Lec 17. Active and Passive Immunity, Dr. Kelley Davis - FS PDF

1. Describe the difference between passive and active immunity and give examples of Lecture each. Objectives 2. Describe how active and passive immunity are used to protect the human body from pathogens and their toxins. 3. Expla...

1. Describe the difference between passive and active immunity and give examples of Lecture each. Objectives 2. Describe how active and passive immunity are used to protect the human body from pathogens and their toxins. 3. Explain herd immunity and its importance in stopping the spread of infectious pathogens. 4. Describe R0 and herd immunity threshold and how they are used to determine herd immunity 5. Describe the principles of vaccination and the various classes of vaccines. Active & Passive Immunity 2  Manipulating Immunity Immunization provides immunity to infectious agents o can occur actively or passively o can be acquired naturally or artificially (i.e. deliberately induced → vaccines) Vaccination is one form of immunization 3  Passive immunity Rapid – receiving antibodies, so protection is immediate Temporary – antibodies have a short half- life so they degrade & protection declines Does NOT result in memory – no recipient B or T lymphocytes are involved Does not rely on the recipient’s immune system to make a response o the donor made the response & antibodies 4  Passive immunity Natural – maternal abs passed to fetus or infant o What are the ways that this can occur? Artificial – receive serum containing antibodies o Human Immune Serum Globulin (HISG) – serum pooled from previously exposed individuals o Hyperimmune/convalescent serum – from individuals recently exposed with high titers of specific antibody o Antitoxin/antivenom – antibodies against toxin or venom (from animals exposed) 5  Passive Immunity Passive Passive Natural Artificial 6  Passive Protection Examples of passive artificial immunity o IVIG – IgG (mostly) antibodies pooled from humans for those who need them o Antithymocyte immunoglobulin (rabbit anti- human) for thymic transplant recipients to reduce rejection o Obiltoxaximab (IgG1κ mAb) for prevention & treatment of anthrax (PrEP or PEP) o HepA immune globulin (human) – can be PrEP or PEP o HepB immune globulin (human) – can be PrEP or PEP 7  Passive Protection Examples of passive artificial immunity o Measles immune globulin – PEP for those who aren’t/can’t be vaccinated o Rabies immune globulin (RIG) (human) – PEP o Tetanus immune globulin (TIG) (human) – PEP o RhoGAM (human) – for Rh incompatibility (Rh- mother with Rh+ fetus or Rh incompatible blood transfusion) 8  Passive Protection Examples of passive artificial immunity o Varizig – (human) is used in adults, pregnant women, children, & babies (including newborn or premature infants) who could become severely ill if exposed to varicella zoster virus (PEP) o Zinplava (bezlotoxumab - mAb) – used to treat C. difficile infection along with an antibiotic ▪ Zinplava binds to/neutralizes the bacterial toxin 9  Passive Protection Antitoxins/antivenom (passive artificial) o antibodies collected from horses who were injected with a specific toxin or venom or ophiophagous birds for snake antivenom despite ongoing research, synthetic antitoxins or antivenoms have not yet successfully been developed for treatment 10  Active immunity Introduction of antigen which develops an active immune response Slower to develop – requires T & B lymphocyte activation, proliferation, & differentiation Long-term protection – memory T & B lymphocytes develop when the person’s own immune response is activated Can be natural or artificial 11  Active immunity Natural – contact with the antigen through the infectious process Artificial – intentional exposure to an antigen BEFORE an infection (usually through vaccination) 12  Active Protection Active immune protection of the patient o exposure to the pathogen & developing an active immune response ▪ disease may be mild or subclinical, but exposure & immune activation can still provide antibodies & memory for future protection o vaccines – intentional exposure to a pathogen or part of the pathogen (including the toxin it may produce) to illicit an active immune response 13  Active Immunity Active Active Natural Artificial 14 15  Herd Immunity Herd immunity o when enough individuals in a population are immune, transmission of the disease is interrupted, thereby protecting non-immune individuals in that population Vaccines are an effective way for a population to develop herd immunity & interrupt the spread of a disease o vaccines are a way to help protect those in a population who cannot be vaccinated 16  Herd Immunity http://images.theconversation.com 17  Ro & HIT Ro (R naught) (or basic reproduction #) o a mathematical calculation representing how many people are likely to become infected by 1 infected individual Herd immunity threshold (HIT) o the number (or percentage) of the population that needs to be immune (either naturally or through vaccination) in order for herd immunity to be effective (referred to as the herd immunity threshold) o dependent on the Ro of that pathogen 18  Ro values of some pathogens The number of people that one infected person can infect, on average, is referred to as R0 Seasonal Flu 1.3 MERS 0.8 Diphtheria 6-7 Pertussis 12-17 19 Original COVID-19 ~1.25-1.75 Delta Variant ~2.5 Omicron ~3.5  Herd Immunity Thresholds Herd immunity threshold o Measles: R0 is 12-18, HIT ~ 95% o Pertussis: R0 is 12-17, HIT ~ 93% o Mumps: R0 is 4-7, HIT is ~ 80% o Polio: R0 is 5-7 , HIT is ~ 80% o Ebola: R0 is 1.5-2, HIT is ~ 50% o Herd immunity is important for those who cannot be vaccinated 20 Vaccines ruralhealthinfo.org 21  Principles of vaccination Any preparation intended for active immunologic prophylaxis The vaccine should mimic the natural pathogen as much as possible & as safely possible o the vaccine should stimulate an immune response similar to the natural pathogen & produce the appropriate antibodies & memory