Autoimmune 3

Question 1

two main biological therapy techniques used in humans

Answer 1

• monoclonal antibodies against specific target proteins
• receptor constructs (fusion proteins) - usually based on a naturally occur receptor linked to an immunoglobulin frame
  
  • soaks up all the bad thing

Question 2

5 Anti-TNF biologic therapies

Answer 2

• Infliximab - chimeric m. antidbody - take with methotrexate
• Etanercept - p75 TNF receptor/IgG1-Fc Fusion construct
• Adalimumab - human anti-TNF antibody
• Golimumab - anti-TNF m. antidbody
• Certolizumab

Anti-TNF - ieagc

Question 3

TNF in inflammation + mechanism and enzyme

Answer 3

TNF- transmembrane and then cleaved and released by TACE

• TACE - TNF converting enzme
• Macrophages main source of TNF in RA
• TNF receptors p55 and p75 - on cells but can also be cleaved and go bind/inactivate TNF
• TNF
  
  • stimulates release of IL-1, ILL-6, IL-8
  • Matrix metalloproteinases - eats up collagen
  • activates osteoclasts
  • upregulates adhesion molecules on leukocytes
• really big help for RA

Question 4

Side effects from Anti-TNF drugs

Answer 4

• infusion/injection reactions
• increased infection risk
  
  • opportunistic infections - TB risk
  • also reactivation of latent TB in system
• induction of autoimmune disorders - autoantibodies
• Myelination disorders
• congestive heart failure

Question 5

Anakinra

Answer 5

• IL-1 antagonist
• goal to decrease inflammation in joints of RA caused by IL =-1
• very mild injection site rxns
• les effective than Anti-TNF

Question 6

IL-6 in RA pathogenesis + treatment directed at IL-6

Answer 6

• IL-6 stimulates B and T cells
• IL-6 leads to VEGF production
• Activates liver to make CPR
• stimulates osteoclasts
• Tocilizumab - m. antibody that blocks the IL-6 receptor

Question 7

Abatacept

Answer 7

• RA?
• CTLA4/ IgG constant region combined
• CTLA4 is a co-stim that is expressed when T-cells activated and binds better to B7 than CD28 does - usually holds T-cells together
• so Abatacept - binds the B7 on APC molecules preventing their interaction with T-cells
• So Abatacept blocks tthe costim of T-cells by APC and therefore prevents T-cell activation and inhibits humoral immunity
• abatacept has slight risk of upper respiratory infections

Question 8

Rituximab

Answer 8

• chimeric monoclonal antibody for CD-20 to treat RA
• CD20 is expressed on mature NAIVE B-cells (not pre-cursors and not plasma cells)
• depletes circulation B-cells
• two intravenous, site rxn, overall cumulative lower in Ig
• most depletes Naive B cells (some plasma/memory survive)
• takes 6 months for B cells to get back up, high levels of BLyS during this time

Mechanism:

• depletion of RF and anti-dsDNA autoantibodies
• dimished APC activity of B-cells (and less co-stim)
• diminished cytokine (TNF, IL-1, IL-6) B-cell production
• less CD20+ T-cells that help with auto-antibody production

Question 9

BAFF

Answer 9

• B-cell activating factor
• elevated in SLE, RA, SS
• essential for the development and transition of B-cells
• Belimumab targets BAFF in SLE treatment

Question 10

Natalizumab

Answer 10

• mAb for leukocyte adhesion molecule.
• blocks lymphocytes from getting to CNS and intestinal parenchyma
• induces T-cell apoptosis/anergy
• prevents T-cell mediate inflammation
• Muscular sclerosis
• Progressive multifocal leukoencecephalopathy (PML)