The adaptive immune system

Vivian Imbriotis | July 5, 2026

Adaptive immunity is that part of the immune system which

  • is specific to an antigen
  • requires prior exposure to that antigen to be fully effective

Adaptive immunity depends on lymphocytes.

  • Antigen-presenting cells (mostly dendritic cells, also macrophages and neutrophils) present extracellular antigen on MHCII or intracellular antigen on MHCI
  • This activates T-cells and B-cells which are specific against that antigen, which clonally proliferate
  • This can produce humoral or cytotoxic responses

Cytotoxic system

  • CD8 t-cells are activated
  • They are further stimulated by Th1 cells
  • They bind to cells expressing non-self antigen on MHC1 and lyse them, destroying intracellular pathogens

Humoral system

  • B cells are activated
  • They are further stimulated by Th2 cells
  • They differentiate into plasma cells and produce antibodies which hamper extracellular pathogens

Production and maturation

  • Produced in foetal bone marrow
  • Migrate to thymus, where they undergo positive and negative selection
  • Undergo V(D)J recombination \(\to\) sister cells have randomly varying T-cell receptors
  • Positive selection: cells that cannot bind MHC die.
  • Negative selection: cells that become activated in thymus (by self-antigen) are killed. Cells that are weakly stimulated by self-antigen become T-reg cells.
  • Remaining cells exhibit activity against non-self and tolerance to self
  • They migrate to lymphoid tissues (nodes, spleen, tonsils)

Subtypes (determined in thymus)

  • T-helper CD4+ cells
  • T-regulatory CD4+ cells
  • Cytotoxic CD8+ cells

Activation is stimulated by the T cell receptor binding to...

  • An MHC1-antigen complex (CD8 cells)
  • An MHC2-antigen complex (CD4 cells)

Costimulation is necessary for activation

  • An antigen-presenting cell expresses B7, which binds CD28 on the t-cell
  • No costimulation \(\to\) anergy
  • CAR-T cells are modified to self-co-stimulate \(\to\) reduce anergy

Coinhibition (immune checkpoint)

  • T-cell CTLA4 competes for B7 binding, inhibiting immune response \(\to\) anergy
  • Immune checkpoint inhibitors block CTLA4 (or similar molecules) \(\to\) reduce anergy

Result of activation

  • T-helper cells differentiate into Th1 (cell-mediated immunity promoting) or Th2 (humoral immunity promoting)
  • Activated cell \(\to\) clonal proliferation
  • Some clones become memory cells, others become active t-cells and leave lymphoid tissue

Functions of activated cells

  • Th1 produces INF-\(\gamma\) \(\to\) activate macrophages and cytotoxic T cells
  • Th2 costimulate B-cells \(\to\) enhanced antibody production
  • Treg cells \(\to\) dampen immune response \(\to\) preserve tolerance to self, foetus, and commensural flora
  • CD8 cells \(\to\) lyse human cells expressing non-self on MHC1

Production and maturation

  • Produced in foetal bone marrow
  • Undergo V(D)J recombination \(\to\) sister cells have randomly varying B-cell receptors (membrane bound immunoglobulin)
  • In bone marrow and spleen, undergo positive and negative selection
  • Positive selection: cells without functional B-cell receptor are killed
  • Negative selection: cells that become activated in bone marrow are killed.
  • Remaining cells exhibit activity against non-self and tolerance to self
  • They migrate to lymphoid tissues (nodes, spleen, tonsils)

Activation is stimulated by the B cell receptor binding to unmodified antigen

Costimulation is necessary for activation

  • CD40L from Th2 cells binds CD40 on B-cell
  • Alternatively, activated complement proteins can costimulate B cells

Result of activation

  • Activated cell \(\to\) clonal proliferation
  • Some clones become memory cells, others become active plasma cells and synthesize immunoglobuin

Functions of immunoglobulin

  • Agglutination of antigens
  • Precipitation
  • Neutralization
  • Opsonization
  • Classical complement activation \(\to\) pathogen destruction by MAC