Autoimmunity I and II

Question 1

What is the difference between type II and type III HSR since they’re both antibody mediated?

Answer 1

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

Question 2

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?)

Answer 2

(see image below)

Type II distribution - linear and smooth/localized, Type III distribution - all over (irregular)

Question 3

Goodpasture syndrome arises from auto-antibodies against ___ in the glomerular basement membrane (and also alveolar basement membrane

Answer 3

Type IV collagen

Question 4

Goodpasture syndrome can lead to pulmonary symptoms such as __, coughing and shortness of breath

Renal symptoms include hematuria/RBC casts and ___

Answer 4

hemoptysis (bloody sputum)

cough and shortness of breath

hematuria / RBC casts

rapidly progressive renal failure

Question 5

What are two ways to diagnose Goodpasture’s? (hint: one’s in the tissue and the other is in circulation)

Answer 5

see below

Question 6

How do you treat Goodpasture’s?

Answer 6

Plasmapheresis/plasma exchange

Decrease new auto-Ab formation: corticosteroids or cyclophosphamide (immune suppresant)

Question 7

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?

Answer 7

Complement activation leading to receptor destruction

Internalization of the receptor

Functional AChR block

Complement activation plays the major role in mediating injury

Question 8

Symptoms of Myasthenia Gravis (ocular and muscular)

Answer 8

ptosis and diploplia, limited adduction

generalized proximal muscle weakness

(some pts also hav thymic hyperplasia and develop thymoma

Question 9

How do you treat MG?

Answer 9

Thymectomy

Anticholinesterase agents (inhibit AChE) - accumulate more ACh to outcompete the antibody that’s blocking the receptor

Question 10

What are some other ways to treat MG?

Answer 10

Steroids and immunesuppresants to lower formationof other antibodies

Removal of antibodies via plasmapheresis

IVIG

Question 11

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

Answer 11

Falsehood. You can also have TSH present and the antibody can still bind.

Question 12

What are two classical symptoms of Graves disease?

In general, how would you classify hyperthyroidism symptoms?

Answer 12

Goiter and proptosis

Everything is too much (see image below)

Question 13

Why is Hashimoto’s thyroiditis a mixed HSR?

Answer 13

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

Question 14

Describe the pathways involved in the pathogenesis of SLE

Answer 14

Loss of tolerance >> dysregulation of immune system >> end organ targeting

Question 15

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?

Answer 15

Cellular debri from apoptosis

Failure to clear the immune complexes that form from antibodies binding to cellular debri

Question 16

How do you Dx lupus?

Answer 16

see below

(remember that lupus has those anti nucleic acid antibodies)

Question 17

The two categories of SLE treatment are ___ and ___

Answer 17

Question 18

3 diseases with combined HSRs are Hashimoto’s thyroiditis, ___ and ___

Answer 18

• Hashimoto Thyroiditis
• Scleroderma
• Rheumatoid Arthritis

Question 19

Scleroderma is a mixed HSR of Types ___ and ___

Answer 19

Type II and IV

Question 20

The giveaway symptom for Systemic sclerosis is ___

Answer 20

Raynaud’s phenomenon - triphasic color change

Question 21

What are some pro-fibrotic cytokines that can clue you into scleroderma?

Answer 21

• PDGF
• TGF-b
• IL-4
• Oncostatin M

MCP-1

Question 22

Auto antibodies in scleroderma can attack structures involved in ___

Answer 22

see below

Question 23

Which autoantibody in sceloderma is associated with CREST syndrome?

The anti-topo antibody is associated with (diffuse/limited) skin involvement

Answer 23

see below

Question 24

Rheumatoid arthritis is a mix of which HSR’s?

Answer 24

see below

Question 25

What is #Sjogren's syndrome and what type of HSR is it?

Answer 25

"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)

Question 26

What is immune deviation (aka cytokine deviation)?

Answer 26

Th2 to Th1 switch which can be protective \*\*note that most of the auto immune dieases are mediated by Th2\*\*

Question 27

What does "immunologically privileged" mean? Which sites in the body are considered immunologically privileged?

Answer 27

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

Question 28

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 \_\_\_

Answer 28

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 **FAS**t with **T**ravis so that's why he keep giving them **B**abies. Too bad they're **reactive** and not proactive -

Question 29

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 \_\_\_

Answer 29

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

Question 30

Two ways through which infection can lead to autoimmunity are ___ and \_\_\_

Answer 30

**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)

Question 31

Examples of molecular mimicry include ___ and \_\_\_

Answer 31

Infection with Streptococcus leading to Rheumatic fever Infection with Herpes simplex leading to Myasthenia gravis

Question 32

How does Herpes simplex virus infection cause Myasthenia gravis?

Answer 32

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

Question 33

How does Strept infection demonstrate molecular mimicry?

Answer 33

•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)

Question 34

What is sympathetic opthalmia?

Answer 34

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

Question 35

Alopecia areata is caused by T cell mediated autoimunne damage to which immunologically privileged site?

Answer 35

#Hair\_Follicle

Question 36

What are examples of peripheral tolerance?

Answer 36

Question 37

Cryopyrin associated periodic syndromes are due to mutations in ___ that encodes the ___ component of the Inflammasome

Answer 37

Mutations in NLRP3 Cryopyrin

Question 38

CAPS are examples of what types of diseases? \_\_\_\_ results from a gain of function mutation in NLRP3

Answer 38

Autoinflammatory diseases - IL-1β-mediated systemic inflammation Muckle Wells Syndrome

Question 39

Other CAPS include ___ and \_\_\_

Answer 39

see below