Immune therapies & Transplantation

Question 1

Which cells to anti T cell monoclonal antibodies act on?

Answer 1

Resting T cells

Question 2

Muromonab-CD3

Answer 2

Anti T cell
Blocks CD3
Used in active rejection

Question 3

Basiliximab

Answer 3

Anti T cell
Blocks CD25 (in IL-2 Receptor)
Prevents rejection

Question 4

Tocilizumab

Answer 4

Anti T cell
Blocks IL-6 Receptor
Used in Rheumatoid arthritis if anti-TNF drugs have failed (like Abatacept)

Question 5

Abatacept

Answer 5

Anti T cell
Anti CTLA-4. Prevents costimulation of T cells.
Used in Rheumatoid arthritis if anti-TNF drugs have failed (like Tocilizumab)

Question 6

Cyclophosphamide

Answer 6

Anti-proliferative 
  Alkylating agent 
Affects B > T cells. 
Used in multi-system connective tissues diseases (SLE) 
and cancer. 
SFX: Hair loss, sterility.

Question 7

Azathioprine

Answer 7

Anti-proliferative:
Liver metablises to 6-mercaptopurine,
Blocks de novo purine synthesis.
Used in: inflam & AI disease, transplantation.

Question 8

Mycophenelate mofetil

Answer 8

Anti-proliferative:
Blocks de novo nucleotide synthesis
Affects T > B cells.
Used in: AI disease, vasculitis, transplantation.

Question 9

Tacrolimus and Ciclosporin

Answer 9

Inhibit calcineurin (cell signalling), lowering IL-2 transcription. 
Used for rejection prophylaxis in transplantation, with sirolimus.

Question 10

Sirolimus

Answer 10

Blocks clonal proliferation (by stopping cell signalling).

Used for rejection prophylaxis in transplantation, with tacrolimus and ciclosporin.

Question 11

Prednisolone

Answer 11

Corticosteroid: inhibits Phospholipase A2:
- lowers Platelet Activating Factor
- lowers Arachidonic Acid
- less trafficking of phagocytes
- lymphopaenia (apoptosis of T and B cells)
Used as anti-inflam and in AI disease.

Question 12

Plasmapheresis

Answer 12

Replace 50% of plasma.
Used in Goodpasture’s, inflam and AI disease.
(Rebound Ab production limits efficacy.)

Question 13

Infliximab

Answer 13

anti-TNF-alpha

Used for psoriasis, Crohns, RA …

Question 14

Ustekinumab

Answer 14

anti-IL-12/23
Binds to p40 subunit of IL-12 and IL-23.
Used in psoriasis.

Question 15

Riuximab

Answer 15

anti-CD20
Decreases B cells (expressed until maturity, so doesn’t affect plasma cells).
Used for lymphoma and AI disease.

Question 16

Methotrexate

Answer 16

Inhibits DHFR, so stops DNA synthesis. 
Uses: 
 - AI disease: RA, psoriasis, Crohns ... 
 - Cancer 
 - Termination of pregnancy
Teratogenic and hepatotoxic.

Question 17

Alemtuzumab

Answer 17

anti-CD52,
depletes lymphocytes
Used in CLL.
Susceptibility to CMV.

Question 18

Hyperacute transplant rejection

Answer 18

Minutes - hours.
Preformed Abs activate complement, causing
thrombosis and necrosis.
Prevent by HLA matching.

Question 19

“Acute” cellular transplant rejection

Answer 19

Weeks - months.
CD4, so type IV hypersensitivity,
cellular infiltrate.
Tx: T cell immunosuppression

Question 20

“Acute” antibody mediated transplant rejection

Answer 20

Weeks - months.
B cell activation;
Abs attack vessels: Vasculitis, C4d.
Tx: Ab removal and B cell suppression.

Question 21

Chronic transplant rejection

Answer 21

Months - years.
Immune and non-immune mechanisms.
Leads to fibrosis.
Tx: minimise organ damage.

Question 22

Graft versus Host Disease

Answer 22

Days - weeks.
Donor immune cells attack host body cells.
Rash, bloody diarrhoea, vomiting, jaundice.

Question 23

CDC, FACS, Luminex

Answer 23

• Complement Dependent Cytotoxicity,
• Flow Assisted Cell Sorting Cytometry,
• Luminex is a sort of solid phase FACS.
  All to check presence of Ab against ABO.

Question 24

Pre-transplant induction

Answer 24

Suppress T cells

eg. Alemtuzumab (a-CD52) or Basiliximab (a-CD25)