Immunodeficiency

Question 1

Most common primary immunodeficiency

Rate

Answer 1

IgA

Often asymptommatic

1 in 500

Question 2

PAMPs activate…

Examples

Cellular receptors that bind called

Answer 2

Innate immune system

Lipopolysaccharides
Peptidoglycans
Flagellins

Pattern recognition receptors

Question 3

Pattern recognition receptors
Are on what cells

End result of interaction

Answer 3

Dendritic cells, macrophages

Cytokine production
IL-1b, IL-6, TNF

Release of additional cytokines
Phagocytosis
NK cell killing

Question 4

How do macrophages activate adaptive immunity

Answer 4

APC take up antigen
Process & present antigen to T cells

Activated helper T cells stimulate production of antibody producing B cells, cytotoxic cells

Question 5

Mechanism of immunodeficiency
Lab findings

Manifestations

Xlinked agammaglobulinemia

Answer 5

Arrest of cell maturation in pre B lymphocyte stage

Decreased IGs
Decreased B cells
Normal B cell precursors

Recurrent sinopulmonary
Enterovirus
Arthritis
Skin & bone infection

Question 6

Chronic mucocutaneous candidiasis

Mechanism

Labs

Manifestations

Answer 6

Failure of T cells to proliferate or stimulate cytokines in response to Candida albicans

Mucosal swabs, scrapings, biopsy specimens for Candida

Thrush & oesophagitis
Autoimmune endocrinopathies ( thyroiditis, adrenal insufficiency) vitiligo

Question 7

CVID

Mechanism
Labs
Manifestations

Answer 7

Normal levels of B cells
Unable to differentiate into plasma cells

Reduced IgG, IgA +- low IgM
Normal or reduced B cell numbers

RTI
Cytopenia
Diarrhoea, IBD like illness

Question 8

CGD

Defect

Tests

Manifestations

Answer 8

Defect in NADPH oxidase activity

DHR or NBT
Diminished respiratory burst activity

Skin infection, abscesses, lymphadenitis, colitis, hepatic abscess, oral ulcers

Question 9

IPEX

Defect

Labs

Manifestations

Answer 9

FoxP3 mutation, impaired T cell development

Eosinophilia, increased IgE and IgA

Eczema, atopy, lymphadenopathy, DM, thyroid is, severe enteropathy

Question 10

What protects against disease in IgA deficiency?

Rate of coeliac in IgA def?

Answer 10

Compensatory increase in IgM

5-15%

Question 11

Omenn syndrome
What 
Inheritance 
Features 
Gene

Answer 11

AR form of SCID

Dermatitis, alopecia, chronic diarrhoea, FTT, lymphadenopathy, HSM

RAG1/RAG2 gene mutation
Absent B cells, oligoclonal autoreactive T cells (Th2)

Elevated IL4, IL5
Eosinophilia and elevated IgE

Question 12

What proportion of SCID has B cells

Answer 12

70%

Question 13

Most common genetic mutation in SCID

Answer 13

mutation to common gamma chain of the interleukin receptor for IL 2, 4, 7, 9, 15, 21

50% cases

X linked

Question 14

Loss of IL-2 receptor

Answer 14

Loss of lymphocyte proliferation signal

Question 15

Loss of IL4 R

Answer 15

Inability of B cells to class switch

Question 16

Loss of IL 7 R

Answer 16

Loss of antiapoptotic signal
Loss of T cell selection in thymus

And
TCR rearrangement

Question 17

Loss of IL-15 R

Answer 17

Ablation of NK cell development

Question 18

T -
B+
NK -

SCID
XL form
AR form

Answer 18

Common gamma chain mutation

JAK3 deficiency
Associated with common gamma chain of IL receptors

Same clinical manifestations as XL SCID

Question 19

ADA is…

Answer 19

An enzyme that breaks down purines

When absent dATP builds up inhibits enzymes needed for lymphocyte proliferation

B-, T-, NK-