Viral Immunology and Viral Vaccines Flashcards
______ defenses are not specific to the pathogen but the general class of pathogen
Innate
Describe what happens on initial exposure to a pathogen
On initial exposure, innate defenses are first. Innate defenses slow or stop the pathogen
What happens upon secondary exposure to a pathogen?
The neutralizing antibodies and CTLs from the adaptive response can act fast to prevent disease
Describe the barriers to infection
-The physical barriers can stop a microbe from infecting a person: skin, coughing, sneezing, mucus, and stomach acidity
-Antimicrobial compounds can also act on viruses to prevent infection
When is type I interferon triggered?
If a virus can circumvent the physical barriers and infect a cell, type I interferon is triggered, telling the body than an infection is occurring
What do pattern recognition receptors recognize?
Recognize viral RNA and DNA in an infected cell and stimulate type I interferon
What do interferons induce?
Can induce a wide variety of genes in the infected cells and help guide the immune response. It is most well-known for activating a large number of proteins that have antiviral properties
Many viruses have devised ways to reduce the ___________ response
type I interferon
Describe NK cells and their function
1) NK cells are important cells in viral infections
2) They can kill infected cells stopping viral spread
3) They are most well-known for recognizing cells that have down-regulated their MHCI. Many viruses can down-regulate MHCI. They do this to escape CTL killing
Describe macrophages and dendritic cells and their function
-They are essential in bridging the innate and adaptive immune responses
-A type of dendritic cell called a plasmacytoid DC can make large amounts of type I interferon in a viral infection. This is because they can sense a viral infection without being actively infected. No active infection means most of the ways the virus has to stop interferon production will not work in plasmacytoid DC.
A critical part of the adaptive immune response to viral infections is the _________
neutralizing antibody response
Neutralizing antibodies will bind to the surface of a virus preventing the virus from infecting a cell
Viral antigens encountered in the mucosa primarily produce dimeric _____
IgA
These antibodies are produced in large quantities in the mucosal surfaces, gut, and upper and lower respiratory tract
Viruses that a viremic stage (virus in the blood) primarily produce _____
IgG
Another critical adaptive response in viral infection is the activation of ________
cytotoxic T lymphocytes (CTLs)
CTLs are critical for viral infections because they kill infected cells. They are also crucial in keeping chronic viral infections in check
List the 4 ways viruses subvert the immune system
1) Escape neutralizing antibodies by antigenic drift
2) Blocking the type I interferon response
3) Down-regulating MHC I which prevents killing CTLs
4) Killing immune cells - like HIV killing CD4 cells
What happens if you encounter the same strain of virus?
1) If you encounter the same strain of virus, you are generally protected from reinfection due to the long-lived plasma cells and secreted antibodies
2) These neutralizing antibodies are present in your mucosa and blood before re-encountering the virus
3) The neutralizing antibodies present bind to the virus, prevent infection and induce sterilizing immunity. In fact, you may go through another round of affinity maturation and end up with even better antibodies and higher levels
Describe cross-protection
The new strain is recognized with good affinity by antibodies from a previous strain, resulting in no infection or sickness
Describe partial cross-protection
Antibodies bind with lower affinity. As a result, the antibodies cannot prevent some cells from being infected. The infection will generally clear faster, and there might be fewer symptoms because you will get helpful neutralizing antibodies quicker than in a primary infection. This will result in less spread of the virus. Also, the memory CTLs from the previous infection might be able to recognize and clear the infected cells, reducing the infections severity.
Describe no cross-protection
It is like a new infection
What do you need to get an effective vaccine?
1) Need to induce a protective neutralizing antibody response to the virus. The vaccine needs to include viral proteins that produce neutralizing antibodies, i.e., proteins on the surface of the virion
2) Stimulate an immune response
-Have an attenuated virus or whole killed/inactivated virus. These have viral-specific signals that will activate pattern recognition receptors in immune cells turning on the immune response
-Or include an adjuvant. An adjuvant is a substance that activates the immune system.
Describe attenuated virus vaccine
Attenuated viruses replicate just a little, and the immune system sees it as a regular viral infection and mounts an immune response. The immune response can clear the virus before you get sick. These tend to be excellent vaccines
List the 9 infections that have an attenuated vaccine
1) Measles, mumps, rubella (MMR)
2) Varicella Zoster (chickenpox)
3) Rotavirus
4) Nasal Influenza Vaccine
5) Yellow fever vaccine
6) Smallpox/Mpox (vaccinia)(not for the general public)
7) Oral polio (not used in the US)
8) Military only - Adeno type 4 and 7
9) Adenovirus modified vaccines for Coronavirus
Describe Whole killed virus/Inactivated virus
Here the virus does not replicate at all. It can still start an immune response because it has viral proteins and nucleic acid that trigger it. Although, adding an adjuvant will usually result in a better immune response. Many more virus particles are needed in an inactivated vaccine than in an attenuated vaccine. Also, in general, more booster shots are required for complete immunity.
List the 4 viruses than need a whole killed virus/inactivated virus vaccine
1) Inactivated polio vaccine (use in the US)
2) Hepatitis A vaccine
3) Rabies vaccine
4) Influenza vaccine
Describe subunit vaccines
Here you just have a part of a virus; there is no chance of infection. You have to make sure you use the correct protein to get a neutralizing antibody response. An adjuvant is very helpful in subunit vaccines.
List the 5 viruses that use subunit vaccines
1) HA only influenza vaccine
2) Hepatitis B vaccine
3) Human Papilloma vaccine
4) New Shingles vaccine
5) mRNA vaccines producing one or two viral proteins
Why are some immunizations not done until the baby is one year of age?
Because of naturally occurring maternal antibodies.
-This is most important with the measles/mumps/rubella vaccine
-The maternal antibodies will bind the attenuated virus preventing replication of the virus. This will inhibit the attenuated strain from infecting cells and prevent an immune response in the infant. Then when the maternal antibodies leave the baby, the baby has no protection
Natural in babies, ____ is transferred to the baby in the third trimester, and ______ in colostrum and breast milk
IgG; IgA
Sometimes antibodies are given post-exposure to help prevent infection. List the illness associated with Immunoglobulin from healthy blood donors
Hepatitis A
Measles
Sometimes antibodies are given post-exposure to help prevent infection. List the illnesses associated with Hyperimmune IG is from people with a high titer to a specific infection.
Hepatiti B
Rabies
Chickenpox
CMV
Vaccinia
Sometimes antibodies are given post-exposure to help prevent infection. List the illnesses associated with Monoclonal antibodies to specific viruses
RSV-Given pre-exposure
SARS-CoV-2
In some cases, it is possible to prevent infection after exposure by vaccination if done quickly. What illnesses is this the case for?
-Rabies/with Rabies Immune Globulin
-Hepatitis A
-Hepatitis B/with Hepatitis B immune globulin
-Smallpox
Describe herd immunity
Herd immunity refers to the fact that the spread of infectious disease requires contact between a non-immune person (susceptible) and an infected person. The lower the number of non-immune people, the less chance the
infection has of spreading. Herd immunity will ultimately benefit non-immune people
What percentage of the population does a vaccination to reach to protect the community
depends on the virus but usually spans 75-95%
Who is protected by herd immunity?
-Babies
-People allergic to vaccine components
-Immunocompromised people
-People unresponsive to vaccine
-People with waning immunity to vaccine
