Immunology

Question 1

definition of monogenic disorders

Answer 1

single gene defects causing autoimmune diseases

rare

Question 2

features of IPEX syndrome

Answer 2

very early onset insulin dependent diabetes
severe malabsorption syndrome
eczema
autoimmune thyroid disease

Question 3

mutation in what gene causes IPEX syndrome

Answer 3

FOXP3

Question 4

what is HLA

Answer 4

Human leukocyte Antigen complex
what is used to control T cells
Class 1 - controls CD8 cells
Class 2 - controls CD4 cells

Question 5

what diseases in HLA DR3 associated with

Answer 5

Graves disease
SLE
Type 1 diabetes (also DR4)

Question 6

what HLA is associated with RA

Answer 6

HLA DR4

Question 7

what is HLA B27 associated with

Answer 7

Ankylosing Spondylitis

Question 8

what class of HLA do all nucleated cells express

Answer 8

Class I

Question 9

what cells express Class II HLA

Answer 9

antigen presenting cells

Question 10

why do we need polymorphism in HLA molecules

Answer 10

to maximise the net ability to bind peptides

only a few peptides will bind to a specific HLA

Question 11

what are factors contributing to autoimmune disease

Answer 11

Genes
Environment
Immune regulation

Question 12

what are the 4 types of hypersensitivity reactions in the Gel and Coomb’s classification

Answer 12

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

Question 13

what are the two clinical classifications of autoimmune diseases

Answer 13

Organ specific diseases

Non-organ specific or multi-system autoimmune disease

Question 14

example of autoimmune diseases of Type III hypersensitivity

Answer 14

SLE

Question 15

pathogenesis of type III hypersensitive reactions

Answer 15

1 - circulating antigen binds to immune complexes
2 - immune complex deposition in small vessels
3 - causes complement activation
4 - infiltration of macrophages and neutrophils

Question 16

what is the abnormality in SLE

Answer 16

disturbed regulation of B cells activity

characterised by ANA proteins

Question 17

what are antibodies are seen in SLA

Answer 17

Anti-DNA antibodies
Anti-nuclear antibodies
Antibodies to extractable nuclear antigens etc

Question 18

in SLE, what could soft heart sounds be a sign of

Answer 18

pericardial effusions

Question 19

anti-nuclear antibodies are very uncommon and specific for autoimmune diseases - true or false

Answer 19

false
very common and often found in normal individuals
associated with female sex and older age

Question 20

what diseases are anti-nuclear antibodies an intrinsic part of diagnostic criteria

Answer 20

Mixed connective tissue disease

Autoimmune hepatic disease

Question 21

what are speckled antibodies associated with

Answer 21

ENA e.g. Ro and La

SLE and Sjogrens

Question 22

what is anti-centromere associated with

Answer 22

Limited scleroderma (CREST)

Question 23

what is an antibody highly specific for SLE

Answer 23

anti-dna binding antibodies

Question 24

what are the 3 pathways of complement activation

Answer 24

1 - classical pathway C1 C4 C2
2 - lectin
3 - alternative pathway

Question 25

what complement gets switched on in complement activation

Answer 25

C3

Question 26

what does activation of C3 lead to

Answer 26

Membrane attack complex

Question 27

what does the formation of antibody-antigen immune complexes cause

Answer 27

activate complement cascade via classical pathway | causes inflammation of tissues

Question 28

what can be measured to act as a marker of disease activity

Answer 28

unactivated C3 and C4

Question 29

what is the American criteria for SLE

Answer 29

SOAP BRAIN MD Serositis – pleurisy or pericarditis Oral ulcers Arthritis - nonerosive, 2 or more peripheral joints with tenderness or swelling Photosensitivity Blood disorders - Leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia Renal involvement- proteinuria, cellular casts Antinuclear antibodies Immunologic phenomena - dsDNA; anti-Smith (Sm) antibodies; antiphospholipid antibodies Neurologic disorder - Seizures or psychosis in the absence of other causes Malar rash - Fixed erythema over the cheeks and nasal bridge Discoid rash - Erythematous raised-rimmed lesions with keratotic scaling and follicular plugging, often scarring

Question 30

how many of the criteria do you need to be diagnosed with SLE

Answer 30

4 out of 11

Question 31

management of SLE

Answer 31

decrease inflammation - corticosteroids decrease production of antibody - immunosuppressive agents

Question 32

example of Type IV autoimmune condition

Answer 32

RA

Question 33

what is RA characterised by

Answer 33

destruction of joint cartilage | inflammation of the synovium

Question 34

what is Type IV pathogenesis

Answer 34

1 - infiltration of synovium by activated CD4+ cells 2 - production of cytokines 3 - recruitment of phagocytes and activated B cells 4 - B cells produce immunoglobulin 5 - activation of synovial fibroblasts 6 - produce additional synovium

Question 35

synovial histology of RA

Answer 35

- intense infiltration of inflammatory cells - intimal lining layer hyperplastic - accumulation of CD4+ T cells, macrophages, B cells

Question 36

signs of a RA joint

Answer 36

- Infiltration of synovium primarily with activated CD4+ cells - Directly stimulate breakdown of bone and increased vascular formation - Chronic production of inflammatory cytokines in synovium - Destruction of cartillage and bone by matrix metalloproteases (MMPs)

Question 37

what cytokines have a critical role in the pathogenesis of RA

Answer 37

TNF | IL1

Question 38

what do TNF and IL1 do in RA

Answer 38

Potent stimulators of fibroblasts, osteoclasts and chondrocytes Stimulate release of matrix metalloproteinases Mediators of joint damage

Question 39

new revolutionary treatment in RA and how does it work

Answer 39

Anti-TNF antibodies e.g. Infliximab, adalimumab blocks attachment of cytokine to receptor

Question 40

what are serological test for RA

Answer 40

Rheumatoid factor - antibody directed against the common region of human IgG - IgM anti-IgG antibody most commonly tested

Question 41

all patients with RA have Rf - true or false

Answer 41

false | only 50% of patients will

Question 42

what is a more specific test for RA then Rf

Answer 42

Anti-CCP antibody