Module 3: Antigens, immunogens, and Vaccine

Antigen

Substance with the ability to combine or recognized with an antibody.

Immunogen

Substance that is capable of inducing an immune response.

TRUE

TRUE OR FALSE:Not all antigens are strong enough to cause a full immune response.

Antigenicity/Specific Reactivity

The ability of the antigen to react specifically with the antibodies or cells it provoked.

Immunogenicity

The ability to provoke an immune response by stimulating the production of antibodies, proliferation of specific T cells, or both.

Immunogens

An immune response is triggered by?

TRUE

TRUE OR FALSE: All immunogens are antigens, but not all antigens are immunogens.

Epitope

• Part of an antigen that reacts specifically with an antibody or T-lymphocyte receptor.

• How the body recognizes an antigen

• Precise molecular shapes or configurations recognized by B cells, or the peptide sequences detected by T cells.

• Known as the antigenic determinant.

• Dictates the shape of the ANTIBODY.

1. Linear epitope

2. Conformational epitope

Two types of epitope:

Linear Epitope

Sequential amino acids on a single polypeptide chain.

Conformational Epitope

Folding of one or more polypeptide chains, bringing together amino acids that may be distant from each other.

1. Foreignness

2. Size

3. Chemical Composition and Complexity

4. Route, Dosage, and Timing

5. Degradability

6. Adjuvants

Factors affecting immunogenicity:

Foreignness

• The higher the different, greater the immune response

• is the degree to which antigenic determinants are recognized as nonself by an individual’s immune system.

TRUE

TRUE OR FALSE: The immunogenicity of a molecule depends to a great extent on its degree of foreignness.

Size

• The higher the molecular weight, the greater the immune response

Proteins

• Most immunogenic

• Higher molecular and structural complexity

Polysaccharide

• Second most immunogenic

• Too small to function as antigen

• Rapidly degraded

Lipids

• Least immunogenic

• Low molecular weight, low stability

• Relatively simple

Nucleic acid

• Single-stranded

• It can become immunogenic

• Molecular flexibility

Structural stability

Important in cases where the goal is to elicit a patient antibody response when administering a vaccine.

Complexity

• Complex proteins are better antigens than large repeating polymers such as lipids, carbohydrates, and nucleic acids.

Route

This includes intravenous (into a vein), intradermal (into the skin), subcutaneous (beneath the skin), intramuscular, and oral.

Oral tolerance

is a phenomenon where antigens delivered via the gastrointestinal tract are ignored by the cells of the adaptive immune system.

Dosage

• may be partially dependent on the nature of immunogen processing.

• The smaller the dose, the less likely the response.

Primary immune response

initial reaction to Ag + production of Ab and immune cells.

Secondary immune response

re-exposure to the same Ag, which is stronger and faster due to memory cells.

TRUE

TRUE OR FALSE: Proper timing between doses, especially for booster shots, can enhance the strength and longevity of the immune response.

Window of opportunity

• The time when the immune response is most effective.

• Administering booster doses or additional exposures within this window can maximize the immune response.

Degradability

refers to its ability to be broken down into smaller fragments that can be recognized and presented by cells of the immune system, primarily antigen-presenting cells (APCs).

Adjuvants

• Known as antigen systems/immunopotentiators. delivery

• They are substances added to vaccines to enhance/boost the body’s immune response to the vaccine antigen.

• Stimulate T, B, and phagocytic cells.

• They are especially important when the antigen itself is weakly immunogenic (doesn’t trigger a strong immune response).

1. Antigen presentation

2. Inflammation and cytokine release

3. Enhanced T cell activation

4. Memory cell formation

5. Stimulation of innate immunity

How adjuvants enhance the immune response:

Hapten

• A small molecule that cannot elicit an immune response on its own.

• Not immunogenic

• Low MW

• Non-protein (lipids, NA, Carbs).

Becomes immunogenic when attached to a carrier.

Function of Hapten

Carrier

• Large molecule (usually protein) that can elicit an immune response.

• Immunogenic

• Protein

Provides a the structural support needed for the hapten to be recognized the by immune system,

Function of carrier

Complete Antigen

• Capable of stimulating Ab synthesis and can also react with the antibody.

• Bacterial cells and proteins.

Hapten/Incomplete Antigen

Capable of stimulating Ab synthesis and can also react with the antibody.

Autologous antigen

• Found within the same individual.

• Not foreign.

• The body's immune system usually exercises tolerance to self-antigens.

• In some situations, antibodies may be produced in response to normal self-antigens → Autoimmune disease.

Sequestered antigen

Autologous antigens that do not usually come in contact with antibody-producing cells since they are inaccessible to antibody-forming tissues.

Tissue specific antigen

• Various organs contain antigens that are both common and unique to those organs.

• These are proteins or molecules predominantly expressed in specific tissues or organs of the body.

