Transplantation & Immunization Flashcards

Question

What are the 2 types of immunity following Antigen exposure?

Answer 1

Sterilizing immunity → neutralizing Abs when 2ndary infection (prevents re-infection) Disease prevention → so the infection doesn't become a pathology (doesn't prevent re-infection, but prevents it from becoming a disease) - Even if a disease enters the body, the immune system controls preventing any symptoms *Vaccine mimics natural infection, but bypasses the pathology and goes directly to immunization (Active or passive immunization) - Contributes to development of memory cells

Answer 2

1. Causative agent: measles virus in genus of morbillivirus, family Paramyxoviridae (-ssRNA genome) 2. Transmitted through aerosols, surfaces, coughing 3. Symptoms: - high fever for 4-7 days, runny nose, watery red eyes, rash covering face & then spreading over whole body - 1/10 children have ear infections which can result in hearing loss - 1/20 children develop pneumonia (most common cause of death) - 1/1000 children develop encephalitis (brain swelling) leaving child deaf or with permanent intellectual disabilities - 1-2/10,000 children measles can reactivate several years later causing a progressive, fatal brain inflammation (SSPE: subacute sclerosing panencephalitis) NO treatment

Answer 3

1. Causative agent: family Picorna virus (+ssRNA genome) 2. Transmitted by fecal-oral route 3. Symptoms: - 75% of cases asymptomatic or not recognized as polio - 25% of cases: fever, sore throat, headache, GI tract symptoms - 1% of cases: irreversible paralysis (poliomyelitis) – polio invades the nervous system, death in some cases (paralysis of the heart can lead to death, paralysis of lungs requires breathing machines)

Answer 4

Salk (1955) → inactivated poli vaccine (IPV) Sabin (1961) → oral polio vaccine (OPV, it is active) 1988 = launch of eradication program; currently still cases in Pakistant, Afghanistant (wild poliovirus)

Answer 5

1. Safe → no side effects 2. Protective → must protect from exposure to live pathogen 3. Gives sustained protection → for several years 4. Induces neutralizing antibody → prevent infection of cells that can not be replaced ex: neurons 5. Induces protective T cells → intracellular pathogens are more effictively dealt with by cell-mediated responses (vs humoral responses) 6. Practical considerations → low cost/dose, biological stability, ease of administration, few side-effects

Answer 6

- Side-effects have to be very rare (given to healthy population so strict rules) - Efficacy (protective protection) has to be high - Induce long-lived memory (avoid too many boosters) - Low cost/dose ratio - Ideally primes both B and T cells

Answer 7

Herd Immunity → resistance to the spread of an infectious disease within a population that is based on pre-existing immunity - Lowering the number of susceptible people (through vaccination) in the population reduces the likelihood of transmission even for unimmunized individuals R0 = # of secondary cases from a single primary case in a completely susceptible population - Disease-dependent, population-dependent (depending on how contagious, the route of transmission) - The larger R0, the more people you have to vaccinate in order to protect a population from an epidemic

Answer 8

Based on the R0 and the concept of herd immunity qc = 1 - 1/R0

Answer 9

Measles → R0 = 15, Pv = 94% Smallpox → R0 = 5, Pv = 80% Polio → R0 = 5, Pv = 80% COVID is similar to polio and smallpox, a bit lower

Answer 10

16 recommended vaccines: - HepB, Polio, tetanus, pneumonia, Flu, Menigococcus C, measles, mumps, rubella, chicken pox, HPV Others are also available: - Vibrio cholerae, Yersinia pestis, salmonella typhi, Bacillus anthracis, yellow fever, hepatitis A, varicella zoster, tick- borne encephalitis, small pox

Answer 11

2-3 million deaths of children prevented per year (but ~19.5 million children globally are still missing out on basic vaccines) Investing in child health has economic benefits, raises child IQ, improves parent productivity Every $1 spent on vaccines yields an ~$44 economic return

Answer 12

human papilloma virus (HPV): in US 14 million infections/year, causes 30,700 cancers in men & women annually - HPV 16 & 18 strains are associated with 70% of cervical cancers - HPV 6 & 11 strains are associated with 90% of genital warts Gardasil (Merck) vaccine against all 4 strains - Recommended in US from 2006, age 11/12 boys & girls - recent report by CDC: precancer incidence in women aged 20-24yrs has decreased by ~80% (2008-2022)

Answer 13

- natural infection does not generate protective immunity/clear infection = correlates of protection undefined Why do we not have an HIV vaccine? - huge diversity in strains circulating in the population (if your vaccine targets 1 strain, it is not very efficient) - correlates of protective immunity are unclear - virus rapidly escapes antigen specific immunity (antibody & T cell) - establishment of latent viral reservoir - no such thing as safe “attenuated” HIV

Answer 14

PASSIVE Transfer of preformed antibodies from an immune individual to a non-immune recipient ACTIVE Inoculation of people with microbial pathogens and/or Ag(s) that induce adaptive immunity without causing disease

