Immunology

Question 1

monogenic disorder

Answer 1

single gene defects causing autoimmune diseases are rare

Question 2

example of a monogenic autoimmune disorder

Answer 2

IPEX syndrome

Question 3

what is IPEX syndrome

Answer 3

a fatal X-linked autosomal recessive disorder presenting in early childhood causing immune disregulation, enteropathy & polyendocrinopathy

Question 4

what are the symptoms of IPEX syndrome?

Answer 4

Very early onset T1DM (before 6 months)
severe malabsorption syndrome
eczema
autoimmune thyroid disease, autoimmune haemolytic anaemia, 
severe infections

Question 5

what is the pathogenesis of IPEX syndrome?

Answer 5

Mutation in FOXP3 gene - essential for the development of regulatory T-cells which are essential in protection against auto-immunity

Question 6

HLA

Answer 6

human leukocyte antigen complex (controls T cells)

Question 7

what is the susceptibility allele associated with ankylosing spondylitis?

Answer 7

HLA B27

Question 8

what is the susceptibility allele associated with goodpastures syndrome?

Answer 8

HLA DR2

Question 9

what is the susceptibility allele associated with Graves disease?

Answer 9

HLA DR3

Question 10

what is the susceptibility allele associated with SLE?

Answer 10

HLA DR3

Question 11

what is the susceptibility allele associated with T1DM?

Answer 11

HLA DR3/DR4

Question 12

what is the susceptibility allele associated with rheumatoid arthritis?

Answer 12

HLA DR4

Question 13

which class of HLA do all nucleated cells express on the cell surface?

Answer 13

class 1

Question 14

give some examples of class 1 HLA

Answer 14

HLA-A
HLA-B
HLA-C

Question 15

which class of HLA do specialised antigen-presenting cells also express?

Answer 15

class 2

Question 16

give some examples of class 2 HLA

Answer 16

HLA-DR
HLADQ
HLA-DP

Question 17

why is polymorphism of HLA molecules important?

Answer 17

to maintain diversity

Question 18

what are the 3 factors contributing to autoimmune disease?

Answer 18

genetics
environment
immune regulation

Question 19

what pathological classification scheme is used in the classification of autoimmune disease?

Answer 19

Gel & Coombs classification

Question 20

how are autoimmune diseases clinically classified?

Answer 20

organ-specific diseases or non-organ specific multi system autoimmune disease

Question 21

what are hypersensitivity reactions?

Answer 21

Immune response that results in bystander damage to the self, usually exaggeration of normal immune mechanisms

Question 22

what is the Gel & Coombs classification of hypersensitivity reactions?

Answer 22

Type I: Immediate hypersensitivity
Type II: Direct cell killing
Type III: Immune complex mediated
Type IV: Delayed type hypersensitivity

Question 23

what type of hypersensitivity reaction according to Gel & Coombs is SLE?

Answer 23

type III

Question 24

what is the fundamental abnormality of SLE?

Answer 24

disturbed regulation of B cell activity

Question 25

what is SLE?

Answer 25

Prototypic multisystem autoimmune disease

Question 26

which stage of life is frequency the highest?

Answer 26

2nd & 3rd decades of life

Question 27

in which sex is SLE more common?

Answer 27

females

Question 28

what is SLE characterised by?

Answer 28

antibodies to nuclear proteins

Question 29

what does ANA bind to?

Answer 29

can bind to many different nuclear components

Question 30

what are speckled antibodies associated with?

Answer 30

antibodies to extractable nuclear antigens eg Ro and La

Question 31

which antibodies are more sepcific for SLE & sjorgen's syndrome the ANA?

Answer 31

speckled antibodies

Question 32

what do anti-centromere antibodies bind to?

Answer 32

chromosomes (kinetochore)

Question 33

what disease are anti-centromere antibodies very specific for?

Answer 33

scleroderma

Question 34

what are auto antigens?

Answer 34

proteins associated with nucleolar RNA including fibrillarin, U1RNP

Question 35

what disease are neuclolar ANA associated with?

Answer 35

scleroderma

Question 36

what are extractable nuclear antigens?

Answer 36

nuclear antigens that are soluble and can be extracted from the nucleus

Question 37

levels of which complements can act as a surrogate marker of disease activity in SLE?

Answer 37

C3 & C4 | - low levels = high activity

Question 38

what investigations are done for type III hypersensitivity reactions?

Answer 38

specific IgG to putative antigen low serum complements characteristic biopsy features

Question 39

how are type III hypersensitivity reactions managed?

Answer 39

decrease inflammation- corticosteroids | decrease production of antibody - immunosuppressive agents

Question 40

what type of hypersensitivity is rheumatoid arthritis?

Answer 40

type IIII

Question 41

what is rheumatoid arthritis?

Answer 41

Inflammatory autoimmune disease characterized by the destruction of joint cartilage and inflammation of the synovium

Question 42

what are the clinical features of rheumatoid arthritis?

Answer 42

initially: stiffness, pain, swelling, erythema later: osteoporosis, destruction of joint cartilage, bone resorption, displacement by ankylosing, subcutaenous nodules at pressure points

Question 43

what is the immunopathogenesis of rheumatoid arthritis?

Answer 43

Characterised initially by infiltration of synovium by CD4+ T cells Secondary involvement of activated B cells and antibody

Question 44

what does the histology of the synovium look like in rheumatoid arthritis?

Answer 44

Redundant folds of synovial lining and intense infiltration with inflammatory cells

Question 45

which inflammatory mediators have critical roles in the pathogenesis of rheumatoid arthritis?

Answer 45

IL1 | TNF

Question 46

how do biologicals work?

Answer 46

cytokine blockade by blocking the TNF network (anti-TNF)

Question 47

what is a rheumatoid factor?

Answer 47

an antibody directed against the common (Fc) region of human IgG

Question 48

what are the major indications for rheumatoid factor testing?

Answer 48

evaluating the prognosis of someone with rheumatoid arthritis or diagnosing sjorgen's syndrome/cryoglobulinaemia

Question 49

what is a more specific test for rheumatoid arthritis then rheumatoid factor?

Answer 49

anti-CCP antibody