Inflammation Flashcards
(43 cards)
How many different types of arthritis are there ? How many people in the UK are affected by these ?
Over 200 types of arthritis and rheumatic disease, with an estimated 7 million people in UK affected by long term direct or related condition.
Identify examples of types of arthritis.
Ankylosing Spondylitis
Rheumatoid Arthritis
Vasculitis
Sjogren’s Syndrome
Classify Rheumatoid Arthritis.
Chronic, systemic AI disease
What are the main pathological features of RA ?
Inflammation of the lining or synovium of the joints (with increase in synovial fluid which is full of inflammatory cells). Eventually possible erosion of cartilage and bone tissue itself. which may lead to long-term joint damage.
Identify the main clinical features of Rheumatoid Arthritis.
Inflamed joints which are warm, tender, swollen, often red and (chronically) painful, and difficult to move
Fatigue
Loss of appetite, weight loss, flu-like symptoms, depression, anaemia
Vasculitis (e.g. accompanied by redness and skin rashes)
Sjorgen’s syndrome
Inflammation surrounding heart and lungs
Loss of function
Describe epidemiology of RA.
3x more common in women
Commonly strikes 30 to 50s, but can affect young children
All ethnic groups
Which parts of the body does Sjorgen’s syndrome affect ?
May affect tear ducts and dryness of mouth
Identify the main joints affected by RA.
- Foot and Ankle, Knee
- Hip (commonly involved but early manifestations not apparent)
- Hands and Wrists (almost always involved)
- Elbow
- Shoulders
What are the main signs of shoulder RA ?
Neck stiffness and general loss of motion
Identify a joint affected by RA where effusion and synovial thickening is easy to detect, and another one where that is not the case.
KNEE- Effusions and synovial thickening of the knee usually are detected easily.
ELBOW- Effusion difficult to detect on physical exam (only objective finding is loss of motion).
Identify organs besides joints affected by RA.
Blood- Hypochromatic microcytic anemia with low serum ferritin and low or normal iron binding capacity
Nerves- due to cervical spine instability, including peripheral nerve entrapment
Heart- pericardial effusion (clinical symptoms rare)
Lungs- interstitial lung disease (may be asymptomatic)
Eyes- keratoconjuctivitis sicca
Skin- Rheumatoid nodules
Describe the immunological mechanism of RA.
ANTIGEN RECOGNITION BY T CELLS
- MHC II: bind peptides derived from proteins from extracellular sources that have been internalised into intracellular vesicles (Dendritic Cells, macrophage or phagocytic cells and B cells all antigen presenting cells)
- Subsequently present peptides to CD4+ T-helper (TH) cells
- When pathogenic peptide (e.g. from virus or bacteria) that T cell receptor has never encountered, T cell becomes activated
- Either TH1 or TH2 T cells can become activated.
- TH1 secrete cytokines (e.g. IFN-gamma, TNF-alpha) which activate cell-mediated response (macrophages, dendritic cells)
- TH1 secretes IL-4, 5, which activate B cells (so antibody response)
•IL-1 and TNF-alpha notably activate synovial fibroblasts, which can invasde cartilage and bone, and regulate monocyte differentiation into osteoclasts
What are MHCs ?
Membrane glycoproteins on the cell surface that display peptide antigens to T cells
Describe the genetics of RA.
•Specific human leukocyte antigen (HLA)-DR (HLA class II) genes have been found to be associated with RA, specifically HLA-DR4 (confers higher risk of severity of RA, further increased by homozygosity) –Reside in the MHC and participate in antigen presentation
Identify potential roles of HLA-DR roles (genes which may be involved in increasing severity of RA).
–Binds to arthritogenic peptides (i.e. peptides from bacteria that are presented look like peptides in our own body, so immune response generated against foreign peptide may also generated response against own peptides)
–Serves as a target for autoreactive T cells
–Closely linked to other genes in the MHC
What is autoimmunity ? How does it occur ?
•Immune-mediated destruction of self-tissues
–Occurs via specific recognition of self-antigens
–Specific activation of self- reactive lymphocytes by
self-antigens
Identify any mechanism in place to dampen down potential autoimmunity.
Regulatory T (Treg) cells help mediate autoimmunity by suppressing autoreactive T cells by secreting inhibitory cytokines such as IL-10 and TGF-Beta (dampen down immune response)
Define tolerance in the context of the immune system.
the process that keeps the immune system from attacking “self”
How is tolerance maintained ?
1) THYMIC DELETION OF AUTOREACTIVE CELLS
- T cells spend time in the thymus where they undergo thymic education.
- There, they can be promoted to leave to the periphery, or can be deleted (90 to 95%)
- This is a way to get rid of potentially autoreactive, or useless T cells
2) T REGULATORY CELLS
- T cell specific for self antigen becomes a regulatory T cell
- Potential autoreactive T cells which have escaped deletion (can cause tissue damage in the periphery) are usually kept in check by T regulatory cells (secrete IL-10 and TGF-beta which inhibit self-reactive T cells)
What are Cytokines ? Chemokines ?
Cytokines: Proteins made by cells that affect the behavior of other cells (i.e. interleukins)
Chemokines: small chemoattractant proteins that stimulate the migration and activation of cells
Identify a potential side effect of monoclonal antibody use.
Secondary infections (antibodies target cytokines which are useful in normal immune response against infectious agents)
Describe diagnosis of RA. To what extent is there a definitive diagnostic test ?
Medical History
-Any joint pain in many joints ? Symmatrical pain ?
Physical Exam
Lab Tests
•Imaging studies: Erythrocyte Sedimation Rate
•Blood tests: C-reactive Protein (CRP) (raised in RA)
•Rheumatoid factor: Antinuclear Antibodies (ANA) (antibodies against certain components)
NO definite test
What are the aims of RA treatment ?
–relieving pain
–reducing inflammation
–stopping or slowing joint damage
–improving functioning and sense of well-being
Describe drug treatment of RA.
1) Symptomatic medications
- NSAIDS
- Analgesics
- Corticosteroids (problem: global immunosuppressor)
2) DMARDs
- Methotrexate
- Cyclosporine and Hydroxychloroquine
3) Biological Modifiers (monoclonal antibodies)
-Infiliximab (anti-TNF)
-Rituximab (anti-CD20)
Can be used in combination with DMARD
