Physiology: autoimmunity Flashcards
Which types of hypersensitivity reactions can lead to autoimmunity?
Types II, III, IV (as these involve reactions to self antigens)
TOLERANCE
What is tolerance?
In healthy people, is the immune system tolerant or intolerant to:
- Self cells
- Non-self cells
Tolerance: the failure of the adaptive immune system to respond to an antigen
Tolerant to self cells
Intolerant to non self cells
TOLERANCE
Why is tolerance necessary?
Somatic recombindation (joining of VDJ segments) will lead to the development of many unique antigen receptors - some of which will be self reactive
TOLERANCE
Central tolerance
- What is it?
- Where does it occur?
- What happens to the remaining lymphocytes?
Involves clonal delection - where lymphocytes with a high affinity for self antigens are deleted.
Occurs in the primary lymphoid organs - thymus for T cells, bone marrow for B cells.
Creates a pool of mature, naive lymphocytes which will undergo clonal selection and expansion
TOLERANCE
Peripheral tolerance
- What kinds of cells does this apply to?
- Where are these cells found?
Self reactive cells that are lower affinity (ie. haven’t been deleted via central tolerance)
Are found in the periphery
TOLERANCE
Peripheral tolerance
- Mechanisms?
T regulatory cells: can be generated in the thymus and induced in the periphery; suppress Th1/17 cells and cytotoxic T cells
Peripheral anergy: occurs when T cells are stimulated by dendritic cells that lack costimulatory signals (eg. PAMPS displayed on MHC) –> turns off the T cell
Chronically activated T cells are killed by apoptosis or are turned off by checkpoint inhibitors
TOLERANCE
Can tolerance be breached by breaching immunoprivileged sites? Example?
Yes - eg. sympathetic ophthalmia
TOLERANCE
Do both environmental and genetic factors impact tolerance?
Including stress?
Yes
TOLERANCE
How does stress contribute to the pathogenesis of rheumatoid arthritis?
TOLERANCE
How can streptococcus infections lead to rheumatic fever (heart valve damage)?
TYPE I DIABETES
- What type of hypersensitivity?
- What role do T cells play?
- What role do autoantibodies play?
Type IV hypersensitivity
Th cells have a role - probably help cytotoxic T cells; drive inflammation (recruitment of leukocytes)
Cytotoxic T cells destroy the Islets
Autoantibodies exist; they are diagnostic, but not pathogenic
RHEUMATOID ARTHRITIS
What type of hypersensitivity is it?
Mainly type 4, with elements of type 3
RHEUMATOID ARTHRITIS
What elements make it a type 4 hypersensitivity?
What elements make it a type 3 hypersensitivity?
Type 4: T cell involvement
- It is associated with HLA (MHC) - T cells respond to MHC
Type 3: immune complexes
- anti IgG - rheumatoid factor
RHEUMATOID ARTHRITIS
What kinds of antigens may be implicated?
Collagen, proteoglycans, vimentin shock protein
Citrullination creates novel antigens
RHEUMATOID ARTHRITIS
Immune mechanisms?
RHEUMATOID ARTHRITIS
Treatment?
Infliximab (anti-TNFa mAb); especially in combination with low dose methotrexate
SYSTEMIC LUPUS ERYTHEMATOUS
What type of hypersensitivity?
Type III
SYSTEMIC LUPUS ERYTHEMATOUS
What immune complexes form?
How do these contribute to the two main signs of SLE?
DNA + anti-DNA autoantiboddies
These immune complexes lodge in blood vessels of skin (leading to butterfly rash) and kidneys (leading to glomerulonephritis)
SYSTEMIC LUPUS ERYTHEMATOUS
Role of TLR9 and BAFF in the pathogenesis of SLE?
An unknown trigger leads to the release of DNA and histones
Antibodies bind to the DNA
The resultant immune complex stimulates the TLR9 on a type of dendritic cell known as a plasmacytoid dendritic cell - these are superb secretors of type I inferferon
Type I interferon secretion stimulates monocytes/dendritic cells to produce BAFF - a cytokine that promotes B cell survival
–> BAFF keeps autoreactive B cells alive
Myasthenia gravis
- What type of hypersensitivity?
- Mechanism?
- Sign?
Type II hypersensitivity
Antibodies aganst ACh receptor of motor end plates interrupt neuromuscular communication
Eye drooping
GRAVES DISEASE
- What type of hypersensitivity?
- Mechanism?
Type II hypersensitivity
Self reactive B cells make antibodies against the TSH recepto –> auto-antibodies bind to TSH receptors –> overproduction of thyroid hormones
