Autoimmune disease, Allergy and Diagnosis

Question 1

What is positive selection in central tolerance?

Answer 1

T cells undergo positive selection in the thymus

T cells need to be able to bind to MHC in order to survive .

Question 2

What is negative selection in central tolerance?

Answer 2

B cells and T cells undergo negative selection in the bone marrow and thymus respectively

B cells and T cells that react with self antigens are eliminated

Question 3

Which genes encode for MHC class I?

Answer 3

genes in HLA-A, HLA-B, HLA-C

Question 4

Which genes encode for MHC class II?

Answer 4

genes in HLA-DP, HLA-DQ, HLA-DR

Question 5

mutation of FoxP3 causes what?

Answer 5

mutation of FoxP3 causes failure to develop regulatory T cells – severe autoimmunity from birth

Associated with:
Immune dysregulation, polyendocrinopathys, enteropathy

Question 6

mutations in PTPN22 cause what?

Answer 6

mutations in PTPN22 cause T cells to be activated more easily – stronger immune response in general

Associated with:
Type 1 diabetes, Rheumatoid arthritis, autoimmune thyroid disease

Question 7

What is an example of an infection causing autoimmunity due to molecular mimicry?

Answer 7

Rheumatic fever

antibodies against M protein of Streptococcus A also react against the glycoproteins of the heart

Question 8

Which parts of the immune system are involved in autoimmunity?

Answer 8

Adaptive immunity 
B and T cells
Break down of self tolerance
Autoantibodies present 
Continuous progression of clinical features 

eg. Rheumatoid Arthritis and SLE

Question 9

Which parts of the immune system are involved in autoinflammation?

Answer 9

Innate immunity
Neutrophils and macrophages
Few or no autoantibodies
Recurrent, seemingly unprovoked attacks

eg. Crohn’s diease

Question 10

What is sensitivity of a diagnostic test?

Answer 10

measure of how good is the test in identifying people with the disease

Question 11

What is specificity of a diagnostic test?

Answer 11

measure of how good is the test at correctly defining people without the disease

Question 12

What is the positive predictive value of a diagnostic test?

Answer 12

The proportion of people with a positive test who have the target disorder

Question 13

What is the negative predictive value of a diagnostic test?

Answer 13

The proportion of people with a negative test who do not have the target disorder.

Question 14

What is C- reactive protein?

Answer 14

CRP is produced in the liver during an acute phase reaction in response to IL-6.
It binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria.
This activates the complement system, promoting phagocytosis by macrophages

Question 15

How is C-reactive protein useful as a diagnostic marker of inflammation?

Answer 15

Measuring and charting CRP values can prove useful in determining disease progress or the effectiveness of treatments
CRP is a more sensitive and accurate reflection of acute phase response than ESR

Question 16

What are the ENA’s ?

Answer 16

Extractable Nuclear antigens (ENAs)

The six main antigens used in immunological laboratories for detection are:
Ro, La, Sm, RNP, Scl-70 and Jo1,

Question 17

Which autoantibody is more sensitive for diagnosing SLE and which is most specific?

Answer 17

ANA is most sensitive (>95%)
but less specific (60%)

dsDNA is less sensitive (70%)
but most Specific (95%)

Question 18

Which autoantibody is most specific for rheumatoid arthritis?

Answer 18

Anti-citrullinated protein antibody (ACPA)

95% specificity
ACPA positive patients tend to have more severe and erosive disease

Question 19

What antigen is most likely to be the target of autoantibodies in Cytoplasmic ANCA?

Answer 19

PR3 (90%) in cANCA

Question 20

What antigen is most likely to be the target of autoantibodies in Perinuclear ANCA?

Answer 20

MPO (70%) in pANCA

Question 21

What are the ANCA associated systemic vasculitidies? (AASV)

Answer 21

Microscopic polyangiitis
Granulomatosis with polyangitis
(Wegener’s granulomatosis)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Question 22

What are anti-mitochondrial Ab specific for?

Answer 22

Primary biliary sclerosis

Question 23

What are anti-smooth muscle and anti-Liver kidney microsomal type 1 (LKS) autoantibody found in?

Answer 23

autoimmune hepatitis

Question 24

What autoantibodies are found in Type I diabetes mellitus?

Answer 24

islet cell antibodies
anti-GAD65, anti-GAD67
anti-insulinoma antigen 2 (IA-2)
insulin autoantibodies (IAAs)

Disappear with progression of disease and total destruction of β islet cells

Question 25

What kind of hypersensitivity reaction is Farmer’s lung?

Answer 25

Type III - Immune complex

Question 26

What are the effector cytokines of Th1 cells?

Answer 26

IFN-y, IL-2

Question 27

What are the effector cytokines of Th2 cells?

Answer 27

IL-4, IL-5, IL-13

Question 28

What is the atopic triad?

Answer 28

Asthma, Rhinitis, Eczema

Question 29

Which cytokine is released from Th2 cells that activated Eosinophils?

Answer 29

IL-5

Question 30

Which cytokines released from Th2 cells activate B cells?

Answer 30

IL-4 and IL-13

Question 31

What is a main cause of atopic dermatitis?

Answer 31

House dust mites

Question 32

What tests can be done to help diagnose hypersensitivity?

Answer 32

Specific IgE 
Skin prick test 
Intra-dermal test
Oral challenge test – Gold standard
Basophil activation test
Component resolved diagnostics