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FIIS > 7. Switching off the immune system > Flashcards

7. Switching off the immune system Flashcards

1
Q

What is tolerance?

A

Switching off the immune response

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2
Q

What are the points of tolerance for B cells?

A

Failure of T cell help
Central tolerance in bone marrow
Peripheral tolerance

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3
Q

What are the points of tolerance for T cells?

A

Positive and negative selection
Absence of co-stimulatory signal
Active regulation by cytokines

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4
Q

What are the steps in the T cell activatory response?

A

MHC and CD3, 4 and 8 co-receptors

Co-stimulatory receptor CD28 binds to B7 on the APC

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5
Q

What is the inhibitory T cell response?

A

CTLA-4 binds to B7

or PD-1 to PD-L1 on APC

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6
Q

What are the results of the inhibitory T cell response?

A

Apoptosis
Anergy
Suppresion by T regulatory cells

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7
Q

What are the functions of T regulatory cells?

A

Create an immunosuppressive environment
CTLA-4 pathway
Consume IL-2 (autocrine T cell growth factor)

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8
Q

How do T regulatory cells create an immunosuppressive environment?

A

Produce inhibitory cytokines TGFB and IL-10

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9
Q

What is ALPS?

A

Autoimmune Lymphoproliferative Syndrome

Mutation in FAS pathway of apoptosis so immune cells don’t die when they should

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10
Q

What diseases can ALPS be associated with?

A 
Chronic lymphoproliferation
Autoimmune disease
Lymphomas
Skin rashes
Family history
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11
Q

How is ALPS diagnosed?

A

BOTH: >6 months non-malignant lymphadenopathy/spenomegaly
and increase a/B double negative T cell count
AND ONE OF
-2 assays of defective lymphocyte apoptosis
-gene mutation in FAS, FAS ligand or caspase-10

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12
Q

How is ALPS cured?

A

Haematopoietic stem cell transplant or BMT

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13
Q

What are the methods tumour cells use to evade immune detection?

A

Invisibility by reducing MHC
Tumour produces proteins which reduce the immune response
Exploiting macrophages

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14
Q

How do tumour cells exploit macrophages?

A

Use them to secrete immunosuppressive cytokines

  • Suppress NK cells
  • Reduce T cell activity and recruitment
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15
Q

What are the methods of cancer immunotherapy?

A 
Synthetic anti-tumour antibodies
Checkpoint inhibitors
Boost immune response
CAR T cell therapy
Cancer vaccines
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16
Q

What is necessary for synthetic anti-tumour antibodies to work?

A

Antigen must be on tumour surface
Must be specific to tumour (antibody to something upregulated or at a specific stage of differentiation)
Must be important to a tumour’s life or it could switch it off

17
Q

How do checkpoint inhibitors work?

A

Inhibit inhibition of immune cells

18
Q

What is a side effect of checkpoint inhibitors and how is it managed?

A

May cause autoimmune conditions

Manage with anti-inflammatories

19
Q

Name a synthetic CTLA-4 antibody which is used to treat melanoma

A

Ipilimumab

20
Q

Name 2 anti-PD1 drugs

A

Nivolumab

Pembrolizumab

21
Q

Name 2 methods of boosting the immune response towards cancer

A

CK/interferon therapy

Non-specific inflammatory response

22
Q

How does CK/ interferon therapy work?

A

Increasing MHC on tumour cells which enhances antigen presentation to T cells

23
Q

How is a non-specific inflammatory response used to treat cancer?

A

Induce inflammation to a toxin in the area to increase the response
Eg. BCG vaccine and bladder cancer

24
Q

What is CAR T cell therapy?

A

‘Training’ of T cells out of the body to kill cancer

Used in B cell malignancies

25
Q

What factors are needed for an effective anti-cancer vaccine?

A

Tumour antigen is specific, increases T cell response and important to tumour survival

26
Q

What are the components of an anti-cancer vaccine?

A

Killed tumour cells/recombinant tumour antigens/DCs incubated with the antigen
and
adjuvants used to increase T cell response

27
Q

What are the limitations of anti-cancer immunotherapy?

A

Risk/benefit in immunocompromised patients
Autoimmune and inflammatory effects
Effects of steroids used to manage drug side effects
Side effects appear late
Monoclonal antibodies are expensive
CAR T cells are difficult to produce

FIIS (24 decks)

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