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MedEd + PathSoc + Laz's Qs + Romesh Path > Immuno 9 - Immune modulating therapies 1 > Flashcards

Immuno 9 - Immune modulating therapies 1 Flashcards

1
Q

How do steroids help modulate the immune response?

A

Activity on phagocytes

Activity on lymphocytes

Inhibiting NF-KB (pro-inf cytokines)

Inhibiting phospholipase A2

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2
Q

What effect do steroids have on phagocytes?

A
  1. ↓ trafficking to areas of inflammation
    - Adhesion molecule expression
    - Blocks chemotactic signals
  2. ↓ phagocytosis
  3. ↓ release of proteolytic enzymes
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3
Q

What effect do steroids have on lymphocytes?

A
  1. Lymphocytes sequestered in lymphoid tissue
    CD4+ve > T cells >CD8+ve > B cells
  2. ↓ cytokine gene expression
  3. ↓ Ab production
  4. ↑ apoptosis
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4
Q

What effect do steroids have on Prostaglandin synthesis?

A

Inhibits phospholipase A2 –> ↓ breakdown of phospholipids to arachidonic acid –> ↓ conversion to prostaglandins and leukotrienes by COX2 –> ↓ inflammation

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5
Q

What effect do steroids have on NF-KB?

A

↓ NF-κB = ↓ production of inflammatory cytokines and chemokines

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6
Q

What are the adverse effects associated w/ steroid use?

A 
STEROIDS
Stomach ulcers
Thin skin
Edema 
Right heart failure
Osteoporosis
Infections
Diabetes
Cushing’s Syndrome (Central obesity, Moon face, Hirsutism, Proximal myopathy)
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7
Q

What are anti proliferative agents + some examples?

A

Antiproliferative drugs target cells with high turnover rates, leading to their use as immunosuppressants and anti-cancer drugs (inhibit DNA synthesis)

Azathioprine
Mycopheolate
Cyclophospamide
Methotrexate

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8
Q

What is the MoA of Azathioprine

A

Prodrug converted to 6-mercaptopurine in the liver –> inhibits de novo purine synthesis

azaThioprine inhibits T> B cells

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9
Q

What is azathiprine used for?

A

Transplantation – preventing graft rejection, autoimmune disease, autoinflammatory disease

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10
Q

What are the adverse effects associated w/?

A

Accumulation if have thiopurine methyltransferase (TPMT) polymorphisms -> Unable to metabolise azathioprine
+ Hepatotoxicity

Check TPMT activity or gene variants before treatment!!!

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11
Q

What is mycopheolate used for?

A

Blocks de novo guanosine synthesis

Affects T>B cells

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12
Q

What are the indications for mycopheolate use?

A

Transplantation – preventing graft rejection, autoimmune disease, vasculitis

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13
Q

What are the adverse effects associated w/ mycophenolate

A

Infection, particular risk of HSV reactivation and
progressive multifocal leukoencephalopathy (PML) (reactivated JC virus)

mycoPhenolate => Pml

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14
Q

What is the MoA of cyclophosphamide?

A

Alkylate guanine base -> stop DNA replication

Affects B>T cells

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15
Q

What is the indication for cyclophosphamide?

A

CTD, vasculitis, anticancer

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16
Q

What is the adverse side effect associated w/ cyclophosphamide?

A

Haemorrhagic cystitis + bladder cancer (Toxic metabolite acrolein excreted via urine so accumulate in bladder)

Haematological malignancies

Non-melanoma skin cancer

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17
Q

What is the MoA of Methotrexate?

A

Anti-folate, inhibit dihydrofolate reductase -> stop DNA synthesis

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18
Q

What is the indication for Methotrexate?

A

Autoimmune
RA, Psoriasis, Crohn’s

Anti-tumour

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19
Q

What is the adverse side effects associated w/ Methotrexate?