Answer 15

Natural: Transfer of maternal Abs across placenta to developing fetus or during breastfeeding to infant Therapeutic: - antiserum treatment to toxins/venoms with immediate threat to life (generated on other animals) - babies with immunodeficiency - unvaccinated individuals to infections (tetanus, diptheria, measles..) are given Abs if they get infected - ZMapp: combination of 3 anti-ebola monoclonal antibodies → mouse neutralizing Abs chimerized to have human Fc component, came before the Ebola vaccine

Answer 16

Phase I → small number of volunteers, testing for safety Phase II → effectiveness against pathogen evaluated (efficacy) through correlates of protection (ex: Ab titres measured) - You can’t expose the people to the actual virus for safety reasons so have to find another way to measure the efficacy of the vaccine Phase III → large # of people assessed for protection against pathogen The testing process is so long because vaccines belong to the preventive branch of health care → high safety standards - All vaccines must go through rigourous testing in animals and humans → expensive process and many vaccines never progress to use in humans

Answer 17

1. Whole organisms 2. Purified macromolecules 3. Recombinant vectors 4. DNA vaccines 5. mRNA vaccines

Answer 18

1. Live attenuated Take pathogenic virus from someone infected → culture it in cells from a different species → the virus adapts (mutations) to better grow in that other specie which attenuates its ability to infect human cells - measles, mumps, polio (Sabin), rota, yellow fever 2. inactivated or killed Inactivated through heat or chemical treatment (ex: formaldehyde) - hep A, cholera, influenza, plague, polio (Salk), rabies

Answer 19

Live attenuated: Take pathogenic virus from someone infected → culture it in cells from a different species → the virus adapts (mutations) to better grow in that other specie which attenuates its ability to infect human cells Pros → Very effective Cons → Refrigerated storage, may mutate back to virulent form Inactivated or killed: - Inactivated through heat or chemical treatment (ex: formaldehyde) - Grow very large amounts → purify → inactivate Pros → Very safe, stable without refrigeration Cons → Less durable immune responses (boosters required) - Not alive so can't revert to virulent form, but doesn't mount as strong of an immune response

Answer 20

They are vaccines that use specific components of a pathogen rather than the whole organism Toxoids → Use inactivated bacterial toxins to induce immunity Ex: diphtheria, tetanus Subunits → Contain only specific antigenic parts of a pathogen Ex: Hepatitis B, pertussis, S. penumonia Pro → very low chance of adverse reactions

Answer 21

1. Break up pathogen to small pieces → Extract Ags from pathogen → NATIVE 2. Clone gene encoding for Ag → Express and purify recombinant Ag → RECOMBINANT

Answer 22

1. Causative agent: Clostridium tetani 2. Found in soil/animal intestines 3. Produces an exotoxin which causes rigidity and convulsive spasms of skeletal muscles - 500-600 case per year prior to vaccine (USA) - 1948 vaccine became available - now ~ 20 cases/year (USA) - renew every 10 years

Answer 23

Vaccines based on purified proteins require the addition of adjuvants → enhance immunogenicity of antigens, as not very potent on their own - Are not approved on their own – only in context of specific vaccine formulation

Answer 24

1. Alum: inorganic aluminium salts, results in slow release of Ag at injection site and recruits APCs - Contains PAMPs → activtaes innate immune response 2. MF59: oil in water emulsion to aid in slow Ag deliver 3. AS04: alum plus TLR4 agonist 4. CpG 1018 (heb B vaccine): TLR9 agonist - CpG: DNA analogs containing unmethylated cytosine/guanine motifs that mimic bacterial DNA

Answer 25

Conjugate = polysaccharide capsule linked to a protein carrier Polysaccharides alone typically trigger a T-cell-independent immune response (low affinity IgM Abs, not much immunological memory) T cell response → class-switching, hgiher affinity, memory Example: 1. B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein 2. Antigen is internalized and processed 3. Peptides from protein component are presented to the T cells 4. Activated B cell produces Ab against polysaccharide antigen on the surface of the bacterium Other definition: A conjugate vaccine is a type of purified macromolecule vaccine in which a bacterial polysaccharide capsule (poorly immunogenic on its own) is chemically linked to a protein carrier (usually a toxoid like diphtheria or tetanus toxoid) to enhance the immune response.

Answer 26

Haemophilus influenzae type B S. penumonia

Answer 27

Recombinant vector vaccines: - live attenuated vectors that express gene products of pathogens to be vaccinated against Pro: cannot revert to virulence

Answer 28

- Inject DNA encoding antigenic proteins directly into muscle of recipient - Host cells take up DNA and produce immunogenic protein, generating immune response pro: inexpensive to make, very stable (no refrigeration needed)

Answer 29

- lipid nanoparticles with mRNA → easy to scale, produces harmless piece of pathogen Moderna and Pfizer-BioNTech against COVID19 mRNA encodes for spike proteins → uptaken by local APCs or muscle cells

Answer 30

mRNA vaccine Pancreatic cancer: kills 467,000 people world wide/year; 90% die within 5 years of diagnosis = ineffectiveness of current treatments (few mutations so hard to target with checkpoint blockade) Phase I trial, bespoke mRNA vaccines with cancer-specific mutant proteins, 16 patients vaccinated Outcome: 8 of 16 people had vaccine-elicited CD8 T cell responses (responders) and 6 remained cancer free at 3.2 years, while non-responders had cancer recurrence by 13.4 months