Immun_Block 7_ Vaccines

Modern vaccines are created from ...

killed bacteria or viruses, or fragments of proteins from these microbes. - proteins are recognized as antigens by our immune systems. This causes mild immune response. Goal: produce Memory T-cells and B-cells that will fight off illness if it is encountered again

Give examples of natural and artificial active and passive immunity

know!

Effective vaccines induce ... What is required against pathogens that enter via mucosa? Which pathogens can enter body through mucosal surfaces?

long-lasting memory T and B- cell responses Since vaccinations ideally need to induce host defense at point of entry, stimulation of mucosal immunity is important requirement for effective vaccines against pathogens entering via mucosa Examples of pathogens that infect via mucosa include: - Bordetella pertussis - Influenza viruses - Enteric microbes: Vibrio cholerae, Salmonella typhii; Shigella

Live vaccines are made from ... What is the only live vaccine?

made from live infectious agents without any amendment ***only live vaccine is "variola" small pox vaccine, made of live vaccinia cow-pox virus which is not pathogenic but antigenic, giving cross immunity for variola antigenic = microorganism wasn't able to cause disease, but can induce immune response

Advantages and disadvantages of passive immunity

no memory since preformed antibodies are given and there's no exposure to antigen Can lead to serum sickness because antibodies that are there can form antigen-Ab complex

Effector and memory B and T cells are produced during ... immune response

primary Effector cells control infection Memory cells are needed for future protection against same pathogen

What are the types of vaccines?

1. Live vaccines 2. Attenuated live vaccines 3. Inactivated (killed vaccines) 4. Subunit 5. Toxoids 6. Conjugated

Most effective vaccines generate antibodies that ....

1. Prevent toxins from binding their receptors - antibodies neutralize toxins by binding to them and not letting them bind to receptors on the cell 2. Bind the pathogen and prevent infection - viruses usually get neutralized by production of antibodies

What is herd immunity, how does it work? What is the overall percentage of people who need to be vaccinated to protect the population at large from a vaccine-preventable epidemic?

Herd immunity does not protect against all vaccine-preventable disease Best example of this is tetanus, which is caught from bacteria in environment, not from other people who have the disease - No matter how many people around you are vaccinated against tetanus, it will not protect you from tetanus

Live attenuated/modified vaccines are made from ... Who should get these?

- pathogens are active but have reduced virulence - colonize/infect and replicate, but do not cause disease (reduced virulence) - generate robust immunological response If given to <1 year old -> maternal Ab may kill pathogen

What are adjuvants and why they added in some vaccines?

= ingredient of vaccine that help create stronger immune response Adjuvants help vaccines work better 1. Aluminum gels or aluminum salts; used in vaccines since 1930s: - Hepatitis A - Hepatitis B - Diphtheria-tetanus-pertussis - Haemophilus influenzae type b (Hib) 2. Monophosphoryl lipid A has been used since 2009 in one vaccine in US (HPV, cervarix) pic: effects of adjuvants on antibody responses of mice to egg albumin pic: injecting antigen in saline, antibody titer is small - injecting antigen+adjuvant leads to much higher production of antibodies

What is active immunization and what are the types?

= refers to immunity produced by body after exposure to antigens Naturally: - following exposure to infection (virus, bacteria) Artificially: - by vaccination: attenuated organisms, killed organisms, toxoids etc

What is vaccine? Vaccines are usually prepared from ....

= substance used to stimulate production of antibodies and provide immunity against one or several diseases - B-cells and T-cells responses without overt infections - Protection via immune memory Vaccines are usually prepared from: 1) causative agent of disease 2) products of causative agent

Toxin neutralization Why is it important?

Ab attaches to toxin Physical binding of antibody (IgG is most plentiful) may prevent protein toxin from binding to its receptor site and thereby inhibit toxic activity Many diseases are caused by toxins of different microorganisms ex. Tetanus, Cholera etc.

