Immunology Final Exam (Part 1) - Vaccines

What type/mechanism of immunity is immunity acquired from antibodies passed in breast milk or through the placenta?

Passive Natural Acquired

(ex: IgA, IgG)

NOTE: Passive always = person not doing the work

What type/mechanism of immunity is immunity gained thorough illness and recovery?

Active Natural Acquired

What type/mechanism of immunity is immunity acquired through a vaccine?

Active Artificial Acquired

What type/mechanism of immunity is immunity gained through antibodies harvested from another person or an animal?

Passive Artificial Acquired

What is the process where people who had not had smallpox were exposed to material from smallpox sores, people usually developed symptoms associated, but only 3% contracted actual smallpox?

Variolation

What is the attempt to stimulate the adaptive immune system to create MEMORY?

Vaccination

What cell involved in creating memory is an antigen coming to a secondary lymph organ via lymph or blood?

Memory B cells

What cell involved in creating memory are APC that must present the antigen on MHC II?

Memory helper T cells

What cell involved in creating memory are infected cells that must present the antigen on MHC I?

Memory killer T cells

T/F: Memory Helper T cells and Killer T cells can be produced even when an invader does not infect an APC. In contrast, Memory Helper B cells need an attacker to infect an APC to be made.

FALSE

Memory B & Th produced w/o invader

Memory Tk must have attacker present

What are the three strategies for vaccine development?

1) Non-infections

2) Attenuated

3) Carrier (kind of infectious!)

What type of non-infectious vaccine includes dead organisms (treatment w/ physical or chemical agent) such as Polio, and it should not be able to infect or replicate?

Killed Vaccines

What type of non-infectious vaccine has materials isolated from disrupted or lysed organisms (not whole) such as acellular vaccine for pertussis?

Subunit Vaccine

What type of Subunit vaccine doesn't contain viral genetic information (capsid), and looks like a virus but not "alive"?

Virus-like particle

What type of Subunit vaccine is inactivated/weakened toxins, such as Diphtheria and tetanus?

Toxoids

What type of Subunit vaccine is terminology to describe genetic modification?

Recombinant vaccines

What type of non-infectious vaccine combines different antigens to improve the response, such as carbohydrate antigens?

Conjugated Vaccines

What type of non-infectious vaccine is a genetically modified live virus (replicating and non-replicating)?

Carrier Vaccine (Vector Vaccine)

What type of non-infectious vaccine is naked DNA extracted from a pathogen, with the host cell taking up the DNA and makes the proteins of the pathogen?

DNA Vaccines

What type of non-infectious vaccine has modified mRNA delivered by lipid nanoparticles?

mRNA Vaccines

T/F: Non-infectious vaccines will cause the body to make more B and helper T cells, and does not cause the production of memory killer T cells

TRUE

Maybe on the killer T cell thing...

______________ is not only an efficient mechanism exploited by DC to initiate immunity to viruses that do not infect DC, but also to viruses that do infect DC, because this mechanism has many conceptual advantages and bypasses direct immune modulatory effects of the virus on its infected target cell.

Cross-presentation

What are two killed examples of non-infectious vaccines?

1) Inactivated polio vaccine (killed virus)

2) Typhoid vaccine (killed bacteria)

What are 3 ways in which microbes are killed in non-infectious vaccines?

1) Chemicals

2) Heat

3) Radiation

Which type of subunit vaccine (using only part of the pathogen) is a recombinant protein? Which is a polysaccharide conjugate? Which is a protein conjugate?

Recombinant protein = Hepatitis B vaccine

Polysaccharide conjugate = Haemophilus influenza type B (Hib)

Protein conjugate = Acellular pertussis vaccine

How are non-infectious subunit vaccines made?

Recombinant technology (using another organism to make vaccine antigen)

-- talk parts of pathogens (getting rid of harmful portions and keep non-harmful parts)

-- conjugate protein to carbohydrate antigen to make more "visible" to immune system

Which COVID vaccine is a protein subunit vaccine, where it contains harmless S proteins, and once the immune system recognizes the S proteins, it creates antibodies and defensive WBC, then if you later become infected with COVID-19 virus, the antibodies will fight the virus?

