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Year 5 > Immune Modulation > Flashcards

Immune Modulation Flashcards

1
Q

Steroids

A
  • Glucocorticoid steroids

Actions

  • Block phospholipase A2, so there is less prostaglandin production and less inflammation
  • Blocks phagocyte recruitment and phagocytosis
  • Keeps lymphocytes sequestered in lymphoid tissue (T cells > B cells)

Effects on blood:

  • neutrophilia
  • lymphopenia
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2
Q

Cyclophosphamide

A
  • Alkylating agent - alkylates guanine on DNA, preventing DNA replication
  • Acts on B-cells more than T-cells
  • Used in antibody-mediated disease e.g. SLE
  • Side-effects - haemorrhagic cystitis can occur due to toxic metabolite acrolein
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3
Q

Azathioprine

A
  • Metabolised in the liver to 6-mercaptopurine
  • This is a purine analogue, blocks de novo purine synthesis
  • Affects T-cells more than B-cells

Indications

  • Autoimmune disease e.g. SLE
  • Autoinflammatory disease e.g. Crohn’s

Side-effects

  • Some people can get complete bone marrow suppression - associated with TPMT polymorphism
  • They cannot metabolise azathioprine, so it builds up in bone marrow and causes pancytopenia
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4
Q

Mycophenalate

A
  • Binds de novo guanosine analogue synthesis
  • Main use is post-transplant

Main worry - risk of reactivated infection

  • HSV reactivation
  • JC virus + progressive multifocal leukoencephalopathy

TERATOGENIC

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5
Q

Plasmapheresis

A
  • Patient’s own blood is passed through a cell separator and the pathogenic antibody is removed
  • Plasma is either re-infused, or replaced with albumin
  • Give with immunosuppressive agent, as there is usually a rebound increase in antibody production

Indications

  • Goodpastures disease
  • Myasthenia gravis (severe acute disease)
  • Severe transplant rejection
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6
Q

Calcineurin inhibitors

A

Ciclosporin and Tacrolimus

  • Bind to calcineurin, preventing T-cell signalling
  • This blocks activation of NFATc and IL-2 expression
  • Used in psoriasis and severe eczema

Side effects

  • Nephrotoxic
  • Hypertension
  • Diabetes (tacrolimus > ciclosporin)
  • Can be neurotoxic
  • High doses of ciclosporin can cause gum hypertrophy, hirsutism
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7
Q

JAK 2 inhibitors

A
  • Block JAK2-STAT pathway
  • This is involved in cytokine inflammation
  • Effective in rheumatoid arthritis
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8
Q

Apremilast

A

PDE4 (phosphodiesterase 4) inhibitor

  • There is increased cAMP production
  • Increased Protein Kinase A (PKA)
  • Decreased cytokine production and inflammation
  • Used in psoriasis and psoriatic arthritis
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9
Q

Rabbit anti-thymocyte globulin

A
  • Human thymocytes injected into rabbits
  • Rabbits produce a number of thymocyte antibodies
  • Serum containing anti-thymocyte antibodies can be injected into humans

Effects

  • T-cell depletion
  • inhibits T-cell activation
  • Inhibits T-cell migration

Uses

  • NOT SPECIFIC
  • Can be used in allograft rejection e.g. renal/heart transplant

Side-effects

  • Infusion reactions
  • Leukopenia
  • Malignancy
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10
Q

Basiliximab

A
  • Anti-CD25 antibody
  • Targets IL-2, so IL-2 cannot acts on T-cells
  • Blocks T-cell proliferation and function

Uses
- prophylaxis for allograft rejection (given before and after transplant surgery)

Side-effects

  • Infusion reactions
  • Leukopenia
  • Malignancy
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11
Q

Abatacept

A
  • Fusion protein of CTLA4 and human IgG Fc
  • Blocks binding of CD80 and CD86 on APCs, with T-cells
  • used in rheumatoid arthritis

Side-effects

  • Infusion reactions
  • Leukopenia
  • Malignancy
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12
Q

