primary immunodeficiency Flashcards
secondary immunodeficiency causes
malnutrition infection diabetes malignancy immunosuppressive Rx chronic renal failure burns, surgery splenectomy
primary immunodeficiency
part of immune system missing/not working
often genetic, can be autoimmune
predispose to infection, tumours
1ry: abnormality may be in
response of mature lymphocytes to antigenic stimulation
components of innate immune system
stages of lymphocyte development
primary defects of innate system
phagocyte defects
complement defects
phagocyte defects may be in
phagocytosis
phagocyte adhesion to epithelium
intracellular killing
chemotaxis
ex phagocyte defects
chronic granulomatous disease
leucocyte adhesion deficiency
features of phagocyte defects
liver abscess skin/mucous membrane infection suppuration of lymph nodes osteomyelitis pneumonia
complement pathway defects may be in
classical pathway
alternative pathway
terminal pathway
proteins that control activity of complement system
clinical features complement pathway defect
immune complex disease
infection: staph, Hib, meningococcal
primary defects adaptive immunity
SCID
antibody deficiency
T cell deficiency
T and B cell deficiency
what is repeated infection with encapsulated bacteria a sign of
defective antibody production
causes of primary immunodeficiency
mutations e.g. SCID
polymorphisms: HLA, mannan-binding lectin
polygenic disorders e.g. CVID
autoimmunity e.g. APECED
common variable immunodeficiency
polygenic disorder
low IgG
variable levels of IgA, IgM, B cells and T cells
recurrent resp tract infections
APECED
autoimmune polyendocrinopathy candidiasis ectodermal dysplasia
severe recurrent candidia infection
defect in central tolerance
SCID
low t cells and B cells
can be defects in: pluripotent stem cells, lymphoid stem cells, T + B cells
features of SCID
infections in 1st few weeks life: candida, bacterial sepsis, bronchiolitis
rashes
diarrhoea
FTT
SCID FH
neonatal death
consanguinity
SCID lymphocyte count
very low total lymphocyte count <1
measured by flow cytometry
SCID supportive Rx
prophylactic antib, antiv, antif
avoid live vaccines
Ig replacement
nutritional support
SCID definitive Rx
stem cell transplant (earlier the better)
gene therapy if no suitable STC donor
for gene therapy to be successfull…
- genetic mutation must be identified and evidence correcting it will improve outcome
- transfected gene must confer proliferative/survival advantage
- gene therapy must’t cause Ca
when does antibody deficiency usually present
later in life
(babies born w maternal Ig)
CVID doesnt present till adulthood
Di George syndrome - what is it result of
defective fusion of 3rd and 4th pharyngeal pouches
Di George syndrome CATCH-22
cardiac abnormalities abnormal face thymic hypoplasia - T cell dysfunction cleft palate hypocalcaemia
chromosome 22 abnormalities
immune deficiency: infections SPUR
serious
persistent
unusual
recurrent
