Infection and Microbiology 12 (FLAG)

Overview of the Adaptive Immune System

• The adaptive immune system is designed to destroy/eliminate invading microorganisms and toxins.
• Capable of raising immune responses against unfamiliar pathogens.
• Highly specific immune responses that provide long-lasting protection (memory).
• Antigens: Any substance capable of generating an adaptive immune response.
• The innate immune system trains the adaptive immune system.

Key Steps of Adaptive Immune Response

1. Immunisation - Introduction of an antigen to elicit an immune response.
2. Instruction - Training and activating immune cells to recognize specific pathogens.
3. Attack - The immune system's effector cells eliminate the pathogens.

Understanding Immunization

• Most knowledge of the adaptive immune system comes from immunization experiments, often conducted on mice.
  • Injection process:
    1. An antigen is injected as a harmless molecule, often with an adjuvant.
    2. Adjuvant: Activates innate immunity, comprised of immunological stimulants and irritants (e.g. inactivated mycobacterial proteins, aluminium hydroxide).
    3. The innate immune response gets activated by both adjuvant and antigen.
    4. This trains the adaptive immune response which can distinguish slight molecular differences.

Benefits of Immunizations

• Vaccination has drastically reduced the incidence of diseases (e.g. diphtheria).
• Case notifications demonstrate a decline in diseases due to vaccination, though significant infectious diseases like tuberculosis persist.
  • Historical context shows spikes in disease occurrence countered by vaccination efforts.

Role of Lymphocytes in Adaptive Immunity

• Lymphocytes: Key players in adaptive immunity; include T and B cells.
  • They develop in central (primary) lymphoid organs (bone marrow, thymus) and migrate to peripheral (secondary) lymphoid organs (e.g., lymph nodes, spleen).
  • Total lymphocyte count can reach approximately $2 imes 10^{12}$ in the human body.
  • Recruitment of lymphocytes into the immune response is critical, as demonstrated by experiments where irradiated mice couldn't mount adaptive responses post-radiation.

Dendritic Cells (DCs) and T Cell Activation

• Dendritic cells are essential for linking the innate and adaptive immune response:
  • They express various receptors and are activated by pathogen binding.
  • Activated dendritic cells phagocytose pathogens, degrade them, and present peptides on their surface.
  • Dendritic cells migrate to lymphoid organs to activate T cells, leading to adaptive immune response.

T Cell Maturation and Response

• T cells develop from thymocytes:
  • They recognize and respond to non-self antigens, leading to activation and clonal expansion when presented by APCs.
  • T cell activation depends on co-stimulatory signals from antigen-presenting cells (APCs).

Types of T Cells

• Helper T cells (TH): Activate macrophages, dendritic cells, B cells.
• Regulatory T cells (Treg): Suppress immune responses to prevent overreaction.
• Cytotoxic T cells (TC): Kill infected cells through apoptosis mechanisms.

Mechanisms of Cytotoxic T Cells

• Cytotoxic T lymphocytes utilize two strategies to kill aim cells:
  1. Granzyme and perforin mechanism:
     • Secretes perforins that form channels in target cells.
     • Secretes granzyme entering cells to activate apoptotic caspases.
  2. Receptor binding: Activates caspases through targeted receptors on infected cells.
• Apoptotic bodies are cleared by DCs and macrophages, retraining the immune response (amplifying process).

Summary of Immune System Interaction

• Innate Immune System recognizes PAMPs and mounts an attack against pathogens.
• Dendritic cells bridge the innate and adaptive systems, activating pathogen-specific T cells that enhance and regulate overall immune functions.
• Adaptive and innate systems complement each other, ensuring an efficient response against infections, with lymphoid organs being critical sites for activity and training of immune cells.