Immunology Basics

Study Notes

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

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

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

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

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

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

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.

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.

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.

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.

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.