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YR5 Immunology > Immune Modulation > Flashcards

Immune Modulation Flashcards

1
Q

What are ways of boosting the immune system?

A

Vaccination

Replacement of missing components

Blocking immune checkpoints

Cytokine therapy

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2
Q

What are features of the adaptive immune response?

A

Wide repertoire of antigen receptors: Receptor repertoire not entirely genetically encoded.
Genes for segments of receptors are rearranged + nucleic acids deleted/ added at the sites of rearrangement almost randomly.
Potential to create in order of 10^11 to 10^12 receptors.
Autoreactive cells are likely to be generated.
Mechanisms must exist to delete or tolerise these autoreactive cells.

Exquisite specificity: Able to discriminate between very small differences in molecular structure.

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3
Q

What are antigen presenting cells?

A

Cells that can present peptides to T lymphocytes to initiate an acquired immune response.

Include:

  • Dendritic cell
  • Macrophage
  • B lymphocyte
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4
Q

What are 5 types of osteoclasts?

A

Langerhans cells

Mesangial cells

Kupffer cells

Osteoclasts

Microglia

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5
Q

What is clonal expansion after exposure to an antigen?

A

T cells with appropriate specificity will proliferate + differentiate into effector cells (cytokine secreting, cytotoxic).

B cells with appropriate specificity will proliferate +
differentiate to T cell independent (IgM) (memory) plasma cells
undergo germinal centre reaction + differentiate to T cell dependent IgG/A/E(M) memory + plasma cells.
Plasma cells secrete high affinity specific antibodies.

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6
Q

What is immunological memory?

A

Pre-formed pool of high affinity specific antibodies.

Residual pool of specific T + B cells with enhanced capacity to respond if re-infection occurs.

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7
Q

What are features of T-cell memory?

A

Longevity: Memory T cells are maintained for a long time without antigen by continual low-level proliferation in response to cytokines.

Different pattern of expression of cell surface proteins involved in chemotaxis/cell adhesion: Allow memory cells to access non-lymphoid tissues, the sites of microbial entry.

Rapid, robust response to subsequent antigen exposure: There are more memory cells. These cells are more easily activated than naïve cells.

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8
Q

What are features of B-cell memory?

A

Pre-formed antibody: Circulating high affinity IgG antibodies.

Longevity: Long lived memory B cells + plasma cells.

Rapid, robust response to subsequent antigen exposure: Memory B cells are more easily + rapidly activated than naïve cells.

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9
Q

How do vaccines promote immunity against influenza?

A

CD8 T cells control virus load AFTER infection

Neutralising antibody provides a protective response to prevent infection.

Hemagglutinin (HA) is the receptor-binding + membrane fusion glycoprotein of influenza + the target for infectivity-neutralizing antibodies.

Clear correlation between resistance to infection + levels of IgG antibody to HA.

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10
Q

How is the BCG effective at mounting a protective response?

A

Attenuated, strain of bovine tuberculosis

Some protection against primary infection

Some protection against progression to active TB

T cell response is important in protection

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11
Q

What is the test for immunity against TB?

A

Mantoux test

Inject 0.1ml of 5 tuberculin units of liquid tuberculin intradermally.

The tuberculin used in the Mantoux skin test is AKA purified protein derivative, or PPD.

Patient’s arm is examined 48-72h after the tuberculin is injected.

Reaction is an area of induration (swelling that can be felt) around the site of the injection.

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12
Q

What are the different types of vaccines?

A
  1. Live vaccines
  2. Inactivated/ Component vaccines
    (Conjugates + Adjuvants increase immunogenicity)
  3. RNA vaccines
  4. Adenoviral vector vaccines
  5. Dendritic cell vaccines
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13
Q

What are 7 examples of live attenuated vaccines?

A

MMR

BCG

Yellow fever

Zostavax

Typhoid (oral)

Polio (Sabin oral)

Influenza (Fluenz tetra for children 2-17y)

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14
Q

How do live attenuated vaccines work?

A

Induce immune response
Modified (attenuated) organism to limit pathogenesis

Avoid if immunosuppressed

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15
Q

What are advantages of live attenuated vaccinations?

