Immuno - primary immunodeficiencies Flashcards
Reticular dysgenesis
Failure of stem cells
Failure of production of neutrophils, lymphocytes, monocytes, Plts
FATAL unless BM transplant
Autosomal recessive severe SCID, most severe form. Mutation in mitochondrial energy metabolism enzyme adenylate kinase 2 (AK2)
Kostmann syndrome
Failure of NEUTROPHIL maturation
Autosomal recessive
Classical form associated with mutation in HAX1
Cyclic neutropenia
Autosomal dominant, episodic neutropenia every 4-6 weeks
Mutation in neutrophil elastase (ELA2)
Leukocyte adhesion deficiency
Deficiency of CD18 (b2 integrin subunit) in LAD1
CD11a/CD18 and CD11b/CD18 are usually expressed on neutrophils and bind to ligands on endothelial cells, regulating transmigration
FAILURE TO EXIT FROM BLOODSTREAM
- Very high neutrophil counts in blood
- Absence of pus formation
- Delayed umbilical cord separation
Chronic granulomatous disease
Absent respiratory burst - deficiency of NADPH oxidase
Excessive inflammation
Granuloma formation
Lymphadenopathy and hepatosplenomegaly
Suspetible to bacteria especially catalase positive bacteria, PLACESS
Pseduomonas, listeria, asperigillus, candidida, E. coli, Staph Aureus, Serratia
Negative nitro-blue tetrazolium test (normally changes from yellow to blue following hydrogen peroxide interaction)
Dihydrorhodamine flow cytometry test - normally oxidized to rhoadmine which is strongly flourescent, following interaction with hydrogen peroxide
Deficiency of IL12 and IFNgamma and their receptors
Susceptibility to TB and salmonella
Infection with TB activates IL12 IFNy network
Factor B, I and P deficiency
Recurrent infections with encapsulated bacteria: pneumococcus, haemophilus, meningococcus
NK cell deficiencies
Classical NK deficiency: GATA2 or MCM4 genes
Functional NK deficiency: FCGR3A gene
Give prophylactic antivirals e.g. acyclovir, give cytokines
SCT
Deficiency in early classical pathway
C1/2/4
Immune complexes fail to activate complement pathway
Increased susceptibility to infection
Increased load of self-antigens - may promote auto-immunity ie SLE
Deposition of immune complexes –> inflammation, ie SLE
Almost all patients with C2 deficiency have SLE
Note can get secondary complement deficiency caused by active lupus, due to persistent production of immune complexes and subsequent depletion of complement.
Depletes C4 first, then C3
C3 deficiency
Severe susceptibility to bacterial infections, especially encapsulated (pneumonoccus, meningococcus, strep, haemophilus)
Secondary C3 defieincy due to nephritic factors, often associated with glomerulonephritis
THIN TOP HALF, FAT BOTTOM HALF
Membrane attack complex defect
Neisseria meningitis
Strep pneumonia
Haemophilus influenza
SCID (in general)
Unwell by 3 months, protected before by maternal IgG)
FTT, persistent diarrhoea, infections of all types
Colonisation of infant’s empty BM by maternal lymphocytes –> GVHD
FH of early infant death
Many different mutations
Possible mutation - ADA deficiency. Enzyme required for cell metabolism in lymphocytes.
X linked SCID
Most common (45%)
Mutation of gamma chain of IL2 receptor on chromosome Xq13.1
Inability to respond to cytokines, early arrest of T and NK cell development, and immature B cells
Very low or absent T cell numbers
Normal or increased B cell numbers
Poorly developed lymphoid and thymus tissue
May have some IgM, but not IgG or IgA, as these are dependent on CD4 cells
DiGeorge
22q11.2 deletion CATCH 22 Cardiac abnormalities (tetralogy of Fallot) Abnormal facies (high forehead, low set ears) Thymic aplasia (T cell lymphopenia) Cleft palate Hypocalcaemia/hypoparathyroidism 22 - chromosome
Improves with age
Normal B cell numbers, reduced T cells Reduced T cells may mean reduced class switching, if profound CD4 deficiency
Bare lymphocyte syndrome type 2
Absent expression of MHC class 2 molecules Profound deficiency of CD4 cells Failure to make IgG or IgA (lack of CD4 help)
Unwell by 3 months, FTT, infections of all types
SCLEROSING CHOLANGITIS
(type 1 also exists, failure of HLA class 1 expression)
