I - Suppressing The Immune Response

Question 1

do steroids have glucocorticoid or mineralocorticoid activity or both?

Answer 1

only glucocorticoid

Question 2

how are steroids anti inflammatory

Answer 2

phospholipase a2 breaks down phospholipids to form arachidonic acid –> prostaglandins –> inflam
therefore, block phospholipase a2 –> anti inflammatory

Question 3

what do steroids do to neutrophil count and what is the effect

Answer 3

increase neutrophils
reduced cell trafficking to site

Question 4

4 effects steroids have on the adaptive immune system

Answer 4

lymphocytes sequestered therefore low WCC
block cytokine gene expression
block AB production
increase apoptosis of BTT cells

Question 5

side effects of steroids

Answer 5

metabolic - DM, obesity, moon face, change in lipids, osteoporosis, hirsuitism, adrenal suppression
other - cataracts, glaucoma, peptic ulcer, pancreatitis, avascular necrosis
IMMUNE SUPPRESSION and infection

Question 6

give 3 examples of anti proliferative agents

Answer 6

cyclophosphamide
azathioprine
mycophenolate

Question 7

how do anti proliferative agents cause immune suppression

Answer 7

inhibit DNA synthesis of rapid turnover cells ie immune cells

Question 8

SE of anti proliferative agents

Answer 8

BM suppression
infection
malignancy
teratogenicity

Question 9

SE of cyclophosphamide

Answer 9

toxic to proliferating cells - hair loss, BM support, sterility
haemorrhagic cystitis
malignancy - bladder, blood, non melanoma skin
infection - PCP

Question 10

SE of azothioprine

Answer 10

BM suppression - variable severity
hepatotoxicity
infection

Question 11

which anti proliferative agent gives more infections as a SE

Answer 11

cyclophosphamide

Question 12

mycophenolate SE

Answer 12

BM suppression
infection

Question 13

which infections are most common with mycophenolate

Answer 13

HSV reactivation
JC virus causing progressive multifocal leucoencephalopathy

Question 14

aim of plasma exchange

Answer 14

removal of pathogenic ABs

Question 15

what happens in plasma exchange

Answer 15

pts own blood put through cell separator
removes Ig from plasma, then re infused
rebound AB production (however only temporary)

Question 16

indications for plasma exchange

Answer 16

AB mediated disease ++severity
eg Goodpastures, MG, ABO incompatibility

Question 17

which classes of drugs are used to inhibit cell signalling

Answer 17

calcineurin inhibitors
mTOR inhibitors
JAC inhibitors (Jakinibs)
PDE4i

Question 18

how do calcineurin inhibitors suppress the immune system

Answer 18

T cell proliferation inhibitors

Question 19

indications for calcineurin inhibitors

Answer 19

transplant
SLE
psoriatic arthritis

Question 20

examples of calcineurin inhibitors

Answer 20

ciclosporin
tacrolimus

Question 21

indication for mTOR inhibitors

Answer 21

transplant

Question 22

examples of mTOR inhibitors

Answer 22

rapamycin
sirolimus

Question 23

indications for jakinibs

Answer 23

RA
psoriatic arthritis
axial spondylrthritidies

Question 24

how do jakinibs work

Answer 24

inhibits JAK-STAT signalling
inhibits production of inflammatory molecules and influences gene transcription

Question 25

example of PDE4i

Answer 25

apremlias

Question 26

indications for PDE4i

Answer 26

psoriatic arthritis psoriasis (not used commonly)

