Micro- Autoimmunity

Question 1

What is a defining characteristic of an autoimmune disease?

Answer 1

-autoantibodies or auto reactive T cells specific for self antigens

Question 2

What affect does the release of sequestered agents have on the activation of T cells?

Answer 2

• Developing T cells may not have been exposed to sequestered agents while developing in the thymus.
• exposure to released sequestered agents may cause activation of the T cells.

Question 3

What can cause the release of normally sequestered agents?

Answer 3

-trauma and infection agents

Question 4

What is the concept of molecular mimicry?

Answer 4

-some pathogens express proteins withe regions that are similar to self components

(post rabies encephalitis, rheumatic fever, other MBP and peptides)

Question 5

What is AIRE? What is it’s purpose?

Answer 5

Autoimmune regulator.

-Allowes for the exporsure of self antigent for T cells to aid in negative selection

Question 6

What is the affect of a lack of AIRE?

Answer 6

Self antigens are not present in the thymus and autoimmun reactions can occur in peripheral organs.

-e.g. Autoimmune polyglandular syndrome

Question 7

What is autoimmun polyglandular syndrome?

Answer 7

-Lack of AIRE leading to a wide range of autoantibodies against endocrine glands, liver and skin, blood cells and platelets

Question 8

What is an example of a Type II non-cytotoxic hypersensitivity?

Answer 8

Myasthenia Gravis

Question 9

What is the HLA type associated with Myasthenia gravis?

Answer 9

HLA DR3

Question 10

What are the symptoms of MG?

Answer 10

droopy eyelids, double vision, facial muscle weakness and eventually breathing impairment

Question 11

What is the etiology of MG? How is it diagnosed?

Answer 11

• Autoantibodies against ACh receptors in the NMJ activated complement and result in endocytosing of the ACh receptors.
• It is diagnosed by dosing with AChE inhibitor dosing

Question 12

What are the two major Type III hypersensitivities?

Answer 12

• Rhematoid Arthritis
• Systemic Lupus Erythematosis

Question 13

What is rheumatoid factor?

Answer 13

-an IgM antibody specific for the Fc portion of joint IgG

Question 14

What is typically fonnd in the joint synovium in people with rheumatoid arthritis?

Answer 14

Leukocytes (CD4 and CD8, B cells, plasma cells, neutrophils, macrophages)

Question 15

What are the two ways RA is diagnosed?

Answer 15

-Presence of Rheumatoid factor

or

-Elevated IgG and IgM in examination of the joint fluid

Question 16

What is the treatment for RA?

Answer 16

• NSAIDS (coz-2 inhibitors)
• corticosteroids
• immunosuppression
• gold therapy
• anti-TNF-alpha (infiximab)

Question 17

What HLA allotype is associated with SLE?

Answer 17

HLA DR3

Question 18

What antibodies are present in SLE?

Answer 18

-autoantibodies to almost every tissue antigen inclding histones, DNA, RNA, clotting factors

Question 19

What is the histologic appearence of SLE?

Answer 19

-LUMPY-BUMPY die to the deposition of immune complexes into tissues

Question 20

How is SLE diagnosed?

Answer 20

-used to be ANA, now anti-dsDNA is the specific test

Question 21

What is a type IV hypersensitivity that involves the CNS?

Answer 21

-Multiple Sclerosis

Question 22

Which HLA allotype is associated with MS?

Answer 22

HLA DR2

Question 23

What is the mechanism of MS tissue destruction?

Answer 23

T_DTH cells infiltrate the CNS white matter and react specifically with myelin basic protein

Question 24

What is secreted from the sclerotic plaques in the CNS in MS?

Answer 24

oligoclonal IgG

Question 25

What is the diagnosis and treatment of MS?

Answer 25

- Diagnosis via MRI - Treatment with: INF-beta, corticosteroids, and immunosupperssion

Question 26

What HLA allotype is associated with ankylosing spondylitis?

Answer 26

HLA B27

Question 27

A patient presents after infection with Klebsiella, Shigella, or Yersinia, and is complaining of spinal pain. HLA B27 is found after testing. What is the diagnosis?

Answer 27

Ankylosing Spondylitis

Question 28

What if a patient presents with a HLA B27 but is experiencing fevers, and conjunctivits?

Answer 28

Reiter's syndrome

Question 29

What is different about the male to famle ration of Reiter's syndrome as compared to most other autoimmune diseases?

Answer 29

-It has a higher male ratio (9:1)

Question 30

What kind of infection is Reiter's syndrome experienced after?

Answer 30

Post STD or enteric infection: --\> Chlamydia, Yersinia, Shigella

Question 31

A sexually aged male is experiencing knee and ankle pain and is also experiencing urethritis. He has recently been treated for chlamydia. What is the diagnosis and treatment?

Answer 31

Reiter's syndrome. --\> antibiotics, NSAIDS, Cox-2 inhibitors (coxibs)

Question 32

What is the basis of T cell vaccination?

Answer 32

-people with autoimmune disorders are vaccinated with autoimmune T cells and then an immune reaction is directed at the autoimmune clones

Question 33

What is the basis of treatment of autoimmune diseases with peptide blockade of MHC?

Answer 33

-dose with synthetic peptide that have a 1AA change that binds better to MHC and out competes the self peptides that are causing the autoimmune reaction.

Question 34

What are monoclonal antibodies?

Answer 34

Anti-CD4, Anti-TCR, anti-MHC, anti IL-2R