Immunology

Question 1

Name one monogenic autoimmune disease?

Answer 1

IPEX syndrome (fatal autosomal recessive disorder presenting early in childhood)

Question 2

What is IPEX syndrome?

Answer 2

Immune dysregulation, polyendocrinopathy, enteropathy and x-linked inheritance syndrome

Question 3

Give 5 symptoms of IPEX syndrome?

Answer 3

1. Early onset insulin dependent diabetes mellitus
2. Severe malabsorption syndrome
3. Eczema
4. Autoimmune thyroid disease, autoimmune haemolytic anaemia
5. Severe infections

Question 4

What is the pathogenesis of IPEX syndrome?

Answer 4

Mutation in FOXP3 gene - essential for development of regulatory T-cells (regulatory T cells are essential in protection against autoimmunity)

Question 5

What do most autoimmune diseases result from?

Answer 5

Complex genetic interplay

Question 6

Name three immune response genes that most autoimmiune diseases result from?

Answer 6

HLA (human leukocyte antigen complex)
Cytokine genes
Costimulatory molecules

Question 7

In autoimmunity - what recognises foreign antigens?

Answer 7

T lymphotcytes

Question 8

During recognition of a foreign antigen - what do T cells see peptides exhibited on?

Answer 8

A defined HLA framework

Question 9

What do all nucleated cells express on the cell surface?

Answer 9

Class I (HLA-A, HLA-B, HLA-C)

Question 10

What do specialised antiven-presenting cells also express on their surface?

Answer 10

Class II (HLA-DR, HLA-DQ, HLA-DP)

Question 11

What can help maintenance of diversity?

Answer 11

Polymorphism in HLA molecules

Question 12

What is the susceptible allele for - Ankylosing spondylitis?

Answer 12

HLA B27

Question 13

What is the susceptible allele for - Goodpastures syndrome?

Answer 13

HLA DR2

Question 14

What is the susceptible allele for - Grave’s disease?

Answer 14

HLA DR3

Question 15

What is the susceptible allele for - SLE?

Answer 15

HLA DR3

Question 16

What is the susceptible allele for - type 1 diabetes?

Answer 16

HLA DR3/DR4

Question 17

What is the susceptible allele for - RA?

Answer 17

HLA-DR4

Question 18

What can alter the course of some autoimmune diseases?

Answer 18

Pregnancy

Question 19

What is there sex bias in?

Answer 19

Predisposing genetic factors

Question 20

What environmental factor contributes to autoimmune disease?

Answer 20

iNFECTION

Question 21

What reaction is an immune response that results in bystander damage to the self?

Answer 21

Hypersensitivity

Question 22

Name two IMMUNE COMPLEX MEDIATED autoimmune diseases?

Answer 22

1. SLE

2. RA

Question 23

Name an autoimmune disease which is a prototypic multisystemc disease, 1:2000, has female preponderance and genetic predisposition?

Answer 23

SLE

Question 24

What is the fundamental abnormality in SLE?

Answer 24

Disturbed regulation of B cell activity characterised by antibodies to nuclear proteins

Question 25

In SLE because it is mediated by immune complexes - what mediates inflammation?

Answer 25

Complement

Question 26

Give three antibodies produced against contents of cell nuclei in SLE?

Answer 26

1. Anti-DNA 2. Anti-nuclear 3. Antibodies to extractable nuclear antigens

Question 27

Give four non-specific clinicakl features of SLE?

Answer 27

Malaise, fatigue, myalgia and fever

Question 28

What disease can patients present with mouth ulcers, malar rash and photosensitivity?

Answer 28

SLE

Question 29

What is the speckled antibody associated with and more specific for?

Answer 29

Associated with antibodies to extractable nuclear antigens | More specific for SLE and Sjorgrens

Question 30

What pattern of ANA antibody is very specific for limited Scleroderma (CREST) and binds to chromosomes?

Answer 30

Anti-centromere antobdy

Question 31

What ANA antibody pattern is associated with scleroderma and proteins associated with nucleolar RNA including fibrillarin, U1RNP?

