Triggers of Adaptive Immunity

Triggers of Adaptive Immunity

Introduction to Adaptive Immunity

  • Triggers of Adaptive Immunity: The adaptive immune system can recognize and respond to nearly all foreign macromolecules present in invading microbes, termed antigens.

  • Antigenicity: The inherent ability of a molecule to be recognized by the immune system, crucial for triggering responses.

  • Types of Antigens:

    • Microbial Antigens: Includes agents from bacteria, viruses, fungi, protozoan parasites, arthropods, and helminths.

    • Non-Microbial Antigens: Includes cell surface antigens and autoantigens, which provoke responses against normal body components.

Basic Antigen Definitions and Properties

  1. Antigen: Any substance that is recognized by the immune system and can provoke an immune response.

  2. Hapten: A small molecule that is not immunogenic on its own but can elicit an immune response when linked to a larger carrier molecule.

  3. Carrier: The larger protein molecule that haptens are attached to in order to form a complex that can trigger an immune response.

Characteristics of Antigens

  • Good Antigens: Large, complex, and foreign molecules that elicit a strong immune response.

  • Factors Influencing Antigenicity:

    • Size

    • Complexity

    • Stability

    • Foreignness

Examples of Antigens

  • Bacterial Antigens:

    • Peptidoglycans

    • Lipoteichoic Acid

    • Lipopolysaccharides

    • Lipoproteins

    • Capsular antigens (K)

    • Pili

    • Flagellar antigens (H)

    • Porins

    • Heat-shock proteins

    • Exotoxins

    • Bacterial nucleic acids

  • Viral Antigens:

    • Simple structure includes a nucleic acid core surrounded by a protein shell called capsid.

    • Antigenic properties stem from capsid proteins and surface viral proteins expressed on infected cells.

  • Other Microbial Antigens:

    • Fungal, protozoan, arthropod, and helminth components may serve as antigens.

    • Responses may vary and effectiveness can differ.

  • Non-Microbial Antigens:

    • Food allergens and inhaled particles like pollen.

    • Blood-group antigens, which trigger responses in tissue graft rejection.

    • Autoantigens: Proteins like thyroglobulin, myelin, and mitochondrial proteins that lead to autoimmunity when the immune system attacks them.

Size and Complexity of Antigens

  • Size: Larger molecules are generally more antigenic. For example:

    • Glucose: 1nm

    • Angiotensin: 1031 Da

    • Albumin: 69,000 Da

    • Immunoglobulin G: 156,000 Da

    • Fibrinogen: 400,000 Da

    • Immunoglobulin M: 900,000 Da

    • Molecules <1000 Da are typically poor antigens.

  • Complexity:

    • More complex molecules tend to be more antigenic. Repeated small units (like lipids, nucleic acids, carbohydrates) show poor antigenicity.

Stability of Antigens

  • Flexible molecules like flagellin and gelatin are poor antigens due to their changing conformations.

  • Stability enhances the ability of an antigen to be recognized; thus, complex molecules can be stabilized to boost antigenicity.

Immunogenicity of Various Antigen Types

  • Protein Antigens: Optimal for immune recognition, especially large, complex proteins. Antigenicity is a function of stability and molecular structure.

  • Polysaccharide Antigens: Sometimes not immunogenic alone but can become so when linked to proteins (glycoproteins).

  • Lipid and Nucleic Acids: Typically poor antigens due to rapid degradation, though they may be antigenic when associated with protein carriers.

Epitopes and Immune Responses

  • Epitopes (Antigenic Determinants): Regions on antigens that trigger immune responses; larger proteins can have multiple epitopes, including immunodominant ones.

  • Epitopes frequency: One epitope is estimated per ~5 kDa of protein.

Haptens and Their Role in Immunogenicity

  • Haptens require a carrier to elicit a response; when chemically linked, they can form new epitopes leading to an immune response.

    • Example: Penicillin’s breakdown forms antigenic complexes (penicilloyl-albumin), leading to allergic reactions.

  • Case Study: Poison Ivy Allergic Contact Dermatitis: Urushiol binds proteins causing an immune response leading to dermatitis.

Cross-Reactivity of Antigens

  • Cross-reactions occur when antibodies from one antigen interact with similar epitopes on an unrelated antigen.

    • Examples include reactions between food and bacterial antigens, or between specific viruses.

    • Potential Transfusion reactions linked to this phenomenon where antibodies target blood group antigens.

Conclusion: Key Takeaways of Antigen Recognition

  • Key Concept 1: The adaptive immune system effectively identifies microbial macromolecules.

  • Key Concept 2: Best antigens are large, complex, stable, foreign proteins.

  • Key Concept 3: Small molecules (<5000 Da) are typically poor antigens.

  • Key Concept 4: Small molecules can achieve antigenic status when associated with larger proteins, termed haptens.

  • Key Concept 5: Immune cells possess receptors to detect specific regions on foreign molecules called epitopes.