Immunology of Autoimmune Disease

Question 1

Autoimmune conditions are more common in men. True or False

Answer 1

False they are more common in women

Question 2

A breakdown of self tolerance (loss of immune regulation results in what 2 possibilities

Answer 2

Autoimmune phenomena

Autoimmune disease

Question 3

What is a monogenic disorder

Answer 3

Single gene defect which causes an autoimmune disease and is rare

Question 4

Give an example of a single gene defects associated with autoimmune disease

Answer 4

IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy and X linked inheritance syndrome

Question 5

What are some of the symptoms of IPEX syndrome

Answer 5

Very early onset of Diabetes Type 1 
Severe malabsorption
Eczema 
Autoimmune thyroid disease 
Autoimmune haemolytic anaemia 
Severe infections

Question 6

What is the pathogenesis

Answer 6

Mutation in FOXP3 gene - essential for development of regulatory T cells

Question 7

What cells are essential in protection against autoimmunity

Answer 7

Regulatory T cells

Question 8

What do most autoimmune diseases result from

Answer 8

complex genetic interplay

Question 9

What is the generalised susceptible allele in autoimmune diseases

Answer 9

HLA

Question 10

Why is HLA important

Answer 10

It is what is used to control T cells

Question 11

What happens if a person does not carry a specific HLA allele

Answer 11

Their risk of developing the a specific autoimmune disease is much higher

Question 12

How odes the body recognise foreign antigens in terms of T cells

Answer 12

The foreign body is chewed up by antigen presenting cell and then it is expressed on the cell surface as peptide and it is enclosed in the HLA molecule and this is the only thing that a T cell can see

Question 13

How many variants of each HLA molecule does each individual possess

Answer 13

2

Question 14

How can we maximise the net ability to bind peptides

Answer 14

Individual HLA molecules exhibit significant diversity

Question 15

What are some factors that contribute to autoimmune disease

Answer 15

HLA: association but not a prerequisite for disease
Importance of immune regulation in maintaining tolerance
Infection: cross-reactivity between antigens expressed by pathogen and self

Question 16

What do hypersensitivity reactions result in

Answer 16

Immune response that results in bystander damage tot he self
Usually exaggeration of normal immune mechanisms
Pathophysiological basis for many autoimmune diseases

Question 17

What is the classification tool that is used to classify hypersensitivity reactions

Answer 17

Gel and Coomb’s

Question 18

How do Type 3 sensitivity reactions arise?

Answer 18

You get antibody binding to antigen which circulated in the system and form these immune complexes - these get deposited in small blood vessels and clog them up which causes complaint activation

Often in the Bowmen’s Capsule

Question 19

What is an example of a Type 3 hypersensitivity reaction

Answer 19

SLE

Disorganisation of the B cells

Question 20

Describe the pathophysiology of SLE

Answer 20

Antibodies produced against contents of cell nuclei
—Anti-DNA antibodies
-Anti-nuclear antibodies
—Antibodies to extractable nuclear antigens
Immune complexes form
—deposited in small vessels in skin, joints, kidneys
—Result in complement activation
—Inflammation
—Recruitment of other cells

Question 21

What are some of the clinical features of SLE

Answer 21

CNS - Seizure
Skin - Butterfly rash, Discoid lupus 
Heart - Endocarditis, Myocarditis 
Arthritis 
Lymphadenopathy 
Pleuritis
Pericarditis
Glomerulonephritis

Question 22

What investigations should be done for suspected SLE

Answer 22

FBC
inflammatory markers
Renal function
ANA

Question 23

Autoimmune diseases are associated with a high level of Anti-nuclear antibodies. True or False

Answer 23

True

Question 24

The speckled antibody is more specific for what 2 diseases

Answer 24

SLE and Sjogrens

Question 25

What is the speckled antibody associated with

Answer 25

Antiboddies to extractable nuclear antigens e.g Ro and La

Question 26

What is the anti-centromere antibody very specific for

Answer 26

Limited scleroderma

Question 27

What is the nuclear ANA associated with

Answer 27

scleroderma

Question 28

If an ANA test is positive, what is useful to establish

Answer 28

Which nuclear component is being recognised

Question 29

What are extractable nuclear antigens

Answer 29

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

Question 30

The Rheumatological Association criteria for the classification of SLE requires 4 of what 11 aspects

Answer 30

Serositis Oral ulcers Arthritis Photosensitivity ``` Blood disorders Renal involvement Antinuclear antibodies Immunologica phenomena Neurologic disorder ``` Malar Rash Discoid Rash SOAP BRAIN MD

Question 31

What is used to decrease inflammation

Answer 31

Corticosteroids

Question 32

What is used to decrease production of antibody

Answer 32

Immunosuppressive agents - anti-proliferative agents such as: Azathioprine Mycophenolate Cyclosphosphamide

Question 33

What type of hypersensitivity reaction is rheumatoid arthritis

Answer 33

Type 4

Question 34

What occurs during a type 4 hypersensitivity

Answer 34

Infiltration of synovium by CD4+ T cells to produce cytokines Secondary involvement of activated B cells and antibody

Question 35

The treatment of rheumatoid arthritis interrupts what

Answer 35

The cytokine networks | eg. anti-TNF antibodies: Infliximab

Question 36

What other treatments do anti-TNF agents work for

Answer 36

RA Crohns Psoriatic arthritis Ankylosing spondylitis

Question 37

What serological tests for Rheumatoid arthritis

Answer 37

Rheumatoid factor - antibody directed against the common (Fc) region of IgG

Question 38

The absence of RhF is insufficiently sensitive to rule out the diagnosis of rheumatoid arthritis. True or False

Answer 38

True

Question 39

What is a more specific test for Rheumatoid Arthritis

Answer 39

Anti-CCP antibody