Vaccines (EXAM 3)

Question 1

Herd immunity

Answer 1

-most of the population is vaccinated to protect the few vulnerable
-reduces infection rate in the poulation

Question 2

How do Vaccines impact Public health

Answer 2

-The number of incidences decreases
-Sanitation is a major factor in the decrease of water-borne diseases

Question 3

How is active immunity obtained?

Answer 3

Natural: by infection
Artificial: by Vaccination

Question 4

What are examples of diseases protected by active immunity?

Answer 4

-COVID, Measles, Mumps, Rubella (MMR), Polio, Hep A, Hep B
-safer alternative to natural infection

Question 5

How is passive immunity obtained?

Answer 5

Natural: Maternal antibodies; IgA (breast milk), IgG (placenta)
Artificial: Monoclonal Ab -> Tetanus Antitoxin (TAT); Diphtheria antitoxin (DAT); Snake antivenins etc
-> Serum sickness can be caused by immune complexes due to passive immunization (mAb)

Question 6

Difference between innate and adaptive immunity

Answer 6

Innate: immediate response, non-specific, no memory -> Macrophages, NK-cells, dendritic cells, Granulocytes

Adaptive: specific, take time build T-cells and Ab, strong immune memory

Question 7

Difference in primary and secondary infection in an adaptive immune response

Answer 7

-Second exposure by the same pathogen leads to a strong and fast
immune response due to rapid clonal expansion of T and B cells

-Vaccination mimics the first infection

Question 8

How do bodies recognize antigens?

Answer 8

TLRs recognize patterns on antigens (PAMPs) (like repeated patterns in aggregates of protein drugs)
-some TLRs are intercellular to bind endogenous antigens (viral) or broken particles of microbes
-C-type lectins recognize yeast-produced antigens

Question 9

Process of Vaccine mediated active immunity

Answer 9

Antigen exposure -> APC take up and present antigen to CD4 Th cells -> CD4 TH cell secrete cytokines and activate CD8 T-cells and B -cells -> CD8 develop to CD8 cytotoxic Tcells and B-cells secrete Ab
-> formation of memory cells

Question 10

Types of Vaccines

Answer 10

-Live, attenuated: most effective (polio-Sabin/BCG for TB)
-Dead or inactivated: (polio-Salk/choler vaccine)
-Sub-unit vaccine: hepatitis B, meningococcal, pneumococcal, Haemophilus influenza)
-Toxoids (diphtheria and tetanus)

Question 11

What are ways to inactivate Bacteria or Viruses - Attenuation

Answer 11

-elimination of a pathogen’s virulence

-Serial passage in unnatural hosts (oral polio vaccine (Sabin),
MMR and BCG (bacterial)
-Mutagenic treatment (Nitrosoguanidine tx for Salmonella
typhii)
-Heat or chemical treatment (e.g. formaldehyde, phenol etc)

Question 12

How does attenuation in an unnatural host work?

Answer 12

-Isolation from a patient -> grown in vitro in human cells
-infect monkey cells and passaged -> the virus mutates to survive and thereby loses its virulence

Question 13

Advantages and Disadvantages of Live-attenuated

Answer 13

Advantages:
-produce more antigens -> strong cell and humoral (Ab) immune response
-fewer doses

Disadvantages:
-incorporation into host DNA, viral shedding, and contamination
-not suitable for immunosuppressed patients
-not for certain viruses (Hep, HIV, cancer-causing virus)

Question 14

How can pathogens be inactivated for vaccines?

Answer 14

-Chemicals: formaldehyde, glutaraldehyde
-heat

-used in polio (Salk), typhoid, pertussis vaccines

Question 15

Which vaccine has been attenuated genetically?

Answer 15

-Cholera vaccine (Vaxchora)
-through controlled deletions in the DNA

Question 16

How are genetic-mediated attenuations different from Sabin-type attenuations?

Answer 16

Genetically attenuated vaccine cant get virulent again bc the gene causing the virulence is deleted

Question 17

Inactivated Exotoxins

Answer 17

-Exotoxins of Cornybacterium depitheriae, Bordetella pertussis, Clostridium tetani

-Formaldehyde deactivates exotoxins through crosslinking (become toxoid)-> aggregation -> now susceptible to immune system - by adsorbing onto colloidal aluminum salts?

Question 18

Subunit vaccines
What is the characteristics of Subunit vaccines?

Answer 18

Conbining parts of a pathogen that by themselves are not very virulent
-e.g. Vaccine against Anthrax -> B. anthracis + Virus antigen -> adsorbed onto an aluminium salt (adjuvant)

Question 19

Polysaccharide Conjugate

Answer 19

Combining Bacterial cell wall polysaccharides (not enough antigenicity/PAMPs) with tetanus toxoid adjuvant

-e.g.: Haemophilus influenza type b (Hib)

Question 20

Ingredients in Vaccines

Answer 20

Thimerosal - Preservative
Aluminum salts - Adjuvant
Sugar, gelatin - Stabilizer
Formaldehyde - inactivation agent
Neomycin - antibacterial
egg protein - cell culture material

Question 21

Why do adjuvants cause a stronger immune response?

Answer 21

-increases the number of immune cells produced as a response (quantitative effect)
-Depot effect: adjuvanted antigens are exposed to the immune system for a longer time
-enhanced APC function bc of pattern recognition of TLR (aggregated)

-more cytokine release and better delivery into lymph nodes

Question 22

Adjuvants used in Vaccines

Answer 22

-o/w emulsion with squalene

Question 23

Moa SARS-Cov2 Vaccines

Answer 23

DNA Vaccines (AstraZeneca, JJ): non-replicating chimpanzee adenovirus to carry DNA coding for COVID spike protein -> gene to mRNA and mRNA to spike protein -> triggering an immune response

mRNA (Moderna/Pfizer): Lipid nanoparticle carries spike protein mRNA -> nanoparticle fuses with the cell membrane and releases the mRNA into cytosol -> translation into protein -> triggering immune response

Question 24

What happens to the mRNA Vaccine once administered?

Answer 24

spike proteins ae build -> and picked up by APC and carried to adjacent lymph nodes

Question 25

What is the purpose of Lipids in the mRNA vaccines

Answer 25

They build the liposomes, that protects the mRNA, since the mRNA is very unstable

Question 26

What is the purpose of Salts in the mRNA vaccine?

Answer 26

Salts: Buffering agent - multiple buffers can be used to work in pairs -> if the pH goes up or down

Sucrose: Stabilizing agent

Question 27

What are convalescent serum

Answer 27

Anti-bodies gained from humans that recovered from a disease (COVID) -> Isolate and expressed in CHO cells to produce Ab -> for passive immunization

Question 28

What is the pathophysiology of cystic fibrosis?

Answer 28

-Chloride (CFTR) channels in the cell membrane do not work
-> Cl(-) influx/efflux is needed to dilute the secreted mucus -> becomes thick in cystic fibrosis
-difficulties breathing
-disrupts mucociliary clearance through cilia-> causes bacterial infection, chronic inflammation, neutrophil invasion is higher

Question 29

How can be cystic fibrosis treated? (not cured)

Answer 29

Pulmozyme (DNAse)-> breaking down DNA
also helps in post-COVID patients

Question 30

How does Rasburicase help in treating cancer patients?

Answer 30

To prevent gout

-Recombinant Urate oxidase breaking down Uric acid (not soluble) to Allantoin (water-solube -> excreted)

-Anticancer therapy lysis cancer cells causing the release of nucleic acid -> to Hypoxanthine/xanthine -> Uric acids