Identification Of Inflammatory Cells Notes

Inflammatory Cells

The cells participating in acute and chronic inflammation are circulating leucocytes, plasma cells, tissue macrophages and inflammatory giant cells. The structure, function and production of these cells Here, their relevant role in inflammation is discussed. Their morphology, characteristics and functions are summarised in

Read And Learn More: General Pathology Notes

Polymorphonuclear Neutrophils (Pmns):

Commonly called as neutrophils or polymorphs, these cells along with basophils and eosinophils are together known as granulocytes due to the presence of granules in their cytoplasm. These granules contain many substances like proteases, myeloperoxidase, lysozyme, esterase, aryl sulfatase, acid and alkaline phosphatase, and cationic proteins.

The diameter of neutrophils ranges from 10 to 15 µm and are actively motile. These cells comprise 40-75% of circulating leucocytes and their number is increased in blood (neutrophilia) and tissues in acute bacterial infections. These cells arise from haematopoietic stem cells in the bone marrow.

The functions of neutrophils in inflammation are as follows:

• Initial phagocytosis:  Initial phagocytosis of microorganisms as they form the first line of body defence in bacterial infection. The steps involved are adhesion of neutrophils to vascular endothelium, transmigration through the vessel wall, chemotaxis, engulfment, degranulation, killing and degradation of the foreign material
• Engulfment:  Engulfment of antigen-antibody complexes and non-microbial material.
• Harmful effects: Harmful effects of neutrophils are by causing basement membrane destruction of the glomeruli and small blood vessels in immunologic cell injury.

Eosinophils:

These are slightly larger than neutrophils but are fewer in number, comprising 1–6% of total blood leucocytes.

Eosinophils share many structural and functional similarities with neutrophils like their production in the bone marrow, locomotion, phagocytosis (weak), lobed nucleus and presence of granules in the cytoplasm containing a variety of enzymes, of which major basic protein and eosinophil cationic protein are the most important which have bactericidal and toxic against helminthic parasites.

However, granules of eosinophils are richer in myeloperoxidase than neutrophils and lack lysozyme. High level of steroid hormones leads to fall in number of eosinophils and even disappearance from blood.

The absolute number of eosinophils is increased in the following conditions; they participate
in inflammatory responses associated with:

• Allergic conditions
• Parasitic infestations
• Skin diseases, and
• Certain malignant lymphomas.

Basophils And Mast Cells:

The basophils comprise about 1% of circulating leucocytes while mast cells are their morphological and functional counterparts widely distributed in tissues. These cells contain coarse basophilic granules in the cytoplasm and a polymorphonuclear nucleus.

These granules are laden with heparin and histamine. Basophils and mast cells have receptors for IgE and degranulate when cross-linked with antigens.

The role of these cells in acute and chronic inflammation are:

• In immediate and delayed types of hypersensitivity reactions, and.
• Release of histamine by IgE-sensitised basophils.

Lymphocytes:

Next to neutrophils, these cells are the most numerous of the circulating leucocytes in adults (20- 45%). Apart from blood, lymphocytes are present in large numbers in the spleen, thymus, lymph nodes and mucosa-associated lymphoid tissue (MALT). They have scanty cytoplasm and consist almost entirely of a nucleus.

Their role in adaptive immunity for antibody formation (B lymphocytes) and in cell-mediated immunity (T lymphocytes).

These cells participate in the following types of inflammatory responses:

1. In tissues, they are dominant cells in chronic inflammation and late stage of acute
   inflammation.
2. In blood, their number is increased (lymphocytosis) in chronic infections like tuberculosis.

In response to microbes or other etiologic agents, T and B lymphocytes are activated, resulting in increased severity and chronicity of inflammatory response.

This is due to the secretion of cytokines, chemokines and antibody synthesis.

Various lymphocyte subpopulations and their interaction with macrophages as under:

• Activation of macrophages via classical pathway by the release of IFN-γ from activated TH1
  cells.
• Activation of macrophages via alternative pathway by the release of IL-4, IL-5 and IL-13 from activated T H2 cells.
• Recruitment of more leucocytes due to the release of cytokines (IL-17, TNF) by activated CD4+ T cells and chemokines from activated macrophages.
• Antibody synthesis by activated B cells and plasma cells.

Plasma Cells:

These cells are larger than lymphocytes with more abundant cytoplasm and an eccentric nucleus which has a cart-wheel pattern of chromatin. Plasma cells are normally not seen in peripheral
blood.