A

Establishes infection: Ideally mild Sx.

Raises broad immune response to multiple antigens: More likely to protect against different strains.

Activates all phases of immune system. T cells, B cells: With local IgA, humoral IgG.

May confer lifelong immunity, sometimes just after 1 dose.

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16
Q

What are disadvantages of live attenuated vaccines?

A

Possible reversion to virulence (recombination, mutation): Vaccine associated paralytic poliomyelitis (VAPP, ca.1:750,000 recipients).

Spread to contacts: Spread to immunosuppressed/ immunodeficient patients.

Storage problems.

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17
Q

What are 7 examples of inactivated viruses?

A

Influenza (inactivated quadrivalent)

Cholera

Bubonic plague

Polio (Salk)

Hepatitis A

Pertussis

Rabies

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18
Q

What are 3 examples of component/ subunit vaccines?

A

Hepatitis B (HbS antigen)

HPV (capsid)

Influenza (recombinant quadrivalent- less commonly used)

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19
Q

What are 2 examples of toxoid (inactivated toxin) vaccines?

A

Diphtheria

Tetanus

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20
Q

What are 4 advantages of inactivated/ component vaccines?

A

No risk of reversion to virulent form

Can be used with immunodeficient patients

Storage easier

Lower cost

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21
Q

What are 4 disadvantages of inactivated/component vaccines?

A

Often do not follow normal route of infection.

Some components have poor immunogenicity.

May need multiple injections.

May require modification to enhance immunogenicity.
* Conjugate to protein carrier
* Adjuvant

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22
Q

What are conjugate vaccines made of?

A

Conjugate vaccines (often used in children)

Polysaccharide plus protein carrier.

Polysaccharide alone induces a T cell independent B cell response – transient.

Addition of protein carrier promotes T cell immunity which enhances the B cell/ antibody response.

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23
Q

What are 3 examples of conjugate vaccines?

A

Haemophilus Influenzae B

Meningococcus

Pneumococcus (Prevenar)

(Remember NHS for polysaccharide encapsulated bacteria)

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24
Q

What is an adjuvant to a vaccine?

A

Adjuvant increases the immune response without altering its specificity.

Mimic action of PAMPs (pathogen associated molecular patterns) on TLR (toll-like receptors) + other PRR (pattern recognition receptors).

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25
Q

What are 3 examples of adjuvants?

A

Aluminium salts (humans)

Lipids: Monophosphoryl lipid A (humans HPV)

Oils: Freund’s adjuvant (animals)

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26
Q

What is an example of a mRNA vaccine?

A

SARS-CoV

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27
Q

How are mRNA vaccines made?

A

Infect E coli with plasmids containing DNA for spike protein.

Harvest plasmids from the cultures.

Excise DNA + transcribe to mRNA.

Complex with lipids to create the vaccine.

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28
Q

How do mRNA vaccines work?

A

Inject mRNA/lipid complexes:
* Non-infectious
* Non-integrating
* Degraded within days

mRNA enters cells (e.g. muscle cells, endothelial cells, fibroblasts, dendritic cells).

mRNA translated + spike protein synthesised/ expressed on surface.

Stimulates immune response inc. B cells/ antibodies + T cells.

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29
Q

What are adenoviral vector vaccines?

A

DNA of relevant protein (Covid spike protein) inserted to viral vector to produce vaccine.

AZ Covid vaccine vector: ChAdOx1-S

Sputnik Covid vaccine vector: Adenovirus types 26 + 5

Infect cells in vivo

Transcription/ translation to produce protein

Stimulates immune response inc. B cells/ antibodies + T cells.

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30
Q

What are dendritic cell vaccines?

A

Acquired defects in DC maturation + function a/w some malignancy suggests a rationale for using ex vivo–generated DC pulsed with tumour antigens as vaccines.

Focus on tumour associated antigens or mutational antigen.

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31
Q

What is Sipuleucel-T Provenge vaccine?

A

Personalised immunotherapy for prostatic cancer.

Remove white cells from patient’s blood (leukaphoresis).

APCs are harvested + incubated with recombinant protein PAP-GMCSF (Prostatic acid phosphatase-granulocyte macrophage colony stimulating factor).

