Biologics Flashcards

1
Q

What’a GALT?

A

Gut-associated lymphoid tissue

  • it is a mucosal immune system
  • in GIT
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2
Q

Innate immunity vs Adaptive immunity

A
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3
Q

What cells are affected by cytokines?

A
  • immune cells
  • fibroblasts
  • endothelial cells
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4
Q

The role of macrophages a cancerous cell that is over-producing itself?

A
  • Macrophages ‘collect’ the sample from a cell that is over-producing itself
  • some of the collected cells - would be normal cells - if these are presented to antigen presenting cells/T cell -> then nothing would be done
  • If abnormal proteins are presented -> then we can fight the cancer

* Check-Point inhibitors -> will block the pathway of cancer development

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5
Q

What are check-point inhibitors?

A

They block the pathway of a body not being able to fight cancer (due to ‘normal’ cellular antigens being presented to T cells)

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6
Q

Example of a key cytokine that initiates the pathway in responder cell that is specific to that cell?

A

RA -> TNF alpha

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7
Q

What are (2) regions on immunoglobulin?

A
  • Fab -> fragment antigen binding
  • Fc -> determines the type of immune response
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8
Q

What would the variable regions of immunoglobulin protein mean/result in?

A

Genetic variability of immunoglobulins - able to match different antigens

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9
Q

What are antigens?

A

Antigens - proteins on a cell/ micro-organism that are able to activate B cells (and production of antibodies)

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10
Q

How dos elimination of antigen occur? (2)

A
  • directly -> by neutralisation
  • indirectly -> by promoting phagocytosis or complement activation (lysis)
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11
Q

IgM vs IgG

A
  • IgM - early stage
  • IgG - late
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12
Q

What’s the role of IgE in allergic reaction?

A

IgE triggers the release of histamine from basophils

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13
Q

What antibody is linked with mucosal immunity?

A

IgA

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14
Q

What is the function of IgD

A

cellular regulatory function

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15
Q

What most biologics are?

A

Antibodies

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16
Q

How are monoclonal antibodies produced?

A
  • Antigens are injected into the mouse -> mouse will produce antibodies in spleen
  • Antibody-producing cells from the spleen - but they do not have long lives - as cells die
  • We want to make the cells immortal -> so we fuse them with tumour cells (immortal) -> hybridomas are formed
  • Hybridomas produce antibodies -> these can be injected into patient and block specific pathways

*we combine human and mouse immunoglobulins - to reduce allergic reaction to animal antibody (chimeric antibody)

* most recent technologies -> human antibodies only are produced

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17
Q

What are biologics?

A

Medications with near-identity to the original biologic agents (e.g. protein or antibody

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18
Q

What are the problems with biologics?

A

We are not able to monitor entirely how the antibodies circulate and move around the body - not predictable pharmacokinetics and pharmacodynamics

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19
Q

What are biosimilars?

A

Type of biologics

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20
Q

Infliximab

What does it do? (MoA)

A

Infliximab

It binds to TNF-alpha

*TNF-alpha is a cytokine secreted during intial steps of inflammatory response that triggers the enhancement of inflammatory response by other cells (cellular proliferation, differentiation and apoptosis)

21
Q

Indications for Infliximab

A

Crohn’s and UC, RA, psoriasis, ankylosing spondylitis

22
Q

Side effects of Infliximab

A

Same side effects with any other biologics

  • injection site reactions

- infusion reactions

- infections (as TNFalpha cannot get involved -> pathway that induces immunity is lost)

  • malignancy
  • neutropenia
  • demyelinating disease (<0.1%)
  • heart failure
23
Q

Route of administration of biologics

A
  • IV infusions
  • SC

*no other route due to big molecular mass

24
Q

Side effects of biologics

A

Same side effects with any other biologics

  • injection site reactions

- infusion reactions

- infections

  • malignancy
  • neutropenia
  • demyelinating disease (<0.1%)
  • heart failure
25
Q

What so we need Ix for if a patient on biologics comes with unclear symptoms?

A

Ix for malignancy and infections

  • as being on biologics will suppress immune system
26
Q

What’s the mechanism of action of Adalimumab?

A

Adalimumab

Works against TNFalpha

27
Q

What’s the difference between Infliximab and Adalimumab?

A

*Adalimumab very similar to Infliximab (side effects and indications same for Adalimumab and Infliximab) -> they are bothTNF-alpha inhibitors

Adalimumab is first fully human monoclonal antibody (Infliximab is partially human partially mouse)

*less allergic reactions with Adalimumab (as fully human antibody) - but anti-drug antibodies may develop (resistance)

28
Q

Mechanism of action of Etanercept

A

Etanercept

MoA: TNF-alpha and TNF-beta inhibitor

29
Q

What are the benefits of giving Etanercept?