They develop from B lymphocytes and are rich in RNA and γ-globulin in their cytoplasm. There is an interrelationship between plasmacytosis and hyperglobulinaemia. These cells are most active in antibody synthesis.

Their number is increased in the following conditions:

• Prolonged infection with immunological responses for example,
• In syphilis, rheumatoid arthritis, tuberculosis
• Hypersensitivity states, and
• multiple myeloma.

Monocytes-Macrophages:

Collectively called mononuclear-phagocyte system, it includes cells derived from the following two sources with common morphology, function and origin:

1. Blood monocytes:  Circulating monocytes comprise 4-8% of leucocytes.
2. Tissue macrophages: These include the following cells in different tissues:

• • Macrophages or phagocytes in inflammation.
  • Histiocytes are macrophages present in connective tissues.
  • Epithelioid cells are modified macrophages seen in granulomatous inflammation.
  • Kupffer cells are macrophages of the liver.
  • Alveolar macrophages (type II pneumocytes) in the lungs.
  • Reticulum cells are macrophages/histiocytes of the bone marrow.
  • Tingible body macrophages of germinal centres of the lymph nodes.
  • Littoral cells of the splenic sinusoids.
  • Osteoclasts in the bones.
  • Microglial cells of the brain.
  • Dendritic cells in the skin (Langerhans’ cells), under mucosal surfaces and in germinal centres of lymph nodes.
  • Hofbauer cells of the placenta.
  • Mesangial cells of the glomerulus.

Role Of Monocyte-Macrophages In Inflammation:

Their functions in immunity are discussed in Chapter 5. In inflammation, macrophages are activated by one of the following two ways and perform their distinct functions:

Classic macrophage activation :

Here, macrophages are activated by non-immunologic stimuli for example By endotoxins (from microbes), fibronectin, IFN-γ cytokine released by activated T cells, and foreign particulate matter.

1. Classically activated macrophages perform the following functions by the release of free radicals (reactive oxygen species, nitric oxide) and by release of lysosomal enzymes:

• Release of proteases (collagenase, elastase) which degrade collagen and elastic tissue
• Microbicidal actions (phagocytosis, microbial killing)
• Some coagulation factors (factor V and thromboplastin) convert fibrinogen to fibrin
• Chemotactic agents for other leucocytes
• Metabolites of arachidonic acid

2. Alternative macrophage activation Alternatively, macrophages are activated by other cytokines released by T cells (IL-4, IL-13).

Alternatively activated macrophages perform the following functions:

• Induce tissue repair by fibrosis in chronic inflammation by the release of growth factors (PDGF, FGF, TGF-β), fibrogenic cytokines, and angiogenesis-inducing agents.
• Role in the resolution of inflammation by anti-inflammatory effects.

Giant Cells:

• Giant cells are formed by the fusion of various cells. They have the following general features:
• Large size
  (40-120 µm in diameter) Contain multiple nuclei (often 15-30) or more
• Their phenotype depends upon the character of cell from which the giant cell is derived.

Multinucleate giant cells may be normally seen in certain tissues e.g. osteoclasts in the bones, syncytiotrophoblasts in the placenta, and megakaryocytes in the bone marrow.

Pathologic giant cells may be seen in some inflammatory conditions, or they may occur as tumour giant cells in certain neoplasms.

While examples of tumour giant cells (Reed-Sternberg cells in Hodgkin’s disease, in anaplastic malignant tumours etc) are discussed in relevant chapters later, giant cells of inflammatory aetiology may be derived from macrophages or epidermal cells:

Macrophage-Derived Giant Cells:

These giant cells are formed by the fusion of macrophages in chronic inflammation when macrophages fail to deal with a microbe or particulate material for its removal.

These are three types:

1. Langhans’,
2. Foreign body, and
3. Touton type

1. Langhans’ giant cells:

This term is not be confused with Langerhans cells; the latter are antigen-presenting dendritic cells in the skin.

Langhans’ giant cells are formed due to the fusion of epithelioid cells, a variant of macrophages, in tubercular granulomas. The nuclear fusion is induced by mycobacterial lipomannan released from the tubercle bacilli via a TLR-2 dependent (toll-like receptor-2) pathway: mediated by ADAM-9 (a disintegrin and metalloproteinase domain 9) and β1-integrin.

