Innate–Adaptive Link

Overview – Innate–Adaptive Link

The innate–adaptive link describes how the innate immune system communicates with and activates the adaptive immune system. This bridge is formed by cytokines and antigen-presenting cells, which work together to convert early, non-specific responses into a long-lasting, highly specific immune defence. Understanding this link is essential in immunology, vaccine development, and clinical infection control.

Definition

• The innate–adaptive link refers to the mechanisms that connect the innate immune response (rapid, non-specific) with the adaptive immune response (delayed, specific, memory-forming).
• Key components:
  • Cytokines: Chemical messengers that activate, regulate, and recruit immune cells
  • Antigen-Presenting Cells (APCs): Cells that process and display antigens to T-cells via major histocompatibility complexes (MHCs)

Cytokines

Overview

• Cytokines = Small proteins secreted by immune and non-immune cells that alter the behaviour of other cells
• Triggered by toll-like receptor (TLR) activation during innate immune responses
• Regulate:
  • Inflammation
  • Chemotaxis
  • Cell proliferation, maturation, and apoptosis

Classification

• Interleukins (ILs):
  • Originally thought to act only between white blood cells
  • Now known to be produced by T-helper cells, macrophages, endothelial cells
  • Control development of T, B, and haematopoietic cells
• Chemokines:
  • Direct cell migration via chemotaxis
  • Create concentration gradients for immune cell recruitment
• Lymphokines:
  • Secreted by lymphocytes (mainly T-cells)
  • Attract and activate other immune cells at the site of infection

Modes of Action

• Autocrine: Acts on the cell that secretes it (e.g. chemokines)
• Paracrine: Acts on nearby cells (common in immune responses)
• Endocrine: Travels systemically to distant sites (e.g. acute-phase cytokines like IL-6)

Key Cytokines

• IL-1, IL-6, TNF-α:
  • Stimulate acute-phase protein production by the liver
  • Act as pyrogens → induce fever
  • Mobilise neutrophils from bone marrow
  • Stimulate dendritic cell activation and migration to lymph nodes
• IL-8:
  • A chemokine produced by monocytes, macrophages, and damaged epithelium
  • Recruits granulocytes, monocytes, and CD8+ T-cells to the infection site
• Interferon gamma (IFN-γ):
  • Activates macrophages
  • Secreted by CD4+ T-helper cells, CD8+ cytotoxic T-cells, and natural killer (NK) cells

Antigen-Presenting Cells (APCs)

• APCs bridge innate sensing and adaptive response by displaying processed antigens to T-cells on MHC molecules

Dendritic Cells

• Most efficient APCs
• Recognise pathogens via pattern recognition receptors (e.g. TLRs)
• Migrate to lymph nodes after antigen uptake
• Present antigen on both MHC-I and MHC-II, enabling activation of:
  • CD4+ helper T-cells
  • CD8+ cytotoxic T-cells

Macrophages

• Recognise pathogens via TLRs
• Present antigen on MHC-II to CD4+ helper T-cells
• Require helper T-cell activation to become fully phagocytic
• Also secrete cytokines to initiate inflammation

B-Lymphocytes

• Use surface immunoglobulin receptors to bind specific antigens
• Present internalised antigens on MHC-II
• Require CD4+ T-helper cell interaction to:
  • Differentiate into plasma cells
  • Undergo isotype switching
  • Produce high-affinity antibodies

Summary – Innate–Adaptive Link

The innate–adaptive link is mediated primarily by cytokines and antigen-presenting cells, ensuring that the body’s initial broad-spectrum immune defence transitions into a highly specific adaptive response. Cytokines such as IL-1, IL-6, TNF-α, and IFN-γ orchestrate immune cell recruitment and activation, while dendritic cells, macrophages, and B-lymphocytes process and present antigens to initiate T-cell responses. For a broader context, see our Immune & Rheumatology Overview page.