A

Pneumonitis
Pulmonary fibrosis
Cirrhosis

NB: Remember to replace folate + increased risk of NTD in pregnancy hence CI

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20
Q

What are the main features of PML?

A

PML:

  • Reactivated John Cunningham (JC) virus
  • Destroys oligodendrocytes
  • Progressive, fatal condition

NB - associated w/ mycophenolate use

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21
Q

What is plasmapheresis?

A

Removal of pathogenic Ab from plasma

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22
Q

What are the indications for plasmapheresis?

A

Severe Type II Hypersensitivity:

  • Goodpasture
  • Myasthenia gravis
  • Ab-mediated rejection
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23
Q

What are the different cell signalling inhibitors?

A

Calcineurin inhibitor (Tacrolimus)

mTOR inhibitor (Sirolimus)

JAK inhibitor (ofacitinib)

PDE4 inhibitor (Apremilast)

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24
Q

How do calineurin inhibitors work?

A

Blocks calcineurin-stimulated IL-2 expression -> inhibits T cell proliferation

25
Q

What are the adverse effects associated w/ calineurin inhibitors?

A

Nephrotoxicity, neurotoxicity, HTN, gingival hyperplasia (cyclosporine causes this mainly)

26
Q

What is the MoA of mTOR inhibitors?

A

Blocks IL-2 expression -> clonal expansion of T cells

27
Q

What are the indications for mTOR inhibitors?

A

Transplantation

28
Q

What are the adverse effects associated w/ mTOR inhibitors?

A

Similar to calcineurin inhibitors however causes less nephrotoxicitiy as it affects later stage in same chain

29
Q

What is the indications for JAK inhibitors?

A

Inhibits JAK-STAT signalling -> decreases proinflammatory gene transcription

30
Q

What are the adverse effects associated w/ JAK inhibitors?

A

RA
Polycythaemia vera
Psoriatic arthritis
Ank Spond

31
Q

What is the MoA of PDE4 inhibitors?

A

PDE4 inhibition –> increased cAMP –> protein kinase A pathway –> decreased cytokine production

32
Q

What are the indications for PDE4 inhibitors?

A

Psoriasis

Psoriatic arthritis

33
Q

How do Tacrolimus and Sirolimus work?

A

Tacrolimus: “lime tacos in aisle two”
Used “for killing bad people” -> FK binding protein,
Aisle 2 -> blocks IL-2 expression

Sirolimus: “Sirius”
Sirius Black is known “for killing bad people” -> FK binding protein
Aisle 2 ->blocks IL-2 expression

34
Q

What are the main agents directed at cel surface antigens?

A

Basiliximab

Natalizumab

Rabbit anti-thymocyte globulin (ATG)

Rituximad

Abatacept

35
Q

What is the MoA of Basiliximab?

A

Anti-CD25 -> blocks IL-2 -> inhibits T cell proliferation

Basiliximab: “basilisk in HP 2” = IL-2

36
Q

What are the indications and adverse effects of basliximab?

A

Indication:
Allograft rejection prophylaxis

Adverse:
Infusion reactions
Infection + malignancy

37
Q

What is the MoA of Natalizumab?

A

Anti-α4 integrin inhibition -> prevents T cell migration

38
Q

What is the indications and adverse effects associated with natalizumab?

A

Multiple sclerosis

Adverse: PML (JC virus), HBV reactivation, ↑ CVD

Natalizumab: “Natalie Portman” –> MS typically affects young white women

39
Q

What is the MoA of Rabbit anti-thymocyte globulin (ATG)?

A

Specificities to CD proteins allow

  • Lymphocyte depletion
  • Modulation of T cell activation
  • Modulation of T cell migration
40
Q

Indications for rabbit ATG?

A

Acute allograft rejection

41
Q

What is the MoA of Rituximab?

A

CD20 expressed on mature - B cells but not plasma cells
Left plasma cell population intact so Ab level remains

2 infusions can deplete B cell population for 6 months

42
Q

Indications for Rituximab + adverse effects?

