Host Responses and Vaccines

What are some of the intrinsic immunity barriers for viruses?

Skin

Low pH

Mucous

Tears

No virus receptor

Intracellular barriers blocking replication

Physical and anatomical barriers

What is required for the innate immune system to function?

No prior exposure to the virus

What happens if the innate immune system cannot get rid of the infection?

The adaptive immune system with B and T cells will take over

What are the first line of immune defense against a virus?

NK cells

Cytokines

What are interferons?

A type of cytokine produced by virus infected cells to produce nonviral proteins that protect uninfected cells against other viruses

What are PAMPS?

Pathogen-associated molecular patterns

What is a pattern-recognition receptor?

Molecule that recognizes PAMPS

How do dendritic cells respond to PAMPS?

Secreting type 1 interferon

What are Toll-like receptors (TLRs)?

Transmembrane proteins that recognize microbial macromolecular patterns like dsRNA, viral glycoproteins, and other viral proteins

What happens when a TLR is activated?

Cytokine and interferon production

What do macrophages do?

Engulfs the virus infected cells

What does type 1 interferon stimulate the transcription of?

antiviral interferon stimulated genes (ISGs)

What is the prodromal period?

No host response but virus is present

What order do host proteins spike during an infection?

IFN-type 1

NK cells

IgM

IgG

What immune response is tailored to the pathogen?

Adaptive immune system

What is a TH1 immune response?

CTLs

What is a TH2 immune response?

Antibody mediated

How are some viruses like a trojan horse?

They can infect dendritic cells and carry viruses into the lymph nodes

What are some examples of trojan horse viruses?

HIV, DEN, VEE

What are dendritic cells?

The pick up dead cells and present them to a lymph node, also known as antigen presenting cells

What adaptive immunity component is needed to clear most viral infections?

Cell-mediated response (Th1)

Naive T cells can split into what 2 lines?

CD4 helper T lymphocytes

CD8 cytotoxic lymphocytes

What are CD4 helper T lymphocytes?

Make cytokines to help B cells mature, activate macrophages, and inflammation

What are CD8 cytotoxic T lymphocytes (CTL)?

Cytotoxic T cells lyse the virus infected cells

What are the 2 main cytotoxic proteins?

Perforin and Granzymes

What do granzymes do?

Target cell apoptosis and death

What is an MHC?

Major histocompatibility complex

What is a class 1 MHC?

Pathway leading to killing infected cells

What are endogenous antigens and what MHC uses them?

Antigens created in a virus-infected cell and are seen in MHC class 1

What are exogenous antigens and what class of MHC uses them?

Antigens made outside of the cell and exogenous antigens

What are Th1 cells?

CTLs are activat3ed by cytokines and can clear many viral infections

What are Th2 cells?

Activate B cells with cytokines and not as good for clearing viruses

What is a humoral response?

Activation of B cells after they are presented with viral antigens by APCs.

Clones of B cells are selected and amplified to secret antibodies

Some B cell clones become plasma cells

Antibodies can be made for homologous infections in the future

What is the structure of antibodies?

Variable regions bind to the antigen

Constant region does not vary much

At what stages can antibodies block a virus?

Block attachment site on the virus for the cell receptor

Antibodies cause aggregation of viruses and large clump of virions cannot enter the cell

Antibodies can block endocytosis by binding to the virus receptor

Block uncoating by entering the endocytotic pathway with the virus and blocking the uncoating of the viral genome

T/F herd immunity can be achieved via natural infection of vaccination?

True

T/F protected population needs to be 100% for herd immunity?

False

What was the worlds first vaccine?

Smallpox

What are the two general types of vaccines?

Active

Passive therapy

What is an active vaccine?

Long term protection

Vaccine contains a modified form of the pathogen or material that is derived from the pathogen

Induces immunity without disease

What is an example of an active vaccine?

Yellow fever 17D vaccine - attenuated virus

What is a passive therapy vaccine?

Short term protection

Vaccine contains antibodies or immune cells

How long does a passive therapy vaccine last?

a month or two

What is an example of a passive therapy vaccine?

Rabies vaccine - sera from vaccinated people

How does a passive vaccine of convalescent serum work?

1. Infected patient

2. Draw blood to obtain convalescent plasma containing virus neutralizing antibody

3. Transfer antibodies to infected patient

What makes a good vaccine?

Must make the appropriate immune response

Must protect against the disease not just produce antibodies

Stable

No shedding of virus

Why is the problem if a vaccine causes shedding of the virus?

It can spread the virus and cause epidemics

What is an example of an epidemic caused by a vaccine?

VEEV: TC83 vaccine was spread by mosquitoes

ASF shedding in wild boars

What type of vaccine is more likely to be shed?

Partially attenuated live viruses

What type of vaccine creates a subclinical infection?

Attenuation vaccinesq

What type of vaccine destroy infectivity but keeps the immunogenicity?

Inactivated vaccines

What is a subunit vaccine?

A vaccine created from a part of a virus

What is a recombinant DNA vaccine?

A type of active vaccine that has segments of DNA removed from the viral genome to prevent replication

T/F recombinant DNA vaccines have DIVA compatability?

True

What are VLPs?

Virus like particles

What do VLPs do?

Genes that encode the capsid proteins are expressed and lead to self-assembly of the capsid proteins into virus-like proteins

Why are VLPs so safe?

It is essentially an empty capsid with no viral nucleic acid

T/F VLPs can be used for vaccines?

True

What are vaccine adjuvants?

Boost immune response to enhance immunogenicity of inactivated vaccines

What are the 2 traditional methods for vaccination?

Inactivated/killed virus preparations - chemically inactivated whole virions which are non replicating

Live-attenuated virus strains

When is an adjuvant needed?

With inactivated virus vaccines to boost immune response

What type of vaccine usually only needs one dose for long-term protection?

Modified-live virus vaccines

What is an attenuated vaccine?

Virus causes a mild or inapparent disease

What was the first human virus identified?

Yellow fever

What transmits yellow fever?

Mosquitoes

What type of vaccine is the rinderpest vaccine?

Attenuated vaccine it was created by growing the virus in rabbits

What type of virus is rinderpest?

Morbillivirus

When was rinderpest eradicated?

2011

What kind of vaccine is the CSF vaccine?

Attenuated vaccine grown in rabbits to be made

How is classical swine fever (CSF) transmitted?

Oral or nasal routes, mucus membranes, skin abrasions

What are the clinical signs of CSF?

High fever, leukpenia, hemorrhage, depression, anorexia, constipation, diarrhea

T/F CSF is eradicated from the USA?

True