Vaccines (EXAM 3) Flashcards
Herd immunity
-most of the population is vaccinated to protect the few vulnerable
-reduces infection rate in the poulation
How do Vaccines impact Public health
-The number of incidences decreases
-Sanitation is a major factor in the decrease of water-borne diseases
How is active immunity obtained?
Natural: by infection
Artificial: by Vaccination
What are examples of diseases protected by active immunity?
-COVID, Measles, Mumps, Rubella (MMR), Polio, Hep A, Hep B
-safer alternative to natural infection
How is passive immunity obtained?
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)
Difference between innate and adaptive immunity
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
Difference in primary and secondary infection in an adaptive immune response
-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
How do bodies recognize antigens?
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
Process of Vaccine mediated active immunity
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
Types of Vaccines
-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)
What are ways to inactivate Bacteria or Viruses - Attenuation
-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)
How does attenuation in an unnatural host work?
-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
Advantages and Disadvantages of Live-attenuated
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)
How can pathogens be inactivated for vaccines?
-Chemicals: formaldehyde, glutaraldehyde
-heat
-used in polio (Salk), typhoid, pertussis vaccines
Which vaccine has been attenuated genetically?
-Cholera vaccine (Vaxchora)
-through controlled deletions in the DNA
How are genetic-mediated attenuations different from Sabin-type attenuations?
Genetically attenuated vaccine cant get virulent again bc the gene causing the virulence is deleted
Inactivated Exotoxins
-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?
Subunit vaccines
What is the characteristics of Subunit vaccines?
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)
Polysaccharide Conjugate
Combining Bacterial cell wall polysaccharides (not enough antigenicity/PAMPs) with tetanus toxoid adjuvant
-e.g.: Haemophilus influenza type b (Hib)
Ingredients in Vaccines
Thimerosal - Preservative
Aluminum salts - Adjuvant
Sugar, gelatin - Stabilizer
Formaldehyde - inactivation agent
Neomycin - antibacterial
egg protein - cell culture material
Why do adjuvants cause a stronger immune response?
-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
Adjuvants used in Vaccines
-o/w emulsion with squalene
Moa SARS-Cov2 Vaccines
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
What happens to the mRNA Vaccine once administered?
spike proteins ae build -> and picked up by APC and carried to adjacent lymph nodes
What is the purpose of Lipids in the mRNA vaccines
They build the liposomes, that protects the mRNA, since the mRNA is very unstable
What is the purpose of Salts in the mRNA vaccine?
Salts: Buffering agent - multiple buffers can be used to work in pairs -> if the pH goes up or down
Sucrose: Stabilizing agent
What are convalescent serum
Anti-bodies gained from humans that recovered from a disease (COVID) -> Isolate and expressed in CHO cells to produce Ab -> for passive immunization
What is the pathophysiology of cystic fibrosis?
-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
How can be cystic fibrosis treated? (not cured)
Pulmozyme (DNAse)-> breaking down DNA
also helps in post-COVID patients
How does Rasburicase help in treating cancer patients?
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
