immunotherapy

Question 1

general principles

Answer 1

controlling immune system
using immune system to fight disease

(immunosuppresion, immunomodulation)

Question 2

general immunosuppresive strategies

Answer 2

corticosteroids
anti IgE
leukotriene antagonists

Question 3

corticosteroids

Answer 3

affect T and B cell function

affects on cytokine networks, inflammation, T cell and monocyte function

Question 4

azathioprine

Answer 4

purine analogue which inhibits DNA synthesis
inhibits T and NK cell function
antiinflammatory

Question 5

cyclophosphamide

Answer 5

alkylating agent which interferes with DNA syntehsis

useful for suppressive B cell activity and antibody production (esp autoantibodies)

Question 6

cyclosporin

Answer 6

pro-drug, require binding to cytoplasmic receptors to activate
modulation and down-regulation various genes e.g. transcription IL-2
immune suppression of T cells and NK cells

Question 7

rapamycin

Answer 7

decrease IL-2 production by Th cells

Question 8

mycophenolic acid

Answer 8

transplant rejection, Crohn’s

inhibitor of purine synthesis, prevents T cell proliferation

Question 9

cytokine therapy

Answer 9

inhibit activity of harmful cytokines or enhance the activity of beneficial cytokines

Question 10

immunoglobulin for post-exposure prophylaxis

Answer 10

human normal Ig: hepatitis A, measles, polio, rubella

specific Igs

• hep B
• rabies
• tetanus
• varicella zozster

Question 11

IVIg

Answer 11

plasma derived IgG

key biologic for replacement therapy in 1ry and 2ry immunodeficiencies
also for some autoimmune disorders

Question 12

what is IVIg

Answer 12

polyclonal IgG preparation usually given IV but can also be SCIg

very high dose - 1-3g/kg

Question 13

IVIg indications

Answer 13

1ry immunodeficiency 
wiskott alrdick syndrome 
IgG subclass deficiencies with recurrent infections 
idiopathic thrombocytopenic purpura
kawasaki disease

Question 14

direct (targeted) immunotherapy

Answer 14

antibody related fragments that detect an antigen on tumour cell + destroy it by recruiting immune cells or delivering toxin/radioisotope to it

target = tumour

Question 15

indirect immunotherapy

Answer 15

immune system is activated rendering it able to seek and destroy tumour cells
boost immune response to kill cancer

target = immune system

Question 16

direct immunotherapy examples

Answer 16

monoclonal antibodies
chimeric antigen receptors (CARs)
bi-specific antibodies

Question 17

indirect immunotherapy examples

Answer 17

tumour vaccines
dendritic cell vaccines
adoptive cell transfer
cytokine therapies
checkpoint inhibitor therapies
stimulatory antibodies

Question 18

cytokine therapy

Answer 18

immunomodulatory cytokines to activate anti-tumour immunity

pegylated IFN-alpha, IL-2

Question 19

polyclonal response

Answer 19

immunisation with antigen will typically lead to a polyclonal response

many different B cell clones will generate antibodies specific for antigen
a number of epitopes will be bound by antibody
antibodies with different variable regions bind multiple epitopes

Question 20

monoclonal antibodies

Answer 20

isolate single antibody producing clone and grow it in vast quantities

specific sensitivity, recognises one epitope

Question 21

rituximab

Answer 21

1st line for NH lymphoma
specific for the CD20 molecule of cell surface of small sub-population B cells

benefits in RA and SLE too

Question 22

how does rituximab work

Answer 22

targets leukaemic/lymphoma B cell

recruits immune system to kill it: macrophages, NK cells, complement system

Question 23

infliximb: anti-TNF

Answer 23

RA, ank spond, Crohn’s UC

chimeric antibody that blocks function of TNF-alpha

Question 24

herceptin

Answer 24

antibody binds to HER2 on cancer cells and marks them for destruction by immune system

HER2 +ive breast cancer

Question 25

the checkpoint inhibitors

Answer 25

powerful anti-tumour responses

Question 26

CAR T cell therapy

Answer 26

CAR T cells are engineered to express antigen-targeted receptors for specific tumour antigens

T cell modifies with CAR has new antigen specificity
activation and killing target cell