cells 22  Oral Vaccines Oral vaccines have proven less effective than IM vaccines o few antigens survive the acidity of the stomach RotaTeq is a rotavirus vaccine administered orally o requires 3 doses The oral polio vaccine has been replaced & was discontinued in 2000 The travel-related oral typhoid vaccine consists of 4 capsules 23  Nasal Vaccines FluMist was the first truly successful nasal vaccine o live attenuated quadrivalent o this promotes a mucosal response which is appropriate for an influenza infection ▪ it creates SIgA antibodies needed in the respiratory tract o it has greatly reduced efficacy (~20%) compared to the regular flu “shot” (~50- 70%) 24  IM Vaccines IM/SQ vaccines have several advantages o tissues are full of DCs for efficient uptake, processing, & presentation o antigen can precipitate, increasing exposure time & phagocytosis of the (larger) precipitated antigen, allowing more effective antigen uptake & presentation o results in good memory & IgG antibodies (in a person with a healthy immune system) 25  IV Vaccines IV vaccines are not as effective o antigens are cleared rapidly (complement, splenic mΦs) providing less time & opportunity for the immune system to take up antigen & present it 26  Vaccines There are two major classes of vaccines o Live ▪ utilizes live organisms that have been made non-pathogenic (attenuated) ▪ utilizes pathogens that are not pathogenic to humans (e.g. insect or bovine pathogen) to deliver the vaccine antigens o Inactivated ▪ utilizes whole organisms (dead or inactivated), or parts of the organism (proteins, polysaccharides, or toxins) 27  Live vaccines Because the organisms are alive, they can persist, allowing longer exposure, fewer doses, & mimics infection by the pathogenic strain Good for viral pathogens to mimic the intracellular infection & develop a CMI response Not given until 12 moa 28  Live attenuated Disease-causing organisms are modified to be non-pathogenic The live organisms can multiply which more closely emulates the natural infection o this results in a stronger & more natural response Because these vaccines contain live organisms, they cannot be given to those who are immunocompromised 29  Live attenuated Can develop both humoral & cell-mediated immunity Effective for intracellular pathogens May cause inflammatory response Potential to revert to pathogenic form o occurred with the oral polio vaccine a few times in those who were malnourished & therefore didn’t have a healthy immune system 30  Live vaccines Live Reassorant o combination of human & non-human viruses together Live Recombinant o inserting the gene(s) from a human pathogen into the genome of a non- pathogenic organism (e.g. baker’s yeast, Baculovirus) Because these vaccines contain live organisms, they cannot be given to those who are immunocompromised 31  Inactivated Killed whole cell Fractional – protein o toxoid, subunit Fractional – polysaccharide o conjugate, pure DNA/RNA 32  Inactivated Inactivated vaccine general properties o dead pathogen or parts of the pathogen o develop only humoral response o not as effective against intracellular pathogens o multiple doses (3-5) & boosters may be needed o adjuvant may be needed o safe for newborns & those who are immunocompromised 33  Inactivated Killed Whole Cell Whole dead pathogens o the whole pathogen is killed & used in the vaccine o examples ▪ Polio (IPV) ▪ Hepatitis A ▪ Rabies ▪ Cholera ▪ Plague*** *** Available only to military personnel 34  Inactivated Fractional – protein Toxoid o the whole toxin may be heat or chemically inactivated o may be only a part of the toxin o only bacterial toxoid vaccines exist o examples ▪ Tetanus, Diphtheria ✓ DTaP, DT are vaccines for children 7 yoa/adults 35  Inactivated Fractional – protein Subunit o contains specific antigenic protein(s), but not whole organisms o examples ▪ Influenza (shot) ▪ Acellular Pertussis (DTaP, TDaP) ✓ pertussis proteins ✓ the diphtheria & tetanus portions of these combined vaccines are toxoids 36  Inactivated Fractional – polysaccharide Conjugate o links a poorly-immunogenic portion of the pathogen to an unrelated protein to make it more immunogenic o bacterial capsular polysaccharides are common examples o IgG response o examples ▪ Pneumococcal (PCV13, PCV15, PCV20) ▪ Meningicoccal ▪ Hib 37  Inactivated Fractional – polysaccharide Pure polysaccharide o immunity not consistently established in children under 2 yoa o IgM & IgG2 response (infants cannot make IgG2) o no booster response upon subsequent vaccination o examples ▪ Pneumococcal (PPSV23) ▪ Salmonella Typhi (Vi) shot 38  Inactivated DNA Cutting & inserting DNA pieces into a plasmid “Infecting” bacteria with the plasmid which then replicates in the bacteria Plasmid is purified to use in the vaccine Only FDA approved DNA vaccine for human use is for Japanese Encephalitis Virus 39  Inactivated RNA mRNA that codes for a protein that would be recognized by antibodies (i.e. on the surface of the pathogen) is injected into the tissues mRNA is taken up by DCs & translated into protein The protein is processed & presented to T cells via MHC molecules to activate T cells & develop memory cells B cells also take up the mRNA, make & process the protein & present it to TH cells which allows production of memory B cells 40  VAERS Vaccine Adverse Event Reporting System o VAERS is a national vaccine safety surveillance program jointly administered by CDC & the FDA o created in 1990 in response to the National Childhood Vaccine Injury Act of 1986 o anyone can report an adverse event (Dr., nurse, caregiver, parent, etc.) o the person reporting does not have to be certain the adverse event was related to the vaccine, they just have to suspect it was 41  VIS Vaccine Information Sheet o provided to the patient or the patient’s guardian o includes information about the vaccine & potential adverse effects (e.g. soreness or redness at the sight of the injection) o what to look for o who should get the vaccine o when to seek medical help 42