Immunology - Types of Acquired Immunity and Vaccines

What are some conditions that warrant the use of passive immunizations? (3)

1) Immune deficiency (congenital or acquired B-cell defects and/or other immunodeficiencies.) 2) Toxin or venom exposure with immediate threat to life - antibody may help suppress effects of toxin (eg. tetanus, diptheria, botulism) 3) Exposure to a pathogen that can cause death faster than an effective immune response can develop.

What are three types of whole organism vaccines?

1) Inactivated (killed) vaccine 2) Live attenuated (weakened) vaccine 3) Recombinant vector vaccines

What are three key factors in the development of successful vaccines?

1) Must be safe 2) Must be effective in preventing the infection 3) The strategy for administration of the vaccine and schedule of the boosters must be achievable, given the population in question.

What are some goals of active immunization (2)?

1) To elicit protective immunity and immunological memory in the recipient. ---> Proliferation of Ag-reactive T and B cells results in formation of Ab and memory cells which provides a more robust and faster secondary response upon contact with the same pathogen. Some memory cells slowly proliferate to maintain steady supply of memory cells to replace those which die. 2) To increase "heard immunity" to a level in the population such that the chance of a susceptible individual contacting an infected individual is so low that the susceptible one is not likely to become infected.

What are some types of subunit vaccines? (4)

1) Toxoids 2) Subunit (acellular) vaccines 3) Conjugated vaccines 4) Multivalent subunit vaccines

What are four types of active immunization vaccines?

1) Whole organism vaccines: Contain whole, non-virulent microorganisms. 2) Purified macro molecule (sub-unit) vaccines: contain some part or produce of the microorganism that can induce an immune response in the recipient 3) Multivalent subunit vaccines: Synthetically produced. Presents multiple copies of peptide or mixture of peptides to immune system 4) DNA vaccines: plasmid DNA encoding antigenic proteins is injected directly into muscle of recipient and is then expressed by muscle cells leading to an immune response

What is naturally acquired passive immunity?

Ab passes from mother to fetus (crosses placenta) Ab passes from mother to infant (via breast milk)

What is artificially acquired active immunity?

Antigen enters body in a vaccine. Body produces antibody and immunological memory.

What is naturally acquired active immunity?

Antigen enters the body naturally (i.e. antigen on infectious particle) Body produces antibody and immunological memory.

What is artificially acquired passive immunity? How is it administered? (2)

Artifically acquired passive immunity is acquired by injecting pre-formed antibody into recipient. Can be administered by: 1) Immune globulin: Ab-containing solution derived from human blood, obtained by cold ethanol fractionation of large pools of plasma. 2) Antitoxin: antibody derived from serum of animals that have been stimulated with specific antigen.

What is antiserum?

Blood-derived fluids containing antibodies.

How are subunit (acellular) vaccines made?

Can be made by genetically engineering a harmless microbe to produce pathogenic organism's Ag and then isolate Ag in pure form. Ex. Hepatitis B vaccine: cloned gene for major surface Ah of hepatitis B virus (HBsAg) and expressed it in yeast cells. Then grew the yeast cells in a large fermenter, allowing HBsAg to accumulate in cells. Then harvested the cells and purified Ag.

What are DNA vaccines? How are they synthesized?

Currently experimental. Currently human trials with malaria, HIV, influenza, Ebola and herpes virus. Plasmid DNA encoding anyigenic proteins are injected directly into the muscle of the recipient. Muscle cells and dendritic cells in area take up the DNA and encode protein leading to the expression of antigen and a humoral and cell mediated response. DNA either integrates into chromosomal DNA or is maintained for long periods in episomal form resulting in long term exposure.

When are vaccinations reccomended for adults?

Depends on risk group. Vaccines for meningitis, pneumonia, influenza are given to groups living in close quarters (military) or to individuals with reduced immunity (elderly) International travelers are routinely immunized against diseases endemic in the area of travel.

What are some key factors to keep in mind when developing vaccines?

Development of measurable immune response does not necessarily mean that a state of protective immunity has been achieved. Often it is critical which branch of the immune system in activated (humoral or cell-mediated.)

What is DTaP?

Diphtheria/Tetanus/Pertussis Vaccine

What are some advantages of DNA vaccines?

Encoded protein is expressed in natural form (no denaturation) meaning the immune response is directed to antigen as it is expressed by pathogen. DNA Vaccines induce both humoral and cell mediated immune responses. DNA vaccines lead to prolonged exposure to antigen. Hypothetically good immunological memory. Refrigeration of DNA vaccines is not required - this lowers the cost and complexity of delivery. It is possible to coat microscopic gold beads with plasmid DNA and deliver to muscle with an air gun (gene gun) allowing rapid delivery of vaccine to large populations without massive quantities of needles and syringes.

What are recombinant vector vaccines?

Genes encoding major antigents of especially virulent pathogens can be introduced into attenuated viruses or bacteria - the attenuated organism serves as a vector, replicating within a host and expressing gene production of the pathogens. This is experimental, not yet available.

What is Hib?

Hemophilus influenzae b (meningitis) vaccine.

What are some advantages of using ISCOMs and Liposomes?

ISCOMs and liposomes can fuse with plasma membrane to deliver Ag intracellularly leading it to be processed by endogenous (cytosolic) pathway and presented with Class I MHC molecules leading to a cell mediated response.

What are some pros and cons of artificially acquired passive immunity?

Immune serum confers immediate protection against the disease but protection is short lived, because the body produces no new antibody (half life of injected antibody is ~3 weeks.) Serum sickness may result from injection of foreign serum (eg. horse antitetanus) Must therefore select stringent conditions that warrant use of passive immunization.

What are two types of immunity?