A

B cell lymphomas (MAIN)
RA, SLE

Adverse:
Infections - esp PML (JCV) + Hep B reactivation

43
Q

What is the MoA of Abatacept?

A

CTLA4 is an inhibitory checkpoint for T cell activation. Abatacept enhances it

Opposite of Ipilimumab!

44
Q

What is the indication for and side effect associated with abatacept?

A

RA

Adverse:
Infection - esp TB, HBV and HCV

45
Q

What are anti-TNFa (Infliximab, adalimumab, certolizumab, golimumab, ETANERCEPT) used for + their mechanism?

A

RA, PsA, psoriasis, ankylosing spondylitis, IBD

Anti-TNFα mAB (etanercept = Anti-TNFα/TNFβ fusion protein)

46
Q

What is the MoA of Anti-IL12/23(Ustekinumab) and what are they used for?

A

Inhibits differentiation of DCs to Th1 (IL-12) and Th17 (IL-23)

Psoriasis, psoriatic arthritis
Ank spond
IBD (IL23)

47
Q

What is the MoA of Anti-IL23 (only) and what are they used for?

A

Inhibits differentiation of DCs to Th17

Psoriasis, psoriatic arthritis
Ank spond

48
Q

What is anti-RANKL used for and its MoA?

A

RANK-L blocking inhibits osteoblast stimulation of osteoclast differentiation

Osteoporosis

49
Q

What is anti-IL-6R used for + MoA?

A

Decreases neutrophil, macrophage, T/B cell activation

RA
Castleman’s disease

50
Q

What therapies have broad use against autoinflammatory conditions?

A

Anti-TNFα and IL12/23

51
Q

What is used to treat osteoporosis?

A

Anti RANKL therapy

52
Q

What are antiproliferative drugs used for?

A

Immunosuppressants and anticancer drugs

53
Q

What is generally used to prevent graft rejection following transplantation?

A

Cell signalling inhibitors tacrolimus, cyclosporine and sirolimus

54
Q 
A 30 year old woman with rheumatoid arthritis is seen in metabolic bone clinic with a t score of -3.5. Which medication is likely to have contributed to her condition?
A – Infliximab 
B – Carbamazepine 
C – Prednisolone 
D – Methotrexate 
E – Tocilizumab
A

C – Prednisolone - steroids increase risk of osteoporosis

55
Q

A 23 year old woman presents to her GP with loss of sensation and paraesthesia over the left foot. She reports an episode of blurry vision 6 months ago. She is treated and her symptoms improve.
Unfortunately, her condition worsens with time and she suffers two disabling relapses in the sixth year since her diagnosis. Which therapy may slow the progression of her disease?
A – Basiliximab
B – Ipilimumab
C – Rituximab
D – Natalizumab
E – Tocilizumab

A

D – Natalizumab - Used in mx of multiple sclerosis (natalie portman = MS)

56
Q

Which type of rejection can be treated with plasmapheresis?

Acute antibody mediated
Acute cell mediated
Chronic
Graft versus Host Disease
Hyperacute
A

Acute antibody mediated

57
Q

Which type of rejection leads to fibrosis? what do the others cause?

Acute antibody mediated
Acute cell mediated
Chronic
Graft versus Host Disease
Hyperacute
A

Chronic = 6+m = fibrosis, glomerulonephropathy

Hyperacute = mins to hrs - preformed abs activate complements -> thrombosis + necrosis
Acute cell mediated = <6m - Type IV hypersensitivity, cell infiltration
Acute antibody mediated = <6m -> vasculitis (ab attacking endothelium)

58
Q

Which HLA antigens are the most important in matching organs?

A

DR > B > A

Theres 2 alleles for each of these hence there’s 6 possible oppurtunities for organ mismatch

MedEd + PathSoc + Laz's Qs + Romesh Path (99 decks)

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