Congenital Immunodeficiencies Flashcards
What are the 3 SCID immunodeficiencies?
All Rats Amazing
(1) ADA
(2) RAG1/RAG2
(3) Artemis
(SCID) ADA (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T-, B-, NK-
(2) IgM-, IgG-, IgA-
(3) Autosomal
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT
- susceptible to viral, bacterial, fungal infections at birth
- leads to accumulation of metabolic byproducts (Deoxyadenosine) which is toxic to lymphocytes
(SCID) RAG1/RAG2 (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T-, B-, NK+ (CD56)
(2) IgM-, IgG-, IgA-, high IgE
(3) Autosomal
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT
- impaired VDJ recombination which leads to defective expression of pre-TCR and pre-BCR
(SCID) Artemis (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T-, B-, NK+ (CD56)
(2) IgM-, IgG-, IgA-
(3) Autosomal
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT
- increased risk of developing lymphomas
What are the 7 selective B cell immunodeficiencies?
ALL HAVE T+ and NK+
Bad Cats Are Good At HuMping TooMuch
- BTK agamma-globulinemia
- Common variable (CVID)
- IgA
- IgG subclass
- Agamma-globulinemia
- Hyper-IgM syndrome
- Transient hyper-IgM
(SELECTIVE B CELL) BTK Agamma-Globulinemia (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B-, NK+
(2) IgM-, IgG-, IgA-
(3) X-linked
(4) Recurrent bacterial infections
(5) No live vaccines
(6) HSCT
- mutation in tyrosine kinase – BTK
- BTK gene found on X chromosome
- caused by defect in rearrangement of IgG heavy chain genes
- B cell maturation halted at Pre-B cell stage and doesn’t leave bone marrow
- likely find normal or decreased Pre-B cells in bone marrow and IgM heavy chains in cytoplasm
(SELECTIVE B CELL) Agamma-Globulinemia (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B-, NK+
(2) IgM-, IgG-, IgA-
(3) Autosomal
(4) Recurrent bacterial infections
(5) No live vaccines
(6) HSCT
(SELECTIVE B CELL) Common Variable (CVID) (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B-, NK+
(2) low IgG, low IgA, SOMETIMES low IgM
(3) N/A
(4) Recurrent (extracellular) bacterial infections, autoimmune diseases, lymphomas
(5) No restrictions
(6) Depends on sxs
- caused by mutations in either receptors for B cell growth factors (maturation/activation) or costimulators (T-B collab)
- characterized by defect in Ab production
- B cells fail to differentiate into plasma cells
- not typically dx until 20-30 YO
(SELECTIVE B CELL) IgA (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B+, NK+
(2) IgM+, IgG+, IgA-
(3) Autosomal but higher in male
(4) Mostly asymptomatic – higher risk of developing mucosal infections b/c IgA found in mucous membranes, dx based on hx of recurrent encapsulated bacterial infections
(5) No restrictions
(6) Depends on sxs
- IgA produced in response to B cell secretion of IL-5 or TGF-β (NOT HAPPENING HERE)
- B cells respond to lack of IgA by overproducing IgE which leads to increase in allergic rxns
- pathogens causing infection in mucosal lining often look similar to self antigens which causes immune system to start attacking our own cells (molecular mimicry)
(SELECTIVE B CELL) IgG Subclass (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B+, NK+
(2) IgM+, IgG+, IgA+, IgE+
(3) Autosomal
(4) Mostly asymptomatic
(5) No restrictions
(6) Depends on sxs
- typically associated with poor responses in children to vaccines that contain polysaccharide Ags
(SELECTIVE B CELL) Hyper-IgM Syndrome (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B+, NK+
(2) IgM+, IgG-, IgA-
(3) X-linked and autosomal
(4) Encapsulated opportunistic infections – esp bacterial infections
(5) POLIO not recommended
(6) HSCT is definitive treatment for this
- believe X-linked version caused by defect in CD40L (males only), most common form
- could be due to autosomal deficiency in CD40
(SELECTIVE B CELL) Transient Hyper-IgM (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T+, B+/-, NK+
(2) IgM+, IgG-, IgA-
(3) N/A
(4) Encapsulated opportunistic infections
(5) POLIO not recommended
(6) Depends on sxs
- instead of producing IgG beginning at 6 months of age, these infants don’t produce IgG and IgA for up to 36 months
- IgM normal or HIGH
- typically normalize btwn 2-4 years of age
What are the 7 selective T cell immunodeficiencies?
(1) Common γ Chain
(2) IL-7R α Chain
(3) Jak3
(4) CD3
(5) MHC Class I (BLS I)
(6) MHC Class II (BLS II)
(7) DiGeorge Syndrome
(SELECTIVE T CELL) Common γ Chain / Jak3 (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T-, B+, NK-
(2) IgM+, low IgG, low IgA
(3) Unknown – common deficiency is inherited as autosomal recessive
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT
- results from mutation in JAK3 (tyrosine kinase)
- causes defect in IL-2R signaling which is key cytokine in proliferation of all T cells – can’t have proliferation of CD4 or CD8
- causes defect in IL-15R signaling which is key cytokine in proliferation of NK cells
(SELECTIVE T CELL) IL-7R α Chain (1) Immune phenotype (2) Ab panel (3) Inheritance (4) Infections (5) Vaccination (6) Treatment
(1) T-, B+, NK+
(2) IgM+, IgG & IgA & IgE are absent or VERY LOW
(3) Autosomal recessive
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT
- IL-7 normally functions in promoting proliferation of B and T cells, and survival of memory cells
- Abs low or absent due to absent T cell co-stimulatory signaling