Besides, a critical role is played by CD40 molecule and its ligand (CD40-CD40L) and IFN-γ released from activated T cells in the formation of Langhans’ giant cells.

The nuclei in Langhans’ giant cells have phenotypic characteristics of epithelioid cells and may be arranged in one of the two patterns: around the periphery in the form of a horseshoe or ring, or clustered at the two poles of the giant cell.

Langhans’ giant cells may be seen in the following conditions:

Mycobacterial infections (tuberculosis, tuberculoid leprosy)

• Sarcoidosis
• Syphilis in late-stage
• Crohn’s disease
• Deep fungal infections
• Leishmaniasis

2. Foreign body giant cells:

Foreign body giant cells are often larger than Langhans’ giant cells and contain more numerous nuclei (up to 100) which are randomly spread throughout the cytoplasm.

They are formed by the fusion of macrophages when they fail to remove a foreign particle. Important mediators in the formation of foreign body giant cells are β1 and β2 integrin receptors, IL- 4 and MMP-9 (matrix metalloproteinase).

Foreign body giant cells are seen in response to the following conditions:

• Exogenous substances, for example, Starch, talc, vegetable matter, tattoo, bristles of cacti, particles of wood, suture, injected oils, and micro implants.
• Endogneous materials, for example, Deposits of calcium, urates, oxalate, keratin, hair etc.
• Microbial infections All conditions which are associated with Langhans’ giant cells may also contain foreign body giant cells.

3. Touton giant cells:

Also called xanthelasmic giant cells, they were first discovered by Karl Touton. These multinucleated cells have a central ring of nuclei and periphery contains vacuolated cytoplasm due to lipid content. In these cells, the stimulus for the fusion of nuclei is accompanied by a factor that promotes lipid uptake.

Based on immunohistochemical stains, the phenotype of Touton cells is histiocytic (positive for lysozyme, α-1 antitrypsin, α-1 antichymotrypsin).

Touton giant cells are seen in the following conditions:

• Xanthoma and xanthelasma
• Xanthogranulomas
• Fat necrosis
• Dermatofibroma

4.  Aschoff giant cells:

These are formed by the fusion of two or more nuclei of myocardial macrophages and are seen in Aschoff nodules in rheumatic heart disease.

Epidermal Cell-Derived Giant Cells:

Giant cells formed from epidermal cells may be Tzanck giant cells or rarely multinucleate epidermal giant cells:

• Tzanck giant cells: These giant cells are formed due to viral infection of the skin which stimulates rapid nuclear division of epidermal cells while the cytoplasm fails to divide. Some nuclei in these giant cells may appear quite bizarre or atypical.
• Tzanck giant cells may be seen in the following viral infection of the skin:
  • Herpes simplex
  • Herpes zoster and varicella
  • Cytomegalovirus
• Multinucleate epidermal giant cells: Rarely, 2-3 nuclei of epidermal cells forming giant cells may seen in certain inflammatory dermatoses for example,
  • Chronic eczema
  • Dermatitis herpetiformis
  • Lichen amyloidosis
  • Lichen planus

Inflammatory Cells:

• The cells participating in acute and chronic inflammation are circulating leucocytes, plasma cells, tissue macrophages and inflammatory giant cells.
• Polymorphs or neutrophils are the first line of defence against invading agents and perform initial phagocytosis.
• Eosinophils participate in allergic conditions, parasitic infestations, certain skin diseases and malignant lymphomas.
• Basophils and mast cells are involved in IgE-mediated immediate and delayed type of hypersensitivity reactions.
• Lymphocytes are immunocompetent cells — B cells in humoral immunity and T cells in cell-mediated immunity.
• Besides, lymphocytes are the dominant cells in chronic inflammation.
• Plasma cells develop from B cells and are immunoglobulin-synthesising cells and are seen in chronic inflammation.
• The mononuclear phagocyte system is comprised by circulating monocytes and tissue macrophages. On activation, macrophages perform microbicidal actions and play a role in repair by fibrosis.
• Besides other inflammatory cells, giant cells derived from macrophages may appear in chronic inflammation. These are Langhans (in mycobacterial infections) and foreign body (in exposure to exogenous and endogenous materials), and Touton giant cells (in xanthoma, fat necrosis etc).
• Besides, giant cells derived from epidermal cells may be seen in certain viral infections (Tzanck cells).