Physiology: autoimmunity Flashcards

1
Q

Which types of hypersensitivity reactions can lead to autoimmunity?

A

Types II, III, IV (as these involve reactions to self antigens)

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2
Q

TOLERANCE
What is tolerance?
In healthy people, is the immune system tolerant or intolerant to:
- Self cells
- Non-self cells

A

Tolerance: the failure of the adaptive immune system to respond to an antigen

Tolerant to self cells
Intolerant to non self cells

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3
Q

TOLERANCE
Why is tolerance necessary?

A

Somatic recombindation (joining of VDJ segments) will lead to the development of many unique antigen receptors - some of which will be self reactive

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4
Q

TOLERANCE
Central tolerance
- What is it?
- Where does it occur?
- What happens to the remaining lymphocytes?

A

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

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5
Q

TOLERANCE
Peripheral tolerance
- What kinds of cells does this apply to?
- Where are these cells found?

A

Self reactive cells that are lower affinity (ie. haven’t been deleted via central tolerance)
Are found in the periphery

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6
Q

TOLERANCE
Peripheral tolerance
- Mechanisms?

A

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

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7
Q

TOLERANCE
Can tolerance be breached by breaching immunoprivileged sites? Example?

A

Yes - eg. sympathetic ophthalmia

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8
Q

TOLERANCE
Do both environmental and genetic factors impact tolerance?
Including stress?

A

Yes

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9
Q

TOLERANCE
How does stress contribute to the pathogenesis of rheumatoid arthritis?

A
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10
Q

TOLERANCE
How can streptococcus infections lead to rheumatic fever (heart valve damage)?

A
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11
Q

TYPE I DIABETES
- What type of hypersensitivity?
- What role do T cells play?
- What role do autoantibodies play?

A

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

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12
Q

RHEUMATOID ARTHRITIS
What type of hypersensitivity is it?

A

Mainly type 4, with elements of type 3

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13
Q

RHEUMATOID ARTHRITIS
What elements make it a type 4 hypersensitivity?
What elements make it a type 3 hypersensitivity?

A

Type 4: T cell involvement
- It is associated with HLA (MHC) - T cells respond to MHC

Type 3: immune complexes
- anti IgG - rheumatoid factor

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14
Q

RHEUMATOID ARTHRITIS
What kinds of antigens may be implicated?

A

Collagen, proteoglycans, vimentin shock protein
Citrullination creates novel antigens

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15
Q

RHEUMATOID ARTHRITIS
Immune mechanisms?

A
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16
Q

RHEUMATOID ARTHRITIS
Treatment?

A

Infliximab (anti-TNFa mAb); especially in combination with low dose methotrexate

17
Q

SYSTEMIC LUPUS ERYTHEMATOUS
What type of hypersensitivity?

A

Type III

18
Q

SYSTEMIC LUPUS ERYTHEMATOUS
What immune complexes form?
How do these contribute to the two main signs of SLE?

A

DNA + anti-DNA autoantiboddies
These immune complexes lodge in blood vessels of skin (leading to butterfly rash) and kidneys (leading to glomerulonephritis)

19
Q

SYSTEMIC LUPUS ERYTHEMATOUS
Role of TLR9 and BAFF in the pathogenesis of SLE?

A

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

20
Q

Myasthenia gravis
- What type of hypersensitivity?
- Mechanism?
- Sign?

A

Type II hypersensitivity
Antibodies aganst ACh receptor of motor end plates interrupt neuromuscular communication
Eye drooping

21
Q

GRAVES DISEASE
- What type of hypersensitivity?
- Mechanism?

A

Type II hypersensitivity
Self reactive B cells make antibodies against the TSH recepto –> auto-antibodies bind to TSH receptors –> overproduction of thyroid hormones