Rituximab

A
  • Anti-CD20 antibody
  • Depletes B-cells, but not plasma cells

Uses

  • Lymphoma
  • Rheumatoid arthritis
  • SLE

Side-effects

  • Infusion reactions
  • Infection, especially JC virus and PML
  • Exacerbation of CVD
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13
Q

Natalizumab

A
  • Anti-alpha 4 integrin antibody
  • Alpha-4 is part of an integrin complex with B1/B7
  • The integrin complex is involved in leukocyte arrest, adhesion and migration
  • Natalizumab block leukocyte migration to tissue

Uses

  • Highly active relapse-remitting MS
  • Crohn’s disease (in the past, not anymore)

Side-effects

  • Infusion reactions
  • Infection - HIGH RISK of JC virus and PML
  • hepatotoxic
  • Malignancy
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14
Q

Tocilizumab

A
  • IL-6 antibody
  • Wide immunosuppressive effect, as IL-6 is involved in macrophages, T-cells, B-cells and neutrophils

Uses

  • Castleman’s disease (IL-6 producing tumour)
  • Rheumatoid arthritis - very effective

Side-effects

  • infection
  • hepatotoxic
  • dyslipidaemia
  • malignancy
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15
Q

Antibody replacement therapy

A
  • Human normal Ig is derived from pools of 1000s of donors
  • Can be given as SC injection every 3-4 months
  • Used in primary antibody deficiency (e.g. Bruton’s) and secondary antibody deficiency e.g. MM
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16
Q

Checkpoint inhibitors

A
  • Block the inhibitory checkpoints on T-cells
  • This boosts T-cell response
  • Used in advanced melanoma

IPILIMUMAB

  • Binds to CTLA4 on T-cells, which is the inhibitory receptor
  • APCs can only bind to CD28, the activatory receptor, on T-cells
  • Activates T-cell response

NIVOLUMAB

  • Binds to phosphodiesterase 1 on T-cells
  • Dampens the inhibitory effect on T-cells
17
Q

Cytokine therapy

A

IFN-alpha - Hep B, Hep C, Kaposi Sarcoma, CML

IFN-beta - Bechet’s disease

IFN-gamma - chronic granulomatous disease

18
Q

Anti-TNFa antibodies

A

Infliximab
Adalimumab
Certolizumab
Golimumab

These bind to circulating TNFa, so TNFa cannot bind to target cells

Uses:

  • Crohn’s disease
  • Rheumatoid arthritis
  • V. effective in reducing pain in ankylosing spondylitis
  • Psoriasis

Side-effects

  • Injection site reactions (given IV or SC)
  • Infections (HBV, HCV, TB)
  • T-cell depletion leading to lupus-like conditions
  • Increased risk of skin cancer (but not solid tumours)
19
Q

Etanercept

A
  • Fusion of TNFa receptor p75, with human IgG antibody
  • This acts as a decoy receptor so that TNFa cannot bind to its target receptor

Uses
- Same as TNFa receptor, but not used in Crohn’s

Side-effects
- Same as above

20
Q

Ustekinumab

A
  • Antibody that binds to p40, a subunit shared by IL-12 and IL-23
  • Depleted IL-12 and IL-23
  • This blocks IL-17 expression by T-cells

Uses

  • Psoriasis (very effective)
  • Psoriatic arthritis
  • Crohn’s disease

NOT useful in Rheumatoid arthritis

Side-effects

  • Injection site reactions
  • Infections (TB)
21
Q

Denosumab

A
  • Antibody binds to the RANK ligand
  • RANK-L usually binds to RANK on osteoclasts to stimulate bone resorption
  • Denosumab reduces bone resorption

Uses
- Effective 2nd line treatment for osteoporosis (After alendronate)

Side effects

  • Injection site reactions
  • Infection - mildly immunosuppressive
  • AVN of jaw
  • Long-term increased risk of atypical femoral fractures
22
Q

Secukinumab

A
  • Antibody to IL-17A

Uses

  • Psoriasis - very effective
  • Psoriatic arthritis - very effective (as effective as TNFa)
  • Ankylosing spondylitis

Side-effects
- Infection (TB)

Year 5 (22 decks)

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