Novavax COVID-19 vaccine

How are Virus Like Particles (VLPs) non-infectious vaccines generated?

Empty virus particle (doesn't contain viral genetic information)

-- displays antigens form agent of interest

What are 3 examples of DNA vaccines of non-infectious vaccines?

1) Clinical trial of Zika vaccine

2) ZyCoV-D

3) West Nile Virus

How are DNA vaccines (non-infectious vaccines) generated?

Isolate DNA that encodes for pathogenic genes

-- DNA packaged into recombinant viral vectors (such as retrovirus which can reproduce)

-- Inject into patient, host machinery transcribes & translates DNA information

What is a type of mRNA vaccine (non-infectious vaccines)?

COVID 19 vaccines

How are mRNA vaccines (non-infectious vaccines) generated?

mRNA packaged in lipid nanoparticle and injected

-- mRNA code translated and displayed as foreign

Which two COVID vaccines are mRNA vaccines, where the mRNA gives your cells instructions for how to make the spike protein found on the surface of the COVID-19 virus, and after vaccination, your immune cells begin making the spike protein and displaying them on the cell surface, causing the body to create antibodies that can fight the virus?

Pfizer-BioNTech & Moderna

Non-infectious Vaccines Summary

Do NOT infect our cells

-- works well w/ some extracellular bacteria that never infect cells

-- will cause B cells to make antibodies sufficient to protect against many pathogens

Works well with SOME that do infect cells (Poliovirus & Hep B) but does not work well for other that do infect cells (Measles/Mumps)

So whether memory CTLs are required for protection depends on the particular microbe and its lifestyle

What type of vaccine is the weakened version of the pathogens that mimic the kind of protective immunity found in people that have survived the live infection and infects the host's APC?

Live Attenuated Vaccines

What 3 things does Live attenuated vaccines result in?

Memory B cells

Memory Th cells

Memory Tk cells

What are two examples of Life Attenuated vaccines?

Sabin polio vaccine

(normally reproduces in human nerve cells but reproduced in monkey kidney cells, resulting in weaker virus but still infectious)

Measles, Mumps, Rubella (MMR)

(elicits strong immune response that can give lifelong immunity after only 1-2 doses)

What type of vaccine introduces a single gene from a pathogenic microbe into a virus that doesn't cause disease (live), replicating vs nonreplicating, and a carrier infects the host's APCs, producing pathogenic microbes proteins?

Carrier Vaccines (viral vector)

What is most commonly used as the carrier in Carrier Vaccines (viral vector)?

Adenovirus MC (replicating/non-replicating)

The pathogenic microbe protein fragments are presented on _____________ molecules in carrier vaccines?

MHC I molecules

What 3 things does Carrier Vaccines (viral vector) result in?

1) Memory B cells

2) Memory Th cells

3) Memory Tk cells

What COVID vaccine is a viral vector vaccine made when genetic material from COVID-19 virus is inserted into a unrelated, harmless virus, so when it enters your cells, it delivers the genetic material that gives the cells instructions for how to make the spike protein found on the virus, and once the cells displace the spike proteins on their surfaces, the immune system creates antibodies that fight the virus?

Johnson & Johnson Vaccine

AstraZeneca & University of Oxford

What is a siltation in which a sufficient proportion of a population is immune to an infectious disease to make it spread form person to person unlikely, so that even individuals not vaccinated are offered some protection because the disease has littel opportunity to spread within the community?

Community Immunity

(Herd Immunity)

Efficacy of Vaccines Summary

Non-infectious vaccines

-- cant contract actual illness

-- easy to manufacture

-- don't elicit the same response as live pathogen

Live vaccine

-- much more closely mimic real pathogen

-- difficult to manufacture

-- we can get sick!

What 3 diseases is the MMR vaccine used for? What "organism" is this used against?

Measles, Mumps, & Rubella

Virus

What type of vaccine is the MMR vaccine?

Life attenuated

What 3 diseases is the DTaP vaccine used for? What "organism" is this used against?

