Tolerance and Autoimmunity Flashcards
What is an antigen?
Any substance capable of generating an immune response
not just an inflammatory response
What is immunological tolerance?
Unresponsiveness of the immune system to an antigen
E.g. fetus, gut flora, plant pollens
What is autoimmunity?
An immune response to self-antigens
Due to failure of immunological tolerance
What process is mainly responsible for immunological tolerance?
When does this happen?
Central tolerance
In fetus and declines after birth
What is clonal deletion?
Part of central tolerance
Immature lymphocytes (in fetus) that recognise self-antigens are deleted by apoptosis
What is clonal anergy?
Part of central tolerance
Immature lymphocytes that recognise self-antigens are regulated by regulatory T lymphocytes
Where does central tolerance develop?
Thymus and bone marrow
Most active in fetus
What is peripheral tolerance?
Prevents immune responses to fetus, gut flora, plant pollens etc.
Active throughout life
Develops in peripheral lymphoid tissues
What is clonal suppression
Part of the peripheral tolerance immunity system (throughout life)
Mature lymphocytes that recognise self antigens are suppressed by regulatory T lymphocytes
How can autoimmunity be measured?
By measuring the activity of B cells and their antibodies they produce
Almost all loss of tolerance seems to be B cell mediated
Which HLA gene is linked to ankylosing spondylitis?
HLA-B27
Which HLA gene is linked to systemic lupus erythematosus?
HLA-DR2
Which HLA gene is linked to autoimmune hepatitis, Sjogren’s syndrome, T1DM, SLE?
HLA-DR3
Which HLA gene is linked to RA, T1DM?
HLA-DR4
What do class I MHC/HLA genes present?
What cells are they found on?
Present self antigens, cancer, viruses
Are on every cell
What do class II MHC/HLA genes present?
What cells are they found on?
Present antigens from phagocytosis
On phagocytes and antigen presenting cells
How can autoimmunity and MHC antigen presentation cells be linked?
It is thought that variance in Class I MHC proteins can predispose people to autoimmune conditions
Describe the principle of molecular mimicry
The immune system is exposed to a foreign antigen and reacts, however the antigens can sometimes look like self antigens
This can lead to a cross reaction in another part of the body leading to an autoimmune response
Streptococcal infection - the antigens look similar to self-antigens on the heart valve, and so the heart valve is attacked which leads to rheumatic fever
Which auto-antibody can be identified in Grave’s disease?
TSH receptor
Which auto-antibody can be identified in rheumatoid arthritis?
RhF
Which auto-antibody can be identified in coeliac disease?
Anti-gliadin and anti-endomysial
Which auto-antibody can be identified in Hashimoto’s thyroiditis?
Thyroid peroxidase enzyme
Which auto-antibodies can be identified in SLE?
Which is more sensitive?
ANA - 95% sensitivity
dsDNA - 50% sens, 99% specific
Why are steroids useful in treating acute presentations of autoimmune disease?
They have anti-inflammatory and immunosuppressive properties
They reduce cytokines (IL-2) and cell-mediated and humoral immunity
Give an example of a monoclonal antibody drug.
What can it be used to treat?
Infliximab - anti-TNF cytokine
Used in RA, Crohn’s, ankolysing spondolysis
What is the prevalence of autoimmune disease in developed countries?
Which diseases have the top prevalence?
1-3%
Grave’s
RA
