Pathogenesis of Autoimmune Disease Flashcards
(31 cards)
Give examples of autoimmune musculoskeletal disorders
Rheumatoid arthritis
Ankylosing spondylitis
Systemic Lupus Erythematosus (SLE)
What are HLA molecules
Human leukocyte antigens
The first regions of the MHC to be sequenced
genes within the MHC class I and class II regions encode cell surface proteins
Which MHC gene is associated with Rheumatoid arthritis
HLA-DR-4
Which MHC gene is associated with systemic lupus erythematosus
HLA-DR3
Which MHC gene is associated with Ankylosing spondylitis
HLA-B27
Describe MHC class I (expression, antigen, recognition and response)
Found in all nucleated cells
Endogenous antigen
CD8 +ve T cells
Cell killing
Describe MHC class II (expression, antigen, recognition and response)
Found in antigen presenting cells
Exogenous antigens
CD4 +ve T cells
Antibody response
Give examples of APCs
Dendritic Cells
B cells
Macrophages
Give examples of endogenous and exogenous antigens
Endogenous - viral peptide, tumour antigen, self-peptides
Exogenous - Bacterial peptides, self peptides
What are the key auto-antibodies in rheumatoid arthritis
Rheumatoid factor
Anti-cyclic citrullinated peptide antibody
What are the key auto-antibodies in systemic lupus erythematosus
Antinuclear antibodies (ANA) Anti-double stranded DNA antibodies (anti-dsDNA)
Describe the disease activity in systemic lupus erythematosus
Low complement levels
High serum levels of anti-ds-DNA antibodies
Describe the pathogenesis of systemic lupus erythematosus
- Apoptosis leads to translocation of nuclear antigens to membrane surface
- Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells
- B cell autoimmunity
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
What cytokines are release by T cells and what are their effects
γ-IFN - Activated macrophages
IL-2 - Activates T and B cells
IL-6 - Activates B cells, acute phase response
What cytokines are release by macrophages and what are their effects
IL-1 - Activates T cells, fever, pro-inflammatory
TNF-alpha - similar to IL-1, more destructive
What cytokines do Th1 cells release and what are they involved in
IL-2 and γ-IFN
Response is important in CD8 +ve cytotoxicity and macrophage stimulation
What cytokines do Th2 cells release and what are they involved in
IL-4 (IgE responses)
IL-5 (eosinophils)
IL-6 (B cells to plasma cells)
IL-10 (inhibit macrophage response)
What cytokines do Th17 cells release and what are they involved in
develop in response to IL-23 Secrete IL-17, a potent cytokine which triggers IL-6, IL-8, TNFα, matrix metalloproteinases and RANKL in target cells
Important in mucosal immunity but also in disease including arthritis, psoriasis, inflammatory bowel disease and multiple sclerosis
What is RANKL and what is it produced by
RANKL (receptor activator of nuclear factor kappa-B ligand)
Produced by T cells and synovial fibroblasts in rheumatoid arthritis
What is the action of RANKL
Stimulates osteoclast formation
What is RANKL unregulated by
Interleukin-1, TNF-alpha
Interleukin-17 – potent action on osteoclastogenesis via RANKL-RANK pathway
PTH-related peptide
Give an example of a drug used that targets RANKL
Denosumab – monoclonal antibody against RANKL
indicated for treatment of osteoporosis, bone metastases, multiple myeloma and Giant cell tumours
Give examples of therapies use for SLE therapy
Rituximab - chimeric anti-CD20 used to deplete B cells
Belimumab - monoclonal antibody against B cell survival factor BLYS
What are prostaglandins
lipid mediators of inflammation that act on platelets, endothelium, uterine tissue and mast cells
