Immunology 2: Tolerance and autoimmunity Flashcards
Recall 5 factors that influence risk of autoimmune disease
Gender Infection Diet Stress Microbiome
Recall 4 examples of auto-immune disease that resembles type 2 hypersensitivity
AI haemolytic anaemia
Goodpasture’s (causes glomerulonephritis)
Grave’s
Myasthenia gravis
What type of hypersensitivity reaction is at play in MS?
DTS Type IV
What is the antigen implicated in MS?
Myelin-basic protein proteolytic protein
Recall the 3 “a”s of tolerance
Aquired
Antigen-specific
Active
Which types of cells are involved in central tolerance?
T cells
Ab-secreting B cells
Summarise the selection of T cells
Positive selection: T cells that can’t “see” MHC –> apoptosis
Negative selection: T cells that react too strongly to MHC –> apoptosis
Survival: T cells that “see” MHC weakly
Summarise the selection of B cells
- No self reaction –> migration to periphery
- Multivalency leading to too strong a reaction –> apoptosis
- Cell recgonises soluble auto-antigen –> migration to periphery
- weak interaction with soluble antigens –> survival (–> potential for AID)
What is anergy?
Absence of costimulation by CD40 on APC
Which gene is required for Treg development?
FOXP3
Recall the 3 mechanisms of peripheral tolerance
Anergy
Treg
Ignorance
Name the disease that results from a FOXP3 mutation
IPEX (Immune dysregulation, polyendocrinopathy, enteropathy and x-linked inheritance syndrome)
Recall 2 immunologically-priveleged sites where peripheral tolerance occurs as a result of ignorance
Nervous system
Eye
Recall the pathophysiology of ophthalmia
Eye cells have never been tolerised to auto-antigen, and are MHC II neg
Physical trauma to eye –> lymph vessels leak antigen into the eye –> inflammation
What does APECED stand for?
Autoimmune Poly Endocrinopathy Candidiasis Ectodermak Dystrophy
Recall the pathophysiology of APECED
Failure to delete T cells in the thymus due to mutations in AIRE gene
Recall 2 examples of where infection can lead to a breakdown of peripheral tolerance
MS
EBV
How can infection lead to a breakdown in peripheral tolerance?
- Molecular mimickery
2. Lead to cytokine release, triggering inflammation
What name is given to AI hypothyroidism?
Hashimoto’s