A

Etanercept is a combination of TNF-receptr and IgG (blocks TNF alpha, TNF beta pathways)

  • less resistance will develop
30
Q

Rituximab - mechanism of action

A

Rituximab blocks CD20 receptor on B cells and: (destruction of B cells)

a) activation of complement cascade -> apoptosis of B cell
b) Natular Killer cells are attracted -> killing of B cell
c) activation of intracellular pathways -> apoptosis of B cells

*useful where (ie. blood malignancies) where B cells produce antibodies against our own tissues -> so we want to reduce B cells

31
Q

Indications of Rituximab

A

*useful where (ie. blood malignancies) where B cells produce antibodies against our own tissues -> so we want to reduce B cells

In general: autoimmune conditions and blood cancers

32
Q

Side effects of Rituximab

A
  • reactions at the side of infection
  • being prone for opportunistic and latent infection reactivation (Hep B,CMB, Herpes)
33
Q

Latent infections and biologics

A

Biologics will remove immune action on the latent infections (infections not active but present in the body) -> activated infections

So always check for EBV, CMG, Hep before e.g. bone marrow transplant (in donor and recipient)

34
Q

What’s Acute Cytokine Release Syndrome?

A

It is a side effect of any biologics (but particular Rituximab)

  • Administration of big molecules of biologics -> immune system will pick up the antigens from biologics -> presentation to the T cells -> massive response of immune system -> massive amount of cytokines released
  • response like for an infective antigen (but to biologics antigen) -> massive exacerbation of fever, headache, chills, myalgia, bronchospasm, hypotension etc

*it may cause angioedema and anaphylaxis

35
Q

Why do we administer anti-histamines of steroids with Rituximab?

A

To prevent angioedema and anaphylaxis (Acute Cytokine Release Syndrome)

36
Q

What’s MoA of Alemtuzumab?

A

Alemtuzumab = Campath

MoA:

  • Alemtuzumab is directed against CD52
  • CD52 is found only on B and T lymphocytes
  • CD52 blocked -> production of cytokines inducing cellular apoptosis

End effect: we try to kill B and T cells

37
Q

What is the danger of Alemtuzumab?

A

Malignancy and infection (immunosuppression as T cells and B cells are ‘killed)

38
Q

Uses of Alemtuzumab

A

Uses: CLL, relapsing MS (remains effective long after the drug itself is undetectable), transplantation (off-label)

*MoA of Alemtuzumab: B and T cells are killed

39
Q

Side effects of Alemtuzumab

A

​​Similar to other biologics

  • Infusion reactions (>90%)
  • Secondary autoimmunity (20-30%) up to 5 years after treatment
  • thyroid autoimmunity (Graves’ disease)
  • glomerulonephritis
  • Infections
  • Malignancies
40
Q

Secondary autoimmunity as a side effect of biologics - what’s that?

A

As biologic is an antibody that is introduced to the body -> detected by immune system -> possible immune response against it -> cytokine production and T/B cells against own tissues

Possible consequences:

*antibodies against lung -> pneumonitis

* kidneys -> glomerulonephritis

* colitis -> against GIT

* antibodies against thyroid

41
Q

What are the examples of other ‘biologics’ (apart from Infliximab etc)>

A
  • blood products (RBC, FFP)
  • insulin and other hormones
  • growth factors (EPO) and immunoglobulins
  • enzymes
  • human tissues/organs
  • vaccines
  • other monoclonal antibodies
42
Q

Kinase Inhibitors

  • class name
  • MoA
A

Kinase inhibitors

Class: small molecules -> end in ‘-nib’

MoA: regulators of cell cycle progress and cell proliferation

43
Q

Kinase Inhibitors

  • use
  • MoA
A

Use: targeted anti-cancer therapy

Advantage: promising selective therapeutics (very targeted - target specific pathways; low toxicities)

44
Q
A

D. All of the above

*immune imbalance may be blamed for miscarriages

45
Q
A

F. RA, Crohn’s, Lymphoma

*C Diff is an infection - we do not want to suppress the immune system here

46
Q
A

B. Most common: Injection/infusion reactions & infections

* Serum sickness - rale

*Acute Cytokine release syndrome - are not as common as we administer steroids and anti-histamines with biologics

47
Q
A

Secondary autoimmunity - potentially with all biologics

* the most frequent with Adaliumab

48
Q

What’s the general name of biologics?

A

To suppress immune over-activity and restore balance