• Thyroglobulin

• Myelin Basic Protein

Example of tissue-specific antigen

Syngeneic antigen

• Found in individuals of an inbred strain (or between identical twins), who are genetically identical.

• Same genetic markers.

• An antigen that comes from a genetically compatible source.

Allogeneic/Homologous antigen

• Known as an alloantigen.

• Antigens that are found on the surface of cells from individuals of the same species but with different genetic backgrounds, particularly in the context of MHC.

Xenogeneic/Heterologous antigen

• Known as heteroantigen or heterophile antigens.

• Antigens present in the tissues or cells of a different species that can trigger an immune response if transplanted or introduced into a human.

Superantigen

• They are a special class of microbial proteins (usually toxins) that cause massive, non-specific activation of T-cells, leading to an exaggerated immune response.

• Can interact with a much broader range of T cells, leading to a massive immune response, causing cytokine storm causing self-damage.

Vaccine

• An antigen suspension derived from a pathogen.

• Routinely administered to healthy individuals to stimulate an immune response to an infectious disease.

• Immunoprophylaxis

• Significantly reduce the incidence of illness and death from diseases.

• Active immunization

• Passive immunization

Types of vaccines

Active immunization

• Exposure to an antigen leads to immunity through the creation of antibodies by the recipient

• Natural: a person contracted the disease and the immune system creates antibodies naturally.

• Artificial: vaccination with an antigen (live, killed, subunit, toxoid, mRNA, etc.) stimulates the immune response

Passive immunization

• Transfer of humoral immunity in the form of antibodies

• Natural: transfer of maternal antibodies to the fetus via the placenta or breast milk.

• Artificial: injection of pre-formed antibodies (immunoglobulins, antisera, monoclonal antibodies)

1. Live, attenuated (nonpathogenic) microorganism.

2. Inactivated (killed) microorganism.

3. Antigenic components of microorganism (subunit vaccine).

Types of active vaccines:

Live, attenuated vaccines

• Use of live bacteria or viruses that have been weakened through exposure.

• Able to replicate at a low level in the host and are therefore capable of inducing both humoral and cell-mediated immune responses.

1. Immunocompromised individuals

2. Pregnant women

Limitations of live, attenuated vaccines

Inactivated (killed) vaccines

• Consists of intact, killed viruses or bacteria.

• Killed by heat or chemical treatment so that they are not pathogenic but retain their antigenic properties.

• Safely given to immunocompromised people.

• Necessary to provide a larger amount of antigen in order to stimulate an effective immune response.

• Mostly induces a humoral response.

• Need adjvants and booster.

• BCG Vaccine

• Measles Vaccine

• MMR Vaccine

• Varicella Vaccine

• Rotavirus Vaccine

• Influenza Attenuated Vaccine (Intranasal)

• Typhoid Fever (Oral) Vaccine

• Oral Polio Vaccine

• Dengue Tetravalent Vaccine

• Oral Cholera Vaccine

• Yellow Fever Vaccine

• Japanese B Encephalitis Vaccine

Live Attenuated Virus or Bacteria (Weakened):

• Hepatitis B Vaccine

• DTwP or DTaP or Tdap

• H. influenzae B Vaccine

• Pneumococcal Vaccine

• Hepatitis A Vaccine

• Meningococcal Vaccine

• Influenza Vaccine (IM)

• Human Papillomavirus Vaccine

• Typhoid Fever Vaccine (IM)

• Rabies Vaccine

• Inactivated Polio Vaccine (IPV)

• Cholera Vaccine Japanese B Encephalitis Vaccine

Inactivated Vaccine (Killed Microorganisms)

Subunit vaccines

• Contains specific purified parts of the pathogen (protein, polysaccharide, toxoids, or recombinant antigen).

• Need adjuvants and boosters.

• Toxoid Vaccine

• Polysaccharide Vaccine

• Purified Protein Vaccine

Subunit vaccines:

Toxoid vaccine

• Bacterial exotoxins that have been chemically inactivated.

• Used to induce the production of antibodies that can bind to exotoxins and neutralize their effects.

• Tetanus toxoid

• Diphtheria toxoid

Example of toxoid vaccine:

Polysaccharide vaccine

• Virulence factor possessed by encapsulated bacteria.

• They can facilitate clearance of the bacteria by inducing opsonization or complement-mediated lysis.

• Pneumococcal polysaccharide vaccine (PPSV23)

• Pneumococcal conjugate vaccine (PCV13)

• Haemophilus influenzae type b (Hib)

• Meningococcal vaccine

Example of Polysaccharide vaccine:

Purified Protein vaccine

• Composed of proteins from a pathogen.

• Recombinant Protein is a more highly purified protein vaccine through gene coding of protein.

• Hepatitis B vaccine

• HPV vaccine

• Shingles vaccine

• Recombinant influenza vaccine

Example of Purified protein vaccine