Primary immune deficiencies Flashcards
Problem in X linked agammaglobulinaemia?
Cannot rearrange light chains, so B cell precursors do not mature (still pre B cells in bone marrow)
- no IGs at atll
- No B cells
- treat with IVIG
- increase autoimmunity
- recurrent sinupulmonary
- recurrent enterovirus, echovirus, coxsackie
- persistent giardia
- polyarthropathy
CVID problem?
B cells cannot differentiate into plasma cells
- recurrent sinopulmonary
- recurrent herpesvirus
- serious enterovirus–>meningoenceph
- persistent candida
- increase autoimmune
- increase gastric ca and NHL
Normal B cells in 90%
Hyperplastic lymphoid follicles
Isolated IgA defic problem
IgA producing plasma cells cannot develop from precursors-
associated with intrauterine TORCH infections
Not secretory or inside body IgA- recurrent sinopulmonary or GI or GU infection
Tend to have resp tract ALLERGY
Autoimmune increase- celiac, IBD, RA, Sjogrens, thyroiditis, pernicious anaemia
Watch out for transfusion anaphylaxis!
Stop NSAIDS, sulfasal, anticonvuls- can precipitate
Avoid live vaccines
Prompt Abx if sick
Not IVIg as mucosal not systemic- may consider if assoc IgG subclass def but need to take IgAs out
For celiac need to check anti-Gliadin!!!
Late complement defect and tend to see…
neisseria
other pyogenic bacterial infection
T cell defect, tend to see…
bacterial sepsis
MUCOSAL candida, PCP
CMV, EBV, chronic resp and GI infections with virus
Listeria
B cell defect tend to see…
strep/staph/haemophilus enteroviral encephalitis GIARDIA severe recurrent sinopulmonary meningitis
Granulocyte defect tend to see…
high grade bacterial infections... staph pseudomonas SYSTEMIC candida nocardia aspergillus
Hyper IgM problem?
T cells unable to signal B cells to make Ab other than IgM- ie isotype switch
Usually a problem with CD 40 LIGAND def on T cells
Loads of IgM, none of the others, normal B and T counts
See pyogenic infections, esp RESP and PCP
Chronic diarrhoea with cryptosporidium, oral ulcers
uncommon to see enterovirus
IgM can opsonise so may see cytopaenias
Enlarged lymphoid organs
See high IgM, low everything else
Check flow cytometry for CD40L
Treat IVIG , bactrim proph, G-CSF
SCID where is the problem?
Lack of component essential for T cell function eg lack gamma common chain- cannot respond to cytokines
“EARLY BLOCK IN T AND NK DIFFERENTIATION”
Often CK production problem so T cells cannot develop
die in first year without BM tx
B and T cells low
DiGeorge where is the problem?
Failure of third and fourth pharyngeal pouches to develop so no thymus of PG gland
Reduced Cell mediated immunity- poor viral and fungal and protozoal defense
B cells can also develop
IgG2 subclass def- what hapens
encapsulated bacteria cannot fight off
IF IgG subclass def and do not respond to vaccines, what to do?
re try with protein conjugated as may be able to stimulate different Ig subtype
What does chronic granulomatous disease come from?
Defective ROS production after phagocytosis
This leads to deep bacterial and fungal infections
sterile granulomas form in spleen, liver and can cause obstruction
Diagnose with DHR or NBT assay
zTreat with bactirm and itraconazole that can penetrate cells
Granulomas are steroid sensitive but increase infection risk
IgG4 disease, often have a history of….
Allergy
Do IgG4 people have high IgG4 in serum?
normal in 30%
