Primary Immunodef Flashcards
granulomas, hepatosplenomeg and LN
CGD
nadph oxidase defect leading to absent respiratory burst
CGD
excessive inflammation due to lack of antigen breakdown. granuloma formation. DHR test negative (does not fluoresce). TBT test - yellow.
CGD
increased susceptibility to mycobacterial infections including NTM and BCGosis. cant make granulomas.
macrophage signalling defect of IL-12/IFN-Y pathway
AK2 enzyme deficiency. AR inherited.
Reticular dysgenesis SCID
Absolute deficiency of mono/macrophages, platelets, PMN and lymphocytes.
Reticular dysgenesis. incompatible with life without BMT
CD18 B2 subunit defect (LFA-1) - leads to inability to activate ICAM-1 on endothelium. High neutrophils in the blood. no pus.
LAD
High neutrophils, no pus formation. Recurrent deep bacterial infections/fungal infections.
LAD
ELA-2 gene defect leading to defective neutrophil elastase production. AD inheritance.
Cyclical neutropenia
neutropenia every 4-6 weeks. FHx positive.
cyclical neutropenia ELA-2 defect
Defect in HAX-1 protein leading to chronically low neutrophils
Kostmann syndrome
AR inherited defect leading to chronically low neutrophils, severe bacterial and fungal infections. BM shows arrested neutrophil precursors.
Kostmann syndrome
delayed cord separation, high neutrophil counts in the blood. bacterial infections in neonatal period, no pus.
LAD
can be used to treat CGD
IFN-Y
can be used to treat Kostmann
G-CSF
Recurrent infections with high neutrophil count on FBC but no abscess formation
LAD
Recurrent infections with hepatosplenomegaly and abnormal dihydrorhodamine test
CGD
Recurrent infections with no neutrophils on FBC
kostmann
Infection with atypical mycobacterium. Normal FBC
IFN/IL-12 pathway defect
Absence of NK cells within peripheral blood
Abnormalities described in GATA2 or MCM4 genes
NK cell deficiency
increased susceptibility to viral infections i.e HSV, CMV, EBV, VZV
NK cell defects
GATA2 or MCM4 gene defects leading to increased susceptibility to viral infection
NK deficiency
FCGRA gene defects. Viral infections. Normal FBC.
NK functional defect
cells in the peripheral tissues which have numerous receptors capable of recognition of inflammation, immune complexes, and pathogens. can migrate to LN to present ag to T cells.
Dendritic cells
cells capable of phagocytosis and communication with T cells to stim adaptive response.
DC
branch of complement pathway dependent on the acquired immune system (abs)
classical pathway - activated by ag-ab complexes binding C1
causes a secondary complement deficiency via activation of the classical pathway and consumption of C4 +/- C3 in severe disease.
SLE.
auto-antibodies which stabilise C3 convertases leading to increased C3 activation and consumption –> depletion. associated with membranous GN and partial lipodystrophy.
Nephritic factors.
increased infections with encapsulated bacteria in immunocompromised patients
MBL pathway defect
proteins B I P defect leading to increased infections with encapsulated bacteria
Alternative pathway defect
Severe susceptibility to encapsulated organisms and increased risk of connective tissue disease
C3 def
Inability to form MAC, infections with Neisseria Meningitides, Strep Pneum and H. Influezae particularly
C5-C9 final common pathway defect
increased risk of encapsulated bacterial infections, presents with SLE/severe skin disease, deposition of complexes in skin, joints and kidneys
Classical pathway defect, most likely C2 deficiency
pathway activated by direct binding to carbohydrates on microbial cell surface. presents with infections in immunodeficient pts.
MBL defect
decreased levels of C1 inhibitor
hereditary angioedema
CH50 tests
classical pathway
Membranoproliferative nephritis and bacterial infections
c3 def with nephritic factors
Meningococcus meningitis with family history of sibling dying of same condition aged 6
C9 def
Severe childhood onset SLE with normal levels of C3 and C4
C1q/Classical pathway defect
Recurrent infections when receiving chemotherapy but previously well
MBL
immune cell that kills cells directly via 1) fas-fasligand 2)perforin-granzyme
CD8
mutation of the common gamma chain of the IL-2 receptor, leading to inability to respond to cytokines and early arrest of immune cell development.
X linked SCID. leads to early arrest of NK and T cell +/- immature B cell production.
most common form of SCID
X linked - 45%
unwell by 3mo, FTT, infections of all types and FHx of early death. may also present with unusual skin disease (GvHD)
All SCID
Very low or absent T cell numbers
Normal B cell numbers
Poorly developed lymphoid tissue and thymus
X-linked SCID
developmental defect of the pharyngeal pouch leading to absence of T cells, normal B cells, IgM production but little to no IgA/IgG
DiGeorge 22q11.2
hypocalcaemia, congenital cardiac defects, low set ears, cleft palate, oesophageal atresia and presents with recurrent viral and fungal infections
DiGeorge
no CD4, normal CD8, no IgG and IgA. Associated with primary sclerosing cholangitis. Unwell by 3mo.
Bare Lymphocyte syndrome type 2 - no MHC II expression leads to no CD4 prod
defect in Class II Transactivator and Regulatory factor X in the thymus - leading to low numbers of CD4 cells.
BLS type 2
Severe recurrent infections from 3 months,CD4 and CD8 T cells absent, B cell present but immature phenotype, some IgM present, IgA and IgG absent. Normal facial features and cardiac echocardiogram
X linked SCID
Young adult with chronic infection with Mycobacterium marinum
Il-12/IFN-Y pathway defect
Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, normal IgM, borderline low IgA and IgG
DiGeorge
6 month baby with two recent serious bacterial infections. T cells present – but only CD8+ population. B cells present. IgM present but IgG absent
BLS type 2
abnormal B cell tyrosine kinase caused by X-linked gene defect. leads to inabilty of Pre-B cells to mature into B cells. Absence of mature B cells in the blood, no Igs >3mo. Recurrent bacterial infections.
X-linked Brutons Hypogammaglobinaemia
X-linked defect in the CD40L leading to increased IgM levels but decreased IgG/IgA. increased risk of malignancy and autoimmunity.
No germinal centre development in lymph nodes.
X-linked hyper IgM
1 year old male presents with PCP. Normal B cells, normal CD4/CD8. High IgM, no IgA/G
X-linked Hyper IgM
immunodeficiency with a prevalence of 1 in 600. presents with recurrent resp and GI infections. 2/3rds ASx.
IgA def
Recurrent bacterial infection, often with severe end organ damage, and poor responses to vaccination. increased incidence of AI disease and malignancy. Bloods show low IgA, IgG and IgE.
common variable immunondef
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
CVID
Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, T and B cells present, high IgM, absent IgA and IgG
X-linked hyperIgM
1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent
X-linked Bruton’s Hypogammaglobulinaemia
Recurrent respiratory tract infections, absent IgA, normal IgM and IgG
IgA def
