Flashcards in Overview of immunodeficiency Deck (61):
what is primary immunodeficiency?
this is congenital caused by defects in the immune system
what is primary immunodeficiency?
This is secondary caused by another disease
what are warning signs of primary immunodeficiency?
at least 2 of:
- 8 or more new ear infections in one year
- 2 or more sinus infections
- 2 or more months on antibiotics with little effects
- 2 or more pneumonias within 1 year
-failure of an infant to gain weight or grow normally
- recurrent deep or organ abscesses
- persistant thrush
- need for IV antibiotics
what cells are important for the adaptive immune system?
T and B cells
what cells are important for the innate immune system?
If the primary immunodeficiency is aT cell defect what is affected?
As part of primary immunodeficiency what are the major B lymphocyte disorders?
- brutons disease
- common variable immunodeficiency
- selective IgA deficiency
-IgG2 subclass deficiency
- specific Ig deficiency
what is the proper name for brutons disease?
X linked agammaglobulinaemia
where is the defect in brutons disease?
btk gene on theX chromosome thatencodes brutons tyrosine kinase
what is the immune problem in brutons disease?
The mutation leads to a block in B cell development so it stops at pre-B cells
how does brutons disease normally present?
with repetitive severe bacterial infections in the 2nd half of their first year of life.
In brutons disease there is a defect in brutons tyrosine kinase what is this normally for?
pre B cell receptor signalling leading to a block in B cell development at pre-B stage
what cell levels will be low in brutons disease?
- B cells
- plasma cells
- all Igs
what treatment is given for brutons disease?
IV Ig at 2-3 week intervals or S/C weekly
- prompt antibiotic therapy
- NO LIVE VACCINES
what is the peak age for presenting with common variable immunodeficiency?
Early childhood or early adulthood
what immune cells are at fault in common variable immunodeficiency?
- the b cells can't differentiate into plasma cells leading to a antibody deficiency
what is the T cell levels in common variable immunodeficiency?
what is the treatment for common variable immunodeficiency?
- IV Ig
- prophylaxis antibiotics
what primary immunodeficiencies affects T cells?
- DiGeorge syndrome
- wiskott-aldrich syndrome
- ataxia telagiectasia
what is the inheritance for SCID?
Majority X linked
Rest is autosomal recessive
what is the typical presentation of SCID?
- well when born then problems after the first month of life
- weight loss
- persistant candidias
- failure to clear vaccines
What are the causes of SCID?
- defect in the common cytokine receptor on the gamma chain defect
- RAG 1/RAG2 defect
- adenosine deaminase deficiency
In SCID there is a adenosine deaminase deficiency what is the problem with this?
Causes an accumulation of deoxyadenosine and deoxy ATP which is toxic for dividing thymocytes
what are the investigations and findings for SCID?
- low total lymphocyte count
- low/absent T cells
- Igs low
- decreased T cell function
what is the genetic defect in DiGeorge syndrome?
22q11 deletion leading to a failure to develop 3rd and 4th pharyngeal pouches
what are the facial features in DiGeorges syndrome?
low set ears
fish shaped mouth
why is there an immunodeficiency in Digeorges syndrome?
Can have an abscent thymus leading to lack of T cell development
where is the mutation in bare lymphocyte syndrome?
mutation of transcription factors that regulate the expression of MHC class II gene
what is the immune problem n barelymphocyte syndrome?
Lack of MHC II leading to lack of CD4 development
what is the inheritance pattern in wiskott Aldrich syndrome?
where is the defect in wiskott Aldrich syndrome?
in the WASP preventing actin polymerisation
what immune cells are affected in wiskott Aldrich syndrome?
Progressive decline in T cells
Reduction in antibody production
what is the common presentations of wiskott Aldrich syndrome?
what is the inheritance pattern of ataxia telangiectasia?
what is the defect in ataxia telangiectasia?
A defect in the cell cycle checkpoint gene ATM so p53 is activated leading to apoptosis of cells with damaged DNA
The ATM gene is damaged in ataxia telangiectasia what is it's normal role?
normally stabilises the DNA double stand break complexes during recombination
what immune cells are affected by the defect in ataxia telangiectasia?
lymphocyte antigen receptors and therefore lymphocyte development
what is the presentation of a patient with ataxia telangiectasia?
- childhood presentation
- progressive cerebellar ataxia
- telangiectasia on the ear lobes and conjunctivae
what immune cell lineage is affect in ataxia telangiectasia?
both B and T cells
defect in the antibody production
where are the mutations in hyper IgM syndrome
Mutations in the gene for CD40L
what cells are defect in hyper IgM syndrome?
Igm is normal
defects in IgG, IgA and IgE
what hyper IgM syndrome there is a defect in CD40l what is it's normal role?
In macrophages getting T cell help
what is defect in innate immunity defects?
- phagocyte defects
- complement defects
what is defective in chronic granulomatous disease?
The oxidative killing of phagocytosed microbes due to a mutation in NADPH components
how is chronic granulomatous disease diagnosed?
- NBT test
- flow cytometry assay
what gene is defect in chediak higashi syndrome?
what part of phagocytosis is defective in chediak higashi syndrome?
the fusion of phagosome-lysosome function meaning defective killing
how is chediak higashi syndrome diagnosed?
- there is a low number of neutrophils
- neutrophils present have giant granules
where is the defect in leucocyte adhesion deficiency?
- defect in beta 2 chain integrins (LFA 1, MAC 1) and in sialyl lewis X
what infections are more likely in leucocyte adhesion deficiency?
what immune cells are defective in leucocyte adhesion deficiency?
- decreased neutrophil chemotaxis
- decreased integrins on phagocytes
how does defects in TLR3 present?
how does defects in MyD88 present?
Patients with defects in MAC complement are at risk of?
Patients with C3 deficiency are at risk of?
Patients with C1q, C2,C4 deficiency are at risk of?
SLE like syndrome
what are causes of secondary immunodeficiency?
- chronic renal disease
why can premature delievery lead to secondary immunodeficiency?
interruption in the placental transfer of IgG leaving them deficient
what are clinical indications for primary immune deficiencies for bone marrow transplant ?
- phagocyte defects
- lymphomas, leukaemia, myeloma
what is an allogenic bone marrow transplant?
Uses genotypically matched individuals