, IgA
- caused by defective rearrangement of Ig heavy chains
IgA Deficiency
- occurs in 1/700 individuals
- no IgA, but normal levels of IgG and IgM
The classic triad for Digeorge syndrome (DGS)
- cardiac anomalies
- hypocalcemia
- hypoplastic thymus
X-linked vs Autosomal Hyper IgM Syndromes
- X-linked: CD40L deficiency
- Autosomal: CD40 deficiency
Noted by failure of class switching and somatic hypermutation
Transient Hypogammaglobinemia of Infancy
- low IgG/IgA and normal levels of IgM (or low)
- increased susceptibility to sinopulmonary infections
- Ig concentrations normalize between 2 and 4 years of age
Common Variable Immune Deficiency (CVID)
- autosomal disorder
- defect in Ab production associated
- B cells fail to become plasma cells
- history of recurrent pyogenic sinopulmonary infections
Common y Chain Deficiency (yc or IL-2Ry)
- MOST COMMON form of SCID
- no functional B cells
- very Low IgG, IgA, IgM
- immunophenotype (T-, B+, NK-)
IL-7R Alpha Chain Deficiency
- autosomal recessive
- T-B+NK+ phenotype
What is the result of mutations in genes encoding for either IL-17, IL-17R, or transcriptional factors STAT1, STAT3, or AIRE?
Th17 deficiency
- high susceptibility to chronic mucocutaneous candidiasis
Wiskott-Aldrich Syndrome (WAS)
- low IgM; normal to elevated IgA and IgG
- X-linked recessive disorder
- thrombocytopenia, eczema
- recurrent bacterial infections with encapsulated bacteria
- T-B+NK-
Chronic Granulomatous Disease (CGD)
- most common phagocytic deficiency
- NADPH oxidase deficiency that causes failure to generate superoxide anion and other O2 radicals
G6PD Deficiency
- lack of substrate for NADPH
- X-linked recessive
- similar manifestation of CGD
Leukocyte Adhesion Deficiency I
- mutation in the gene for Beta-2 integrins CD11 and CD18
Leukocyte Adhesion Deficiency II
- impaired adhesive functions of P-selectin glycoprotein ligand 1
- fucose transporter mutation causes PSGL-1 defect
Leukocyte Adhesion Deficiency III
- defective activation-dependent signaling of Beta-2 integrins
- LAD-1
What are the clinical manifestations of LAD?
- delayed detachment of the umbilical cord
- slow wound healing
- severe bacterial infections
- failure to form pus
Chediak-Higashi Syndrome
- autosomal recessive
- abnormal giant granules that for not contain cathepsin G and elastase
- abnormal chemotaxis and degranulation
Agammaglobulinemia
- X-linked trait usually, but sometimes autosomal recessive
- early B cells are arrested at pre-B cell stage causing circulating B cells to be absent or present in low numbers
- X-linked form of this is Btk mutation
T/F: A microdeletion in chromosome 22 at the 22q11.2 region can lead to complete DiGeorge Syndrome
True
