Immunology 4: Autoimmunity Flashcards

1
Q

What are AID a dysregulation of?

A

Breakdown of self tolerance of the normal autoimmunity action-symptoms often adaptive (all have it)
Mix of environemental factor and genetic componets (diet/infection/genes, etc)

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2
Q

What are the criterias for a disease to be AID?

A

Evidence of ADAPTIVE response
Can transfer disease by transfering autoreactive cells/AB
If can control Autoimmune response, eliminate the disease
History of AID-personal or family and/or MHC associations

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3
Q

What genetic and environemental factors most important for AID?

A

Genes-many twin studies/family + GWAS (eg SLE: 40 loci)–run in families, and if have one more likely to have another
Gender-depends on condition but women are much higher chance
Infections-inflammatory environement
Diet-Obesity, high fat (effects on microbiome +direct on Autoimmune cells)-may relieve AID symptoms
Stress-phsyical and psychological
Microbiome-gut microbiome crucial for regulation and development of microbiome

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4
Q

What are the mechanism leading to AID?

A

Adaptive response is same than for pathogens
AID involve T cell tolerance loss and IgG production
Because self tissue always present-AID are chronic and can become latent
Mechanisms ressemble type II, III, IV

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5
Q

What is the epiedemology of AID?

A

100 chronic disorders exist-80% in women
8% of people are AID
increasing incidence–maybe because higher hygene-immune system reacting to other things

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6
Q

What AID are most common in men? And women?

A

women-Sjorgens, SLE, thyroid
Men-T1DM, UC (equal)

some get better during pregancy, some get worse
AB mediated usually get worse, while cell mediated get better (because switch to Th2 cells a lot)

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7
Q

List 5 important AID?

A

RA, T1DM, MS, SLE, Autoimmune thyroid disease (ATD-hashmotos, graves, etc)

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8
Q

Do AID diseases target specific organs?

A

Spectrum-some go from organs-graves

SOme are a lot more general-RA, SLE

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9
Q

Are AB involved in AID?

A

Yes-very
AUtoantibodies have been seen in many diseases-
Anti erythrocytes-heamolytic aneamia
Graves in pregnant mother-IgG can cross placenta and cause graves in young child after birth

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10
Q

What are the mechanisms of Type II, III and IV hypersensitivity? relation to AID?

A

AID ressemble these 3 types–
Type II-AB response -eg: AI heamolytic aneamia, Goodpastures (angaisnt collagen IV in BM), graves (stimulate), myasthenia gravis (AChR)
Type III-immune complexes (SLE-vs Nuclear components-desposit activate complement)
Type IV-tcells-delayed-T1DM, RA, MS
NO TYPE I AID

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11
Q

How do normal T cells recognise pathogens? Does that differ in AID?

A

Recognise AG presented on MHC II
TCL-MHC I

in AID-gene modifications can change a lot
most common genes-MHC II alleles-certain alleles increase that-DR3/4
Very polymorphic-so suceptibility differe a lot

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12
Q

Why arent AID super common? What are the mechanisms present to stop it?

A

Tolerance-if cattle share Ag in Utero-then can get graft with no reaction–

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13
Q

How important is timing of Ag presentation in tolerance?

A

Timing-how early in life–if cattle share Ag in Utero-then can get graft with no reaction–

In neonates, if give Ag from adult-then transfer graft-tolerated
BUT its Ag specific-only with those
And wont accept anything else from another donor

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14
Q

What are the 3 As of tolerance? define tolerance

A

Acquired
Antigen specific
Active process, specially active in neonates

Aqcuired inability to respons to Ag stimulus

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15
Q

What are the 2 forms of tolerance? And subgroups if present?

A

Central-during lymphocyte development (T-thymus, B bone marrow-rearage of Segments–deletion of self reaction

Peripheral-after development
–Anergy, active supression (also not tolerance but similar-immune privilege (sites in body where immune doest go) and Ag ingoring

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16
Q

How is central tolerance achieved?

A

Thymic epithelial cells and DC cells in THYMUS present SELF-Ag on CD4 cells on MHCii
Useless cells-cant see MHC-death
Dangerous-react to self Ag-negative selection
USeful-bind weakly to MHC-positive selection

only 5% survive

Similar for B cells, but in BM
if no react, then can go
If they bind to cell surface-deletion/or degenerate receptor
If bind to soluble self molecule-migrate to periphery but dont do anything in periphery-anergic
Low affinity-non cross linking binding to self molecule–go to periphery but have potential to becaume AI-just hasnt seen the Ag yet

17
Q

Does Central tolerance fail in AID?

A

YES-but very rarely
APECED (disease)-mutations in AIRE (helps expression of self Ag, normally in other tissues, in thymus)-
Large amount of autoreactive cells-complex conditions

18
Q

Why are most AID linked to multiple genes?

A

Lot of the genes involved in lymphocyte activation and Ag clearance–important
mess with peripheral tolerance too

19
Q

How is peripheral tolerance achieved?

A

Central tolerance can fail
Need mechanism to regulate outside
Anergy, supression by Tcells, not seing Ag
Anergy-need co stimulation with MHC for activation of b cell-if no stimulation-cell become anergic-cant proliferate-very hard to reverse

Ignorance/not seing Ag-if conc too low for Lympho to see it-fine. Most cells in body dont have MHC II-cant activate T cells. Inflammation can cause MHCII to be expressed on epitheial-can stimulate. Also places where lympho dont go-eye, PNS-cant be exposed to that self Ag (can fail, like trauma to one eye-Ag leak to lympho-and then activate T cells, which can suddently attack BOTH eyes)

Tregs (see other slide)

20
Q

What are Tregs and their role in AID?

A

CD4 T cells (also have CD25, CTLA)-need FOXP3 (TF) to develop

IPEX (disease)-mutation in FOXP3-no Tregs–large amounts of AID, accumulation of self reactive T cells–so know its important

21
Q

What is the evidence that infection are linked to AID? Why?

A

Over years, incidental evidence that infections linked to certain AID
MS-Epstein barr, etc

Why-
Infections, like streptococci-molecular mimicry-produce nearly self Ag
Induce changes in exression and recontion or self protein
Co stimulatory molecules upregulate MHC, and produce co-stimulatory molecules
Failure in regulation-activate APC that have some Self Ag on their MHC-more co-stimulatory molecules-activate other cells
Immune deviations-shift in type-Th1->2–has a potential to alter
Tissue damage at immunological previledged sites