Autoimmunity Flashcards
What are the 2 regions in a t cell and b cell receptor
Constant region
Variable region
Which region of the t/b cell receptor binds to the antigen
Variable region
What is the t cell response
T cell proliferation
Cytokine production
Help b cells
Cytotoxicty
What is the b cell response
Antibody production
Antigen presentation
What is the variable region produced of in the heavy chain
V
D
J
What is the light chain produced of
V
J
What is a problem that can happen by shuffling these genes
You can create an immunoglobulin or t cell that recognises its own self
What are the ways to stop t cells or b cells form recognises self cells
T cell tolerance
B cell tolerance
What happnes in central t cell tolerance
- Pre t cells emerge from the bone marrow and gro through the thymus
- Thymus carries out positive and negative selection
- Positive selection: when the t cell binds to something
- Negative selection: when the t cell bidns to something tightly it is killed
- When the t cell passess positive and negative selection it becomes a t naive cell
If the t cell during negative selection binds moderately what happens to it instead of being deleted
Becomes a T regular cell
What is the role of t reg cells
Have immunosupression molecules
Directly kill other immune cells
Why are t reg cell important
If t reg binds to a mhc that is expressing self peptide it activates t reg cells
What is another way of producting t reg cells
- Dendritic cell picks up self protein and displays it onto the MHC
- Naive cd4 t cell that recognises it becomes a induced t reg cell
Describe what happens in b cell tolerance
- In the bone marrow chains of immunoglobulin are made
- If the b cell cant present the immunoglobulin on the surface it will die of apoptosis
- The heavy chain and then the light chain rearranges which causes the intact immunoglobulin on the surface of the b cell
- The b cell is checked by positive selection is there is self reactivity
- If there is no self reactivity it is released as a transition b cell which becomes naive b cell in the lymph nodes
- If there is an autoreactive signal in the b cell, the chains are rearranged and check for autoimmunity
What is an autoimmune disease
A self directed inflammation caused by auto reactive t and b cell repsonse arising from a failure of immune tolerance to self antigens
What are the 2 types of MHC
MHC 1
MHC 2
Where do we find mhc 2
On atigen presenting cells
Where do we find mhc 1
On all nucleated cells
What does mhc 1 present its peptide to
CD8 t cells
What does MHC 1 present its peptide to
CD4 cells
What happens in type 1 diabetes
There is autoimmunity of beta cells of islet of langerhans
Why do beta cells decrease
Dye to CD8 t cells infiltrating and killint them
Describe the immunopathogenesis in type 1 diabetes
- Key auto antigens are expressed on beta cells
- Something triggers the inflamation and additional signal in dendritic cells telling you that there is danger
- You therefore develop autoreactive t cells
What is myasthenia gravis
An antibody mediated disease caused by disruption of the acetycholine receptors on the post synaptic membrane
Describe the immunopathogenesis in myasthenia gravis
- Antibody is directed against an acetycholine receptor which block and internalise the protein causing the receptor to become destroyed
- Antibody also activates the complement cascade
- Complement cascade causes assemebtl of c5-c9 membrane attacl complex which unregulared the ion moving into the membrane
What happens in rheumatoid arthritis
- There is a genetic background of HLA-DR4 and smoking
- Smoking induced inflammation in the lung which breasks immunological toleracne to cirtrulinated peptides
- This result in overactive t cell generated to cause systemic autoimmunity
What is the generic treatment for autoimmune disease
Steroids
When is calceineurin inhibitors used
In renal transplant paitents
What is the mechanism of calcineurin
Inhibit calcineurin which is a molecule that acts downstream at t cell receptors to change gene expression to produce il2 receptor required for t cell proliferation
What is ipilimumab
Monocloncal antibody that acts on the CTLA4 on CD4 t cells to stop anti tumout activity
What is pembrolizumab
Blocks PD1 on CD8 cells to stop them from receiving negaitve signal from tumour PD1L