APCs infused back to patient.

Stimulates patient’s immune response.

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32
Q

How can missing components of immune systems be replaced?

A

Haematopoietic stem cell transplantation: donor or autologous.

Antibody replacement

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33
Q

What are indications for stem cell transplant?

A

Life-threatening primary immunodeficiencies:

  • Severe combined immunodeficiency
  • Leukocyte adhesion defect

Haematological malignancy:

  • Offers potential for complete + permanent cure
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34
Q

What is antibody replacement?

A

Human normal immunoglobulin prepared from pools of >1000 donors.
Contains preformed IgG antibody to a wide range of unspecified organisms.

Blood product:

  • Donors screened for Hep B, Hep C P+ HIV
  • Further treated to kill any live virus

Administration

IV or SC

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35
Q

What are indications for antibody replacement therapy?

A

Primary antibody deficiency:

  • X linked agammaglobulinaemia
  • X linked hyper IgM syndrome
  • Common variable immune deficiency

Secondary antibody deficiency:

  • Haematological malignancies
    • Chronic lymphocytic leukaemia
    • Multiple myeloma
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36
Q

What is specific immunoglobulin modulation?

A

Human immunoglobulin used for post-exposure prophylaxis (passive immunisation).

Derived from plasma donors with high titres of IgG antibodies to specific pathogens.

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37
Q

Which diseases can be modulated using specific immunoglobulins?

A

Hep B immunoglobulin: Needle stick/ bite/ sexual contact: from HepBSag+ve individual.

Rabies immunoglobulin: To bite site following potential rabies exposure.

Varicella Zoster immunoglobulin: Women <20w pregnancy or immunosuppressed where aciclovir or valaciclovir is CI.

Tetanus immunoglobulin: No specific preparation available in UK: use IVIG for suspected tetanus.

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38
Q

What are examples of adoptive cell transfer (T-cells)?

A

Virus specific T cells

Tumour infiltrating T cells (TIL–T cell therapy)

T cell receptor T cells (TCR-T cell therapy)

Chimeric antigen receptor T cells (CAR–T cell therapy)

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39
Q

What are indications for virus specific T-cell therapy?

A

EBV related B cell lymphoproliferative disease

Severe persistent viral infection in immunocompromised

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40
Q

What are indications for chimeric antigen receptor T-cell therapy?

A

Acute lymphoblastic leukaemia

Non-Hodgkin lymphoma

CAR T cells less successful in solid tumours

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41
Q

How does chimeric antigen receptor T cell therapy work?

A

T-cells with chimeric receptors targeting CD19:

  • Patient’s own T cells
  • Genetically engineered to express receptor
  • Expanded in vitro

Used for ALL in children.

Used for some forms of non-Hodgkin lymphoma.

42
Q

What is the significance of PD1 and PD1 ligand?

A

Immune checkpoint
PD1 binds to PD1 ligands (on APCs + some tumours)
This stimulates programmed death of the T cell
If tumour expresses PD1 ligand, it can kill off the T cells that are trying to infiltrate + control the tumour

43
Q

Other than PD1-PD1L interaction, what other immune checkpoint are expressed on T cells?

A

CD28 on CD8 T cells binds CD80 + CD86= ACTIVATING signal
CTLA4 on T cells binds CD80 + CD86 = INHIBITORY signal

44
Q

What is ipilimumab and how does it function?

A

Action:

  • Antibody binds to CTLA4
  • Blocks immune checkpoint (blocks programmed death)
  • Allows T cell activation

Indications: Advanced melanoma

Complications: Autoimmunity

45
Q

What are Pembrolizumab and Nivolumab and how do they function?

A

Action:

  • Antibody binds to PD-1
  • Blocks immune checkpoint (+ thus blocks programmed death signal)
  • Allows T cell activation

Indications + dosing:

  • Advanced melanoma
  • Metastatic renal cell cancer

Complications: Autoimmunity (broad T cell activation)

46
Q

What are the clinical uses of recombinant cytokines?

