Antigens: Immunogenicity and Antigenicity Flashcards
Define an antigen.
This is a foreign substance that can stimulate an immune response.
Define:
(a) immunogenicity
(b) antigenicity
(a) immunogenicity: The ability of an antigen to induce an immune response.
(b) antigenicity: The ability of an antigen to bind to antibodies or T cell receptors.
Define:
(a) epitope
(b) paratope
(a) epitope: [aka. antigenic determinant] A specific part of an antigen that is recognized and bound by an antibody.
(b) paratope: This is the part of an antibody that binds to an epitope.
Define:
(a) exogenous antigens
(b) endogenous antigens
(c) autoantigens
(d) allergens
(a) exogenous antigens: Antigens that originate outside the body, such as bacteria, viruses, and toxins.
(b) endogenous antigens: Antigens generated within the body. [They can be normal cellular components or produced by cells infected with pathogens like viruses or bacteria.]
(c) autoantigens: These are normal proteins or complexes of proteins that the immune system mistakenly targets and attacks, leading to autoimmune diseases. [Essentially, they are self-antigens that the body identifies as harmful.]
(d) allergens: Harmless substances that trigger allergic reactions in sensitive individuals.
What are some factors that influence immunogenicity?
(1) Foreignness: Antigens must be perceived as foreign by the host’s immune system. [Self-antigens, while recognized by the immune system, typically do not induce an immune response due to mechanisms of tolerance.]
(2) Molecular size: Larger molecules tend to be more immunogenic than smaller ones.
(3) Chemical composition: Proteins are generally the most immunogenic antigens, followed by carbohydrates and lipids. Nucleic acids are less immunogenic unless they are associated with proteins.
(4) Physical form: Particulate antigens (e.g. bacteria, viruses) are often more immunogenic than soluble antigens.
(5) Genetic factors: Both host and antigen genetics can influence immunogenicity.
(6) Host factors:
(i) Genetics: MHC genes play a critical role in antigen presentation and recognition.
(ii) Age: The immune system matures over time, and immunogenicity can vary with age.
(iii) Health status: Immune system function can be compromised by various diseases and conditions.
(7) Adjuvants: Substances that enhance immunogenicity. Adjuvants can increase antigen persistence, stimulate immune cell activation and prevent the development of a strong immune response.
(8) Timing: Multiple doses of antigen adminstered over time can boost the immune response.
T cell receptors recognize antigens presented on MHC molecules. State the respective functions of the variable and constant regions of a T cell receptor.
☛ The variable region of a T cell receptor determines its specificity for a particular antigen.
☛ The constant region of a T cell receptor mediates effector functions, such as cytokine production and cytotoxic activity.
How do adjuvants increase immunogenicity?
Adjuvants increase immunogenicity by:
🧪 Prolonging the persistence of the antigen, thus giving the immune system more time to respond.
🧪 Increasing the “size” of the antigen by causing aggregation.
🧪 Stimulating lymphocyte proliferation and/or activation.
🧪 Stimulating a local inflammatory response, thus recruiting cells to the site of the antigen.
🧪 Enhancing co-stimulatory signals.
List some common adjuvants.
[Know examples before details.]
(1) Alum (Aluminium Potassium Sulfate)
Function: Alum works by precipitating the antigen, which means it helps to form a solid complex with the antigen. This increases the antigen’s persistence at the injection site, allowing for prolonged exposure to the immune system.
Effect: The presence of alum induces a mild granuloma, which is a small area of inflammation caused by the immune response. This helps to enhance the immune response to the antigen.
Usage: Alum is commonly used in vaccines for humans, such as the hepatitis B and DTaP (diphtheria, tetanus, and pertussis) vaccines. It is favored for its safety profile and ability to boost antibody production.
(2) Incomplete Freund’s Adjuvant
Composition: IFA is a mineral oil-based adjuvant without any microbial components.
Function: It increases the persistence of the antigen at the injection site, similar to alum, but does not contain any additional immune-stimulating components.
Effect: IFA induces mild granuloma formation and provides co-stimulatory signals that help activate the immune system.
Usage: IFA is often used in research settings for animal studies to enhance the immune response to experimental antigens. It is not typically used in human vaccines due to safety concerns.
(3) Complete Freund’s Adjuvant
Composition: CFA is similar to IFA but includes killed mycobacteria (usually Mycobacterium tuberculosis).
Function: The inclusion of mycobacteria stimulates a stronger and more prolonged immune response by activating various components of the immune system.
Effect: CFA induces a chronic inflammatory response, leading to granuloma formation and providing strong co-stimulatory signals.
Usage: CFA is primarily used in animal research to study immune responses and to develop experimental models of diseases. It is not used in human vaccines due to its potential to cause severe inflammation and adverse reactions.
(4) Bacterial Lipopolysaccharides
Function: LPS are components of the outer membrane of Gram-negative bacteria. They act as potent stimulators of the immune system by activating nonspecific lymphocyte activation and proliferation.
Effect: LPS provide strong co-stimulatory signals that enhance the immune response, particularly by activating macrophages and dendritic cells.
Usage: LPS are used in research to study immune responses and inflammation. They are not used in human vaccines due to their potential to cause strong inflammatory reactions and toxicity.
Compare B Cell and T Cell epitopes. Use the following criteria: Recognition, Types and Location.
(a) Recognition
🧪 B cell epitopes are recognized by B cell receptors or antibodies. They can bind directly to the paratope without the need for antigen processing.
🧪 T cell epitopes are recognized by T cell receptors (TCRs) in the context of Major Histocompatibility Complex (MHC) molecules. They require antigen processing and presentation by antigen-presenting cells.
(b) Types
🧪 B cell epitopes include: Linear epitopes and conformational epitopes. Linear epitopes are composed of a continuous sequence of amino acids, whereas conformational (discontinuous) epitopes are formed by amino acids that are brought together in the three dimensional structure of a protein.
🧪 T cell epitopes include: class I MHC epitopes [presented by MHC class I molecules and recognized by CD8+ cytotoxic T cells] and class II MHC epitopes [presented by MHC class II molecules and recognized by CD4+ helper T cells].
(c) Location
🧪 B cell epitopes are typically found on the surface of antigens.
🧪 T cell epitopes are typically derived from intracellular proteins, including those from pathogens or abnormal self proteins.
