Immunity to Viruses Flashcards
Virus composition
- obligate intracellular parasites
- composed of:
- DNA - dsDNA
- RNA - ssRNA or dsRNA
- can be 10 genes (poliovirus) up to 200 genes (herpes)
- contains protein coat (capsid) - protects NA
Virus entry into body
- via mucosal surfaces
- viral primary infections - epi cells
- viremia via bloodstream - leads to some secondary infections at distant sites (e.g poliovirus)
EBV
- member of herpesvirus family
- causes infections mononucleosis (glandular fever)
- elevated WBC count (B-cells)
- can establish lifelong dormant infection
- Burkitt’s lymohoma
- Nasopahryngeal carcinoma
- MS
Example of virus, its receptor and cell type infected
- most viruses can only infect a specific cell type if it is receptor positive
- HIV - CD4r - Th cells
- SARS COVID-19 - ACE2- lungs, heart, kidney, GIT
Types of acute viral infection
- acute recovery & elimination of virus (influenza)
- acute latency - on reactivation new virus shed (herpes)
- acute persistence - continuance or intermittent shedding (EBV)
Early stages of infection
TLRs
- TLR 3 - detects dsRNA (rotavirus) and ssRNA (influenza)
- TLR 7 - detects ssRNA (norovirus)
- TLR 9 - detects CpG dsDNA (herpes)
- TLR trigger leads to IFN and cytokine production
IFN - 𝛼, β, y
- by plasmacytoid DCs (pDCs)
- by virus-infected cells
IFNs activate anti-viral response in neighbouring cells
Main IFN-producing cells in the body
Plasmacytoid dendritic cells (pDCs)
- rare DC
- upon stimulation and activation via TLR7 and TLR9 - large amounts of type 1 IFN produced (IFN𝛼, IFNβ)
Downstream signalling of IFN𝛼 and IFNβ
Antiviral effects of ab
- virus carried by lymphatic fluid to nearest lymph node
- virus recognised by subset of B cell - differentiate into ab-producing plasma cell
Neutralizing Ab examples
- rhinovirus - blocks attachment to cells
- poliovirus - blocks virus inciting of capsid
- influenza A - abs enter cell with virus and prevent replication
How are virus-infected cells recognised and killed?
- ab binding triggers ADCC via Fc-r
- CTL - recognition of virus peptides bound to MHC Class I on surface of infected cell
- NK - recognition of loss of MHC Class I on surface on infected cell
*all 3 mechanisms result in apoptosis and removal of apoptotic bodies carried out by macrophages
2 main cells involved in killing viral and cancer cells
- CTL
- NK
Recognition of target cells by CTL and NK cells
- all cells express MHC class I
- MHC I and foreign antigen - killed by CTL cell
- No MHC I - killed by NK cell
*viruses associated with persistent infection and cancer cells - downregulat MHC I on their surface - prevents detection and destruction by CTLs
How are apoptotic bodies removed?
- apoptotic bodies are recognised via exposed phosphatidylserine residues
- these residues are normally expressed on inner plasma membrane
- redistributed to the outer surface of apoptotic bodies
- phagocytes have phosphatidylserine receptors - allows them to bind, engulf and destroy apoptotic bodies and the virus within them
Cell mediated pore formation on target cells
- Degranulation of CTL/NK cell granules content onto surface of target cell (virus or cancer cell)
-
Perforin - a granule protein
- Polymerises to generate trans-membrane pores on target cell surface
- this allows further granule contents to enter target cell
- Engagement of Fas on target cell by Fas ligand (FasL) - expressed on activated CTL - triggered apoptosis
Granule examples
-
Granzyme B - activates apoptosis by activating caspase-3
- cleaves substrates …. including
- DNAse leading to degradation of cells DNA
Methods by which immune evasion occurs by viruses
-
alteration of surface antigens - avoids existing memory immunity (e.g. Variants)
- no pre-existing ab and T cell memory response - protein coat of virus has changed
- production of protein that inhibits stages (e.g. antigen processing)
- blockade of TAP transporter - removal of MHC I molecules from ER
- acquired homologs of cytokines or cytokine receptors - limits how recognition (IL-10 with immunosuppressive properties)
