Immunology of Joint Conditions RA Flashcards
what are the natural barriers to prevent infection
- Mechanical
- chemical
- microbiological
what are the two types of immune system
- Innate immune system
- adaptive immune system
How does innate immune system recognises patterns
common molecular
patterns (PAMPs) by conserved receptors
How does the adaptive immune cells recognise pathogens
- they have antibodies that are produced by B cells
- T. cells have TCR that have foreign antigens that are presented to them by dendritic cells
describe how the variable region on an antbody is made
- random gene recombination
- have Variable (V) Diversity (D) and Joining (J) genes that are randomly placed on the variable region
How is the autoimmunity and cells against are own antigens inhibited from being made
by central tolerance and peripheral tolerance
Describe central tolerance
- pro apoptotic and signalling molecules that inhibit it if they are strongly self reactive
- non or weakly self reactive get through and they are combated by peripheral tolerance
Describe how peripheral tolerance works
Growth limiting mechanisms
- lack of a second degree signal
- inhibitory signalling
- Treg cells
Growth overing
- pro apoptotic signals
- T reg cells
name some lipid mediators and what they do
leukotrienes, PAF and PG
- increase vascular permeability
- smooth muscle contraction
name some chemokine and what they do
- IL-8, MCP-1, Fractalkine
- attract and activate phagocytic cells, vascular endothelial cells
name some complements and what they do
- C2a, C3a, C5a
- attract/activate immune cells, vascular permeabiity
what is inflammation critical for
1- Inflammation is a critical physiological response that facilitates immunity and tissue repair
What happens when inflammation doesn’t switch of
Chronic inflammation results and Chronic inflammation causes pathology: tissue damage in autoimmune diseases and cancer.
name types of chronic inflammatory joint conditions
Rheumatoid arthritis
Psoriatic arthritis
What is a Pannus
- hyper proliferation of a synovial membrane
what is RA strongly associated with
MHC genes
describe how chronic inflammation happens
1- A “trigger(s)” initiates immunity and acute inflammation. These then mediates responses to local self proteins.
2- This starts chronic inflammation by cytokines and other pro-inflammatory mediators.
3- This process persists and protease enzyme are produced that destroy the joint
Why does the immune system attack joints in patients with joint conditions?
defects in “immunological tolerance”, failure of regulation, or cross reactivity with “pathogens” could mediate autoimmunity
What is central to T cell response and regulation
MHC
- determines which peptides are presented to T lymphocytes
what does MHC determine
Determines T lymphocyte tolerance in the thymus, i.e. what mature T cells we have in the body.
Also determine if and how mature T lymphocytes respond to antigens upon encounter.
what can defects in T cell tolerance cause
Joint disease
- reducing the strength by which T lymphocyte recognition antigens causes joint disease in mice
what cells cause autoimmunity
- CD4+ TH1 cells - lead to IFN gamma and TNF alpha which cause autoimmunity
what causes the production of TH1 cells
- IL-12
- IL-23
what causes the production of TH2 cells
- IL-4