The patient in the previous question tells you she is pregnant. Does her risk from this vaccine increase? A. Yes B. No

B. No - since vaccine is recombinant and not live attenuated - live attenuated would be more risky

What was the first vaccine used on a smallpox virus?

Cowpox vaccine

You have a patient who is a researcher who will be handling blood samples. She wants to get vaccinated against Hepatitis B (which is transmitted through blood). The HepB vaccine is produced by having yeast produce a protein from the outer surface of the virus, and then purifying that protein. What type of vaccine is this? A. Attenuated vaccine B. Whole agent inactivated vaccine C. Toxoid vaccine D. Recombinant subunit vaccine

D. Recombinant subunit vaccine

Vaccination schedule for 0-6 years old

DTaP = PEDIATRIC = 6 weeks to 6 y.o. Tdap = adult = booster of DTaP

Differentiate DTaP and Tdap in terms of relative concentrations of each antigen, and who gets vaccinated with each. What happens if they are mixed up?

DTaP = pediatric = 6 weeks - 6y.o. - to three deadly diseases caused by bacteria: diphtheria, tetanus, and whooping cough (pertussis). Tdap = adult booster - reduced dose of the diphtheria and pertussis vaccines

What is the composition of vaccine for diphtheria? A. Carbohydrate B. Inactivated bacteria C. Live attenuated bacteria D. Protein-conjugated carbohydrate E. Toxoid

E. Toxoid - sometimes toxoids are used to increase efficacy of polysaccharide vaccines

What type of vaccine is used on encapsulated bacteria?

Encapsulated bacteria needs conjugated vaccines to have stronger immune response Examples: - H. Influenza type B (Hib) - Neisseria meningitidis - Streptococcus pneumoniae

What is passive immunization? What are the types?

Immunity can be acquired, without the immune system being challenged with an antigen Naturally: - trans-placental transfer of maternal IgG Abs to developing fetus - transfer of IgA Abs in milk during breastfeeding of newborn Artificially: - injection of immunoglobulin after diagnosis of exposure to toxin/virus - short-term preventive procedure ex. if one is traveling to endemic area like Africa where Yellow fever is present, vaccine can be given but need 3-4 weeks for antibodies to develop. This type of vaccine may not be helpful and instead passive immunization of immunoglobulin will give quick protection ***In diphtheria and tetanus passive immunization is given as prophylaxis or tx In rabies it's given post-exposure

What antibodies are produced during primary and secondary immune response? Why?

In primary immune response: - APC like B cell, which have BCR needed to bind with pathogen. Once antigen binds, positive signal is sent to B cell and it gets activated, becomes plasma cell and starts producing IgM antibodies. ------------ In secondary immune response: - on second exposure with the same pathogen with the same antigen, antibodies that are already present d/t primary exposure will bind to antigen and Fc portion of antibody binds to Fc-gamma R2B1 receptor on B cell. B cells won't get activated and will not produce IgM antibodies (negative signal). Memory B cells bind to antigen on pathogen and this sends positive signal to memory cell , which will differentiate into plasma cell and start producing IgG

Subunit vaccines are made from .... How can they be made? What are the chances of adverse reactions?

Instead of entire microbe, subunit vaccines include only antigens that best stimulate immune system In some cases, these vaccines use epitopes - very specific parts of antigen that antibodies recognize and bind to Can contain 1 - 20 or more antigens Because subunit vaccines contain only essential antigens, chances of adverse reactions to vaccine are lower Ways of making Subunit vaccines: 1) Grow microbe in lab and then use chemicals to break it apart and gather important antigens 2) Manufacture antigen molecules from microbe using recombinant DNA technology. Vaccines produced this way = "recombinant subunit vaccines"

Live attenuated vaccines are available against ...

