Immunotherapy Flashcards

(53 cards)

1
Q

What is autoinflammation?

A

Activation of innate immune response without an apparent cause

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2
Q

What is autoimmunity?

A

T and B cells attack healthy tissues, cuased by multiple factors

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3
Q

What causes autoinflammation?

A

Rare monogenic autoinflammatory diseases

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4
Q

What causes autoimmunity?

A

Rare monogenic autoimmune diseases

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5
Q

What happens in anti-tumour response?

A

T cells recognise tumour antigens and trigger T cell activation

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6
Q

What happens in immume evasion by tumours?

A

There is a loss of tumour antigen due to a decrease in MHC and expression of non-classical HLA molecules. This means that T cells are not able to recognise tumour cells

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7
Q

How does T cell inhibition occur?

A

Tumours produce immunosuppressive cytokines as well as displaying inhibiting ligands that are recognised by T cells

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8
Q

How do immunosuppressive microenvironments work?

A

Inhibits T cell activation or differentiation into Th1 and CD8+ cells

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9
Q

What do immunomodulators take the form of?

A

Small moleucle drugs
Antibodies
Cytokines
Cell Therapy

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10
Q

What are major differences between small molecules and biologics?

A

SM have low MW, high permeability and are preferred orally
Biologics have large MW, low permeability and preferred parentally

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11
Q

What are cytokines?

A

Family of small molecules used for communication in the immune system. They play a diverse role in the regulation of immune response

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12
Q

What are cytokines important for?

A

The development or differentiation of immune cells in bone marrow

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13
Q

An example of pro-inflammatory cytokine

A

TNFα

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14
Q

An example of an anti-inflammatory cytokine

A

IL-10

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15
Q

What is recombinant DNA technology?

A

Joins DNA from different sources to multiply the gene or to produce the protein product
Transfer of genes to another organism for propagation or expression

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16
Q

Production of recombinant human cytokines

A

Human gene for the cytokine is inserted into a vector and the vector/gene combo is introduced into a cell which produces the protein product

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17
Q

What is a vector in recombinant cytokine production?

A

A DNA molecule used to carry the gene of interest into a cell and drive its expression

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18
Q

What are B cells?

A

Cells of the adaptive immune system that express antigen receptors

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19
Q

What are antibodies?

A

Antibodies are secreted versions of B cell receptors and have the same antigen specificity as the B cell

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20
Q

How are antibodies produced in animals?

A
  1. Inject antigen into rabbit - usually a protein or peptide
  2. Antigen activates B cells
  3. Plasma B cells produce polyclonal antibodies
  4. Obtain antiserum from rabbit containing polyclonal antibodies
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21
Q

How are self-antigens recognised?

A

Most lymphocytes with self-reactive receptors are killed during development
If they survive, they are functionally inactive

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22
Q

What is the structure of an antibody?

A

2 heavy chains and 2 light chains

23
Q

What is the complementary determining region?

A

Short, hyper-variable sequences of amino acids in the variable region of the antibody

24
Q

What is the Fc region of an antibody?

A

Binds to cell surface receptors and complements proteins to mediate antibody function

25
What is the issue with using horse produced serum proteins?
They are identified by the human body as foreign and Fc mediated antibody functions need human Fcs
26
Why are antibodies engineered?
To retain original specificity To introduce human antibody segments to improve functionality and reduce immunogenicity
27
What do humanised antibodies end with?
-zumab
28
What do human antibodies end with?
-mumab
29
What do chimeric antibodies end with?
- ximab
30
What are natural killer cells used for?
Antibody dependent cellular cytotoxicity
31
How does complement mediated cytotoxicity work?
Punches holes in the tumour cell membrane to kill the cell
32
How do checkpoint inhibitors work?
By blocking T cell inhibitory receptors
33
How do conjugated mAbs work?
Deliver cytotoxic drugs to tumour cells
34
How do biospecific mAbs work?
Consist of 1 arm that recognises cancer cells and the other activates antigens on immune effector cells
35
How does CAR-T cell therapy work?
Genetically engineered T cells target specific antigens on tumour cells
36
What is allogenic cell therapy?
Taken from a donor
37
What is autologous cell therapy?
Taking patient's own cells to be processed and re-injected
38
What is a disadvantage to allogenic cell therapy?
Potential for graft-vs-host disease
39
What are small molecule immunosuppressants used for?
Prophalaxysis to prevent organ transplant rejection Treatment of autoimmune disease
40
Azathioprine
Immunosuppressant pro-drug that is converted to active metabolites Metabolites inhibit purine synthesis and halt DNA replication via incorporation into newly founded cells 6-TGN inhibits activation of rac1 in T cells, including apoptosis
41
What is Azathioprine used to treat?
Severe acute Crohn's disease Suppression of transplant rejection Myasthenia gravis
42
Cyclosporin
Cyclic peptide chain of 11 amino acids Produced from a fungus Calcineurin inhibitor by forming complex with cytosolic protein in lymphocytes
43
What do calcineurin inhibitors do?
Inhibit activation of calcineurin which increases IL-2 to drive T cell differentiation
44
What is cyclosporin used to treat?
Severe acute UC Prevent organ transplant rejection Severe psoriasis
45
How does methotrexate work?
1. Folate antagonism, which is required for DNA synthesis 2. Adenosine accumulates which has anti-inflammatory effects on immune cells 3. Downstream signalling stimulates cytokine receptors 4. ratio of Th17 to Treg cells is altered - Th17 are reduced
46
What is methotrexate used to treat?
Severe Crohn's disease and rheumatoid arthritis
47
Fingolimod
A sphingosine 1-phosphate modulator used in MS Prevents egress of T cells from lymph nodes so reduces recirculation of autoreactive T cells to the CNS
48
Corticosteriod mode of action
Reduce migration of immune cells to the site of inflammation, inhibit NFkB and drive production of IL-10
49
What effect do high dose corticosteroids have?
Immunosuppresive
50
What effects do low dose corticosteroids have?
Anti-inflammatory
51
What is Muromab?
An imunnosuppresant antibody that kills T cells and is used for acute transplant rejection
52
What are examples of TNFα inhibiting drugs?
Infliximab, adalimumab and golimumab
53
What is TNFα and how does it work in the body?
A pro-inflammatory cytokine Acts on multiple cell types to drive inflammation Implicated in the pathogenesis of autoimmune diseases such as Crohn's and UC