What is autoimmunity and autoimmune disease
We do have autoantibodies but they do not result in autoimmune disease
Common autoimmune diseases and their target autoantigens clinical features
Set of criteria for the diagnosis of a disease as autoimmune
Autoimmune ( Immune response against the host due to the loss of immunological tolerance of self-antigen(s)) diseases produce ANTIBODIES (substances causing the autoimmune disease)
Which diseases have poor and good sensitivities?
Why may this test not be useful?
What do we mean by sensitivity?
1. Pernicious anaemia has a poor sensitivity will have to see clinical manifestations aswell
2. The production of autoantibodies are not always produced at the start of the disease
Primary detected straight away
Secondary detected later on -> as produced later on?
3. Is the proportion of the people with the disease who are test positive -> detection rate
The second criteria is we must locate these autoantibodies at their sites of tissue damage.
State the sites of tissue damage in these diseases.
State the technique we use to see if the autoantibody is there.
State how we get the tissue.
Can use patients tissues in biopsy’s to see if patients antibodies are there or
Can use FISH etc some markers
Pernicious anaemia use patients serum (containing autoantibody) to see if it binds to the rat stomach
Transfer of autoantibody or autoreactive T cells to a healthy host induces the autoimmune disease, how do we see this in humans? Give examples of the diseases.
IgG transfer during pregnancy and autoimmune diseases
In the diseases in the image below
Which disease is the most serious, state what disease would develop in the neonate
Breakdown of tolerance: Mechanisms of induction of autoimmunity not really important to know
E.g. in the thymus where T cells develop failure to delete autoreactive T cells can be due to gene mutation
Most likely cause is breakdown of peripheral tolerance
regulatory T cells defect - cytokinesis
Altered self antigen due to infection
B cells do not get activated need T cells to produce IgG (in some infectious cases can be activated by pathogens)
carrier effect - infectious microbe/protein binds to host protein
What triggers autoimmunity?
• Increased risk with an affected sibling (8X)
• Increased risk with an affected identical twin (30X) - also shows environmental factors are important as not 100% concordance
• AIRE mutations (APECED syndrome) that affect central tolerance (autoimmune regulatory
• Autoimmune disease associated with MHC variants (HLADR3/DR4-highly associated with diabetes)
• Hormones - women higher prevalence
Give examples of Infection-induced autoimmune disorders
Campylobacter jejuni -> main cause of food poisoning
immune response to the microbial agent will get an immune response against the similar structure host protein
IMMUNE SYSTEM IS MISLED BY MOLECULE OF MIMICRY
Drug-induced autoimmune syndromes
Current and future therapeutic strategies for autoimmune diseases
Mab means monoclonal antibody
Zu means humanised