Autoimmunity I and II Flashcards
What is the difference between type II and type III HSR since they’re both antibody mediated?
Type II HSR - typically local/organ or tissue specific. Caused by antibodies attacking surface antigen
Type III HSR - typically systemic. Caused by antibodies forming immune complexes with free antigen
What kind of tissue distribution of the antibodies would you see with type II vs III hypersensitivity? (which one is which in the image below?)
(see image below)
Type II distribution - linear and smooth/localized, Type III distribution - all over (irregular)
Goodpasture syndrome arises from auto-antibodies against ___ in the glomerular basement membrane (and also alveolar basement membrane
Type IV collagen
Goodpasture syndrome can lead to pulmonary symptoms such as __, coughing and shortness of breath
Renal symptoms include hematuria/RBC casts and ___
hemoptysis (bloody sputum)
cough and shortness of breath
hematuria / RBC casts
rapidly progressive renal failure
What are two ways to diagnose Goodpasture’s? (hint: one’s in the tissue and the other is in circulation)
see below
How do you treat Goodpasture’s?
Plasmapheresis/plasma exchange
Decrease new auto-Ab formation: corticosteroids or cyclophosphamide (immune suppresant)
In Myasthenia Gravis, the ACh receptor can be blocked leading to 3 different outcomes, What are they?
Which of these outcomes plays the major role in mediating injury?
Complement activation leading to receptor destruction
Internalization of the receptor
Functional AChR block
Complement activation plays the major role in mediating injury
Symptoms of Myasthenia Gravis (ocular and muscular)
ptosis and diploplia, limited adduction
generalized proximal muscle weakness
(some pts also hav thymic hyperplasia and develop thymoma
How do you treat MG?
Thymectomy
Anticholinesterase agents (inhibit AChE) - accumulate more ACh to outcompete the antibody that’s blocking the receptor
What are some other ways to treat MG?
Steroids and immunesuppresants to lower formationof other antibodies
Removal of antibodies via plasmapheresis
IVIG
Graves disease results from auto-antibodies mimicking TSH and causing TH hormone secretion to be always on.
T/F: This happens only in the absence of TSH
Falsehood. You can also have TSH present and the antibody can still bind.
What are two classical symptoms of Graves disease?
In general, how would you classify hyperthyroidism symptoms?
Goiter and proptosis
Everything is too much (see image below)
Why is Hashimoto’s thyroiditis a mixed HSR?
Mixed because there’s a Type II response involving autoantibodies directed at thyroglobulin or thyroid peroxidase, and there’s also a Type IV response where CD4+ T cells recruit mononuclear cells and cause inflammation/tissue destruction etc
Describe the pathways involved in the pathogenesis of SLE
Loss of tolerance >> dysregulation of immune system >> end organ targeting
Where does the antigen that auto-antibodies bind to to form immune complexes in lupus come from?
What is the main contributor to the pathogenesis of SLE?
Cellular debri from apoptosis
Failure to clear the immune complexes that form from antibodies binding to cellular debri
How do you Dx lupus?
see below
(remember that lupus has those anti nucleic acid antibodies)
The two categories of SLE treatment are ___ and ___
3 diseases with combined HSRs are Hashimoto’s thyroiditis, ___ and ___
- Hashimoto Thyroiditis
- Scleroderma
- Rheumatoid Arthritis
Scleroderma is a mixed HSR of Types ___ and ___
Type II and IV
The giveaway symptom for Systemic sclerosis is ___
Raynaud’s phenomenon - triphasic color change
What are some pro-fibrotic cytokines that can clue you into scleroderma?
- PDGF
- TGF-b
- IL-4
- Oncostatin M
MCP-1
Auto antibodies in scleroderma can attack structures involved in ___
see below
Which autoantibody in sceloderma is associated with CREST syndrome?
The anti-topo antibody is associated with (diffuse/limited) skin involvement
see below
Rheumatoid arthritis is a mix of which HSR’s?
see below
What is #Sjogren’s syndrome and what type of HSR is it?
“Showgrin’s” syndrome - show off those glands
see below
(jury’s out on which HSR it is but she said both Type II and Type IV)
What is immune deviation (aka cytokine deviation)?
Th2 to Th1 switch which can be protective
**note that most of the auto immune dieases are mediated by Th2**
What does “immunologically privileged” mean?
Which sites in the body are considered immunologically privileged?
Immunologically privileged = inflammation at these sites is less likely due to presence of may anti-inflammatory cytokines and other mechanisms because you can’t afford to lose those organs
Brain
Eye
Testis
Uterus (fetus)
Hair follicle
Mutations in AIRE result in ___
Autosomal dominant immune dysregulation syndrome is impaired T and B cell regulation due to a mutation in ___
FOXP3 mutation leads to ___
Autoimmune lymphoproliferative syndrome results from a mutation in ___
See image below
**AIRE - think Addison’s aires**
Autosomal dominat immune dysregulation syndrome (some people always want to dominate (dominant) the conversation and don’t care which side they’re on (autosomal) b/c they can’t think like adults 4 (CTLA4) some reason)
**FOXP3 - the Foxy lady at the IPEX of her career**
Autoimmune lymphoproliferative syndrome - these hoes outchea being FASt with Travis so that’s why he keep giving them Babies. Too bad they’re reactive and not proactive -
Defects in IL23R have been ass’d with which diseases?
Mutations in CTLA4 have been ass’d with ___
MS has been ass’d with a mutation in ___
SLE has been ass’d with mutations in ___ and ___
see table below
(once you turn 23, you start getting IBD)
(you can’t think like an adult if you got rheumatoid arthritis)
at 25, you’re too young to have MS
BrianGamma and Loopy complement each other pretty well
Two ways through which infection can lead to autoimmunity are ___ and ___
Induction of costimulation on APCs and molecular mimicry (basically the microbial peptide looks similar to self so a self reactive T cell can recognize to peptide, get activated, and then go and kill self cells expressing self antigen)
Examples of molecular mimicry include ___ and ___
Infection with Streptococcus leading to Rheumatic fever
Infection with Herpes simplex leading to Myasthenia gravis
How does Herpes simplex virus infection cause Myasthenia gravis?
Herpes simplex virus has the same peptide sequence as the ACh receptor so your body’s immune cells don’t know if they’re reacting to the ACh receptor or to the virus so the ACh receptor can actually be mistaken for the virus
How does Strept infection demonstrate molecular mimicry?
•Streptococcal infection – molecular mimicry – rheumatic fever: Anti-streptococcal antibodies react with self antigens in the myocardium and the joints.
(if you don’t treat Strept infection in munchkins, they can end up getting heart disease when they get older)
What is sympathetic opthalmia?
When there’s trauma or damage to one eye that results in retinal antigens being release and the body (since the imune system isn’t used to them) attacks them and immune cells make their way to the other to damage it because those retinal antigens in the other eye are now considered foreign by the immune system
Alopecia areata is caused by T cell mediated autoimunne damage to which immunologically privileged site?
Hair_Follicle
What are examples of peripheral tolerance?
Cryopyrin associated periodic syndromes are due to mutations in ___ that encodes the ___ component of the Inflammasome
Mutations in NLRP3
Cryopyrin
CAPS are examples of what types of diseases?
____ results from a gain of function mutation in NLRP3
Autoinflammatory diseases - IL-1β-mediated systemic inflammation
Muckle Wells Syndrome
Other CAPS include ___ and ___
see below
