describe the sequence of events that occurs during a primary immune response with reference to the roles of: macrophages, B-lymphocytes, including plasma cells, T-lymphocytes, limited to T-helper cells and T-killer cells

Primary Immune Response

Overview

The primary immune response is the first encounter of the immune system with a novel antigen. It involves innate immune cells that recognise the pathogen, antigen‑presenting cells that activate adaptive lymphocytes, and the subsequent activation and differentiation of B‑ and T‑lymphocytes to eliminate the threat and establish immunological memory.

Sequence of Events

1. Antigen Recognition by Macrophages

   Macrophages patrol tissues and bind pathogen‑associated molecular patterns (PAMPs) via pattern‑recognition receptors (PRRs). Upon binding, they engulf the pathogen and begin intracellular digestion.

2. Phagocytosis and Antigen Processing

   Inside the macrophage, the pathogen is degraded into peptide fragments. These peptides are loaded onto major histocompatibility complex class II (MHC II) molecules in the endosomal compartment.

3. Antigen Presentation to T‑Helper Cells

   The peptide‑MHC II complex is transported to the cell surface and presented to naïve CD4⁺ T‑helper cells (Th). Recognition of the complex by the T‑cell receptor (TCR) initiates Th activation.

4. Activation of T‑Helper Cells

   Upon activation, Th cells proliferate and secrete cytokines such as IL‑2, IL‑4, and IFN‑γ. These cytokines provide help to B‑lymphocytes and cytotoxic T‑killer cells.

5. Activation of B‑Lymphocytes

   Naïve B‑cells bind the same antigen via their surface immunoglobulin receptors. Presentation of the antigen to Th cells (via MHC II) and receipt of cytokine signals lead to B‑cell activation.

6. Differentiation into Plasma Cells and Memory B Cells

   Activated B‑cells proliferate and differentiate into plasma cells, which secrete large amounts of specific antibodies (IgM initially, then class‑switched IgG, IgA, or IgE). Some activated B‑cells become long‑lived memory B cells for rapid response upon re‑exposure.

7. Activation of T‑Killer (Cytotoxic) Cells

   Antigen peptides presented on MHC I molecules by infected cells are recognised by CD8⁺ T‑killer cells. Cytokines from Th cells (especially IFN‑γ) enhance this activation. Activated T‑killer cells migrate to the site of infection and induce apoptosis of infected cells.

8. Effector Functions and Clearance

   Antibodies neutralise pathogens, opsonise them for phagocytosis, and activate the complement cascade. Cytotoxic T cells eliminate infected cells. Together, these actions clear the pathogen and establish immunological memory.

Roles of Key Immune Cells

• Macrophages

  • First line of defence; phagocytose pathogens.
  • Process antigens and present peptides on MHC II.
  • Produce cytokines (e.g., IL‑12) that polarise T‑cell responses.

• B‑Lymphocytes

  • Recognise soluble antigens via surface Ig.
  • After T‑cell help, differentiate into plasma cells (antibody secretion) and memory B cells.
  • Produce antibodies that opsonise, neutralise, or activate complement.

• Plasma Cells

  • Terminally differentiated B‑cells that secrete large quantities of antibodies.
  • Secretion of IgM during the primary response, followed by class switching to IgG, IgA or IgE.

• T‑Helper Cells (CD4⁺)

  • Recognise antigen–MHC II complexes on antigen‑presenting cells.
  • Release cytokines that activate B‑cells and cytotoxic T cells.
  • Differentiate into Th1, Th2, or Th17 subsets depending on cytokine milieu.

• T‑Killer Cells (CD8⁺)

  • Recognise antigen–MHC I complexes on infected cells.
  • Induce apoptosis of infected cells via perforin/granzyme or Fas‑FasL pathways.
  • Require help from Th cells for optimal activation.

Summary Table