Immune Therapies Flashcards

1
Q

Why do we manipulate the immune response

A

To promote protective immune responses - vaccination, fight tumours, treat immunocompromised patients
Suppress unwanted immune responses - chromic inflammation, autoimmunity, allergy

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2
Q

Describe the evolution of an immunisation programme

A

Stage 1 - prevaccine - disease rates increasing but no vaccine available yet
Stage 2 - vaccine coverage increases and disease starts to decrease
Stage 3 - as disease rates fall, public awareness of disease can decrease and number of adverse events may increase
Stage 4 - resumption of confidence
Stage 5 - eradication

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3
Q

What is the primary aim of vaccination

A

To stimulate adaptive immunity and generate long-term immunological memory

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4
Q

How does the body respond to first exposure of a pathogen

A

Early innate immunity will identify non-self antigens and activate inflammation
Cytokines will recruit other innate immune cells to help with response
Dendritic and other APCs will travel to lymph nodes where they will display parts of the pathogen to T and B cells

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5
Q

What happens to T and B cells when first exposed to a pathogen

A

When the right receptor if found for the antigen, the T or B cell will become active and will proliferate making clones of itself
Activated T cells will become effector T cells and activated B cells will start to make antibodies

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6
Q

How is protective long-term immunity produced

A

After eradicating the infection, most of the plasma cells and effector T cells will die as they are not required anymore
Small population will remain and survive as long lived memory cells
Some cells will stay in the tissue at the site of infection, some will travel throughout the body via the lymph and bloodstream continually searching for the pathogen

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7
Q

How does the body produce specific antibodies to natural infection

A

Initially when B cells are activated they produce IgM - low specificity and affinity
Once B cells start communicating with activated T cells, they differentiate into plasma cells, undergoing somatic hypermutation and isotype switching
This allows the plasma cells to start producing the high affinity IgG antibodies which are highly effective at neutralising and clearing the pathogen

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8
Q

Describe the antibody primary response to infection

A

Low specificity IgM produced first

High specificity IgG takes longer - requires T cell help

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9
Q

Describe the antibody secondary response to infection

A

More rapid
More effective
High specificity IgG produced by long-lived plasma cells

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10
Q

What are the different types of vaccines

A

Live attenuated
Inactivated
Subunit (purified antigens)
Viral vector

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11
Q

Describe a live attenuated vaccine

A

Live but weakened via genetic manipulations
Capable of replication within host cells
Excellent life-long immunity
Potentially pathogenic in immune-compromised

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12
Q

Give examples of live attenuated vaccines

A

MMR
BCG
Rotavirus

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13
Q

Describe inactivated vaccines

A

Pathogen killed through chemical or physical process
Cannot replicate or cause disease
Weak immunity
Several doses required

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14
Q

Give examples of inactivated vaccines

A

Influenza
Polio
Pertussis

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15
Q

Describe subunit (purified antigens) vaccines

A

No live components - takes protein fragments from the organism that can cause an immune response
Recombinant - produced by genetic engineering
Toxoid - inactivated bacterial toxins

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16
Q

Give examples of subunit vaccines

A

Recombinant - Hep B, HPV

Toxoid - Diphtheria, Tetanus

17
Q

Describe viral vector vaccines

A

Use an unrelated harmless virus, modified to deliver genetic material of the pathogen

18
Q

Give examples of viral vector vaccines

A

Ebola

Oxford/AstraZeneca

19
Q

What are adjuvants

A

Molecules included within some vaccines to enhance immune responses to vaccine antigens
Help with granuloma formation, making sure vaccine antigens aren’t just washed away in the bloodstream upon immunisation
Aluminium/calcium salts
Intramuscular delivery

20
Q

What vaccine types are adjuvants most commonly found in

A

Inactivated

Subunits

21
Q

What are the different routs of administration for vaccines

A
Intramuscular
Subcutaneous
Intradermal
Intranasal 
Oral
22
Q

Give examples of conventional immunosuppressive drugs

A

Corticosteroids
NSAIDs
Methotrexate (DMARDs)
Biological therapies

23
Q

What are corticosteroids

A

Synthetic versions of cortisol eg - prednisolone
Non-specific anti-inflammatory function
Systemic or topical application

24
Q

What are the side effects of corticosteroids

A

Weight gain
Risk of infection
Risk of diabetes
Risk of hypertension

25
Q

What are NSAIDs

A

Eg - ibuprofen
Reduce pain, inflammation and fever
Cox-2 inhibitors - involved in the conversion of arachidonic acid to prostaglandins
Constant use can lead to GI bleeding, liver and kidney problems
Interact with other medications - warfarin, diuretics, methotrexate

26
Q

What is methotrexate

A

Disease-modifying anti-rheumatic drug (DMARD)
Used at high doses as chemotherapy agent
Used at low doses to treat inflammatory arthritis
Multi-faceted anti-inflammatory effects
Can be combined with biological therapies

27
Q

What are biological therapies

A

Genetically engineered antibodies made from human genes
Directly target specific components of the immune system to inhibit activity eg - B cell inhibitors or cytokine blockers
Moderate to severe RA patients to slow disease progression
May be combined with DMARDs

28
Q

What are Anti-TNF therapies

A

In patients with arthritis, TNF coordinates pathological immune reactions
Therefore if you can specifically target those pathways and switch them off, you might be able to halt of slow the progression of the disease
Infliximab binds soluble TNFa
Etanercept binds and blocks TNF receptor