Immunology 6a - Immune deficiencies

Question 1

Most severe form of SCID

Answer 1

Reticular dysgenesis

Question 2

What infections seen in phagocyte deficiencies?

Answer 2

Recurrent infections of skin and mouth
Bacterial: S.aueus, enteric bacteria
Mycobactetria: TB and atypical mycobacteria
Fungal infection: C.albicans and aspergillus fumigatus

Question 3

Treatment of phagocyte deficiencies

Answer 3

Antibiotic prophylaxis e.g. Septrin
Antifungal prophylaxis e.g, itraconazole

Definitive: HSCT
For CGD: IFN gamma therapy to stimulate the macrophages

Question 4

What do the activator receptors of NK cells recognise?

Answer 4

Heparan sulphate proteoglycans

Question 5

What do the inhibitors receptors of NK cells recognise?

Answer 5

Self-HLA

Question 6

Treatment of NK cell deficiencies

Answer 6

Prophylactic antivirals
Cytokines e.g. IFN to increase NK cell cytotoxicity
HSCT if severe

Question 7

Failure to produce neutrophils

Answer 7

Reticular dysgenesis
Kostmann syndrome
Cyclical neutropenia

Question 8

Specific failure of neutrophil maturation

Answer 8

Kostmann

Cyclical neutropenia

Question 9

Reticular dysgenesis

Answer 9

Autosomal recessive, severe SCID

NO myeloid or lymphoid cells OR CD4 or CD8

Question 10

Mutation in reticular dysgenesis

Answer 10

AK2

Question 11

Kostmann syndrome

Answer 11

Autosomal recessive severe congenital neutropenia

Question 12

Mutation in kostmann

Answer 12

HAX-1

Question 13

Cyclical neutropenia

Answer 13

AUTOSOMAL DOMINANT, episodic neutropenia every 5-6 weeks

Question 14

Mutation in cyclical neutropenia

Answer 14

ELA-2

Question 15

Defect of phagocyte migration

Answer 15

Leukocyte adhesion deficiency

Question 16

Cause of LAD

Answer 16

Deficiency in CD18 on neutrophils so cannot transmigrate in to endothelial cells

Question 17

Characteristics of LAD

Answer 17

Very high neutrophil count in blood
No pus formation
Delayed umbilical cord separation

Question 18

Failure of oxidative killing mechanisms

Answer 18

Chronic granulomatous disease

Question 19

Why failure of oxidative killing in CGD?

Answer 19

Deficient NADPH oxidase so absence of respiratory burst

Question 20

Which infections are patients with CGD prone to?

Answer 20

PLACESS

Pseudomonas, Listeria, Aspergillus, Candida, E.coli, S.aureus, Serratia

Question 21

Sx of CGD

Answer 21

Excessive inflammation, granuloma formation, lymphadenopathy and hepatosplenomegaly

Question 22

Tests for CGD

Answer 22

NBT (nitro-blue tetrazolium) (-ve)

DHR (Dihydrorhodamine) )-ve)

Question 23

NBT in CGD

Answer 23

Normal = Yellow –> blue

in CGD, stays yellow

Question 24

Which primary immune deficiency is associated with mycobacterial infection?

In this deficiency, what are its unable to form?

Answer 24

Cytokine production deficiency - IL-12, IL-12R, IFNgamma, IFN gamma R

unable to form GRANULOMAS

Question 25

Cytokine cycle between macrophages nad T cells

Answer 25

Infected macrophages stimulated to produce IL12
IL12 acts on t cells to promote secretion of IFN gamma
IFN gamma feeds back to macrophages and neutrophils
Stimulates production of TNF alpha
Activated NADPH oxidase –> oxidative killing pathways

Question 26

2 types of NK cell deficiency

Answer 26

Classical - no Nk cells

FUnctional - NK cells poorly functional

Question 27

Which complement pathways are INdependent of the acquired immune response?

Answer 27

MBL and alternative

Question 28

Alternative pathway of complement

Answer 28

C3 binds to bacterial cell wall components e.g. LPS in gram -ve and teichoic acid gram +ve

Question 29

Which factors involved in alternative pathway? Which factors regulate these?

Answer 29

Factors B, P (properidin), D regulated by factors H, I

Question 30

Which pathway does the MBL pathway stimulate?

Answer 30

The classical complement pathway (C2 and C4) but independent of acquired immune response

Question 31

Complement deficiency susceptibility to which bacteria?

Answer 31

Encapsulated organisms, NHS
Neisseria
Haemophilus
Strep

Question 32

Which complement deficiency is quite common? when is it a problem?

Answer 32

MBL deficiency only common if co-existing immunodeficiency e.g. chemo

Question 33

Classical pathway deficiency is associated with….?

Answer 33

SLE, due to increased load of self-antigens, usually cleared by classical pathway

Question 34

Most common type of classical complement pathway deficiency

Answer 34

C2

Question 35

Secondary deficiency of the classical complement pathway - what is it?!

Answer 35

o Active lupus  persistent production of immune complexes  consumption of complement components resulting in a functional complement deficiency

Question 36

2 things which patients with C3 deficiency are susceptible to?

Answer 36

Encapsulated bacteria infection

connective tissue disease

Question 37

WTF is secondary C3 deficiency

Assoc with?

Answer 37

Nephritic factors present : they are directed against parts of the complement pathway.

They STABILISE C3 CONVERTASES –> increased C3 consumption

Associated with glomerulonephritis (membranoproliferative) and partial lipodystrophy

Question 38

Active SLE and nephritic factors –>

Answer 38

Complement consumption

Question 39

SLE is associated with deficiencies in which components of the complement pathway?

Answer 39

C1, C2, C4

Question 40

Management of complement deficiencies

Answer 40

Vaccination: meningovax, pneumovax and HIB

prophylactiv abx etc

Question 41

Complement deficiency investigations

Answer 41

C3, C4, CH50, AP50

Question 42

What does AP50 test for?

Answer 42

Factor B, P (properidin), D, C3, C5-9

Question 43

abnormality is detected only in CH50 and not in AP50

Answer 43

Suggests issue with C1,2 or 4

Question 44

Abnormality in CH50 and AP50

Answer 44

Problem with C3, C5-C9

Question 45

C1q deficiency …

Answer 45

severe, childhood onset SLE with normal C3 +C4

Question 46

meningococcus meningitis with family history of sibling dying of the same condition aged 6

Answer 46

C5-C9 deficiency