A

Aim: Modify immune response

  • Interleukin 2: Stimulate T cell response:
    Renal cell cancer
  • Interferon alpha: Antiviral effect:
    • Hepatitis B
    • Hepatitis C (with ribavirin)
  • Interferon gamma – Enhance macrophage function: Chronic granulomatous disease.
47
Q

The purpose of vaccination is to stimulate and enhance immunological memory. Which type of cells mediate immunological memory?

A. Neutrophils

B. B and T lymphocytes

C. Platelets

D. Eosinophils

E. Macrophages

A

B. B and T lymphocytes

48
Q

Which of the following vaccines should NOT be given to an immunosuppressed individual?

A. BCG - bacilli Calmette-Guerin

B. Diphtheria toxoid

C. Quadrivalent inactivated influenza vaccine

D. Polio (Salk – injected)

E. Pfizer Covid mRNA vaccine

A

A. BCG - bacilli Calmette-Guerin

49
Q

A 23 year old has metastatic melanoma. Which of the following may reduce disease progression?

A. BCG vaccination

B. Bone marrow transplantation

C. CAR-T cells with specificity for CD19

D. Nivolumab, an antibody specific for PD-1

E. Normal human immunoglobulin

A

D. Nivolumab, an antibody specific for PD-1

50
Q

What are methods of suppressing the immune system?

A
  • Steroids
  • Anti-proliferative agents
  • Plasma exchange
  • Inhibitors of cell signalling
  • Agents directed at cell surface antigens
  • Agents directed at cytokines + their receptors
51
Q

What is the action of phospholipase A2?

A

Breaks down phospholipids to form arachidonic acid which is converted to eicosanoids (e.g. prostaglandins, leukotrienes) by cyclo-oxygenases.

52
Q

What is the effect of corticosteroids on prostaglandins?

A

Inhibit phospholipase A2:
Blocks arachidonic acid + prostaglandin formation
Thus reduces inflammation.

53
Q

What is the effect of corticosteroids on phagocytosis?

A

Decreased traffic of phagocytes to inflamed tissue.

Decreased expression of adhesion molecules on endothelium.

Blocks signals that tell immune cells to move from bloodstream + into tissues. Results in transient increase in neutrophil counts.

Decreased phagocytosis.

Decreased release of proteolytic enzymes.

54
Q

What is the effect of corticosteroids on lymphocyte function?

A

Lymphopenia
Sequestration of lymphocytes in lymphoid tissue: Affects CD4+ T cells > CD8+ T cells > B cells

Blocks cytokine gene expression.

Decreased antibody production.

Promotes apoptosis.

55
Q

What are side effects of corticosteroids?

A

Metabolic effects:

Other effects:

Immunosuppression: Infection.

56
Q

Give 7 metabolic side effects of corticosteroids

A

Diabetes
Central obesity
Moon face
Lipid abnormalities
Osteoporosis
Hiruitism
Adrenal suppression

57
Q

Give 5 non-metabolic side effects of corticosteroids

A

Cataracts
Glaucoma
Peptic ulceration
Pancreatitis
Avascular necrosis

58
Q

What are anti-proliferative immunosuppressants?

A

Cytotoxic agents.
Drugs:
* Cyclophosphamide
* Mycophenolate
* Azathioprine

Action:
* Inhibit DNA synthesis
* Cells with rapid turnover most sensitive

Toxicity:
* BM suppression
* Infection
* Malignancy
* Teratogenic

59
Q

Which anti-proliferative immunosuppressant can be used in pregnancy?

A

Azathioprine

60
Q

What are the side effects of cyclophosphamide?

A

Toxic to proliferating cells:
* BM depression
* Hair loss
* Sterility (M>>F)

Haemorrhagic cystitis:
* Toxic metabolite acrolein excreted via urine

Malignancy:
* Bladder cancer
* Haematological malignancies
* Non-melanoma skin cancer

Infection: Pneumocystis jiroveci

61
Q

Which anti-proliferative immunosuppressant is the most toxic and least used?

A

Cyclophosphamide

62
Q

What drug can be given to prevent infection with PCP whilst using anti-proliferative immunosuppressants?

A

Co-trimoxazole

63
Q

What are side effects of azathioprine?

