antigen basic understanding to learn about immunology
- 2. Antigen • Molecules that can be recognized by the immunoglobulin receptor of B cells or by the T-cell receptor when complexed with major histocompatibility complex (MHC) are called antigens. • The word antigen is a shortened form of the words “antibody generator.
- 3. •Antigenicity vs. Immunogenicity: While related, antigenicity refers to the ability of a substance to bind to antibodies or T-cell receptors, while immunogenicity describes the ability of an antigen to elicit an immune response. All molecules that are immunogenic are antigenic too(to elicit immune response it must bind to antibody/Tcell) but all antigenic molecules cannot be considered immunogenic(all that has binding capacity not necessarily mean has capacity to induce immune response). Thus, haptens can be said to lack immunogenicity
- 5. • Immunogens are molecules that induce an immune response. In most cases, antigens are immunogens, and the terms are used interchangeably. • The antigens that are not immunogenic but can take part in immune reactions(helps in binding) are termed as haptens.
- 6. • Determinants of Antigenicity Some of the important determinants of antigenicity include: • 1. Molecular size • 2. Foreignness • 3. Chemical-structural complexity • 4. Stability • 5. Other factors
- 7. 1. Molecular size •Big protein molecules (weighing about 100,000 Da or more) are usually very good at making your body create an immune reaction. •Tiny substances (weighing less than 5,000 Da) generally don't cause much of an immune response. •Scientists sometimes attach small substances to bigger, inactive particles(bentonite,kaolin) to make them able to trigger an immune reaction.
- 8. 2. Foreignness •Immunogenicity hinges on a molecule's "foreignness," meaning it's recognized as nonself by the immune system. Self-recognition is established during fetal development. •Tolerance to self-antigens occurs through early exposure during lymphocyte development, preventing immune responses against the body's own molecules. •The degree of immunogenicity increases with the evolutionary distance between species; molecules from more distantly related species elicit stronger immune responses. •Graft rejection rates illustrate this principle: grafts from unrelated humans are rejected within weeks, chimpanzee grafts within hours, while identical twin grafts are accepted due to genetic similarity.
- 9. 3. Chemical-structural complexity •Proteins are the strongest immunogens, followed by polysaccharides; nucleic acids and lipids are generally poor immunogens, though they can act as haptens. •Structural complexity enhances immunogenicity: diverse amino acid or sugar combinations are more effective than simple chains. •In cell-mediated immunity, protein structure is crucial for T cell response, as it influences peptide presentation by MHC cells. •Lipid-specific antibodies are difficult to produce and have limited immune roles, but they are useful in assays when lipids are conjugated with carrier proteins.
- 10. 4. Stability •Highly stable, nondegradable substances (like certain plastics and metals) are not immunogenic because they cannot be processed and presented by antigen-presenting cells (APCs). •The stability of certain materials, such as silicon, makes them suitable for non- immunogenic use in medical implants. •Extremely unstable substances may also fail to elicit an immune response as they degrade before APCs can internalize them. •Large, insoluble complexes are more immunogenic than smaller, soluble ones due to easier phagocytosis, degradation, and presentation by macrophages.
- 11. 5. Other factors Biologic system: •Individual biological systems significantly influence antigen immunogenicity, leading to "responder" and "nonresponder" phenotypes. •Variations in genes coding for antigen receptors on B and T cells, or genes necessary for antigen presentation by APCs to helper T cells, account for these differences. •
- 12. Dosage and route of the antigen •Antigen dose significantly affects immunogenicity: both very low and extremely high doses can fail to elicit a proper immune response. •Repeated antigen administration, or booster doses, is often necessary to enhance and maintain protective immune levels, particularly crucial for vaccines. •The route of antigen administration plays a role; parenteral routes are generally preferred for eliciting strong antibody responses. •Subcutaneous administration often proves more effective than intravenous routes in stimulating an immune response
- 13. Adjuvants Adjuvants are the substances that when mixed with an antigen and injected with it boost the immunogenicity of the antigen. Adjuvants increase both the strength and the duration of immune response. Adjuvants boost immunogenicity of antigens in several ways: a)Adjuvants like aluminum potassium sulfate (alum) and Freund’s water-in-oil adjuvant enhance immunogenicity by prolonging antigen persistence through depot formation at the injection site. •Alum precipitates the antigen, allowing for gradual release. •Water-in-oil emulsions create antigen-containing droplets for slow release.
