Inflammatory Cells in Chronic Inflammation: Macrophages, Lymphocytes, Plasma Cells, Eosinophils and Mast Cells

Learning outcomes

• Identify the major inflammatory cells in chronic inflammation and their microscopic appearance.
• Explain how each cell is recruited, activated and removed.
• Compare M1-like and M2-like macrophage functions.
• Describe T-cell subsets, B cells/plasma cells, eosinophils, mast cells and persistent neutrophils.
• Link cells to granulomas, fibrosis, allergy, autoimmunity, infection and cancer.
• Interpret cell-rich pathology and select useful diagnostic tests.

1. Overview of the cellular network

Cell	Main role	Potential harm
Macrophage	Phagocytosis, antigen presentation, cytokines, repair and fibrosis.	ROS/proteases, persistent cytokines and excessive fibrosis.
T lymphocyte	Antigen-specific activation and macrophage/leukocyte control.	Autoimmunity, cytotoxic injury and chronic cytokine loops.
B cell/plasma cell	Antibody production and immune memory.	Immune complexes, autoantibodies and tissue deposition.
Eosinophil	Helminth defence and type 2 inflammation.	Granule-protein injury in asthma and allergy.
Mast cell	Rapid histamine, lipid mediator and cytokine release.	Anaphylaxis, bronchospasm, oedema and fibrosis.
Neutrophil	Acute killing and debris removal.	Persistent neutrophilic injury in chronic infection/COPD.

2. Macrophages

2.1 Origin and recruitment

Macrophages arise from resident tissue populations and recruited monocytes. CCL2, CSF-1, complement and microbial signals guide recruitment. They survive longer than neutrophils and can repeatedly ingest material.

2.2 M1-like inflammatory activation

Microbial products, IFN-γ and TNF induce an inflammatory phenotype. These macrophages produce IL-1, TNF, IL-6, IL-12, ROS, nitric oxide and proteases. They kill organisms and activate T cells but can damage bystander tissue.

2.3 M2-like repair activation

IL-4, IL-13, immune complexes and repair signals produce a matrix-remodelling phenotype. M2-like cells release TGF-β, VEGF and growth factors, promote angiogenesis and activate fibroblasts. Excessive activation causes fibrosis and tumour-supporting stroma.

2.4 Macrophage morphology

• Abundant eosinophilic or foamy cytoplasm.
• Round or oval nuclei; lipid-laden macrophages appear as foam cells.
• Epithelioid macrophages have abundant pale cytoplasm and indistinct borders in granulomas.
• Multinucleated giant cells form by macrophage fusion.

3. T lymphocytes

Subset	Key cytokines/function	Clinical association
Th1	IFN-γ activates macrophages; IL-2 supports cellular immunity.	Tuberculosis, intracellular infection, granulomas.
Th2	IL-4, IL-5, IL-13; IgE, eosinophils, mucus and fibrosis.	Asthma, helminths and allergy.
Th17	IL-17 and IL-22 recruit neutrophils and strengthen mucosal barriers.	Fungal/bacterial defence, psoriasis and autoimmunity.
Regulatory T cells	IL-10 and TGF-β suppress excessive immune activation.	Tolerance, resolution and tumour immune escape.
CD8 cytotoxic cells	Perforin/granzyme and death receptors kill target cells.	Viral hepatitis, graft rejection and tumour surveillance.

4. B cells and plasma cells

B cells present antigen, form memory and differentiate into plasma cells. Plasma cells have eccentric “clock-face” nuclei and basophilic cytoplasm due to abundant rough ER. They produce antibodies in chronic infection, autoimmune disease and mucosal inflammation.

• Autoantibodies can directly injure cells or activate receptors.
• Immune complexes activate complement and neutrophils.
• Tertiary lymphoid structures may form in chronically inflamed organs.
• Monoclonal plasma-cell populations suggest neoplasia and require immunophenotyping.

5. Eosinophils

Eosinophils have bilobed nuclei and bright eosinophilic granules containing major basic protein, eosinophil cationic protein, peroxidase and neurotoxin. IL-5 promotes their production and survival; eotaxins recruit them.

• Protective: kill helminths too large for phagocytosis.
• Harmful: granule proteins injure bronchial epithelium, nerves and endothelium.
• Clinical: asthma, allergic rhinitis, drug reactions, parasitic disease and eosinophilic gastrointestinal disorders.