Diphtheria, Tetanus, & Pertussis

Bacteria

What type of vaccine is DTaP, specifically for Diphtheria & Tetanus? How about Pertussis?

Toxoid

Subunit

What disease is the Hib vaccine used for? What "organism" is this used against?

Hib

Bacteria

What type of vaccine is Hib?

Conjugate

What disease is Prevnar13 or Pneumovax23 used for? What "organism" is this used against?

Pneumonia

Bacteria

What type of vaccine is Prevnar13? Pneumovax23?

Prevnar13 = Conjugate

Pneumovax23 = Polysaccharide

What disease is the Meningococcal vaccine used for? What "organism" is this used against?

Meningitis

Bacteria

What type of vaccine is Meningococcal?

Recombinant

What disease is the Hep B vaccine used for? What "organism" is this used against?

Hepatitis B

Virus

What type of vaccine is Hep B?

Recombinant

What disease is the Rotavirus vaccine used for? What "organism" is this used against?

Rotavirus

Virus

What type of vaccine is Rotavirus?

Live attenuated

What disease is the IPV vaccine used for? What "organism" is this used against?

Polio

Virus

What type of vaccine is IPV?

Whole inactivated

What disease is the Varicella vaccine used for? What "organism" is this used against?

Chickenpox

Virus

What type of vaccine is Varicella?

Live Attenuated

What disease is the Zoster vaccine used for? What "organism" is this used against?

Shingles

Virus

What type of vaccine is Zoster?

Live attenuated

What disease is the Hep A vaccine used for? What "organism" is this used against?

Hepatitis A

Virus

What type of vaccine is Hep A?

Whole inactivated

What disease is the HPV (Gardasil) vaccine used for? What "organism" is this used against?

HPV infection

Virus

What type of vaccine is HPV (Gardasil)?

Recombinant (VLP)

What disease is the Flu vaccine used for? What "organism" is this used against?

Flu

Virus

What type of vaccine is the Flu?

Live attenuated or Whole inactivated

What disease is the BCG vaccine used for? What "organism" is this used against?

Tuberculosis

Bacteria

What type of vaccine is BCG?

live attenuated

Vaccine Name, Disease, & Type SUMMARY

Live Attenuated Vaccines

1 - MMR (Mumps/Measles/Rubella)

2 - Rotavirus

3 - Varicella (Chicken Pox)

4 - Zoster (Shingles)

5 - Flu (also whole inactivated)

6 - BCG (Tuberculosis)

Toxoid

1 - DTaP (ONLY Tetanus & Diphtheria)

Subunit

1 - DTaP (ONLY Pertussis)

Conjugate

1 - Hib

2 - Prevnar13 (Pneumonia)

Polysaccharide

1 - Pneumovax23 (Pneumonia)

Recombinant

1 - Meningococcal (Meningitis)

2 - Hep B

3 - HPV Gardasil

Whole Inactivated

1 - IPV (Polio)

2 - Hep A

3 - Flu (also live attenuated)

mRNA & Viral Vector

1 - SARS CoV2 COVID

Vaccine Types SUMMARY

Attenuated Vaccine

- based on organism that are living; virulence & ability to replicate diminished

Killed Vaccines

- dead organisms; should not be able to infect/replicate

Subunit Vaccines

- materials isolated from disrupted/lysed organisms

- Virus-like particles: doesn't contain viral genetic info (capsid)

- Toxoids: inactivated toxins

- Recombinant vaccines: terminology to describe genetic modification

Conjugated Vaccines

- combine different antigens to improve response; carbohydrate antigens

Carrier Vaccine (Vector Vaccine)

- genetically modified live virus (replicating/non-replicating)

DNA Vaccines

- naked DNA extracted form a pathogen; host cell takes up DNA and makes proteins of the pathogen

RNA Vaccines

-- modified mRNA delivered by lipid nanoparticles

What is a helper ingredient in a vaccine that stimulates the immune system, increasing the immune response to the vaccine, but should not be immunogenic (immune response against the ingredient)

Adjuvants

What are 3 ways in which vaccine adjuvants cause mild inflammation?

