Innate Immunity deficiencies

Question 1

what will we see in a pt with phagocyte def

Answer 1

recurrent skin/mouth def - s.aureus or fungal (candida, aspergillus)
mycobac inf - mycobac Tb, atypical mycobac

Question 2

3 ‘failure of production’ defects of phag

Answer 2

reticular dysgenesis
kostman’s syndro
cyclic neutropenia

Question 3

mutation and path of reticular dysgenesis

Answer 3

mut to AK2 -> no differentiation of haematopoeitic stem cells -> no granulocytes/myeloid/lymphoid cells

Question 4

mutation, inheritance and path of kostman’s syndro

Answer 4

auto rec mut in HAX1 -> severe congen neutropenia

Question 5

mutation, inheritance and path of cyclic neutropenia

Answer 5

auto dom mut in neutrophil elastase -> episodic neutropenia every 4-6w

Question 6

what def is mainly involved in a ‘failure of trafficking’ defect of phagocytosis

Answer 6

leukocyte adhesion def (usually CD18)

Question 7

signs/ sympto of leukocyte adhesion def

Answer 7

recurrent inf
v high neutrophil count in blood
absent pus formation
delayed umbilical cord separation at birth

Question 8

what is the deficiency in chronic granulomatous def

Answer 8

NADPH oxidase def

Question 9

path and sympto of Chronic granulomatous def

Answer 9

cannot kill patho so surrounds inf with cells -> excessive inflam, granuloma formation, lymphadenopathy, hepatosplenomeg

Question 10

what are the inv for chronic granulomatous def

Answer 10

neutroblue tetrazolinium - if yellow -> then -ve (normal)

dihidrorhodamine - if becomes flourescent -> then-ve (normal)

Question 11

defects in phag - what will defects in the IL12-IFN gamma pathway lead to

Answer 11

defects can be in cytokines or Rs -> macrophages cannot activate T cells -> no granuloma formation

Question 12

what are pts with defects in the IL12-IFN gamma pathway susceptible to

Answer 12

v susceptible to TB and atypical mycobac

Question 13

what mut is involved in a classic NK cell def

Answer 13

GATA4 or MCM4 mut -> absence of NK cells in blood

Question 14

what mut is involved in a functional NK cell def

Answer 14

FGR3A gene mut -> NK in blood but dont work

Question 15

how will a pt with a NK cell def present

Answer 15

often presents as child with severe chicken pox and disseminated CMV inf
(have v inc susceptibility to viral inf)

Question 16

what are pts with NK cell def at high risk of

Answer 16

malig

Question 17

What compliment proteins are involved in the classical and MBL pathways

Answer 17

classic - C1,2,4 -> C3

MBL - C2,4, -> C3

Question 18

what are pts with a complement def v susceptible to

Answer 18

bac inf - esp encapsulated bac (NHS) - esp in classical and alt pathway def

neisseria meningitidis
haemophillus influenzae
strep pneumoniae

Question 19

what are pts with a def in C1,2 or 4 at risk of

Answer 19

inc risk of SLA and autoimmunity (esp C2)

Question 20

what is the normal function of the classical complement pathway

Answer 20

med clearance of apoptotic/necrotic cells

med clearance of immune complexes by erythrocytes

Question 21

what will deficiencies in the classical complement pathway lead to

Answer 21

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

Question 22

what is C3 neprhitic factor

Answer 22

anti-C convertase -> depletes C3

Question 23

what is C3 neprhitic factor associated with

Answer 23

glomerulonephritis (-> blood in urine)

lipodystrophy (-> abnormal fat distribution)