6. Mast cells

Mast cells reside near vessels, nerves and epithelial barriers. IgE cross-linking triggers rapid degranulation; complement, physical injury and neuropeptides can also activate them.

Mediator	Effect
Histamine	Permeability, itching, vasodilation and bronchospasm.
Tryptase/chymase	Matrix remodelling and proteolysis.
Leukotrienes/prostaglandins	Bronchoconstriction, mucus, pain and sustained permeability.
TNF/chemokines	Leukocyte recruitment and chronic amplification.

7. Neutrophils in chronic disease

Neutrophils are not exclusive to acute inflammation. They persist when organisms, smoke, crystals, necrotic tissue or cytokines continually recruit them. Chronic neutrophilic conditions include bronchiectasis, COPD, chronic osteomyelitis, inflammatory bowel flares and non-healing wounds.

8. Cells in granulomatous inflammation

• Epithelioid macrophages form the central cellular aggregate.
• Th1 cells produce IFN-γ and maintain macrophage activation.
• Multinucleated giant cells surround indigestible organisms or foreign material.
• Peripheral lymphocytes and fibroblasts form a rim and may create a fibrotic capsule.
• Caseous necrosis suggests some infections but is not diagnostic without microbiology.

9. Cell interactions and fibrosis

Macrophage–T-cell feedback sustains inflammation. Macrophage TGF-β and platelet-derived growth factor activate fibroblasts; IL-13 promotes collagen and mucus; endothelial VEGF drives angiogenesis. Matrix metalloproteinases and their inhibitors determine whether tissue is degraded, remodelled or replaced by scar.

10. Diagnostic clues

Finding	Likely cell/process	Useful test
Foamy macrophages	Lipid, cholesterol or storage material.	Oil Red O, lipid profile, storage-disease testing.
Granulomas	Epithelioid macrophages, giant cells and T cells.	AFB/fungal stains, cultures, polarised light.
Eosinophil-rich infiltrate	Allergy, helminths or drug reaction.	FBC differential, parasite tests, medication review.
Plasma-cell infiltrate	Chronic antigen or autoimmune response.	Immunoglobulins, electrophoresis, clonality studies.
Mast-cell increase	Allergic or mast-cell disease.	Tryptase, CD117 and specialist evaluation.

11. Clinical applications

• Tuberculosis: Th1–macrophage granulomas contain infection but can destroy lung tissue.
• Asthma: Th2 cytokines, mast cells and eosinophils cause bronchospasm, mucus and airway remodelling.
• Rheumatoid arthritis: macrophages, T cells and plasma cells sustain synovitis and pannus destruction.
• Inflammatory bowel disease: lymphocytes, macrophages, neutrophils and plasma cells interact with barrier/microbial signals.
• Chronic hepatitis: lymphocyte and macrophage injury causes fibrosis, cirrhosis and cancer risk.

12. Emergency relevance

• Chronic disease lowers organ reserve; acute infection or trauma can cause rapid decompensation.
• Eosinophilic or mast-cell inflammation can produce life-threatening bronchospasm or anaphylaxis.
• Immunosuppressed patients may have muted cell counts and still develop sepsis.
• Before escalating immunosuppression, exclude occult infection and obtain tissue/microbiology when appropriate.

13. Quick self-test

1. Which cell coordinates chronic inflammation and fibrosis?
   Answer: The macrophage.
2. Which T-cell subset drives macrophage activation in tuberculosis?
   Answer: Th1 cells through IFN-γ.
3. Which subset is associated with allergy and eosinophils?
   Answer: Th2 cells.
4. What granules injure tissue in eosinophilic inflammation?
   Answer: Major basic protein, eosinophil peroxidase and related cationic proteins.
5. Which cell releases histamine rapidly?
   Answer: Mast cells.
6. Why can chronic inflammation persist after the original trigger is small?
   Answer: Macrophage–lymphocyte cytokine feedback loops and ongoing tissue destruction maintain the response.
7. What must be excluded before immunosuppressing a granulomatous lesion?
   Answer: Mycobacterial, fungal and other infections, plus foreign material.

14. Take-home summary

Selected references

• NCBI Bookshelf: Chronic Inflammation
• NCBI Bookshelf: Inflammation and Repair
• NCBI Bookshelf: Granulomatous Diseases

Educational note: This resource supports learning and clinical reasoning. Current local protocols, senior supervision and national guidelines take precedence in patient care.