Immunology

Question 1

Describe the innate immune response

Answer 1

Rapid response to pathogen
Non-specific - same response to everything
No memory system

Question 2

Describe the acquired immune response

Answer 2

Delayed response - time needed for recognition and proliferation
Specific response to each antigen
Has immunological memory so subsequent exposure will have faster, stronger response

Question 3

What must T cells come into contact with in order to become active

Answer 3

Antigens presented by MHC class 1 or 2 proteins

Question 4

How are auto-reactive cells produced and dealt with normally

Answer 4

Random protein arrangement of immune cells during development means everyone will produce some auto-reactive cells
The cells are usually tested before proliferative and killed if found to be self active
If they do mature, regulatory T cells should kill them
Leaves us with few and mostly inactive autoreactive cells

Question 5

What leads to autoimmunity

Answer 5

Failure of the normal control mechanisms allow autoreactive cells to mature and reach high numbers in the body
This leads to tissue/organ damage and inflammation

Question 6

Describe the pathway of autoimmune disease

Answer 6

Starts with genetic susceptibility
An initiating event leads to the breakdown of self-tolerance & loss of immune regulation
This allows activation and proliferation of auto-reactive T/B cells that go on to cause hypersensitivity reaction

Question 7

Mutations in which genes can lead to autoimmune diseases

Answer 7

FOXP3 gene - mutations cause loss of immune regulation
HLA genes - mutations affect MHC molecules that allow for recognition as self
Sex hormone genes

Question 8

What environmental factors can trigger autoimmunity

Answer 8

Molecular mimicry - similar structure of self and non-self antigens
Intercurrent infections
Tissue damage - can expose previously unseen self-antigens
Superantigens - bacterial superantigens can activate T cells

Question 9

List some examples of MSK autoimmune diseases

Answer 9

Rheumatoid arthritis
Myasthenia gravis
Scleroderma
Polymyositis
Dermatomyositis
Lupus
Sjogren’s syndrome

Question 10

What causes myasthenia gravis

Answer 10

Auto-reactive antibodies bind to acetylcholine receptors on muscle cells
Disrupts neurotransmission by stopping ACh binding
Eventually the receptors are destroyed
Sometimes brought on by certain drugs or pregnancy
Thymic tumour is the cause in 10% of people

Question 11

How does MG present

Answer 11

Often starts in ocular muscles - droopy eye ]
Fatigue and muscle weakness that get progressively worse
Facial muscles commonly affected

Question 12

How do you treat MG

Answer 12

Anti-cholinesterases - increase ACh in cleft
Reduce autoimmunity using immunosuppressive drugs &/or corticosteroids, IV immunoglobulins or plasmaphoresis
Eculizumab - inhibits the terminal pathway compliment
Surgery - remove thymic tumour if the cause

Question 13

What is plasmaphoresis

Answer 13

A process that removes circulating immune-complexes and AChR antibodies from the blood

Question 14

What factors are implicated in RA

Answer 14

Genetic - HLA-DR4
Smoking
Increased susceptibly after pregnancy and by breast-feeding

Question 15

What type of hypersensitivity is involved in RA

Answer 15

Type IV

Question 16

How do you manage RA

Answer 16

Decrease inflammation - corticosteroids
Decrease antibody production - immunosupressives
DMARDs
Biologics - target individual molecules in inflammatory process

Question 17

How are antibody tests reported

Answer 17

Antibodies are reported as an absolute value or as a titre
A titre gives the number of dilutions before activity is lost
The higher the titre the greater the concentration of the antibody and the more significant the result
E.g. ANA is reported this way

Question 18

How specific are ANA tests

Answer 18

Not at all
ANA are seen in seen in 98% of those with SLE and systemic sclerosis and 80% of Sjogren’s
Mainly just to suggest a CTD or autoimmune condition is present

Question 19

How sensitive are ANA tests

Answer 19

Extremely
Low titres may be seen in perfectly healthy people, the elderly and those with other autoimmune diseases
Therefore not always relevant

Question 20

Are ANA levels used for disease monitoring

Answer 20

No

Mainly for diagnosis - and not even specific

Question 21

Can antibody titres be used to monitor disease in SLE

Answer 21

Yes
Titres of anti-double stranded DNA antibodies vary with time and disease activity
The higher the titre the more active the lupus so can be used for monitoring

Question 22

RNP antibodies are seen in which diseases

Answer 22

SLE and mixed CTD

Question 23

Scl70 antibodies are seen in which diseases

Answer 23

Diffuse scleroderma

Systemic sclerosis

Question 24

Anti-centromere antibodies are seen in which diseases

Answer 24

limited cutaneous scleroderma - CREST

Question 25

Rheumatoid factor is seen in which diseases

Answer 25

RA and Sjogren’s

Question 26

Anti-CCP antibodies are seen in which diseases

Answer 26

Specific to RA
Only 70% sensitive, not everyone with RA will have it
However, if they have it it will always be positive

Question 27

Anti- CCP antibodies are associated with what prognosis in RA

Answer 27

Associated with more severe or extra-articular disease

Question 28

Anti-CCP antibodies are more likely to be seen in which RA patients

Answer 28

More likely to be seen in current or ex smokers

Question 29

ANCA antibodies are seen in which diseases

Answer 29

Only posiitive in small vessel vasculitis

Not medium or large

Question 30

What are the main subtypes of ANCA antibodies

Answer 30

C-ANCA - PR3 protein is the target
Seen in GPA

P-ANCA - MPO protein is the target
Seen is EGPA and MPA

Question 31

Can ANCA be used to monitor disease

Answer 31

Yes

Levels vary with disease activity

Question 32

Which serum complements can be used to monitor disease

Answer 32

C3 and C4

Useful for monitoring disease - low in SLE whilst anti-dsdna will go up