---

Factors Affecting Antigen Immunogenicity (影响抗原免疫原性的因素)

---

Overview

1. Physicochemical & structural properties of the antigen molecule
2. Host characteristics
3. Route of antigen entry into the body

---

Part I — Physicochemical & Structural Properties of the Antigen Molecule

1. Foreignness (异物性) — THE #1 REQUIREMENT for an antigen

The immune system's job is to recognize and reject foreign substances (异物).

• Its chemical structure differs from the host's own components, OR
• It was never encountered by immune cells during the embryonic period (not recognized as "self")

Three categories of foreign substances:

⚠️ High Yield: Sequestered antigens (精子, 脑组织, 眼晶状体蛋白) are physically isolated from the immune system. If released (e.g., trauma), they are treated as "foreign" and can trigger autoimmune disease.

---

2. Chemical Modification Properties (化学修饰属性)

• The chemical nature and functional groups of an antigen determine its immunogenicity.
• Immune cells most commonly recognize proteins — also polysaccharides, lipids, nucleic acids.
• Ranking: Proteins > Polysaccharides > Lipids/Nucleic acids (weakest)
• Mammalian nuclear components (DNA, histones) are normally non-immunogenic in healthy cells.
  • However, after cell death/activation → DNA undergoes hypomethylation and structural changes → becomes immunogenic → can trigger autoantibodies (relevant to SLE/lupus)

⚠️ High Yield: Proteins are the most potent immunogens. Polysaccharides are moderate. Pure lipids and nucleic acids are generally poor immunogens unless modified.

---

3. Physical State & Molecular Structure (物理性状与分子结构)

Molecular Weight — Critical Factor

• More epitopes (antigen-binding sites) available
• More stable molecular structure
• Harder to be degraded and cleared
• Stronger stimulation of lymphocytes → stronger immune response

Classic Examples:

• Gelatin (明胶), MW = 100 kDa: Despite its large size, it consists only of straight-chain amino acids → very weak immunogenicity
  • Add aromatic amino acids (benzene ring groups, 2% tyrosine) → immunogenicity dramatically increases
• Insulin (胰岛素), MW = only 5.7 kDa: Despite small size, contains complex aromatic amino acids → still relatively immunogenic

⚠️ High Yield: MW alone doesn't determine immunogenicity — chemical complexity (especially aromatic amino acids) matters equally.

Physical State:

• Particulate antigens (颗粒性抗原) — stronger immunogenicity
• Soluble antigens (可溶性抗原) — weaker immunogenicity
• Attaching soluble antigens to particle surfaces increases their immunogenicity (this is the principle behind some vaccine adjuvants/carriers)

---

4. Spatial Conformation (空间构象)

• The 3D shape of the epitope is a key factor affecting immunogenicity.
• BCR (B cell receptor) and antibodies recognize the 3D surface shape of the antigen.
• Chemical group type, position, and spatial arrangement all significantly affect immune reactivity.

• Aminobenzene sulfonic acid → strong reaction (+++)
• Aminobenzene arsenic acid → weak reaction (+)
• Aminobenzene acetic acid → minimal (+/−)

• Meta-position aminobenzene sulfonic acid: +++
• Para-position: +/−
• Ortho-position: ++

⚠️ High Yield: A single change in the position of a chemical group on the epitope can dramatically change the strength of immune recognition. This shows that immune recognition is exquisitely specific for 3D conformation.

---

5. Accessibility (易接近性)

• Defined as: how accessible the epitope is to BCR in 3D space
• Epitopes that are exposed on the surface of the antigen molecule are more easily recognized → stronger immunogenicity
• Buried or hidden epitopes are not recognized → poor immunogenicity

---

Part II — Host Characteristics (宿主的特性)

1. Genetic Factors (遗传因素)

• The immune response capacity is controlled by multiple genes, especially MHC (Major Histocompatibility Complex) genes — in humans called HLA genes
• Different mice strains and different individual humans respond differently to the same antigen
• MHC determines which peptide epitopes get presented to T cells

⚠️ High Yield: MHC/HLA is the genetic controller of immune responsiveness. This explains why vaccines don't work equally in everyone.

2. Age, Sex & Health Status (年龄、性别与健康状态)

⚠️ High Yield: This explains why vaccines are less effective in the very young, elderly, pregnant women, and immunocompromised individuals.

---

Part III — Route of Antigen Entry (抗原进入机体方式的影响)

1. Dose

• Too high OR too low → immune non-responsiveness (tolerance/耐受) is induced
• Optimal dose → best immune response

2. Route of Entry (ranked by immunogenicity, lowest → highest):

Oral < Intravenous (IV) < Intraperitoneal < Intramuscular < Subcutaneous < Intradermal

• Intradermal injection (皮内注射) → strongest immune response (most dendritic cells in dermis)
• Oral route → weakest systemic immune response (may induce oral tolerance)

3. Adjuvants (佐剂)

• Alum adjuvant (铝佐剂) → preferentially stimulates IgG production
• Adjuvants generally enhance and prolong immune responses

⚠️ High Yield: The route of antigen administration is clinically critical for vaccine design. Intradermal > Subcutaneous > Intramuscular for immunogenicity. Alum adjuvant promotes IgG.

---

🔑 Master Summary Table — High-Yield Points