Molecular mimicry occurs when..
-ag receptor has cross-reactivity btw microbial peptide and self peptide
When does molecular mimicry usually happen?
when pathogenic ag has components that mimic self-proteins
What is an example of molecular mimicry?
rheumatic fever - B cells make ab to strep cell wall ag; this ab then cross-reacts w/ epitopes on heart tissue
Bystander activation occurs because…and this happens…
- more likely to occur during inflam response
- autoreactive cell (that escaped tolerance mech) is activated by newly activated APC
Why does bystander activation not normally occur?
APC express MHC molecules w/ self-peptides often, but w/o inflam cytokines, there is no T cell activation due to low co-stim molecules expression on APC
What is it about the inflam response that increases bystander activation?
APCs increase co-stim molecule expression and can then activate T cells that escaped negative selection
What is epitope spreading?
initial autoimmune T cell activation expands to additional self-ag (pathology develops over time)
Example of epitope spreading? What pathology is it related to?
citrullinated peptides - not as well degraded and presented by APCs to T cells
- increased citrullinated peptides promotes damage and infection, promoting immune response
- HLA haplotype related
- rheumatoid arthritis
What is the most common factor for genetic risk factors predisposing to autoimmune disease?
MHC haplotype (can increase or decrease risk)
Are simple mutations a common cause of autoimune disease?
nope!
Why is MHC haplotype important for autoimmune disease?
- regulates T cell repertoire during thymic selection
- regulates efficiency of peptide presentation to peripheral T cells
Example of how we know MHC is important predictor of autoimmune disease (Type I DM)?
Twins w/ HLA hap linkage more likely to present w/ type I DM than twins w/o HLA linkage
Example of Type I Hypersensitivity autoimmune disease
Atopic dermatitis and allergic asthmas
Example of Type II Hypersensitivity autoimmune disease
Pemphigus vulgaris, pemphigus foliaceus, Grave’s disease, Myasthenia gravis, acute rheumatic fever, autoimmune hemolytic anemia
How do Grave’s and myasthenia happen?
- Grave’s: increase thyroid gland activity via ab for TSH receptor
- Myasthenia: Ab against ACh on muscle cells inhibiting signaling at neuromuscular jn
Example of Type III Hypersensitivity autoimmune disease
mixed essential cryoglobulinemia, SLE
Example of Type IV Hypersensitivity autoimmune disease
Psoriasis, type I DM, rheumatoid arthritis, MS (autoimmune demyelinating via T cells)
Treatment of autoimmune diseases that target tolerance mechanisms (4)
- CD28-B7 blocker
- CD40-CD40L blocker
- promote Treg
- promote TGF-beta
Treatment of autoimmune diseases that target effector responses (name one specifically)
- Ab mediated blocking of TNF-alpha receptor (rheumatoid arthritis treatment)
- a bunch more!
