IL6 Immmunity to Viral Infection Flashcards
Structural protection by the skin
Sweat, desquamation, organic acids
Structural protection by the GI tract
Peristalsis, gastric acid, bile acids, digestive enzymes, flushing, thiocyanate, defending, gut flora
Structural protection by the respiratory airway and the lungs
Mucociliary escalator, surfactant, defensins
Structural protection by the nasopharynx
Mucus, saliva, lysozyme
Interferons
Small cytokine proteins produced by virally infected cells. Serve as a warning system and prevent viral replication by stimulating production of antiviral proteins in unaffected cells.
Progress of response during infection timeleine
First four days - IFN-α, IFN-β
Peak at day four - NK cells
Gradual build, peak at day 7-11 - specific CTLs
Finally - antibodies multiply
Mechanism of IFN signalling
Infection, expression of interferon genes and synthesis of IFN, secretion and diffusion of IFN to neighbouring cells, reception and activation of antiviral genes to degrade viral RNA.
Natural killer cells
Cytotoxic lymphocytes that lack specific At receptors (no TCR). Help to regulate innate/adaptive immunity through cytokine secretion, and can recognise/destroy pathogen-infected or abnormal tumour cells.
NO TCR
Origin of NK cells
Lymphoid cells derived from Lymphoid Progenitor (CLP) in the bone marrow. Thymus not required, do not undergo receptor gene rearrangements.
Define trait of NK cells
Express a set of activating and inhibiting receptors. These are used to determine whether or not to kill a target cell.
NK detection function
Decide whether to kill based on detection of activating “stress” receptors, or inhibitory MHC-1 receptors.
Virally infected cells and tumour cells ______ (up/down) regulate major histocompatibility complex I (MHC-I) proteins at the cell surface.
Down.
All normal host cells should have MHCI. Thus acting as an inhibitor of NK cells.
NK killing mechanism
Induce apoptosis, release perforin/granzymes at the junction of two cells.
Granzyme/perforin-mediated cytolysis
Stimulated NK cells release.
Perforin is a pore-forming protein, granzymes are serine proteases. Both are endocytosed, then punch holes in the membrane to induce apoptosis from the inside out.
Cytotoxic T cells
Most important pathway to fig
Cytotoxic T cells basic mechanism outline
VIrus is killed by DC and viral antigens are processed. Antigens are then taken to the local draining node and the DC presents them to T cells in the context of MHC-I.
T cells are activated and leave the node to patrol.
Cross presentation
Dendritic cells uptake an exogenous antigen from the outside, and process it to present on MHC-I
T cell trafficking and recognition of infected cells
Activated cells proliferate and then exit the node via the blood to be transmitted to the site of infection. They recognise infected cells via MHC-I and viral peptide complexes.
MHC Class I function
To present a sample of cellular insides to the immune system.
The CTL “Kiss of Death”
Occurs via TCR activation:
- Perforin/granzyme pathways
- Fas/FasL pathways
MHC diversity
MHC alleles are highly polymorphic and polygenic and expression of different alleles in defined by codominance.
Why so much MHC diversity?
Pathogens can evolve rapidly through mutations that change their protein sequences to avoid recognition.
Fas/FasL C
Drives apoptosis
Antibody mediated protection
Block attachment, aggregate for phagocytosis, activate complement for MAC attack.
