M04.13.003 Mononuclear phagocyte system

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Learning Objective

By the end of this article, you should be able to describe the structure and function of the mononuclear phagocyte system (MPS), identify its key cellular components and the organs in which they reside, explain how the MPS contributes to immune defense and clearance of old or damaged cells, and recognize the clinical consequences of MPS dysfunction, including hyposplenism and susceptibility to infection.

Overview

The mononuclear phagocyte system (MPS) is a vital component of the innate immune system. It is a network of phagocytic cells located in the blood, lymphatic system, lymph nodes, liver, spleen, and other tissues. Previously referred to as the reticuloendothelial system, the MPS is responsible for detecting and eliminating pathogens, clearing damaged cells, and recycling cellular materials such as iron.

This article reviews the composition, function, and clinical relevance of the MPS.

Functions of the MPS

The MPS serves several critical roles:

Immune surveillance: Phagocytoses foreign antigens to prevent infection and initiate immune responses.
Cellular cleanup: Removes old, damaged, or dysfunctional cells.
Resource recycling: Reclaims essential components such as iron from degraded red blood cells.

Cells of the MPS

The primary cells of the MPS are phagocytes, which engulf and destroy foreign antigens or damaged cells through phagocytosis.

Key Phagocytes:

Monocytes: Produced in the bone marrow, circulate in the blood, and migrate into tissues to mature.
Macrophages: Tissue-resident phagocytes derived from monocytes, classified based on location:
- CNS: Microglial cells
- Liver: Kupffer cells
- Lungs: Alveolar macrophages
- Skin and mucosa: Langerhans cells
Dendritic cells: Antigen-presenting cells that originate from monocytes.
Granulocytes: Contribute to phagocytosis during inflammatory responses.

Organs of the MPS

Spleen

Red pulp: Contains macrophages that remove defective or aging red blood cells, recycling iron and other materials.
White pulp: Houses B and T lymphocytes; antigen-presenting cells stimulate lymphocyte activation, enabling adaptive immune responses.
Acts as a reservoir for platelets and red blood cells, mobilized when needed.

Lymphatic System

Lymphatic vessels and lymph nodes filter tissue fluid and detect pathogens.
Lymph nodes contain B and T lymphocytes that respond to antigens, triggering specific immune responses.

Liver

Kupffer cells reside in liver sinusoids, phagocytosing foreign particles and damaged cells.
They metabolize red blood cells and hemoglobin:
- Iron from heme is recycled or stored.
- Globin chains are reused.
- Bilirubin is conjugated and secreted into bile.
Kupffer cells also produce cytokines and reactive oxygen species to stimulate local inflammation.

Clinical Relevance

Hyposplenism

Damage or dysfunction of the spleen increases susceptibility to infections, particularly by encapsulated bacteria:

Causes: trauma, surgery, sickle cell anemia, functional hyposplenism (e.g., coeliac disease).
Normally, splenic macrophages efficiently clear opsonized bacteria using molecules such as C3b and antibodies (e.g., IgM).
Without functional macrophages, opsonized encapsulated bacteria persist in the blood, increasing the risk of sepsis.