Path: Immuno

Question 1

How do you treat chronic granulomatous disease?

Answer 1

interferon gamma

Question 2

What is deficient in chronic granulomatous disease?

Answer 2

NADPH oxidase

Question 3

What is the underlying pathophysiology in chronic granulomatous disease?

Answer 3

deficiency in NADPH oxidase -> absent respiratory burst and superoxide production in neutrophils and macrophages -> impaired killing of IC micro-organisms

Excessive inflammation -> persistent neutrophil/macrophage accumulation, failure to degrade antigens.

Question 4

What particular organisms are like to to cause infections in chronic granulomatous disease?

Answer 4

catalase +ve bacteria (PLACESSSS -> Pseudomonas, Listeria, Aspergillus, Candida, E.coli, Staph aureus, Serratia)

Question 5

What is the role of catalase?

Answer 5

hydrogen peroxide to water and oxygen

found in almost all organisms exposed to oxygen

Question 6

Name catalase positive organisms

Answer 6

PLACESS H

Pseudomonas
Listeria
Aspergillus
Candida
E coli
Staph aureus
Serratia
H pylori

Question 7

inheritance pattern of chronic granulomatous disease

Answer 7

X-linked recessive or AR (2:1)

Question 8

Signs and symptoms of chronic granulomatous disease

Answer 8

recurrent severe infections (chronic skin, LN, bone, resp, with catalase +ve organisms

e.g. recurrent severe pneumonia before the age of 5

lymphadenopathy

Granulomas of the skin/GI/GU tract

Question 9

Investigations for chronic granulomatous disease

Answer 9

NBT (nitro-blue tetrazolium test) -> NEGATIVE (dye changes from yellow to blue in contact with free radicals e.g. hydrogen peroxide therefore negative in CGD)

DHR (dihydrorhodamine) flow cytometry test -> decreased green fluorescence (flow cytometry test showing abnormal NADPH oxidase activity (inability to metabolize dihydrorhodamine to fluorescent product, rhodamine)

genotyping is confirmatory

Question 10

What is the underlying pathology in leukocyte adhesion syndrome?

Answer 10

Leukocytes lack adhesion molecules and are unable to exit the bloodstream

Deficiency in:
CD18 (LAD1) - b2 integral subunit
CD11a, CD1b, CD11c

these are found on the surface of neurophils, bind to ligands on endothelial cells and regulate neutrophil adhesion/transmigration

Question 11

Investigations for leukocyte adhesion syndrome

Answer 11

Flow cytometry: absent CD18 (Cd11a, CD11b, CD11c)

Leukocytosis: however, neutrophils are absent at the site of infections

Question 12

Treatment of Leukocyte adhesion deficiency

Answer 12

prevention of further infections (e.g. adequate dental hygiene)

treatment of infections

BM transplant

Question 13

Which primary immune deficiency has delayed umbilical cord separation as a feature

Answer 13

leukocyte adhesion deficiency

Question 14

What is the mutation seen in leukocyte adhesion deficiency

Answer 14

CD18 missing on the surface on neutrophils (LAD-1)

can also be CD11a, CD11b, CD11c

Question 15

Which cytokine is important in the pathogenesis of rheumatoid arthritis, anyklosing spondylitis and inflammatory bowel disease?

Answer 15

TNF-alpha

Question 16

What is the specific antigen recognised by the immune system in Goodpasture’s syndrome?

Answer 16

type IV collagen

Question 17

How long before skin prick testing must antihistamines be stopped to allow for accurate interpretation?

Answer 17

48h

Question 18

inheritance pattern of reticular dysgenesis

Answer 18

AR

Question 19

What is the most common inherited immunodeficiency

Answer 19

(selective) IgA deficiency

Question 20

presentation of SIgAD (selective IgA deficiency)

Answer 20

often asymptomatic

associated with recurrent respiratory and GIT infections in 30%

increased susceptibility to parasitic infections e.g. by Giardia lamblia

Question 21

What might patients with SIgAD have an anaphylactic reaction to?

Answer 21

products containing IgA e.g. IVIg

To prevent transfusion reactions, IgA-deficient patients must be given washed blood products without IgA or obtain blood from an IgA-deficient donor.

Question 22

How common in SIgAD?

Answer 22

1:600 caucasians affected

it is the most common primary/inherited immunodeficiency

Question 23

The Six A’s of selective IgA deficiency:

Answer 23

Asymptomatic, Airway infections, Anaphylaxis to IgA-containing products, Autoimmune diseases, Atopy

Question 24

What HLA allele is found in 90% of patients with coeliac disease?

Answer 24

HLA DQ2

Question 25

HLA associated with Graves disease

Answer 25

HLA-DR3

Question 26

A mutation in what protein is the most common cause of Hyper IgM syndrome?

Answer 26

CD40

Question 27

What mouse monoclonal antibody targets CD3 on the surface of T cells?

Answer 27

Muromonab

Question 28

What monoclonal antibody can be used in the treatment of osteoporosis?

Answer 28

Denosumab (targets RANKL and therefore prevents the development of osteoclasts)

Question 29

What autoantibody is associated with Granulomatosis with Polyangiitis (Wegner’s Granulomatosis)?

Answer 29

cANCA

cytoplasmic anti neutrophil cytoplasmic antibody

anti-proteinase 3 which is aberrantly expressed on neutrophils in GPA, Ab binding activates them

Question 30

What is the full scientific name of the organism responsible for Cat Scratch Disease? What type of pathogen is it?

Answer 30

Bartonella henselae

gram -ve aerobic bacillus

Question 31

What monoclonal antibodies can be used in PsA and psoriasis and what do they target?

Answer 31

ustekinumab - anti-IL12 and anti-IL23 (bind to p40 subunit)

guselkumab - anti-IL23 (binds to p19 alpha subunit)

secukinumab - anti-IL-17A

Etanercept - TNFa/TNFb receptor

Question 32

What is NOD2 (Card15) associated with?

Answer 32

Crohn’s disease

it is the IBD1 gene

Question 33

Which immunodeficiency is associated with an issue in the common gamma chain?

Answer 33

X-linked SCID