A

BM suppression:

Cells with rapid turnover (leucocytes + platelets) are esp. sensitive. 1:300 individuals are extremely susceptible to BM suppression.

Hepatotoxicity: Idiosyncratic + uncommon.

Infection: Serious infection less common than with cyclophosphamide.

64
Q

Which individuals are extremely susceptible to BM suppression when using Azathioprine?

A
  • Thiopurine methyltransferase (TPMT) polymorphisms.
  • Unable to metabolise azathioprine, levels build up + extremely toxic.
  • Check TPMT activity or gene variants before tx if possible
    *Check FBC after starting therapy.
65
Q

What are the side effects of mycophenolate mofetil?

A

BM suppression:
Cells with rapid turnover (leucocytes + platelets) esp. sensitive.

Infection:
* Particular risk of herpes virus reactivation
* Progressive multifocal leukoencephalopathy (JC virus)

66
Q

What is plasmapheresis and plasma exchange?

A

Aim: Removal of pathogenic antibody.

Patient’s blood passed through cell separator. Own cellular constituents reinfused.

Plasma treated to remove Ig + then reinfused (or replaced with albumin in ‘plasma exchange’).

67
Q

What are disadvantages of plasmapheresis?

A

Rebound antibody production limits efficacy (still have own plasma + B cells), therefore usually given with anti-proliferative agent.

68
Q

What are indications for plasmapheresis?

A

Severe antibody-mediated disease:

  • Goodpasture syndrome: Anti-glomerular basement membrane antibodies.
  • Severe acute myasthenia gravis: Anti-acetyl choline receptor antibodies.
  • Antibody mediated transplant rejection/ ABO incompatible: Antibodies directed at donor HLA/AB molecules.
69
Q

Which conditions in general are plasmapheresis used in?

A

Type II hypersensitivity reactions –where the antibody itself is directly pathogenic (not just a marker)

70
Q

What are calcineurin inhibitors? What are they used in?

A

Inhibit T cell proliferation/ function as block components in T cell activation pathway

Used in:

  • Transplantation
  • SLE
  • Psoriatic arthritis
71
Q

Give 2 examples of calcineurin inhibitors

A

Ciclosporin
Tacrolimus

72
Q

What are mTOR inhibitors? When are they used?

A

mTOR: Mechanistic Target of Rapamycin

mTOR inhibitors block T cell proliferation + function.

Used in: Transplantation.

73
Q

Give an example of an mTOR inhibitor

A

Sirolimus

74
Q

What are Jak inhibitors (Jaknibs)?

A

Inhibit JAK-STAT signalling (a/w cytokine receptors). Influences gene transcription.

Inhibits production of inflammatory molecules. Effective in Rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis.

75
Q

What is Apremilast?

A

PDE4 inhibitor

Inhibition of PDE4 leads to increase in cAMP.

Influences gene transcription via protein kinase A pathway.

Modulates cytokine production.

Effective in psoriasis + psoriatic arthritis.

76
Q

What are agents directed at cell surface antigens?

A

Drugs:

  • Rabbit anti-thymocyte globulin
  • Basiliximab – anti-CD25
  • Abatacept – CTLA4-Ig
  • Rituximab – anti-CD20
  • Vedolizumab – anti-a4b7 integrin

Actions include:

  • Block signalling
  • Cell depletion
  • Inhibit migration
77
Q

What is anti-thymocyte globulin?
Indications + dosing
Action
Toxicity

A

Indications + dosing:

  • Allograft rejection (renal, heart)
  • Daily IV infusion

Action – multiple modes:

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

Toxicity:

  • Infusion reactions
  • Leukopenia
  • Infection
  • Malignancy
78
Q

What is Basiliximab?
Indications + dosing
Action
Toxicity

A

Antibody directed at CD25 (IL-2Ra chain).

Indications + dosing:

  • Prophylaxis of allograft rejection.
  • IV given before + after transplant surgery.

Action: Blocks IL-2 induced signalling + inhibits T cell proliferation.

