Lecture 12: Immunity to Influenza

Question 1

What is Influenza?

Answer 1

A disease caused by dsRNA virus

Question 2

What type of influenza has the biggest burden, and why?

Answer 2

Influenza type A (IAV) is widespread as its receptor is present across animal kingdom

Question 3

Why are there so many different virus types?

Answer 3

High mutation rates

Question 4

How is the innate immune initially triggered?

Answer 4

Infected cells detect influenza virus PAMPs
Or
Macrophages consume infected cells triggering toll-like receptors

Question 5

What cells are first targeted by IAV?

Answer 5

Epithelial cells in the nasal or upper airway areas

Question 6

What feature of influenza virus is recognised to trigger immune response?

Answer 6

dsRNA, as humans don’t usually produce this

Question 7

How does virus infection lead to recruitment of innate effector cells?

Answer 7

• upon infection, virus goes into endoscope and fuses to release viral genome and make copies of itself
• dsRNA is recognised and activates TLR3, TLR7 and TLR8
• TLR activation leads to transcription of genes encoding IFNs and pro-inflammatory cytokines such as TNF, IL6, IL1B
• release of these cytokines causes recruitment of innate effector cells such as NK cells, monocytes, and neutrophils

Question 8

How do NK cells kill infected cells?

Answer 8

• IAV-HA is expressed on infected cell surface
• NK cells recognise and lyse the infected cells
• NK cells can also detect cells with down regulated MHCI

Question 9

How are DCs involved in T cell activation?

Answer 9

• DCs are brought to infection site via inflammation
• DCs detect viral antigens and transport them to lymph nodes to be expressed to T cells

Previous exposure = activates memory T cells
First exposure = expansion of T cells and then B cells, allowing highly specific T cells to engage in killing infected cells and for generation of virus specific antibodies

Question 10

How does antigenic drift affect vaccine development?

Answer 10

IAV is rapidly mutating with significant mutations each season, making it difficult to produce vaccines

Question 11

Why does IAV mutate so much?

Answer 11

RNA is less stable and more prone to mistakes and mutations, and there are also no proof reading enzymes

Question 12

How does antigenic shift affect IAV?

Answer 12

Segmented genome causes genetic variation, so is difficult to predict and causes ineffective vaccines

Question 13

What is the difference between antigenic drift and antigenic shift?

Answer 13

Drift: gradual process of small mutations
Shift: sudden change in viral makeup resulting in new proteins, usually from exchanges with other virus types

Question 14

Why are anti-viral drugs not as useful?

Answer 14

Most target early stages of infection, but usually people don’t seek treatment until symptoms have progressed

Question 15

How do neuraminidase inhibitors work?

Answer 15

Prevent the release of the virus from the cell surface, keeping it highly accessible to immune cells on the cell surface

Question 16

What are M2 vaccines and how are they limited?

Answer 16

Vaccines which target less abundant and less available antigen on the M2 ion channel protein

Limited as anti-M2 antibodies are not neutralising, but can generate fc receptor mediated processes

Question 17

What is NP and how can it be useful for vaccines?

Answer 17

NP is a nuclear protein which is a histone produced in abundance by the virus, so is a good target

Targeting intracellular proteins allows the immune response to get experience of intracellular immunity, so when antigen is presented and T cell response is generated, there is both an internal and external response

Question 18

What are chimeric haemagglutamins?

Answer 18

Influenza viruses that have a combination of globular head and stalk domains from different types

Question 19

In what ways would cell based vaccines be beneficial opposed to egg based vaccines?

Answer 19

Reduction of generation time, as there would be shorter production cycles and allow more specific seasonal strain targeting