Pathogenisis and Therapy of Autoimmunity Flashcards
What are some genetic factors of autoimmunity?
- HLA alleles have the highest association with autoimmune disease
- Genes for proteins that regulate T or B cell activation
- Cytokine/cytokine receptors
- Proteins involved in the response to microbes.
Is there a sex bias in autoimmunity?
Yes - more females have autoimmune disease than males
Why might autoimmunity be higher in females than males?
Chromosomes - there should be inactivation of one X chromosomes and if this does not happen you might get autoimmunity.
Gonadal Hormones - female hormones are more inflammatory than males which are regulatory
How can infection trigger autoimmunity?
APC’s are activated and they might pick up slef antigens and show them to the immune system
What is molecular mimicry?
The microbe you are fighting against have high homology with self reactive T cells which causes them to be activated and destroy self tissue.
What does strep A cause?
Rheumatic fever through molecular mimicricy
How can trauma cause autoimmunity?
Damage to blood brain barrier, blood ovular barrier, placenta and blood testis barrier can lead to autoimmunity
What are immunologically privelagd sites?
Those at which inflammation would be catastrophic such as the brain, placenta, eyes etc.
How does sympathetic autoimmune ophthalmia work?
Trauma to one eye results in the release of sequestered intraocular protein antigens
Released intraocular antigen is carried by lymph nodes and activates T cells
Effector T cells return via blood stream and encounter antigen in both eyes
Dysbiosis - how does this cause autoimmunity
There is an equilibrium between the microbiome and bacteria you do not want. If this is broken it can lead to immune dysregulation and development of autoimmunity.
What is autoimmune pathology usually mediated by?
Autoantibodies and/or autoreactive T cells
What is systemic Lupud Eythematosus?
It is a systemic autoimmune disease which influences kidney, heart, bones etc and is more common in women.
What causes lupus?
Genetic - HLA alleles, mutations in several genes e.g. IRF5, STAT4
Environmental Factors - Ultraviolet light, drugs, smoking, infections
What is the pathophysiology of lupus?
Defects in clearance of apoptotic cells (source of antigens)
Strong type 1 IFN response
Increased polarisation to Th17, reduced Treg
Leads to autoreactive T and B cells and autoantibodies against DNA, DNA-binding proteins, RNA, glycoproteins, phospholipids
These lead to tissue damage, nephritis, arthritis and cutaneous manifestations.
Does UV light cause apoptosis?
Yes and in lupus this is hard to clear
