Immunology of joint conditions Flashcards
What does the innate immunity recognise
Common molecular patterns (PAMP)
What cells make up innate immune system
NK cells
Granulocytes
Monocytes
Dendritic cells
What cells make up adaptive immune system
Lymphocytes
What is the action of lipid mediators
Increased vascular permeability
Smooth muscle contraction increases
What is the action of cytokines
Increased vascular permeability
Activate vascular endothelium
What is the action of chemokines
Attract and activate phagocytic cells and vascular endothelial cells
What is the action of complement
Attract and active immune cells
Give some examples of conditions where immunological tolerance has failed
Rheumatoid athritis Synovial cyst Psoriatic athritis Osteoathritis (?) Carcinoma
What is the evidence for the involvement of the immune system in joint disease (4)
- Patients have autoantibodies in their blood and joints
- Inflamed joints contain immune cells, cytokines and auto AB
- Local immune cells hyperactive and continuously proliferative
- Joint conditions strongly associated with MHC genes
Describe the steps by which immune systems attacks joints causing inflammation and pathology
- Local trigger attacks immune cells– some recognise as self and start to destroy
- Perpetuates cytokine, enzyme and pro-inflammatory cell production
- Process persists because supply of self antigens in unlimited
Why does the immune system attack self in patients with joint conditions
Unsure, but theoretically due to defects in immunological tolerance, failure of regulation or cross reactivity with pathogens
Why is MHC central to T cell tolerance (3)
Determines which peptides are presented to T lymphocytes, determines T lymphocyte tolerance in thymus and determines if and how T lymphocytes respond to antigens
What is the evidence for genetic involvement in joint disease
- Familial segregation
- Higher concordance in non-identical twins
What is the evidence for environmental involvement in joint disease
- Identical twins aren’t 100% both getting JD
What is the evidence for hormonal involvement in joint disease
Females more susceptible
Rheumatoid athritis is what % genetics
50
What evidence is there to suggest that RA is an autoimmune disease
- Autoimmune antibodies to IgG found in patients
- T cell responses- strong association with HLA-DR4
What happens in the early stage of RA
Soft tissue swelling
What happens in the intermediate stage of RA
Mild juxta-articular osteoporosis
Narrowing of joint space and bone erosions
What happens in the late stage of RA
Large erosions and anatomical deformities
Excess of what molecule mediates RA pathology
TNF alpha
