Lecture 11 Immunogens and Antigens Part 1

Antigen

any agent capable of specifically binding to components of the adaptive immune system
(BCRs, TCRs, Antibodies)

Immunogen

any agent capable of inducing (eliciting) and adaptive immune response
(Humoral or Cell-Mediated Activation)

All immunogens are antigens, but

not all antigens are immunogens

epitopes

certain regions of an antigen molecule that stimulate immune responses

What is a hapten?

An incomplete antigen that reacts to specific humoral or cell-mediated receptors but is not immunogenic by itself.

How can a hapten be made immunogenic?

By conjugation with a carrier molecule.

What happens when a hapten is conjugated with a carrier molecule?

The hapten/carrier complex evokes an immune response to both the hapten and the carrier.

Carrier

a chemically complex, high molecular weight protein molecule

Pathogens express

-PAMPs= evoke an innate immune response
-Antigens= May* evoke an adaptive immune response
*if the innate response is not sufficient to eliminate the threat

Factors influencing immunogeniticty

-Immunogen characteristics
-Biological system components
-Administration methods

Immunogen characteristics

For a substance to be capable of inducing an immune response, it must have the following:
-Foreignness
-Molecular size
-Chemical complexity
-Degradability

Foreignness

the immune system discriminates between self and non-self

-Negative selection of B & T-cells

-Self compounds should not be immunogenic

-Autoimmunity = immune system targets self cells

The immune system should recognize foreign substances as non-self

-First and most important factor of immunogenicity

-The more foreign the substance, the more immunogenic is should be

Molecular size

There is no absolute size above which a substance will be immunogenic.
-Small substances have decreased immunogenicity
-Large substances have increased immunogenicity
The number of epitopes is directly proportional to the size of the antigen.

physiochemical complexity

An increase in the chemical complexity of a compound is accompanied by an increase in its immunogenicity
-Complexity is increased by attaching various chemical moieties to the antigen

protein structure

contributes to the molecule's immunogenicity
-Primary= Amino acid sequence
-Secondary= Polypeptide chain backbone structure
-Tertiary= 3D configuration
-Quaternary= interaction of two or more protein subunits

degradability

antigens that are easily phagocytosed are generally more immunogenic
-Antigen-presenting cells (APCs) phagocytize, process, and present antigenic determinants (epitopes)

Antigen enzymatic degradation properties

1. Must be stable enough to reach the site of B-cell or T-cell interaction to initiate an immune response.
2. Must be susceptible to partial enzymatic degradation during antigen processing by APCs

Protein isomers

D-amino acids= resistant to enzymatic degradation
L-amino acids= susceptible to enzymatic degradation

Biological system factor

-Age
-Genetic factors
-B & T-cell Repertoires

Age

-can also influence immunogenicity
-The very young and the very old have a diminished ability to mount an immune response to an immunogen
Young= Fewer exposures; APCs/T-cells don't communicate effectively in newborns
Elderly= Body defense lose flexibility and cell diversity over time; Vaccine responses weaken

Genetic makeup (genotype)

Important role in determining whether a substance will stimulate an immune response
-Individuals may lack or have altered genes that affect their ability to respond to immunogens
-Variations in MHC genes mainly control immune responsiveness (polygenicity and polymorphism)

Polygenicity

MHC class I and II molecules are coded for by multiple independent genes

Polymorphism

multiple stable forms of each MHC gene exist in the population
-MHC is the most highly polymorphic gene system in the body and population

B and T-cell repertories

-Antigenic epitopes binding to antigen-specific B & T-cell receptors trigger and acquired immune response
-Diversity of B & T-cell configurations exit before contact with antigen (clonal selection theory)
-If an individual lacks a particular lymphocyte clone with the right antigen-specific receptor for the antigenic epitope, no immune response will occur

Dose (administration methods)

An optimum dose is necessary for immunogenicity to occur.
-Too high or too low may induce a state of tolerance in the individual
-Insufficient antigen dose referred to as ignorance.

Route (administration methods)

Antigen administration route alters the nature of the response
-Natural routes: Gastrointestinal and intranasal
-Artificial routes: Subcutaneous/ intramuscular and intravenous

Adjuvants (administration methods)

Substances that enhance the immune response to an immunogen
-Use of adjuvants can have undesirable side effect (fever, inflammation)

Primary immunization

Individual's first exposure to an immunogen; Generates a primary response

-Antigen processing and presentation by APCs

-Antigen encounter with B-cells

-B-cell and T-cell activation and proliferation

-Synthesis of antibodies

-Development of memory cells

Secondary exposure

Individual's second exposure to the same immunogen

-Generates a secondary response

Secondary response characterisitcs

-Much quicker onset
-Higher magnitude of the response

Secondary response

exploits the expanded number of antigen-specific lymphocytes generated during the primary response

-also called the memory or anamnestic response

-B & T lymphocytes that participate in the memory response are termed memory cells