Immunity can be ACTIVE (a product of the individual's own immune system) or PASSIVE (antibody produced elsewhere and given to the individual) Both active and passive immunity can be naturally or artificially acquired.

How has immunization compliance changed over the years? What are some consequences of this?

Immunization has lead to dramatic drops (and in some cases elimination) of disease in Canada and the USA. Occurrence of these diseases should remain low as long as widespread immunization programs are maintained. In some areas of California, 60%-70% of parents apply for personal belief exemptions for their children. Such decrease in heard immunity may have serious consequences.

Role of memory cells in immunity depends, in part, on what?

Incubation period of pathogen. Pathogens with short incubation periods (ex. influenza virus) Disease symptoms already under way by the time memory cells are activated. Effective protection against influenza depends on maintaining high levels of neutralizing Ab by repeated (yearly) immunizations. Pathogens with longer incubation periods (ex. polio), do not require high levels of neutralizing Ab because this give memory B cells more time to respond. The polio vaccine is designed to induce high levels of immunological memory.

What is IPV?

Injected polio vaccine

What is vaccination (immunization)?

Intentional administration of harmless or less harmful form of a pathogen to induce a specific immune response that protects against later exposure to the same pathogen.

What are some disadvantages of purified macromolecule (subunit) vaccines?

Less effective at stimulating immune response.

Miscellaneous notes on whole agent vaccines.

Longer retention time (adjuvants or capacity for transient growth in attenuated strains) leads to better immune response (particularly cell-mediated) which is crucial in developing countries where 20% fail to return for boosters. For inactivated vaccines, care must be taken to ensure all organisms are killed (first dose of Salk vaccine for polio contained infectious virus) Reversion to virulent form is possible in attenuated strains. Attenuated strains are less stable (have storage requirements) this is of concern in developing countries. Attenuated strains may be able to cause disease in immunocompromised individuals.

What is MMR?

Measles, mumps, rubella vaccine.

How do live attenuated (weakened) vaccines work? Efficacy? Examples? (4)

Mimics actual infection (bacteria or virus multiply in body) leading to better immunity than inactivated viruses. Virus antigen displayed on target cells leads to cell-mediated immunity (memory CTLs are formed!) Usually derived from mutations acquired in long term cell culture. May provide lifelong immunity. Effectiveness of 95% not unusual. Examples: 1) Sabin polio vaccine 2) measles 3) mumps 3) BCG 4) vaccine for TB

How are immunostimulating complexes (ISCOMs) synthesized?

Mix protein with detergent and glycoside Quil A. Long fatty acid tails of external detergent layer are adjacent to hydrophobic residues of centrally located Ag molecules.

How are protein micelles synthesized?

Mix proteins in detergent and then remove detergent. Proteins orient themselves with hydrophilic residues towards aqueous environment and hydrophobic residues at center.

How are liposomes synthesized?

Mix proteins with suspension of phospholipid under conditions favouring vesicle formation leading to vesicles bound by bilayer (proteins incorporated into bilayer with hydrophilic residues exposed.)

What are some disadvantages of DNA vaccines?

Only protein antigens are encoded (no polysaccharides.)

Why do children typically require multiple boosters at appropriately spaced intervals to achieve effective immunity?

Persistence of circulating maternal antibody in young infant binds to epitopes on vaccine and blocks adequate activation of the child's immune system. Also the immaturity of the immune system makes it necessary for multiple boosters.

What are conjugated vaccines?

Polysaccharide capsule of encapsulated bacteria is poorly antigenic and covers up other antigenic markers on the bacterial cell surface. Polysaccharide vaccines often unable to activate TH cells. Therefore, to increase immune response, couple polysaccharide component to a highly virulent protein (i.e. toxoids of tetanus or diptheria.) Resulting in a polysaccharide-protein complex (a conjugated vaccine) Examples include the haemophilus influenzae type B vaccine.

What is artificially acquired passive immunity?

Preformed antibody is introduced into the body by injection (or other mechanism)

What is a vaccine?

Preparation of antigenic material used to induce immunity against pathogenic organisms.

What is herd immunity?

Presence of immunity in MOST of the population - inability of an infectious disease to spread in a population because of the lack of a critical concentration of non-immune hosts. Herd immunity protects individuals who cannot receive vaccine due to medical issues.

What are multivalent subunit vaccines?

Present multiple copies of a given peptide or a mixture of peptides. Currently experimental. Methods of making multivalent subunit vaccines include protein micelles, liposomes and ISCOMs.

What are some advantages of purified macromolecule (subunit) vaccines?

Safer (cannot replicate in recipient) Contain little or no extraneous material, therefore less adverse side effects.

What are toxoids? How are they synthesized? Examples (2)?

Some bacterial pathogens produce exotoxins that lead to disease symptoms. Toxoids are inactivated bacterial toxins. Toxoid subunit vaccines are created by purifying the bacterial endotoxin and then inactivating it with formaldehyde to form a toxoid. Vaccinations with toxoid induces anti-toxoid antibody which binds to the toxin and neutralizes its effects. Examples include vaccines against tetanus and diptheria.

What is acquired immunity?

Specific resistance to infection developed during life of an individual.

How are inactivated (killed) whole organism vaccines created? What kind of immune response do they generate? Examples (2)

Use chemical means; irradiation (formaldehyde; alkylating agents.) Heat inactivation is usually unsatisfactory as it denatures the antigen. Killed whole organism vaccines require repeated boosters to maintain immune status of host. Induce predominantly humoral response (cell-mediated immunity usually requires that the virus/bacteria infect a target cell to induce CTL activation.) Examples of inactivated/killed whole organism vaccine include: 1) Salk polio vaccine 2) Classic influenza vaccine

What are purified macromolecule (subunit) vaccines?

Use only those antigenic fragments of microbe best suited to stimulating immune response.