Monocytes and macrophages

Morphological characteristics of monocytes

In peripheral blood, monocytes stand out for their size — they are the largest cells (18 to 20 µm), which appear twice as large as a normal erythrocyte in a smear. In microscopy, they often need to be distinguished from lymphocytes. Differential diagnosis is based on two main criteria:

• Nucleus structure. A monocyte is characterized by a large, polymorphic nucleus. Most often, it has a kidney-shaped, horseshoe-shaped, or lobulated form. Chromatin within it is loosely distributed, making it appear relatively light. In contrast, lymphocyte nuclei have a regular round shape and are dark (hyperchromic).
• Cytoplasm features. A monocyte features a wide pale rim of cytoplasm occupying a significant part of the entire cell. Fine azurophilic granularity, representing lysosomes, is often visible in the perinuclear zone. Lymphocytes, by contrast, have a narrow cytoplasmic rim, and granules are typically completely absent.

Transformation of a monocyte into a macrophage

While in the bloodstream, monocytes act as circulating precursors. Their true functional purpose is revealed after migration into tissues, where final differentiation into macrophages occurs.

The maturation process is accompanied by three basic cellular changes:

1. The cell size significantly increases.
2. The organelle apparatus develops: there is an active accumulation of lysosomes and a buildup of the protein-synthesizing system components.
3. The plasma membrane is modified: new specific receptors necessary for capturing antigens appear on the surface.

Mononuclear phagocyte system

All cells originating from blood monocytes and capable of active phagocytosis are united into a single macrophage system. Based on their mobility, they are divided into free (wandering, migrating between blood and tissues) and fixed (resident), which permanently reside in a specific organ.

Specialized tissue macrophages include:

• Typical macrophages (histiocytes) — reside in loose fibrous connective tissue.
• Osteoclasts — degrade the matrix in bone tissue.
• Microgliocytes — protect nervous tissue (in the CNS).
• Nurse cells — are part of the erythroblastic islands of the red bone marrow.
• Interdigitating and dendritic cells — present antigens in lymphoid organs.
• Kupffer cells (stellate macrophages) — localize in the liver.
• Langerhans cells — are present in the epithelium of the respiratory tract and skin.
• Mesangial cells — are located in renal corpuscles.
• Decidual cells — are located in the maternal part of the placenta.

Three main functions of macrophages

Typical macrophages are key participants in inflammatory and immune responses, performing three strictly defined tasks.

A. Phagocytosis Carried out due to the presence of receptors for the $F_c$ fragment of immunoglobulins (Ig) on the macrophage membrane. If a bacterium is pre-coated with antibodies (opsonized), the macrophage easily binds to it and engulfs it — this is receptor-mediated phagocytosis. The cell is also capable of non-receptor phagocytosis (cleanup of cellular debris). The active engulfment process, as in neutrophils, is accompanied by an oxidative “respiratory burst”.

B. Antigen presentation After capture, the foreign agent is digested inside the phagolysosome. The macrophage isolates specific antigenic determinants and displays them on its membrane surface in a complex with proteins. The main goal of this mechanism is to present the antigen to T lymphocytes to trigger an immune response. Important: macrophages are not truly immunocompetent cells. They do not form clones and lack specificity, reacting to any threats stereotypically.

C. Secretory function Cells secrete a spectrum of biologically active substances:

• Immune regulators: interleukins, which activate T and B lymphocyte pools.
• Defense factors: interferon (to combat viruses), lysozyme (to destroy bacteria), and cytolytic factors (against various eukaryotic cells).

Pathological forms of macrophages

The functions of specialized macrophages are fundamentally similar to typical ones, but they often predominate in either phagocytosis or antigen presentation. When overloaded with material that the cell physically cannot digest, pathological morphological forms arise.

Such forms include:

• “Dust” cells — alveolar macrophages whose cytoplasm is totally filled with undigested particles of inorganic dust.
• “Heart failure cells” — macrophages critically overloaded with an iron-containing pigment (hemosiderin). They form in lung tissue during prolonged blood stagnation, when macrophages are forced to phagocytose erythrocytes that have escaped blood vessels.

Class and exam questions

What else to study on this topic

• Mechanisms of the “respiratory burst” during intracellular digestion
• Structure of the macrophage phagolysosome
• Interaction of macrophages with T lymphocytes during antigen presentation
• The role of nurse cells in erythroblastic islands
• The process of bacterial opsonization by immunoglobulins

Other topics in the "Blood" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.