Question 27

3 agents that bind to T cell surface antigens

Answer 27

rabbit anti thymocyte globulins basiliximab / doclizumab abatacept

Question 28

what is rabbit anti thymocyte globulins used for

Answer 28

allograft rejection

Question 29

how does rabbit anti thymocyte globulins work

Answer 29

reduced lymphocytes, modifies T cell activation

Question 30

SE of rabbit anti thymocyte globulins

Answer 30

infusion reactions leucopenia infection malignancy

Question 31

how is rabbit anti thymocyte globulins given

Answer 31

daily IV infusion

Question 32

what are basiliximab / doclizumab

Answer 32

CD25 AB

Question 33

what are basiliximab / doclizumab used for

Answer 33

prophylaxis of allograft reaction

Question 34

how do basiliximab / doclizumab work

Answer 34

blocks IL2 induced signalling and stops T cell proliferation

Question 35

how are basiliximab / doclizumab given

Answer 35

IV pre and post transplant surgery

Question 36

SE of basiliximab / doclizumab

Answer 36

infusion reaction infection malignancy risk long term

Question 37

what is abatacept

Answer 37

CTLA4-Ig fusion protein

Question 38

what is abatacept for

Answer 38

RA

Question 39

how is abatacept given

Answer 39

IV 4x weekly or SC weekly

Question 40

how does abatacept work

Answer 40

reduced co-stimulation of T cells via CD28

Question 41

SE of abatacept

Answer 41

infusion reaction infection - TB, HBV, HCV malignancy

Question 42

2 agents that bind to B cell surface antigens

Answer 42

rituximab vedolizumab

Question 43

what is rituximab

Answer 43

AB to CD20

Question 44

what is rituximab used for

Answer 44

lymphoma RA SLE

Question 45

how is rituximab given

Answer 45

2 x IV every 6-12 months

Question 46

how does rituximab work

Answer 46

depletes mature B cells - leaves plasma cells

Question 47

SE of rituximab

Answer 47

infusion reaction infection - PML exacerbates CVD

Question 48

what is vedolizumab

Answer 48

alpha 4 beta 7 integrin AB

Question 49

how does vedolizumab work

Answer 49

inhibits leucocyte migration stops exavasation into tissues

Question 50

what is vedolizumab used for

Answer 50

IBD

Question 51

how is vedolizumab given

Answer 51

IV every 8 weeks

Question 52

SE of vedolizumab

Answer 52

infusion reaction hepatotoxicity infection malignancy

Question 53

what are TNF alpha blockers used for

Answer 53

RA psoriatic arthritis IBD FMF ank spon

Question 54

examples of TNF alpha blocker ABs

Answer 54

infliximab adalimumab certolizumab golimumab

Question 55

SE of TNF alpha blocker ABs

Answer 55

infusion reactions infection - TB, HBV, HCV Lupus like conditions demyelination cancer

Question 56

example of TNF alpha antagonist

Answer 56

etanercept

Question 57

what is etanercept used for

Answer 57

RA ank spon psoriatic arthritis

Question 58

what are anti IL1 agents used for

Answer 58

FMF gout adult onset stills

Question 59

what are anti IL6 agents used for

Answer 59

RA GCA large vessel vasculitis

Question 60

what can anti IL23 agents be used for

Answer 60

ax spon psoriatic arthritis IBD

Question 61

describe the inflammasome

Answer 61

pyrin / urate feed into the ASC --> procaspase 1 --> IL1 / NFKB / apoptosis

Question 62

what are anti IL4/5/13 agents used for

Answer 62

asthma / eczema

Question 63

what are anti rank and anti rank ligand agents used for

Answer 63

osteoporosis

Question 64

4 main side effects of biological agents

Answer 64

infusion reactions injection site reactions infection malignancy

Question 65

how is infection risk for imm support managed

Answer 65

vaccination - not live attenuated stop imm sup agents if ill appropriate ABx hand hygiene avoid unwell contacts

Question 66

4 potential viruses that can cause chronic infection in someone on imm supp

Answer 66

TB hep B/C HIV JC virus

Question 67

what can JC virus cause in someone imm sup

Answer 67

progressive multifocal leucoencephalopathy

Question 68

what is progressive multifocal leucoencephalopathy

Answer 68

destroys oligodendrocytes - can be fatal

Question 69

what cancers are imm sup people at risk of

Answer 69

lymphoma from EBV non melanoma skin cancer - HPV melanoma - unsure of risk NOT solid tumours