[MCELLBI55] Midterm 1 Review

immune response, vaccines, ssRNA viruses, arboviruses

phagocytosis

phagocytes engulf the germ and destroy it using enzymes → form of endocytosis

neutrophils

first responders, most abundant; most important phagocytes for killing bacteria

dendritic cells

finds and presents antigens to T-cells; bridge innate and adaptive immunity

macrophages

key drivers of inflammation, clean-up crew

cytokines

molecular messengers; released by one cell to act on another cell

PAMPs

pathogen-associated molecular patterns →  relatively invariant (“conserved”) molecular structures unique to microbes

viral PAMPs

DNA in cytosol (host DNA is nuclear); dsRNA (host RNA is typically ssRNA)

bacterial PAMPs

flagelln, lipopolysaccharide (LPS), peptidoglycan, bacterial DNA

TLRs

toll-like receptors → on macrophages and dendritic cells, bind to PAMPs to start immune response

passive immunization

maternal antibodies, antitoxins and antivenom (horses), human IgG shots

active immunizations

most vaccines; establishes memory T-cells and B-cells similar to natural infection

• preventative vaccines → naive individuals

• therapeutic vaccines → infected individuals

live (attenuated) vaccines

less virulent/weakened version of the virus

OPV, measles, FluMist, smallpox

• ADV: self-replicating, more effective at eliciting killer T-cells

• DIS: can become revirulent, no strain variability and antigenic variation

killed (inactivated) vaccines

whole organism or inactivated toxin killed by heat chemicals/irradiation

influenza, IPV, DTP (diphtheria, tetanus, pertussis/whooping cough)

• ADV: no revirulence

• DIS: no replication, poor antigen presentation for killer T-cells

live vector vaccines

genes from pathogen are inserted into harmless carrier virus that goes into the body

vaccinia (smallpox), salmonella, Ebola

• ADV: self-replicating, no adjuvant needed

• DIS: possible pathogenesis

recombinant protein vaccines

uses yeast or bacteria cells to make proteins that are purified and injected

Hepatitis B, HPV, malaria

• ADV: less expensive (only making proteins), very safe

• DIS: no replication (needs adjvants and boosters), less long-term memory

nucleic acid vaccines

RNA; uses genetic instructions inside a lipid nanoparticle to teach cells to make a harmless viral protein

• proteins presented via MHC molecules to activate T-helper cells

• intact surface or secreted proteins stimulate B-cells → antibodies

Moderna SARS CoV-2 mRNA vaccine

• ADV: fast production, safer than most vaccine types

• DIS: needs to be kept frozen until use, must be encapsulated in lipids or sugars

poliovirus

76% asymptomatic, 24% common symptoms → 1/150 paralysis

fecal/oral transmission, can be infected for 14+ days

replicates in GI tract cells

no treatment once infected, inactivated (IPV) and attenuated oral (OPV) vaccines

• OPV → reversion of virulence, vaccine-derived poliovirus (VDPV), vaccine-associated paralytic poliomyelitis (VAPP)

close to being eradicated

measles

infects most cells in the body, including immune cells

• most deaths come from immunosuppression; profound suppression of T and B cells can last 1-36 months

spread via coughing/sneezing, not rash

• shedding virus ±4 days from rash appearing

• R₀ = 18 (high!)

infects CNS → encephalitis (brain inflammation), SSPE

live attenuated vaccine (measles mumps rubella—MMR)

influenza

Type A causes pandemics (antigenic shift in animal reservoir); Type B is only in humans

influenza coded death → must find virus in person

16 hemagglutinin (H) and 9 neuraminidase (N) varients

killed/inactivated vaccine grow in eggs, FluMist intranasal live attenuated vaccine

zoonotic influenza →birds are main reservoir, can be more fatal, e.g. H5N1 and H7N9

hepatitis C (HCV)

transmitted via blood contact → e.g., in Egypt, poorly sterilized medical equipment

infects hepatocytes (liver cells) → chronic infection, cirrhosis, liver cancer

• most people are asymptomatic until disease progresses to severe stages

no vaccine; treatment = oral drugs with direct acting antivirals targeting virus replication ($$$)

West Nile virus (WNV)

flavivirus

bird reservoir, Culex mosquito vector (tropical/temperate climates)

• true zoonosis (natural spread from animals to humans)

80% few/no symptoms, 20% fever/headaches/diarrhea etc.

• 1/150 infections → neuroinvasive disease (CNS infection)

no vaccine or specific antiviral treatments (too many virus strains)

chikungunya virus (CHIKV)

Aedes aegypti and Aedes albopictus mosquito vectors

mostly symptomatic 4-7 days post-exposure

• muscle aches/swollen and painful joints → typically resolve within 7-10 days

• <0.1% mortality

no specific treatments or vaccines

dengue virus (DENV)

same family as WNV (flavivirus), same vectors as CHIKV (Aedes aegypti, Aedes albopictus)

75% asymptomatic; 25% → high fever, nausea, eye/joint/bone pain

• severe dengue → 1:20; shock, internal bleeding, death

4 serotypes → antibodies to one cross-react with other serotypes → antibody-dependent enhancement

• DENV enters cells through antibodies → aberrant cytokine secretion]

Dengvaxia → live attenuated vaccine, worried about antibody-dependent enhancement

Wolbachia bacteria → infect Ae. aegypti → DENV transmission decreases in mosquitoes with it