- 14. b)Freund’s complete adjuvant, containing heat-killed mycobacteria, further boosts the immune response by: •Activating macrophages. •Increasing IL-1 production. •Elevating B7 membrane molecule levels. •Enhancing class II MHC expression, improving antigen presentation to TH cells. •Facilitating costimulation via B7-CD28 interaction, amplifying the T-cell response. c)Certain adjuvants, such as synthetic polyribonucleotides and bacterial lipopolysaccharides, stimulate nonspecific lymphocyte proliferation, thereby augmenting the immune response.
- 15. Antigen Specificity Antigenic specificity refers to the immune system's ability to distinguish and react specifically to unique molecular structures (antigens) and their variations, allowing for targeted responses.
- 16. •How it works: •The immune system lymphocytes that express receptors (antibodies for B cells and T cell receptors for T cells) that are highly specific for particular antigens. •Each lymphocyte clone expresses a receptor that recognizes a unique antigenic determinant (epitope). •The immune system can generate highly specific memory responses against particular antigens. •The specificity of the immune response is determined by the "goodness of fit" between the antibody-combining site (paratope) and the corresponding antigenic determinant (epitope). •Importance: This specificity is crucial for the immune system to: •Differentiate between harmless and harmful substances. •Target specific pathogens or antigens for elimination. •Prevent autoimmune reactions by recognizing self-antigens.
- 17. •Examples: •The immune system can distinguish between different strains of the same virus, or different types of bacteria. •Antibodies developed after influenza infection or vaccination recognize and bind to specific "antigenic sites" on the virus's surface proteins, preventing infection. •Antigenic Variation: Some pathogens, like viruses, can evade the immune system by changing their surface antigens (antigenic variation), making it harder for the immune system to recognize and eliminate them.
- 18. • Epitopes An epitope is defined as the immunologically active region of an immunogen that binds to antigen-specific membrane receptors on lymphocytes or secreted antibodies. The interaction between cells of the immune system and antigens takes place at many levels and the complexity of any antigen is mirrored by its epitope. • There are two types of epitopes: B-cell epitopes and T-cell epitopes.
- 19. B cell epitope: •B-cell epitopes are the specific parts of an antigen recognized by B cells. •B-cell epitopes interact with B-cell receptors only when the antigen is in its native, unaltered state. •The interaction involves complementary surfaces, often with smaller antigen molecules fitting into depressions or grooves on the antibody. •B-cell epitopes typically consist of about six to seven sugar residues or amino acids. •These epitopes tend to be hydrophilic and are frequently located at bends in protein structures. •B-cell epitopes can also be found in mobile regions of proteins, allowing for slight adjustments to facilitate binding.
- 20. T cell epitope: •T cells specifically recognize amino acid sequences within proteins, not polysaccharides or nucleic acids, distinguishing proteins as T-dependent and polysaccharides as T- independent antigens. •The primary amino acid sequence of a protein dictates the T-cell antigenic determinants. •T cells do not recognize free peptides; they recognize peptides presented in complex with MHC molecules. •T-cell recognition is "MHC restricted," meaning T cells must simultaneously recognize both the antigenic determinant and the MHC molecule. •T-cell epitopes are typically short, ranging from 8–15 amino acids, and are limited to sequences that can bind to MHC molecules. •Genetic variability in MHC molecules results in individual differences in T-cell responses, as immunogenicity depends on having MHC molecules that can bind a specific peptide.
- 21. Species Specificity Tissues of all individuals in a species possess certain speciesspecific antigens. However, some degree of cross-reaction occurs between antigens from related species. The species specificity shows phylogenetic relationship. The phylogenetic relationship is useful in: • ■ Tracing evolutionary relationship between species. • ■ The species identification from blood and seminal stains in forensic medicine.
- 22. Isospecificity Isospecificity refers to the ability of an antibody to react with antigens, specifically those found in some but not all members of the same species, like blood group antigens or histocompatibility antigens.
- 23. • Isoantigens (Alloantigens): These are antigens present in some, but not all, members of a species. Examples: • Human Erythrocyte Antigens (Blood Groups): Different blood types (A, B, AB, O) are determined by the presence or absence of specific isoantigens on red blood cells. • Histocompatibility Antigens: These are tissue-specific antigens that are unique to each individual within a species. They are crucial in tissue and organ transplantation. Importance: • Blood Transfusions: Understanding isospecificity is vital for safe blood transfusions to avoid reactions between donor and recipient blood. • Organ Transplantation: Matching histocompatibility antigens is crucial for successful organ transplantation to prevent rejection. • Disputed Paternity Cases: Isoantigens can be used in paternity testing.
