Immunodeficiencies Flashcards
T cell deficiencies
Susceptible to?
Bare lymphocyte syndrome
DiGeorge
SCID (mixed)
IL12 def and IFN def
Viruses and Fungi
B cell deficiencies
Susceptible to?
X linked Bruton’s agammaglobulinaemia
X linked hyper IgM
CVID
Selective IgA def
SCID (mixed)
Bacteria
Phagocyte deficiencies
Susceptible to?
Kostmann syndrome
Leucocyte adhesion deficiency
Chronic granulomatous disease
Cyclic neutropenia
Fungi and Bacteria
Complement deficiencies
Susceptible to?
Deficiencies in Classical, lectin, alternative and common pathways
Encapsulated bacteria
Bare lymphocyte syndrome
Defect of regulatory factor x or class ii transactivator
Absent expression of HLA molecules within thymus so lymphocytes fail to develop BLS type 2 more common (absent MHCII and CD4+ but normal MHCI and CD8+)
B cell class switch needs CD4 therefore less IgA and IgG made
Associated with sclerosis cholangitis Unwell by 3m
NB: Naive T cells require CD80/CD86 for full activation
DiGeorge
Impaired development of the 3rd and 4th pharyngeal pouches
22q11 deletion
CATCH-22
Susceptibity to viral infection
V low numbers of mature T cells
Tx: thymus transplant
Bruton’s agammaglobulinaemia
X linked tyrosine kinase defect
Mutation in BTK gene
Failed production of mature B cells
No antibodies
Sx after 3-6m
CVID
Low IgG, IgE and IgA
Defect in B cell differentiation
Many genetic causes
Failure to thrive
Recurrent infections, AI and granulomatous disease
Selective IgA deficiency
Most common deficiency
Recurrent gastro and resp infections
Affects 1/600 caucasians
70% are asymptomatic
Hyper IgM syndrome
X linked - Xq26
CD40L, CD40, AICDA or CD154 defect
Boys present first years of life with recurrent bacterial infections, esp Pneumocystis Jivorecii and FTT
Activated B cells cannot interact with B cells to class switch
Therefore B cells cannot make IgA and IgG, but elevated IgM
Less lymphoid tissue as no germinal centre development
Risk of autoimmunity and malignancy
SCID
Defects in lymphoid precursors e.g. adenosine deaminase gene: IL-2 receptor
recurrent infections lead to FTT and persisten diarrhoea and early infant death
Present at 3m because maternal IgG protective until then
Low or normal B cell numbers
Reduced T cell
Low Abs
BMT is only establised Tx
45% are X linked
Kostmann syndrome
Severe congenital neutropenia
Mainly AR
1-2 cases per million
Patients have infections shortly after birth
Dx based on chronically low neutrophil count and BM test showing an arrest of neutrophil precursor maturation
Tx: G-CSF, prophylactic Abx and BMT if G-CSF is ineffective
LAD
Failure to express leucocyte adhesion markers
Neonatal bacterial infections, ofetn life threatening
Deficiency of B2 integrin subunit (CD18) of the leucocyte adhesion molecule in LAD1
LAD2 is much rarer and has severe growth restrictin and mental retardation
High neutrophil count in blood (as cannot migrate into tissues), absence of pus formation and delated unbilical cord separation
Tx: BMT
CGD
Failure of oxidative killing - defect of NAPDH oxidase leading to reduced reactive oxygen species
Absent respiratory burst
Excessive inflammation- persistent neutrophil/ macrophage accumulation, failure to degrade antigens
Negative NBT (dye that changes from yellow to blue following interaction with H2O2)
Also use Dihydrorhodamine (DHR) flow cytometry test (DHR oxidised to rhodamine which is strongly fluorescent, following interaction with H2O2)
Pts get pneumonia, abscesses, suppurative arthritis and other diseases
Catalase positive organisms: PLACESS
Pseudomonas
Listeria
Aspergillus
Candida
E. coli
S. aureus
Serratia
Pts can resist catalase neg bacteria
Mostly X linked
Tx: prohpylactic trimethoprim and itraconazole and IFN
Sometimes use SCT
Cyclic neutropenia
Episodic neutropenia occurring every three weeks and lasting several days
Caused by mutations in the ELA1 gene
Treated with G-CSF
