IL6 Immmunity to Viral Infection

Question 1

Structural protection by the skin

Answer 1

Sweat, desquamation, organic acids

Question 2

Structural protection by the GI tract

Answer 2

Peristalsis, gastric acid, bile acids, digestive enzymes, flushing, thiocyanate, defending, gut flora

Question 3

Structural protection by the respiratory airway and the lungs

Answer 3

Mucociliary escalator, surfactant, defensins

Question 4

Structural protection by the nasopharynx

Answer 4

Mucus, saliva, lysozyme

Question 5

Interferons

Answer 5

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.

Question 6

Progress of response during infection timeleine

Answer 6

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

Question 7

Mechanism of IFN signalling

Answer 7

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.

Question 8

Natural killer cells

Answer 8

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

Question 9

Origin of NK cells

Answer 9

Lymphoid cells derived from Lymphoid Progenitor (CLP) in the bone marrow. Thymus not required, do not undergo receptor gene rearrangements.

Question 10

Define trait of NK cells

Answer 10

Express a set of activating and inhibiting receptors. These are used to determine whether or not to kill a target cell.

Question 11

NK detection function

Answer 11

Decide whether to kill based on detection of activating “stress” receptors, or inhibitory MHC-1 receptors.

Question 12

Virally infected cells and tumour cells ______ (up/down) regulate major histocompatibility complex I (MHC-I) proteins at the cell surface.

Answer 12

Down.

All normal host cells should have MHCI. Thus acting as an inhibitor of NK cells.

Question 13

NK killing mechanism

Answer 13

Induce apoptosis, release perforin/granzymes at the junction of two cells.

Question 14

Granzyme/perforin-mediated cytolysis

Answer 14

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.

Question 15

Cytotoxic T cells

Answer 15

Most important pathway to fig

Question 16

Cytotoxic T cells basic mechanism outline

Answer 16

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.

Question 17

Cross presentation

Answer 17

Dendritic cells uptake an exogenous antigen from the outside, and process it to present on MHC-I

Question 18

T cell trafficking and recognition of infected cells

Answer 18

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.

Question 19

MHC Class I function

Answer 19

To present a sample of cellular insides to the immune system.

Question 20

The CTL “Kiss of Death”

Answer 20

Occurs via TCR activation:
- Perforin/granzyme pathways
- Fas/FasL pathways

Question 21

MHC diversity

Answer 21

MHC alleles are highly polymorphic and polygenic and expression of different alleles in defined by codominance.

Question 22

Why so much MHC diversity?

Answer 22

Pathogens can evolve rapidly through mutations that change their protein sequences to avoid recognition.

Question 23

Fas/FasL C

Answer 23

Drives apoptosis

Question 24

Antibody mediated protection

Answer 24

Block attachment, aggregate for phagocytosis, activate complement for MAC attack.

Question 25

CD8+ vs CD4+ T cells and MHC class

Question 26

Down-regulation by viruses

Answer 26

Prevents expression of viral proteins in MHCI. Allows viruses to hide from CTL BUT NK cells can recognise even low levels of expression -they can induce apoptosis.