- 24. Human erythrocyte antigens, or blood group antigens, are surface markers on red blood cells that determine an individual's blood type, with the ABO and Rh systems being the most clinically significant. 1. ABO Blood Group System: • The ABO system classifies blood into four main types: A, B, AB, and O, based on the presence or absence of specific antigens (A and B) on the surface of red blood cells. • Blood Type A: Has A antigens and anti-B antibodies in the plasma. • Blood Type B: Has B antigens and anti-A antibodies in the plasma. • Blood Type AB: Has both A and B antigens, but no antibodies. • Blood Type O: Has neither A nor B antigens, but both anti-A and anti-B antibodies. • The ABO blood types were discovered by Karl Landsteiner in 1901.
- 25. 2. Rh Blood Group System: • The Rh system is another important blood group system, with the RhD antigen being the most significant. • RhD Positive: People with the RhD antigen on their red blood cells are considered RhD positive. • RhD Negative: Those lacking the RhD antigen are RhD negative. • The Rh factor is an inherited protein that can be found on the surface of the red blood cell.
- 26. 3. Other Blood Group Systems: • Besides ABO and Rh, there are many other blood group systems, but they are less clinically significant. • The International Society of Blood Transfusion (ISBT) recognizes 45 different blood group systems . • These systems are genetically determined by 50 genes. • Examples include the Kell, Duffy, MNS, and Lewis systems.
- 27. 4. Clinical Significance: • Blood group antigens are crucial in blood transfusions and organ transplantation to prevent adverse reactions. • Mismatches in blood group antigens can lead to severe complications, including hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDN). • The Rh antigens are highly immunogenic, meaning they can trigger a strong immune response. • Antibodies to Rh antigens can cause hemolytic transfusion reactions and HDN. • The Kell system is another important system, with the Kell antigens being highly immunogenic. • Anti-K antibody causes severe hemolytic disease of the fetus and newborn (HDFN) and haemolytic transfusion reactions (HTR).
- 28. Histocompatibility Antigens • Histocompatibility antigens are the cellular determinants specific for each individual of a species. • These antigens are associated with the plasma membrane of tissue cells. • Human leukocyte antigen (HLA) is the major histocompatibility antigen that determines the homograft rejection.
- 29. Other Specificities: • Auto-specificity: The ability of an antibody to react with antigens from the same species. • Sequestrated antigens (such as eye lens protein and sperm) are, however, exceptions, • As they are developed later in life,not in embryo stage ,when immune tolerance develops.
- 30. Organ specificity •Antigens found in specific organs or tissues are called organ-specific antigens. •Interestingly, these antigens in organs like the brain, kidney, and lens can be very similar across different animal species. •For example, the brain-specific antigens in humans and sheep are alike. •Rabies vaccines made from sheep brain can sometimes cause an immune reaction in people. •This reaction can unfortunately lead to damage in the person's own nerve tissues. •As a result, some people who receive these vaccines might experience neuroparalytic complications (problems with their nerves that can cause paralysis).
- 31. Heterophile specificity arises from heterophile antigens shared across different biological species, classes, or kingdoms. •Cross-reactivity: Antibodies against these antigens in one species react with similar antigens in other species. •Applications: Exploited in diagnostic serological tests, like: •Weil–Felix reaction •Paul-Bunnell test •Cold agglutination tests
- 33. Hapten •Definition: Haptens are small organic molecules that are antigenic but not immunogenic. •Reason for Non-Immunogenicity: •Cannot activate helper T cells due to inability to bind to MHC proteins (only proteins can bind to MHC). •Being univalent, they cannot activate B cells independently. •Activation via Carrier Protein: •Haptens become immunogenic when covalently bound to a carrier protein, forming a hapten–carrier conjugate. •The conjugate binds to IgM receptors on B cells and is internalized. •A peptide from the carrier protein is presented with class II MHC to helper T cells. •Activated helper T cells produce interleukins, stimulating B cells to produce antibodies. •Antibody Production: •Antibodies are specific to: •The hapten determinant. •Unaltered epitopes on the carrier protein. •New epitopes formed by the hapten-carrier combination. •Allergic Responses: •Hapten–carrier conjugates can lead to allergic reactions, such as penicillin hypersensitivity.
- 34. Superantigen •Definition: Superantigens are molecules that interact nonspecifically with antigen-presenting cells (APCs) and T lymphocytes. •Mechanism: •Bind to MHC class II molecules on APCs and the Vβ domain of T-cell receptors. •Activate a significantly larger number of T cells (10%) compared to conventional antigens (1%). •Effects: Lead to massive cytokine expression and immunomodulation. •Examples: Include staphylococcal enterotoxins, toxic shock syndrome toxin, exfoliative toxins, and certain viral proteins.