Lecture 3 : Immunogens, Antigens, & Vaccines

Immunology

The branch of science that deals with the study of the immune system.

The Body’s Defense system against infections, disease, and abnormal cells

Function of the immune system

White blood cells and Molecules/Substances

Components involved in the immune system

• Neutrophils

• Eosinophils

• Monocytes

• Macrophages

• Basophils

• Dendritic cells

• T cells

• B cells

What are the WBCs in the immune system

• Antibodies

• Cytokines

• Lymphokines

• Organs ( bone marrow, thymus, spleen)

Molecules or substances involved in the immune system

Antigen-Antibody Reaction

Basic principle of immunology

Immune response

The reaction of the body against antigens or foreign substances to react or fight the infection

Antigen

Any substance with the ability to combine or recognized with an antibody

Immunogens

Substances (also an antigen) that is capable of inducing an immune response

Bacteria, Parasites, Viruses, fungi

Examples of foreign substance Antigen

Polen, Dust, Transplanted organs, Inhibitor cancer cells

Examples of Non-infectious Sources of Antigen

Self-antigens

Antigens from our body

Antigenicity / Specific Reactivity

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

Immunogenicity

The ability to provoke an immune response by stimulating the production of specific T cells

All Immunogens are antigens but not all antigens are immunogens

General rule in differentiating antigens and immunogens

A

Antigen of type A

B

Antigen of Type B

None

Antigen of Type O

A,B

Antigen of type AB

Anti-B

Antibody of type A

Anti-A

Antibody of type B

Anti-A and Anti-B

Antibody of type O

None

Antibody of type AB

Antigen-Antibody reaction —> immune response —> Hemolytic Anemia

What happens if the antibody and antigen are the same ?

ABO systems

Strong immunogens

Rh Factor

From the Rhesus Monkey

Has D antigen

Epitope

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

• Dictates the shape of the antibody

Antigenic Determinant

Epitope is also known as?

Amino Acids

Building blocks of proteins

Proteins

Can be primary, secondary, tertiary , quarternary structure

• Linear Epitope

• Conformational Epitope

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.

• Foreignness

• Size

• Chemical Composition and Complexity

• Route, Dosage and Timing

• Degradability

• Adjuvants

Factors affecting Immunogenicity

Foreignness

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

Increased immune response

High foreignness

Weak immune response

Low foreignness

Size

High molecular Wight = high immune response

< 5,000

How many daltons can not trigger antibody production or immune response by?

Potential Antigen

> 10,000 Daltons MW

Good Immunogen

40,000 Daltons (albumin)

Excellent Immunogens

1 million Daltons (hemacyanin)

Proteins

They are effective antigens because they have high MW and structural complexity

• most immunogenic

Polysaccharide

Second Immunogenic, too small to function as antigen; rapidly degraded

Lipids

Least immunigenic; low MW and; low stability; relatively simple

Nucleic acid

Building blocks of DNA and RNA; Single-stranded; can become immunogenic; molecular flexibility

Lipoprotein

Only Lipid that is immunogenic because it is combined with protein

Good antigen

If structural stability is stable

Poor antigen

If structural stability is not stable

Complex

_______ proteins are better antigens than large repeating polymers such as lipids, carbohydrates, and Nucleic acids.

Intravenous, intradermal, Subcutaneous, Intramuscular, Oral

Different ways to deliver an antigen

Bacillus Calmette - Guerin (BCG) vaccine

Example of Intradermal

Oral

This route is very convenient but immune response is very weak because of oral tolerance

Oral tolerance

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

Histamine

Responsible for allergic reaction

Dosage

Very important when it comes to vaccines,

Response may be partially dependent on the nature of immunigen processing.

• should be optimal

Might not provide sufficient stimulus

What happens if optimal dose is too low?

Can lead to excessive inflammation or tolerance

What happens when Optimal Dose is too high?

Dose-Response Relationship

As the dose of antigen increase, the immune response also increases up to certain point.

Timing

can enhance the strength and longevity of the immune response

Primary Immune Response

Initial reaction to Ag + productive of Ab and immune cells = immune response is slow

Secondary Immune response

Re - exposure to the same Ag and is stronger and faster due to memory cells = immune response is Faster

Window of Opportunity

Time when immune response is most effective

Degradability

Refers to the immunogen’s ability to be broken down into smaller fragments that can be recognized and presented by cells of the immune system (APCs)

Defective immune response

Failure of degradability will lead to?

Cherika Higashi Syndrome

Rare genetic disorder where lysosomes are defective

Lysosome

Responsible to produce acids in degrading antigens

Adjuvants

Substances added to vaccines to enhance/boost the body’s immune response to the vaccine antigen.

Important for weak immunogenic antigen

Antigen delivery systems/ immunopotentiators

Adjuvants are also known as ?

• Hepatitis B vaccine

• Aluminum salts

• Oil-in-water emulsions

• Micro particles

Examples of an Adjuvant

Amorphous aluminum hydroxyphosphate sulfate

Hepatitis B vaccine is Adjuvated with?

• Antigen Presentation

• Inflammation and cytokines release

• Enhance T cell activation

• Memory cell formation

• Stimulation of innate immunity

How adjuvants enhance the immune response

Aluminum salts

Most commonly used adjuvants in vaccine

Oil - in - water emulsions

Squalene based produces → promote Ag intake and migration of APCs

Virosome

Is a virus-like microparticles without genetic material.

Hapten

Small molecules that cannot elicit an immune response on its own.

• Low MW

• Non-protein

Carrier

Large moleculem(usually a protein) that can elicit an immune response.

• High MW

• Protein

Complete Antigen

capable of stimulating Ab synthesis and can also reacts with antibody

Hapten/ Incomplete Antigen

Cannot by themselves stimulate an immune response but can react with antibody

Autologous Antigen

Known as autoantigen,

Found within the same individual ; not foreign

Insulin

It is an autogène in type 1 diabetes

Sequestered antigen

Autologous antigens that do not usually come in contact with antibody-producing cells since they Aren accessible to anti-body forming tissues

Immune -privileged sites (eyes,testes,Ovaries,CNS)

Examples for sequestered antigen

Tissue Specific Antigen

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

Thyroglobulin and Myelin Basic Protein

Examples of Tissue specific antigen

Thyroglobulin

Protein produced by thyroid gland.

(E.g. Hashimoto’s thyroiditis & Graves‘s disease)

Myelin Basic Protein

protein found in myelin

sheath that surround the

nerve cells

• Multiple sclerosis

Syngeneic Antigen

Found in individuals of an

inbred strain (or between identical twins), who are genetically identical

• Same genetic markers

Allogenic / Homologous Antigen

Known as 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.

Organ transplant

Example of alloantigen

Xenogeneic/ Heterologous Antigen

Known as heteroantigen or 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

Animal to human, Transplants (Xenotransplantation)

Example of Xenogeneic

Superantigens

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

Staphylococcus aureus - Toxic Shock Syndrome, enterotoxin

Streptococcus pyogenes - exotoxin

Example of Superantigens

Vaccines

An antigen suspension derived from a pathogen.

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

Immunoprophylaxis

Prevents but does not treat infections

Active and Passive Immunization

Types of vaccines

Active Immunization

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

Passive Immunization

Transfer of humoral immunity in the form of antibodies

Active immunization, Natural

person contracted the disease and the immune system creates antibodies naturally