Toxicity:

  • Infusion reactions
  • Infection
  • Concern re: long term risk malignancy.
79
Q

What is Abatacept?
Indications + dosing
Action
Toxicity

A

CTLA4–Ig fusion protein

Indications + dosing:

Rheumatoid arthritis: IV 4 weekly; SC weekly.

Action: Reduces co-stimulation of T cells via CD28.

Toxicity:

  • Infusion reactions
  • Infection (TB, HBV, HCV)
  • Caution wrt malignancy
80
Q

What is Rituximab?
Indications + dosing
Action
Toxicity

A

anti-CD-20 antibody

Indications + dose:

  • Lymphoma
  • Rheumatoid arthritis
  • SLE
  • 2 doses IV every 6-12 months (RA)

Action: Depletes mature B cells.

Toxicity:

  • Infusion reactions
  • Infection (PML)
  • Exacerbation CV disease
81
Q

What is Vedolizumab?
Indications + dosing
Action
Toxicity

A

Antibody specific for a4b7 integrin.

Indications + dosing:

  • Inflammatory bowel disease.
  • IV every 8w

Action: Inhibits leukocyte migration.

Toxicity:

  • Infusion reactions
  • Hepatotoxic
  • Infection (? PML)
  • Concern re malignancy
82
Q

What is TNF-alpha?

A

TNFa is a pivotal cytokine in inflammation in many conditions.

TNFa blockade used in:

  • Rheumatoid arthritis
  • Psoriasis and psoriatic arthritis
  • Inflammatory bowel disease
  • Familial Mediterranean fever
83
Q

What are 4 anti-TNF-alpha antibodies?

A

Infliximab

Adalimumab

Certolizumab

Golimumab

84
Q

When are anti-TNF-alpha antibodies used for?
Indications + dosing
Action
Toxicity

A

Indications + dosing:

  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Psoriasis and psoriatic arthritis
  • Inflammatory bowel disease
  • SC or IV

Action: Inhibit TNFa

Toxicity:

  • Infusion or injection site reactions
  • Infection (TB, HBV, HCV)
  • Lupus-like conditions
  • Demyelination
  • Malignancy
85
Q

What is Etanercept?
Indications + dosing
Action
Toxicity

A

TNF-alpha antagonist

Indications + dosing:

  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Psoriasis + psoriatic arthritis
  • Subcutaneous weekly

Action: Inhibits TNFa + TNFb.

Toxicity:

  • Injection site reactions
  • Infection (TB, HBV, HCV)
  • Lupus-like conditions
  • Demyelination
  • Malignancy
86
Q

What is IL-1?

A

IL-1 secretion driven via the inflammasome.

IL-1 blockade may be used in Familial Mediterranean Fever, Gout, Adult Onset Stills Disease.

87
Q

What is IL-6?

A

IL-6 plays an important role in inflammation in rheumatoid arthritis.

IL-6 blockade using an anti-IL6 receptor antibody is effective in rheumatoid arthritis.

88
Q

What are Tocilizumab and Sarilumab?
Indications + dosing
Action
Toxicity

A

Antibodies directed at IL-6 receptor.

Indications + dosing:

  • Castleman’s disease
  • Rheumatoid arthritis
  • Subcutaneous every 1-2w

Action: Reduces macrophage, T cell, B cell, neutrophil activation.

Toxicity:

  • Infusion reactions
  • Infection
  • Hepatotoxic
  • Elevated lipids
  • Caution wrt malignancy
89
Q

What are IL-23 and IL-17?

A

IL23 – IL17 pathway important in spondyloarthritides and related conditions.

  • Axial spondyloarthritis (AS)
  • Psoriasis and psoriatic arthritis
  • Inflammatory bowel disease (not anti-IL17 for IBD)
90
Q

What is Guselkumab?
Indications + dosing
Action
Toxicity

A

Ab vs p19 (alpha) subunit of IL23.

IL-23: IL-23 comprises p40+p19

Indications + dosing: Psoriasis, psoriatic arthritis; Subcutaneous every 8w

Action: Inhibits IL-23

Toxicity:

  • Injection site reactions
  • Infection (TB)
  • Concern re malignancy
91
Q

What are IL-4, IL-5 and IL13?

