Immunology Basics

Immunogen and Antigen Definitions

• Immunogen: a substance that induces a specific immune response
• Antigen (Ag): a substance/molecule capable of stimulating an immune response and reacting with the products of a specific immune response
• Hapten: a small molecule that is non-immunogenic but can react with the products of a specific immune response when coupled to a carrier molecule
• Epitope or Antigenic Determinant: the portion of an antigen that combines with the products of a specific immune response
• Antibody (Ab): a specific protein produced in response to an immunogen that reacts with an antigen

Factors Influencing Immunogenicity

Contribution of the Immunogen

• Foreignness: the immune system discriminates between self and non-self, making foreign molecules immunogenic
• Size: larger molecules tend to be more immunogenic
• Chemical Composition: complex substances are generally more immunogenic
• Physical Form: particulate antigens are more immunogenic than soluble ones, and denatured antigens more immunogenic than native forms
• Degradability: antigens that are easily phagocytosed are generally more immunogenic

Contribution of the Biological System

• Genetic Factors: some substances are immunogenic in one species but not in another, or in one individual but not in others
• Age: the very young and the very old have a diminished ability to mount an immune response

Method of Administration

• Dose: the dose of administration of an immunogen can influence its immunogenicity
• Route: the subcutaneous route is generally better than intravenous or intragastric routes
• Adjuvants: substances that can enhance the immune response to an immunogen, but can have undesirable side effects

Chemical Nature of Immunogens

• Proteins: the vast majority of immunogens are proteins, which are usually very good immunogens
• Polysaccharides: pure polysaccharides and lipopolysaccharides are good immunogens
• Nucleic Acids: nucleic acids are usually poorly immunogenic, but can become immunogenic when single-stranded or complexed with proteins
• Lipids: lipids are generally non-immunogenic, but can be haptens

Types of Antigens

• T-independent Antigens: antigens that can directly stimulate B cells to produce antibodies without requiring T cell help

T-Cell Maturation, Activation, and Differentiation

• Cellular (cell-mediated) immunity is based on the action of specific kinds of T lymphocytes that directly attack cells infected with viruses or parasites, transplanted cells or organs, and cancer cells.

T-Cell Development in the Thymus

• Progenitor T cells migrate to the thymus from early sites of haematopoiesis.
• T-cell maturation involves re-arrangement of the germ line TCR genes and the expression of various membrane markers.

Developmental Stages of T-Cells

• Precursor T cells arrive at the thymus without expressing T-Cell receptor, CD3 complex, CD4, and CD8.
• Recombination Activation Gene (RAG) 1 and RAG 2 are needed for re-arrangement of TCR genes.
• The differentiating T cell passes through a series of stages marked by characteristic changes in their cell surface phenotype.
• These stages are:
  • Double Negative (DN) cells, characterized by the absence of CD4 and CD8.
  • DN1 cells, which are C-kit+, CD44+, and CD25-.
  • DN2 cells, which are C-kit+, CD44 high, and CD25+.
  • DN3 cells, which are C-kit–, CD44–, and CD25+, and halt proliferation with TCR β rearrangement.
  • DN4 cells, which are double positive (DP) with CD4 and CD8 co-receptors expressed.

Pre-TCR and TCR Gene Rearrangement

• The newly synthesized β-chain combines with a 33-kDa glycoprotein known as the pre-T cell receptor or pre-TCR.
• Formation of pre-TCR activates a signal transduction pathway, leading to:
  • Indication of productive TCR β-chain re-arrangement and signaling further proliferation and maturation.
  • Suppression of further re-arrangement of TCR β-chain, resulting in allelic exclusion.
  • Rendering the cell permissive for re-arrangement of the TCR α chain.
  • Induction of developmental progression to CD4+ and CD8+ double positive (DP) state.

Double Positive (DP) Stage

• During the DP stage, TCR α-chain gene rearrangement still has not occurred.
• Rearrangement of α-chain gene begins when the double positive (DP) thymocytes stop proliferating and RAG-2 protein level increases.