Know: 1. MMR 2. Oral polio vaccine = called Sabin - not used in US since there was incidence of it causing disease 3. against bacteria Typhoid BCG (against TB) - not used in US; but used around the world to vaccinate children

What antibody is produced after booster shots?

during initial pathogen exposure: - weak immune response - IgM produced during second exposure/booster vaccine: - strong + faster response - IgG

What are mitogens? Give examples

Mitogens are often used to stimulate lymphocyte to assess immune function The most commonly used mitogens in clinical laboratory medicine are: 1. Phytohaemagglutinin (PHA) - common 2. Concanavalin A (Con A) 3. Lipopolysacchride (LPS) 4. Pokeweed Mitogen (PWM) Mitogens are used to see if vaccine is working or not. Ex. if you vaccinate a group of people and you see they are not responding to vaccine. To see If T and B cells are working, you can stimulate them with mitogens in the lab and see if they are functional or not.

For which diseases we don't have effective vaccines yet?

Need better vaccine for Measles because current vaccine is heat sensitive and cannot transport it easily in hot climates TB vaccine has many disadvantages: - can cross-react with PPD antigen and this compromises PPD used in diagnosis - efficacy varies: some areas it gives good protection in others doesn't - can't be given to immunocompromised Need better vaccine for TB and Measles; other diseases listed don't have vaccine currently

What are the examples of inactivated vaccines, what antibodies do they generate?

Polio => Salk = inactivated vaccine Generate a lot of IgA, which are needed in mucosal surfaces of GI

What are the conjugated vaccines and what are the examples?

Polysaccharide antigens - No T-cell stimulation (T cells can only recognize peptides. B cells won't be activated leading to poor B-cell memory - weak immune response -> weak protection Conjugated to peptide antigen - B-cells generate antibodies to polysaccharides - protein antigen presented to T-cells - T-cells in response will boost B-cell response - Strong immune response -> strong protection Examples: - H. Influenza type B (Hib) - Neisseria meningitidis - Streptococcus pneumoniae ****Encapsulated bacteria needs conjugated vaccines to have stronger immune response

Polio vaccine types

Salk vaccine, which is inactivated and the one used in the US. Sabin vaccine, which is an oral vaccine and used in other countries, carries risk of causing polio.

Why is rabies generally given post-exposure and as a combo human rabies Ig + human diploid cell vaccine (Ag)?

active immunization in form of vaccine is given to give a person long-term immunity and let their body produce antibodies + passive immunization in form of immunoglobulin is given to give immediate protection - can't wait 3-4 weeks for body to produce antibodies

Immunization is designed to increase concentrations of ....

antibodies and/or effector Tcells, which are reactive against infection Immunization procedure called vaccination Immunizing agent called vaccine

What type of immunity results from vaccination? What type of immunity is from preformed antibody administration?

artificially acquired active immunity ACTIVE immunization = vaccines PASSIVE immunization = preformed antibody administration

Toxoid vaccines are prepared by .... What are the examples?

by detoxifying exotoxins of some bacteria rendering them antigenic but not pathogenic Adjuvant (e.g. alum) needs to be added to increase potency of vaccine Antibodies generated are against toxin (antibodies neutralize toxic moiety produced during infection rather than act upon organism itself) Toxoids are highly efficacious and safe immunizing agents pic: toxin is modified to toxoid by treating it with a chemical. Toxoid vaccine gives protection without causing disease Example: - Diphtheria - Tetanus ***Against Toxins **toxoids can be conjugated with polysaccharide vaccines

Innactivated (killed) vaccines are produced by ...

by killing disease-causing microbe with chemicals, heat, or radiation - pathogen killed but antigens remain intact - cannot replicate or cause disease - strong humeral responses (antibodies) - generally requires 3-5 doses since titer of antibodies decreases with time so booster shots are needed Induces weak immune responses -> booster shots

What describes a vaccine that can prevent the most common cause of severe viral gastroenteritis in infants? a. inactivated vaccine b. subunit vaccine c. toxoid d. live attenuated vaccine

d. live attenuated vaccine

Which disease has been eradicated due to vaccinations?

smallpox