Innate Immunity deficiencies Flashcards
what will we see in a pt with phagocyte def
recurrent skin/mouth def - s.aureus or fungal (candida, aspergillus)
mycobac inf - mycobac Tb, atypical mycobac
3 ‘failure of production’ defects of phag
reticular dysgenesis
kostman’s syndro
cyclic neutropenia
mutation and path of reticular dysgenesis
mut to AK2 -> no differentiation of haematopoeitic stem cells -> no granulocytes/myeloid/lymphoid cells
mutation, inheritance and path of kostman’s syndro
auto rec mut in HAX1 -> severe congen neutropenia
mutation, inheritance and path of cyclic neutropenia
auto dom mut in neutrophil elastase -> episodic neutropenia every 4-6w
what def is mainly involved in a ‘failure of trafficking’ defect of phagocytosis
leukocyte adhesion def (usually CD18)
signs/ sympto of leukocyte adhesion def
recurrent inf
v high neutrophil count in blood
absent pus formation
delayed umbilical cord separation at birth
what is the deficiency in chronic granulomatous def
NADPH oxidase def
path and sympto of Chronic granulomatous def
cannot kill patho so surrounds inf with cells -> excessive inflam, granuloma formation, lymphadenopathy, hepatosplenomeg
what are the inv for chronic granulomatous def
neutroblue tetrazolinium - if yellow -> then -ve (normal)
dihidrorhodamine - if becomes flourescent -> then-ve (normal)
defects in phag - what will defects in the IL12-IFN gamma pathway lead to
defects can be in cytokines or Rs -> macrophages cannot activate T cells -> no granuloma formation
what are pts with defects in the IL12-IFN gamma pathway susceptible to
v susceptible to TB and atypical mycobac
what mut is involved in a classic NK cell def
GATA4 or MCM4 mut -> absence of NK cells in blood
what mut is involved in a functional NK cell def
FGR3A gene mut -> NK in blood but dont work
how will a pt with a NK cell def present
often presents as child with severe chicken pox and disseminated CMV inf
(have v inc susceptibility to viral inf)
what are pts with NK cell def at high risk of
malig
What compliment proteins are involved in the classical and MBL pathways
classic - C1,2,4 -> C3
MBL - C2,4, -> C3
what are pts with a complement def v susceptible to
bac inf - esp encapsulated bac (NHS) - esp in classical and alt pathway def
neisseria meningitidis
haemophillus influenzae
strep pneumoniae
what are pts with a def in C1,2 or 4 at risk of
inc risk of SLA and autoimmunity (esp C2)
what is the normal function of the classical complement pathway
med clearance of apoptotic/necrotic cells
med clearance of immune complexes by erythrocytes
what will deficiencies in the classical complement pathway lead to
no clearance of apoptotic/necrotic cells -> autoimmunity and immune complexes (SLE)
no clearance of immune complexes by erythrocytes -> local inflam to skin, joints and kidneys
what is C3 neprhitic factor
anti-C convertase -> depletes C3
what is C3 neprhitic factor associated with
glomerulonephritis (-> blood in urine)
lipodystrophy (-> abnormal fat distribution)