A

IL-4, IL-5 + IL-13 are key cytokines in Th2 + eosinophil responses.

IL-4/13 blockade using an antibody specific for the IL4 receptor alpha subunit may be used for eczema + asthma.

Anti-IL13 antibody may be used for eczema.

Anti-IL5 antibody is used for eosinophilic asthma.

92
Q

What are RANK and RANK-ligand?

A

RANK ligand/RANK receptor pathway important in driving osteoclast differentiation and function.

Anti-RANK ligand antibody is used in management of osteoporosis.

93
Q

What is Denosumab?

A

Antibody directed at RANK ligand.

Indications and dosing: Osteoporosis; Subcutaneous every 6 months.

Action: Inhibits RANK mediated osteoclast differentiation and function.

Toxicity:

  • Injection site reactions
  • Infection – mildly immunosuppressive
  • Avascular necrosis of jaw
94
Q

What are side-effects of biologic agents?

A

Infusion reactions:

  • Urticaria, hypotension, tachycardia, wheeze – IgE mediated.
  • Headaches, fevers, myalgias – not classical type I hypersensitivity.

Injection site reactions:

  • Peak reaction at ~48h
  • May also occur at previous injection sites (recall reactions)
  • Mixed cellular infiltrates, often with CD8 T cells
  • Not generally IgE or immune complexes
95
Q

What is the association between acute infection and immunosuppression?

A
  • Risk often > 2 x background
  • Avoid contact/wash hands etc
  • Vaccination (avoid live vaccines)
  • Temporarily stop immunosuppression in case of infection
  • Consider atypical organisms
  • Appropriate abx
96
Q

What is the association between chronic infections and immunosuppression?

A

Tuberculosis:

  • Hx, Residence, Travel, Contacts, CXR, TB Elispot
  • Prophylaxis or tx if required

HBV and HCV:

  • Check Hep B core antibody pre-tx
  • Check Hep C antibody pre-tx
  • Further investigate for active virus infection if serology is positive

HIV:

  • Check HIV serology pre-tx
  • Balance benefits against possible risks
97
Q

What is the association between JC Virus and immunosupression?

A

Common polyomavirus that can reactivate

Infects and destroys oligodendrocytes

Progressive multifocal leukoencephalopathy

A/w use of multiple immunosuppressive agents

98
Q

What is the association between immunosupression and malignancy?

A
  • Lymphoma (EBV)
  • Non melanoma skin cancers (Human papilloma virus)
  • ?Melanoma

Risks appear lower with targeted forms of immunosuppression than with regimes used in transplantation.

99
Q

What is the association between autoimmunity and immunosuppression?

A
  • SLE and lupus-like syndromes
  • Anti-phospholipid syndromes
  • Vasculitis
  • Interstitial lung disease
  • Sarcoidosis
  • Uveitis
  • Autoimmune hepatitis
  • Demyelination
100
Q

A young woman with SLE is found to have osteoporosis. She has experienced weight gain and easy bruising and has a high blood glucose. Which drug is likely to have caused these effects?

A. Azathioprine

B. Anti-CD20 (rituximab)

C. Mycophenolate mofetil

D. Prednisolone

E. Anti-TNF alpha

A

D. Prednisolone

101
Q

Rituximab is a monoclonal antibody specific for CD20 on B cells. It depletes B cells. For which one of the following diseases is it effective treatment?

A. Ankylosing spondylitis

B. Malignant melanoma

C. Multiple sclerosis

D. Osteoporosis

E. Rheumatoid arthritis

A

E. Rheumatoid arthritis

102
Q

Which of the following are true about management of psoriasis and psoriatic arthritis?

A. It responds to inhibition of RANK ligand (denosumab).

B. It responds to CAR-T cells.

C. Treatment options include IL6 blockade or B cell depletion with rituximab.

D. Treatment options include inhibition of TNF alpha, IL23 or IL17A or use of a PD4 blocker or ciclosporin.

E. Treatment options include use of a checkpoint inhibitor such as nivolumab.

A

D. Tx options include inhibition of TNF alpha, IL23 or IL17A or use of a PD4 blocker or ciclosporin.

YR5 Immunology (14 decks)

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