Immuno: Autoimmune Diseases

Question 1

A patient presents with diplopia and ptosis, with slowly progressing muscle weakness. (bilateral) What does he have? What will you treat him with?

Answer 1

Myesthenia gravis. Pyrigdostigmine is the drug of choice. (Cholinesterase inhibitor)

Question 2

Describe the mechanism of myasthenia gravis.

Answer 2

IgG Antibodies bind AcH receptors at the NM junction and cause them to be endocytosed and degraded.

MUSCLES LESS SENSITIVE TO STIMULATION.

Question 3

Myesthenia gravis is an example of (Antagonism/Agonism) by IgG?

Answer 3

Antagonism.

Question 4

What autoimmune disease is an example of Agonism by IgG antibodies?

Answer 4

Graves’ Disease. (TSU receptor binder)

Question 5

When IgG and IgM bind to a patient’s RBCs during a Direct Coombs test, what autoimmune disease does he have? What are the symptoms?

Answer 5

Atuoimmune hemolytic anemia. Anemia is the main symptom.

Question 6

How are RBCs depleted in Autoimmune hemolytic anemia?

Answer 6

IgG and IgM antibodies bind RBCs and fix classical complement pathway. Macrophages ingest and kill RBCs, or they die by membrane attack complex.

Question 7

What 2 factors/enzymes/cell components are the targets of IgG antibodies in Autoimmune Thrombocytopenic Purpura? What is the resulting pathogenic mechanism?

Answer 7

Von Willebrand Factor and gpIIb/IIIa (an integrin on platelets)

If antibodies bind these molecules, too much clotting occurs, resulting in low platelet count (thrombocytopenia) and decreased ability to clot (purpura…. bleeding where you aren’t supposed to)

Question 8

IgG antibodies bind what in Goodpasture’s Syndrome?

Answer 8

Type IV collagen : major component of every basement membrane in the body.

Question 9

Where is the main site of damage in Goodpasture’s syndrome?

Answer 9

The kidney. Can cause acute glomerulonephritis due to inflammation of the basement membranes within bowman’s capsule.

Question 10

Symptoms of Goodpasture’s Syndrome?

Answer 10

Fatigue, weight loss, weakness, hematuria eventually (progressive kidney dysfx)

Question 11

How would you Dx Goodpasture’s syndrome?

Answer 11

Look for Anti-Type IV collagen antibodies.

Question 12

ANA, ATA, ACA stand for what? What are they diagnostic for?

Answer 12

Anti-nuclear antibodies
Anti-Topoisomerase antibodies
Anti-centromere antibodies

DIAGNOSTIC for Scleroderma!

Question 13

What happens in Scleroderma?

Answer 13

IgG mediated damage to the vascular endothelium of arterioles and replacement with COLLAGEN. HARDENS THE SKIN and GI TRACT.

Question 14

How do you treat scleroderma?

Answer 14

You don’t. Just try to increase blood flow to the area.

Question 15

What happens in Guillain Barre syndrome?

Answer 15

The body makes IgG antibodies specific for gangliosides. (neuronal tissue!!)

DEMYELINATION OF NEURONS

Question 16

GAS (Strep pyogenes) causes molecular mimicry of IgG antibodies resulting in what autoimmune disease?

Answer 16

ACUTE RHEUMATIC FEVER - GAS has antigens that mimic antigens on human cardiac tissue. After infection with GAS, the Abs bind the heart tissue and induce inflammation, causing MYOCARDITIS and heart valve scarring.

Question 17

What example of molecular memory in an autoimmune disease involves Campylobacter Jejuni? What other bacterial infection results due to C. Jejuni infection?

Answer 17

Guillain Barre syndrome.

C. jejuni infection leads to GBS (Strep agalacticae) infection many times.

Question 18

Describe the clinical presentation of Guillain Barre syndrome.

Answer 18

Demyelination of neurons results in progressive neuropathy, beginning in the lower limbs, and RAPIDLY ascends (symmetrically) to the upper limbs and face.

Weakness of extremities (beginning with legs)
Trouble Swallowing/Breathing
Drooling
PARTIAL/TOTAL Paralysis (reversible)

Question 19

What’s the time frame for developing paralytic symptoms following C. jejune infection that turns into Guillian Barre?

Answer 19

Within a week, generally.

Question 20

ANCAs are what, and are diagnostic for what autoimmune disease?

Answer 20

Anti-neutrophil cytoplasmic antibodies (IgG)

Diagnostic for Wegner’s Granulomatosis

Question 21

What do ANCAs do? What is the end result of their mechanism?

Answer 21

Bind neutrophils and activate them. Neutrophils increase cellular adhesion expression, bind vasculature, and degranulate, releasing inflammatory mediators.

VASCULITIS- damage of vessels.

Question 22

True/False: Wegner’s Granulomatosis is an example of molecular mimicry.

Answer 22

TRUE - onset generally follows bacterial/virus infection.

Most common self-determinant is PROTEINASE-3

Question 23

What is the first symptom that presents in Wegner’s Granulomatosis? What are others?

Answer 23

Rhinitis is first.

