Binding of immunoglobulins, complement, and lectins
A wide range of structures is presented on the surface of phagocytes, allowing them to interact with opsonized pathogens and trigger an immune response.
- Lectins (lectin receptors). Recognize carbohydrate structures of microorganisms. Neutrophils and monocytes have dectin-1 on their membrane. Eosinophils lack lectin receptors, whereas monocytes additionally express the specific molecule DC-SIGN.
- Fc receptors. Essential for antibody binding. Common to all three cell types at rest are FcγRII and FcγRIII, as well as FcαR (appears on monocytes only upon activation). Eosinophils are characterized by the presence of receptors for immunoglobulin E — FcεRI and FcεRII. Upon transition to the active state, both neutrophils and eosinophils begin to express FcγRI (which is initially present on monocytes).
- Complement system receptors. Allow cells to respond to components of the complement cascade. CR1 and C3aR are present on all cells in question. Neutrophils and monocytes additionally carry CR3 and C5aR. Monocytes are unique in having CR4, and neutrophils in having the C5L2 receptor.
Cytokine and chemokine receptors
To coordinate actions with other participants in the immune response, phagocytes use receptors for soluble inflammatory mediators.
Regarding cytokines, monocytes possess the richest arsenal: they perceive signals from M-CSF, GM-CSF, interferons (IFNγ, IFNα/β), as well as a whole cascade of interleukins (IL-1, IL-2, IL-3, IL-4, IL-6, IL-10, IL-15, IL-21) and TNFα. Eosinophils selectively respond to GM-CSF, IL-3, IL-4, IL-5, and IL-13. Neutrophils have receptors for G-CSF, GM-CSF, IL-3, and IL-17.
The chemokine receptor system allows cells to move along the concentration gradient of chemoattractants. Neutrophils orient themselves using receptors with the CXC motif (CXCR1, CXCR2, CXCR3, CXCR4). Eosinophils rely on CC receptors (CCR1, CCR2, CCR3, CCR5). Monocytes use a combined set: CCR1, CCR2, CCR3, CCR5, as well as the specific fractalkine receptor — CX3CR1.
Cell adhesion and antigen presentation molecules
Phagocytes require integrins to exit the bloodstream into tissues and for intercellular interaction.
- Neutrophils use β2-integrins (LFA-α, Mac-1, αDβ2) as well as the ICAM-2 receptor.
- Eosinophils carry the β1-integrin (VLA-4) and β2-integrin (αDβ2).
- Monocytes possess the broadest repertoire: multiple β1-integrins (VLA-1, VLA-2, VLA-4, VLA-5, VLA-6), β2-integrins (LFA-1, Mac-1, p150, p45, αDβ2), as well as ICAM-2 and ICAM-3 receptors.
Interaction with lymphocytes requires the involvement of major histocompatibility complex (MHC) molecules. Class MHC-I molecules are present on all cells by default. MHC-II molecules are initially present only on monocytes (their number increases upon activation), whereas on neutrophils and eosinophils they appear exclusively after stimulation.
Among costimulatory molecules, neutrophils lack specific markers. CD154 appears on activated eosinophils. Monocytes weakly express CD86 at rest, while CD80 and CD86 are strongly presented on their membrane upon activation. Other important surface markers include CD14 and CD13 (neutrophils and monocytes) and CD9 (eosinophils).
Internal structure: neutrophil granules
The main weapon of neutrophils is their secretory apparatus. Neutrophil granules are a specialized form of lysosomes and are divided into four types: azurophilic (primary), specific (secondary), gelatinase (tertiary) granules, and secretory vesicles.
The first two types play a special role:
- Specific (secondary) granules. Their enzymes are most active in a neutral or slightly alkaline environment. They contain lactoferrin, lysozyme, alkaline phosphatase, and the BPI protein (responsible for vitamin B12 binding). Markers of these granules are lactoferrin itself and the surface molecule CD66. The main feature of secondary granules is the high concentration of the NADPH oxidase enzyme. It catalyzes the formation of reactive oxygen species (ROS), triggering the so-called respiratory burst. ROS act as the primary bactericidal factor of phagocytes.
- Azurophilic (primary) granules. Unlike specific ones, their contents function at acidic pH values. They store a powerful arsenal of hydrolases and other destructive enzymes, among which myeloperoxidase is the most important.
Briefly: answers to topical questions
What is the enzymatic composition of neutrophil azurophilic granules?
The enzymatic composition of neutrophil azurophilic (primary) granules includes a wide range of acid hydrolases, neutral proteases, and other enzymes whose pH optimum is in the acidic range.
- Enzymes — $\alpha$-fucosidase, 5'-nucleotidase, $\beta$-galactosidase, arylsulfatase, $\alpha$-mannosidase, N-acetylglucosaminidase, $\beta$-glucuronidase, acid glycerophosphatase, lysozyme (muramidase).
- Neutral proteases (serprocidins) — cathepsin G, elastase, collagenase, azurocidin.
- Marker enzyme (myeloperoxidase) — catalyzes the formation of bactericidal halogen-containing compounds.
Which Toll-like receptors (TLRs) do monocytes express?
Monocytes express a maximally diverse set of Toll-like receptors (TLRs 1–11), allowing them to recognize virtually all major pattern groups.
- Surface receptors (TLR-1, TLR-2, TLR-4, TLR-5, TLR-6, TLR-11) — expressed on the plasma membrane of the cell.
- Intracellular receptors (TLR-3, TLR-7, TLR-8, TLR-9) — localized on the membranes of cytoplasmic granules and recognize foreign nucleic acids.
The expression of TLR-2 and TLR-4 is enhanced under the influence of pathogen-associated molecular patterns and cytokines, TLR-7 under the influence of cytokines, and TLR-8 and TLR-9 under the influence of IFN$\gamma$.
Which subunits make up the phagocyte NADPH oxidase enzyme complex?
The phagocyte NADPH oxidase enzyme complex comprises membrane and cytosolic components that are separated in the resting cell.
- Membrane component (flavocytochrome b558) — consists of $\alpha$ (p22$^{phox}$) and $\beta$ (gp91$^{phox}$) subunits and is associated with the Rap1a protein.
- Cytosolic components (p47$^{phox}$, p67$^{phox}$, p40$^{phox}$, Rac-2) — four proteins (including the Rac-2 GTPase), whose attachment is necessary for enzyme activation.
Assembly of the active complex occurs on the phagolysosome membrane with the participation of phosphoinositides.
Class and exam questions
Which immunoglobulin receptors are found exclusively on eosinophils?
Among the cells considered, only eosinophils carry receptors for immunoglobulin E—FcεRI and FcεRII—on their surface.
What is the function of NADPH oxidase?
This enzyme is localized in neutrophil specific granules. It triggers the respiratory burst, leading to the synthesis of reactive oxygen species (ROS), the main agents for destroying engulfed bacteria.
Do neutrophils express MHC-II molecules?
In the resting state, MHC-II molecules are absent on neutrophils. They appear on the membrane only after cell activation.
What else to study on this topic
- The mechanism of the respiratory burst and the biochemistry of reactive oxygen species generation
- Functions of gelatinase granules and secretory vesicles in neutrophils
- The role of the DC-SIGN molecule in monocyte function
- Signaling pathways of CXCR and CCR family receptors
- Participation of CD80 and CD86 molecules in T cell costimulation
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