Answer 31

Nucleolar ANA

Question 32

Antibodies to extractable nuclear antigens: give the disease association for anti-centromere antibody?

Answer 32

CREST variant of scleroderma, occasionally found in primary Raynaud's syndrome

Question 33

Antibodies to extractable nuclear antigens: give the disease association for anti-Jo-1 (anti-histidyl-tRNA syndthease)?

Answer 33

Polymyositis, dermatomyositis or polymyositis-scleroderma, particularly associated with interstitial lung disease in these conditions

Question 34

Antibodies to extractable nuclear antigens: give the disease association for Anti-La antibody?

Answer 34

Sjogrens syndrome, SLE

Question 35

Antibodies to extractable nuclear antigens: give the disease association for Anti-ribonucleoprotein antibody (anti-RNP)?

Answer 35

Mixed connective tissue disease | SLE

Question 36

Antibodies to extractable nuclear antigens: give the disease association for Anti-Ro antibody?

Answer 36

SLE: associated with photosensitivity, thrombocytopaenia and subacute cutaneous lupus. Maternal anti-Ro are associated with neonatal lupus and congenital heart block Sjorgrens syndrome

Question 37

Antibodies to extractable nuclear antigens: give the disease association for Anti-Smith antibody?

Answer 37

SLE

Question 38

Antibodies to extractable nuclear antigens: give the disease association for Anti-topoisomerase I antibody?

Answer 38

Diffuse scleroderma: associated with severe organ involvement, including pulmonary fibrosis

Question 39

What do anti-DNA binding antibodies measure antibodies against?

Answer 39

Double stranded DNA

Question 40

What are very high titres of Anti-DNA antibodies often associated with?

Answer 40

SLE: more severe including renal or CNS involvement

Question 41

What does formation of antibody-antigen immune complexes activate and cause?

Answer 41

Complement cascade via classical pathway | Inflammation of tissues in immune complexes are deposited

Question 42

When measuring complement proteins what type do we measure?

Answer 42

UNACTIVATED COMPLEMENT PROTEINS

Question 43

Quantitation of what acts as a surrogate marker of disease activity?

Answer 43

C3 and C4

Question 44

Give three type III hypersensitivity investigations?

Answer 44

1. Specific IgG to putative antigen 2. Low serum complements 3. Characteristic biopsy features

Question 45

Describe the deposition of IgG in glomerulonephritis associated with SLE?

Answer 45

Deposition of IgG and complement C3 in granular lumpy-bumpy pattern

Question 46

Describe the deposition of IgG in glomerulonephritis associated with Goodpastures?

Answer 46

Linear deposition of IgG along the glomerular basement membrane

Question 47

Name the criteria for classification of SLE?

Answer 47

``` Serositis - pleurisy or pericarditis Oral ulcers Arthritis Photosensitivity Blood disorders Renal involvement Antinuclear antibodies Immunologic phenomena - anti-DNA, anti-Smith Neurologic disorder Malar rash Discoid rash ```

Question 48

What two pharmacological things are used to decrease inflammation and decrease production of antibody in type III hypersensitivity?

Answer 48

Corticosteroids | Immunosuppressive agents - anti-proliferative

Question 49

Name three anti-proliferative agents?

Answer 49

Azathiprine Mycophenolate Cyclospohsphamide

Question 50

Name a type IV hypersensitivity disease?

Answer 50

RA

Question 51

What is the immunopathogenesis of RA?

Answer 51

Infiltration of synovium by CD4+ T cells | Secondary involvement of activated b CELLS AND ANTIBODY

Question 52

What four things happen when the synovium is infiltrated by activated CD4 cells in RA?

Answer 52

1. production of cytokines 2. recruitment of phagocytes 3. recruitment of activated B cells 4. activation of synovial fibroblasts

Question 53

In an RA joint what destroys cartilage and bone?

Answer 53

Matrix metalloproteases

Question 54

Give an example of an antibody which blocks attachment of cytokine to receptor in RA ?

Answer 54

Anti-TNF - infliximab and adalimumab