Conjunctivitis
Lung infiltrates (coin lesions)
Rapid onset glomerulonephritis: RENAL FAILURE
GRANULOMAS EVERYWHERE
Arthritis

Pretty much looks like all autoimmune disease symptoms combined.

Question 24

How does Autoimmune Thrombocytopenic Purpura cause anemia?

Answer 24

DIC: (disseminated intravascular coagulation) microscopic clots everywhere - RBCs can’t get past mini clots in capillaries and end up lysed.

In this disease it’s called microangioplastic hemolytic anemia.

Question 25

How do you diagnose Autoimmune Thrombocytopenic Purpura?

Answer 25

Observe RBC loss. In this case it’s called microangioplastic hemolytic anemia.

Question 26

WTF is Pemphigus Vulgaris?

Answer 26

IgG antibodies specific for DESMOGLEIN 1 and 3. Results in loss of COHESIN in keratinocytes in the epidermis.

SKIN BLISTERS cause your skin isn’t cohesive anymore.

Question 27

How do you treat Pemphigus Vulgaris?

Answer 27

Corticosteroids and Rituximab (CD20 specific B cell marker. Prevents formation of antibodies)

Question 28

What 2 things are diagnostic for SLE? (and what does SLE stand for?)

Answer 28

Systemic Lupus Erythematosis can be diagnosed by the presence of anti-dsDNA antibodies and anti-Smith antibodies in the serum.

Question 29

What is the first symptom that patients with SLE notice?

Answer 29

Arthritis (in 90% of cases)

Question 30

What type of hypersensitivity disease is Lupus?

Answer 30

Type III - IMMUNE COMPLEXES!

Question 31

Why does SLE cause immune complex formation?

Answer 31

Patients with SLE have anutoreactive antibodies that will bind to histones, dsDNA, ribosomes, etc… many intracellular components. These antibodies bind to these cellular macromolecules from damages and form complexes in the blood that disseminate.

Question 32

Where is the first place immune complexes deposit?

Answer 32

Blood vessel walls. Then on to the kidney glomeruli. Always the glomeruli when it comes to immune complexes. Then it goes to the joints, forming arthritic symptoms, which you can see. (1st noticeable symptom of SLE)

Question 33

Insulin-dependent Type 1 diabetes is what type of hypersensitivity reaction? Why?

Answer 33

TYPE IV… mediated by CTLs.

Question 34

What is the disease mechanism of Insulin-dependent Type 1 Diabetes?

Answer 34

CTLs attack and deplete B-islet cells of the pancreas that secrete insulin. Insulin up regulates LPL on cell surfaces to take up glucose-derived products. Without it, the patient has exceptionally high blood sugar.

Question 35

In a patient’s blood test you find IgM, IgG, and IgA antibodies that are specific for the Fc regions of human IgG molecules. What disease does this person most likely have, and what is this characteristic blood component called?

Answer 35

The patient has Rheumatoid Arthritis.

The IgM, IgG, and IgA specific for the Fc region of human IgG = RHEUMATOID FACTOR

Question 36

How do you treat RA?

Answer 36

Infliximab (anti -TNF antibody that prevents inflammation)

Rituximab - anti-CD20 on B cells (acts as a trigger for ADCC on B cells and kills the B cells.)

Question 37

What do you find within the joints of a person with RA?

Answer 37

Inflammatory infiltrate consisting of CD4 and CD8 T’s, B cells, plasma cells, neutrophils, macrophages, etc…

Question 38

A patient presents with loss of coordination, vision problems, motor weakness, and occasional spasticity. What does she have? What is the mechanism of this disease?

Answer 38

Multiple Sclerosis.

Inflammatory response directed at the myelin sheaths of nerve cells.

Sclerotic plaques in white matter are indicative of MS.

Question 39

What cells are responsible for the demyelination observed in MS?

Answer 39

Th1 effector T cells. Activate MACs with IFN-gamma secretion. MACs in sclerotic plaques in the brain secrete cytokines and inflammatory mediators that are responsible for demyelination.

Question 40

How do you treat MS?

Answer 40

High doses of immunosuppressants and IFN-beta 1 injections which decrease incidence of disease attacks.

Question 41

A patient presents with dry eyes and dry mouth. What do they have and what test do you run to make sure?

Answer 41

Sjogren’s syndrome - Autoreactive T cells specific for salivary and lacrimal glands. (pretty much any gland tissue though, cause it can spread to the vagina)

Run the Schirmer test for tear production. (little strip of paper you put in a person’s eye.

Question 42

How do you treat Sjogren’s syndrome?

Answer 42

Punctal plugs ((keep tears in eyes)
Artificial tear replacement
Goggles
Drug therapies to stimulate salivation

Question 43

You have a mutation in HLA-DQ, what disease are you most likely to have?

Answer 43

Insulin-dependent diabetes

Question 44

Which HLA loci is the most involved in autoimmune diseases with molecular mimicry?

Answer 44

HLA-B27

Question 45

Are women of men more likely to get an autoimmune disease?

Answer 45

Women

Question 46

Name 2 immunoprivileges sites in the human body

Answer 46

Eye, Testis

Question 47

What is sympathetic opthalmia?

Answer 47

You get stabbed in the eye. No longer immune privileged site. You develop adaptive immunity to the antigens in the eye that was stabbed. They attack the other eye.