Immune response to virus Flashcards
Are neutrophils important in a immune response against viruses? Give evidence
First and predominant immune cell recruited viral infection
Depletion of neutrophils during influenzas virus infection leads to a more severe disease in mice
HSV infection results in neutrophil depleted mice results in :
Increased viral load
Increased mortality
What do NK cells do in a viral infection?
Rapidly seek out and destroy virus infected cells
Identify markers of stress on infected cells
Has 2 types of receptors
- Activating receptors
Inhibiting receptors (preventing NK cells from killing healthy cells)
They are non-specific
Have no memory and have no MCH restriction
How are normal cells protected from NK acction?
Healthy cells express enough MHC class I molecules to induce a strong inhibatory signal in NK cells. These cells are therefore protected from NK cell attack
Explain how NK cells have a strong activation?
Stong activation—> transformed or infected cells sometimes increase the expression of molecules that are recognised by activating NK cell receptor (activating ligands). NK cells now recieve a much stronger activating signalthan usually. this may override the inhibitory signal and allow NK cells to attack that cell
When they bindthey release perforins, induce apoptosis, and release interferon gamma
What is the role of antigen pressenting cells in viral infection?
Involved early in the host rsponse
Carry Ig Fc and C3b receptors which promote phagocytosis
MHC restricted
Initiates adaptive response
How is the virus recognised as foreign?
Ø Innate responses recognised PAMPs
Ø Un-methylated C-G dinucleotides on DNA viruses
- High freq in virus
- Low freq in mammalian cells
Ø Double stranded RNA
Uracil rich, single stranded RNA
What cell receptors are involved in viral infection/response?
Pattern recognition receptors or PRRs
TLRs: Found on the surface of cells and within endosomes of phagocytic cells (Neutrophils and APCs)
Detect extracellular viruses
Cytoplasmic PRRs: Found in the cytoplasm
RIG-1-like receptor (RIG-1 and MDA-5)
NOD-like receptor
Cytosolic DNA sensors
What binds to:
TLR3
TLR7
TLR8
TLR9
TLR3: ds RNA
TLR7: uracil rich ss RNA
TLR8: ss RNA
TLR9: CpG motifs within viral DNA
What happens when viral products bind to signalling receptors?
Signalling cascade in the result synthesis of cytokines that block virus replication in the infected host
What do RIG-1 and MDA-5 recognise?
RIG-1: ssRNA
MDA-5: ds RNA
What is the action/function/purpose etc. of interferon?
Ø Most important of the broad host defences against viral infections
Ø Protects adjacent cells from infection
Ø Viral replication inhibited
Ø Helps activates T-cell mediated immunity
- Macrophage activation
Up-regulation MHC receptors on virus infected cells
What do INF alpga and beta do?
Activate genes that have antiviral activites
ACtivate NK cells
Induce apoptosis
Produced early in the infection
What does gamma interferon do?
Ø Involved in the regulation of nearly all phases on immune and inflammatory response
Ø Produced by NK cells and T-lymphocytes
Ø Enhances MHC expression on APCs
Ø More important as a immunoregulator that as an antiviral agent
Enhances cytotoxic activity of T-cells, macrophages and NK cells
What would you expect to happen to mice susceptibility when infected with DEN2 infection:
WT mice
IFN alpha and beta deficient mice
IFN gamma deficient mice
IFN gamma alpha and beta deficent mice
WT mice: >80% survive
IFN alpha and beta deficient mice: did not succumb to infection
IFN gamma deficient mice: Succumbed to infection
IFN gamma alpha and beta deficent mice: lacking both types of receptors so fully suscuptible to DNE2-induced disease
What is involved in a cellular immune response?
Cytotoxic T cells CD8+ Kill virus infected cells
Cytokines that eliminates viral RNA
T-helper cells CD4+
Activates macrophages
Cytokines
What is the purpose/function of B-lyphocytes in humoral immune response against viral infection?
Ø Resident in the lymphatic system
Ø Responds t antigenic stimulus by producing and secreting Ab
Ø Carry highly specific receptors tat recognise viral epitopes
Recognise Ag in their native form
What are the main functions of IgG, IgM, IgA?
IgG: main circulating Ab, Important for long term immunity
IgM: Circulating Ab produced early in infection, Diagnostic marker
IgA: Secretory Ab, Priamry defence at mucosal surfaces
What is the role of Ab in a viral ionfection?
Ø Binds to circulating virus- may prevent attachments
Ø Opsonisation- virus coated with Ab activates complement, induces inflammatory response (attract phagocytes)
Ø Neutrophils and macrophages: phagocytose virus coated with Ab
Describe the action of CD8+ T-cells
Recognises viral peptides on the surface of infected cells in associated with MHC class I
Kill virus-infected cells
Granules within the CTL polarise towards the target cell
Perforin is released and creates pores in the cell membrane causing lysis
Describe the action of CD4+ T-cells
Recognises viral peptides on the surface of APCs in associated with MHC class II
Plays essential role in initiation of B cell responses
Secrete cytokines that regulate the immune response
Main types are TH1 and TH2
Describe the differences between TH1 and TH2
TH1: secretes IL-2, inflam response, augments immune response by attracting macrophages to sire of infection, activates IFNgamma and Beta, Promotes IgG2a production
TH2: secretes IL-4,5,6, provides help for Ab production, Promotes switching of B-cells (IgG2a to IgG1)
What are the humoral immune response targets?
Ø Surface exposed proteins
Envelope proteins- capsid proteins
Ø Often spikes or loops that protrude from viral surface
Epitopes can be linear or conformational
Which viral antigens induce which immune response
Surface proteins are recognised by Ab
B-cells epitopes are on surface exposed proteins and more likely to be conformational
Internal and surface proteins are recognised y T-cells
T-cell epitopes can be internal or external proteins, epitopes are linear (continuous)
What is a cut-off in ELISA?
Mean of the known negatives plus 2 or 3 standard deviations, assuming normal distribution
Why is western Blots not used routinely in a diagnostic setting?
It cant be easily standardised or scaled up for automation
