Immunology of joint conditions

Question 1

What does the innate immunity recognise

Answer 1

Common molecular patterns (PAMP)

Question 2

What cells make up innate immune system

Answer 2

NK cells
Granulocytes
Monocytes
Dendritic cells

Question 3

What cells make up adaptive immune system

Answer 3

Lymphocytes

Question 4

What is the action of lipid mediators

Answer 4

Increased vascular permeability

Smooth muscle contraction increases

Question 5

What is the action of cytokines

Answer 5

Increased vascular permeability

Activate vascular endothelium

Question 6

What is the action of chemokines

Answer 6

Attract and activate phagocytic cells and vascular endothelial cells

Question 7

What is the action of complement

Answer 7

Attract and active immune cells

Question 8

Give some examples of conditions where immunological tolerance has failed

Answer 8

Rheumatoid athritis
Synovial cyst
Psoriatic athritis
Osteoathritis (?)
Carcinoma

Question 9

What is the evidence for the involvement of the immune system in joint disease (4)

Answer 9

1. Patients have autoantibodies in their blood and joints
2. Inflamed joints contain immune cells, cytokines and auto AB
3. Local immune cells hyperactive and continuously proliferative
4. Joint conditions strongly associated with MHC genes

Question 10

Describe the steps by which immune systems attacks joints causing inflammation and pathology

Answer 10

1. Local trigger attacks immune cells– some recognise as self and start to destroy
2. Perpetuates cytokine, enzyme and pro-inflammatory cell production
3. Process persists because supply of self antigens in unlimited

Question 11

Why does the immune system attack self in patients with joint conditions

Answer 11

Unsure, but theoretically due to defects in immunological tolerance, failure of regulation or cross reactivity with pathogens

Question 12

Why is MHC central to T cell tolerance (3)

Answer 12

Determines which peptides are presented to T lymphocytes, determines T lymphocyte tolerance in thymus and determines if and how T lymphocytes respond to antigens

Question 13

What is the evidence for genetic involvement in joint disease

Answer 13

• Familial segregation

- Higher concordance in non-identical twins

Question 14

What is the evidence for environmental involvement in joint disease

Answer 14

• Identical twins aren’t 100% both getting JD

Question 15

What is the evidence for hormonal involvement in joint disease

Answer 15

Females more susceptible

Question 16

Rheumatoid athritis is what % genetics

Answer 16

50

Question 17

What evidence is there to suggest that RA is an autoimmune disease

Answer 17

• Autoimmune antibodies to IgG found in patients

- T cell responses- strong association with HLA-DR4

Question 18

What happens in the early stage of RA

Answer 18

Soft tissue swelling

Question 19

What happens in the intermediate stage of RA

Answer 19

Mild juxta-articular osteoporosis

Narrowing of joint space and bone erosions

Question 20

What happens in the late stage of RA

Answer 20

Large erosions and anatomical deformities

Question 21

Excess of what molecule mediates RA pathology

Answer 21

TNF alpha