Immunology transition Flashcards
signs of immunodeficiency
SPUR
serious infections - unresponsive to oral antibiotics
persistent infections - early structural damage; chronic infections
unusual infections - unusual organisms/sites
recurrent infections - 2 major or 1 major + recurrent minor infections in one year
other features suggestive of immunodeficiency
weight loss failure to thrive severe skin rash chronic diarrhoea mouth ulceration unusual autoimmune disease family history
physiological conditions associated with secondary immune deficiency
ageing
prematurity
infectious conditions associated with secondary immune deficiency
HIV
measles
treatment interventions associated with secondary immune deficiency
immunosuppressants
anti-cancer
corticosteroids
malignant conditions associated with secondary immune deficiency
cancer of the immune system - lymphoma/leukaemia/myeloma
metastatic
biochemical/nutritional conditions associated with secondary immune deficiency
malnutrition
renal insufficiency/dialysis
diabetes
mineral deficiencies
most common cause of SCID
X linked (45%)
mutation of component of IL2 receptor
results in inability to respond to cytokines (T/NK failure, immature B cells)
clinical presentation of SCID
unwell by 3m
persistent diarrhoea
failure to thrive
infections - more severe, unusual, opportunistic, vaccine-associated
Graft vs Host disease - colonisation of infants empty bone marrow with maternal lymphocytes
Family history of early infant death
what are granulomas
organised collection of activated macrophages and lymphocytes
what does granuloma formation result in
non-specific inflammatory response triggered by diverse antigenic agents or by inert foreign materials
results in activation of T lymphocytes and macrophages
failure of removal of stimulus results in persistent production of activated cytokines
end result is organised collection of persistently activated cells
how do granulomas form
infected macrophages stimulated to produce IL12
IL12 induces T cells to secrete gIFN
gIFN feeds back to macrophages and neutrophils
stimulates production of TNF
activates NADPH
what is essential for functional granulomas
TNF
name some conditions which may result in granuloma formation
sarcoidosis mycobacterium leprosy beryllosis silicosis chronic stage of hypersensitivity pneumonitis foreign bodies
how may antibody deficiencies present
recurrent bacterial infections - resp, GI
antibody mediated autoimmune disease - idiopathic thrombocytopenia, autoimmune haemolytic anaemia
features of CVID
low IgG, IgA, IgM
recurrent bacterial infections, especially resp
often associated with autoimmune disease
features of selective IgA deficiency
1 in 600 - very common
2/3 asymptomatic
1/3 recurrent resp infections
genetic component but cause unknown
DDx of antibody deficiencies (primary)
CVID
specific antibody deficiencies
Bruton’s agammaglobulinemia (no B cells)
DDx of secondary hypogammaglobulinaemia
protein loss - enteropathy, nephrotic syndrome
failure of protein synthesis - lymphoproliferative disease (CLL, myeloma, NHL)
Type 1 hypersensitivity
immediate
IgE mediated
Type 2 hypersensitivity
direct cell killing
antibody mediated - activation of complement leading to cell lysis; opsonisation leading to antibody mediated phagocytosis
e.g. autoimmune haemolytic anaemia, ITP, ABO transfusion reaction
Type 3 hypersensitivity
immune complex mediated
e.g. SLE
Type 4 hypersensitivity
delayed type hypersensitivity
features of NK cells
kill cells that lack MHC
not specific
no long term memory
