03: Vaccines

Components of innate immunity

• Barriers (physical and chemical)

• Recognition of MAMPs

• Type I IFN

• NK cells

Example of a mechanical/physical barrier

Epithelial tight junctions

Example of a chemical barrier

Low pH due to stomach acid

Example of a microbiological barrier

Normal flora in the GIT or on the skin

Type I IFNs crucial to innate immune response

IFN α and β

Purpose of type I IFNs in the immune response

Induces an antiviral state

How do type I IFNs act on cells

Autocrine and paracrine

End result of IFN action

• Upregulation of MHC I

• Apoptosis

Viral components that may be recognized by a cell

• Glycoproteins

• Capsid proteins

• Nucleic acids where they shouldn’t be (in the cytosol)

• Nucleic acids in the wrong conformation (dsRNA)

At a basic level, how do viruses try to avoid the immune system

Partially blocks IFN production or other events in the innate immune cascade

How are NK cells activated

Recognizing cells that have down regulated MHC I

Cells involved in adaptive immune response

CD4/8 cells and B cells

How are B and T cells activated

Dendritic cells pick up a viral antigen → travels to LNs → presents to B and T cells

Result of activated T cells

CD8 cells go hunting

Result of activated B cells

Turns into Ab factories (plasma cells)

MHC I present to what cell

CD8

Type of Ag presented by MHC I

Endogenous/intracellular antigens

MHC II presets to what cell

CD4

Type of Ag presented by MHC II

Exogenous/extracellular antigens

What type of vaccine produces a weak T cell response and why

Inactivated/killed vaccine has no replication → presented to CD4 instead of CD8 → weaker T cell response

How are endogenous Ags processed for MHC presentation

Digested by a proteosome

How are exogenous Ags processed for MHC presentation

Digested by a lysosome

First antibody produced during a viral infection

IgM

Antibody that quickly follows IgM production and last for a long time

IgG

Antibody that lives in the mucosa

IgA

Which antibody is the best for viral testing

IgM- short term Ab, presence indicates a recent infection!

How do CD8 cells cause cell death

• Apoptosis via Fas/FasL

• Perforin-granzyme pathway

Which part of the immune system is stimulated best by non-replicating vaccines

B cells

How do we increase the CD8 cell stimulation of non-replicating vaccines

Adjuvants and booster vaccines

T/F: certain adjuvants can stimulate a T cell response comparable to a modified live or live vaccine

False; nothing takes the place of true immune stimulation

Pro of non-replicative vaccines

Do not cause disease and are safer for immune compromised patients

Types of replicating vaccines

Attenuated/modified live vaccines and recombinant vector vaccines

Ways to attenuate a MLV

• Heterologous strain

• Serial Passage

• Mutation

• Cold adapted

How do MLVs stimulate the immune system

Virus replicates, eliciting a virus-specific response

How does serial passage attenuate a vaccine

Allows the accumulation of mutations that make the virus less pathogenic

How does cold adaptation attenuate a vaccine

The virus adapts to thrive in slightly lower temperatures, so when it is inoculated into a patient the virus can only survive in cooler areas like the URT, resulting in less severe clinical signs

How does a heterologous host attenuate a vaccine

Development in an un-natural host makes the virus loose virulence for the natural host, so when it is re-introduced as a vaccine it has lower clinical signs

Drawbacks to a MLV

Generally less safe; may produce mild clinical signs or even revert to a pathogenic form

Recombinant vector vaccine

The genome from a pathogenic virus is stuck inside the capsid shell of a non-pathogenic viral vector

DIVA

Distinguishing infected vs vaccinated animals

How do we bioengineer DIVA vaccines

Bioengineer the vax with missing genes, so the real virus produces specific Abs that can be detected on serological testing

Drawbacks of a recombinant vector vaccine

• Lower immunogenicity

• Repeat vaccine with the same vector may result in decreased or no efficacy