1) Attracts phagocytes

2) Accelerates phagocyte activation

3) Accelerates antigen presentation to T cells

T/F: Non-adjuvanted vaccines can cause more local reactions (such as redness, pain, & swelling at injection site) and adjuvated vaccines cause more systemic reactions (such as fever, chills, and body aches)

FALSE

Adjuvated cause local reactions & systemic reactions

Why do we need adjuvants?

Traditional vaccines such as whole cell pertussis or whole virus influenza vaccines are highly immunogenic

-- reduce reactogenicity using reactogenic contaminants such as lipopolysaccharide, DNA, and RNA are removed

-- improves safety of subunit vaccines comes at price of reduced immunogenicity

Which Th bias is for viral or bacterial attacks in tissue, activating macrophages and Nk cells (give of cytokines and force cell apoptosis), opsonizing pathogen and fixing complement?

Th1 Bias

Which Th bias is for parasitic attack or food contaminated w/ pathogenic bacteria, where B cells make IgE for parasites, Mast cell histamine dump, and allergies, and B cells make IgA for mucosal bacteria & GI sensitivities?

Th2 Bias

T/F: Live attenuated vaccines always need adjuvants

FALSE

-- adjuvants may not be necessary

What type of immune response do we want if we are injecting into the tissue, Th1 or Th2?

Th1

Which type of adjuvants has been used since 1930s, with a repository effect, where there is slow release for longer response time, activating IL-1 production, DAMPs/PAMPs, cell necrosis, and cause inflammation resulting in longer lasting immunity and possible Th1 response?

Aluminum (Alum)

What is an issue w/ Aluminum with headaches, arthralgia, myalgia since Alum mediates Th2 responses which may be problematic for some individuals with propensity towards Th2 responses?

Contact dermatitis

Is aluminum toxic?

Implicated in human conditions including neurodegenerative diseases

What are some sources of Aluminum, other than vaccines?

Antacids

Environmental air inhalation

Industrial air inhalation

Antiperspirants

Food/water

What type of adjuvants induce strong response including local cell death and production of danger signals, causing inflammation resulting in longer lasting immunity, likely due to same mechanisms as aluminum and tend to be reactogenic?

Oil-emulsion

What is reactogenic mean?

Reactogenic = ability to provoke adverse affects

What type of Adjuvant activates the TLR pathways (inflammatory cytokines) where you need to be mindful of over-reaction (reactogenicity) and has monophosphoryl lipid A (MPL) and lower toxicity?

TLR Agonists

Which type of adjuvant is highly promising as adjuvants in vaccines against life-threatening and complex diseases such as cancer, AIDS, and malaria?

TLR agonists

What type of adjuvant is monophosphoryl lipid A (MPL) and aluminum salt?

Combination adjuvant

(ex: HPV vaccine)

T/F: MPL manufactured from Salmonella endotoxin?

TRUE

Adjuvants SUMMARY

- Find something that results in "just enough of a reaction" to elicit long term immunity w/o causing harm

- Do adjuvants pose a potential health hazard? Yes, remember using pro-inflammatory materials

- Mild reactions are common; redness at site of injection

- Severe rxn are rare but can happen and may be dpeendent on specific genetic predisposition

T/F: Multiple dose vaccine containers do not contain vaccine preservatives, while single dose does

FALSE

Single dose may not need it; multiple dose does cause needs to remain free of microbes

What are two types of vaccine preservative and ingredients?

1) Thimerosal (ethyl mercury)

2) Residual materials form manufacturing products (Egg protein; tissue culture "ingredients"; formaldehyde inactive "organisms" or toxins

What is an ethyl mercury containing preservative used in some vaccines and other produces, with no convincing evidence of harm with low doses, but was agreed to be eliminated from vaccines as a precautionary measure, only present in some influenza (flu) vaccines nowadays, and is not in routinely recommended childhood vaccines?

Thimerosal

What is the vaccine preservative that is naturally produced in the body and metabolized and excreted or used in other metabolic processes, with most of our exposure coming form the environment and excessive amounts may be linked to cancer (<100 microg/dose in vaccines, 2.5microg/mL of blood)?

Formaldehyde