In the last post, we went through the two branches of immunity, innate immunity and the acquired immunity. In this one and the next post, we shall see the different types of cells involved in the immune system.
All the cells of the immune system are known as leucocytes or white blood cells (WBC). They are all differentiated from the common hematopoietic stem cell. The matured, differentiated leucocytes are morphologically and functionally different from each other. The morphological differences can be visualised by using different stains. Also, each type of WBC has several glycoprotein differentiation antigens on cell surface, belonging to different cluster of differentiation (CD).
All the leukocytes differentiate from a common hematopoietic stem cells by the process called hematopoiesis. Initially, the hematopoietic stem cells differentiate into the multipotent myeloid progenitor cell or the lymphoid progenitor(see fig 1).
These progenitors inturn differentiate into different mature leukocytes.
– Myeloid stem cells or the myeloid progenitors, give rise to granulocytes and monocyte/macrophage. The myeloid progenitors also give rise to the erythrocytes and the platelets.
– Lymphoid progenitors further differentiate into B lymphocytes, T lymphocytes and NK cells (see fig 1).
Let’s see all the leukocytes in details:
I. Cells derived from myeloid progenitor:
As mentioned above, myeloid progenitors, give rise granulocytes and monocytes/macrophage.
1. Granulocytes:
Granulocytes or granular leukocytes are a group of white blood cells that possess a significant number of cytoplasmic granules. This includes cells like eosinophils, neutrophils, basophils and mast cells. Among these, the eosinophils, basophils and neutrophils have multilobed nuclei. Hence, they are also called polymorphonuclear or PMN leukocyte (fig 1). Mast cells have single round nucleus.
(Just for info: Know about the ‘Nuclear morphologies: their diversity and functional relevance’ in this paper.)
The granules of the granulocytes contain enzymes, antimicrobial proteins and other regulating proteins, that are released during infections, allergic reactions and asthma.
The different types of granulocytes are:
a. Eosinophil:
Eosinophils represent 1–3% of the leucocytes. They mostly remain in tissues for several weeks. In blood, they have a half-life of around 16 hours. Eosinophils are granulocytes with bilobed nucleus and around 200 large granules (also known as secondary, specific or crystalloid granules) in the cytoplasm (fig 2). Eosinophils (containing basic components) get stained by the acid stain, like eosin, which imparts red colour to these cells.
The granules of eosinophils are filled with biologically active proteins, including cationic proteins (like major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN)], cytokines, chemokines and growth factors [IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, NGF, GM-CSF, TGF-α and so on].
They express MHC-II and function as antigen-presenting cells. Eosinophils can also modulate the inflammatory response by controlling the activities of mast cells and basophils. Due to the presence of granular cytokines having immunomodulatory effects, the eosinophils are involved in asthma and other allergic diseases. They can also cause clearance of parasites like helminths, through process involving degranulation.
(Just for info: Read this paper titled Functional Extracellular Eosinophil Granules: A Bomb Caught in a Trap.)
b. Neutrophil:
Neutrophils are also polymorphonuclear leukocyte, with characteristic multilobed nucleus with around 3 to 5 lobes (fig 3). They are the most abundant leukocytes in the bloodstream, more than 50% of all the bloodstream leukocytes. However, during a bacterial infection, neutrophils may increase to around 80%. In tissues, their concentration is very low, which increases during infection. Neutrophils get stained by neutral stains like the Wright stain.
Neutrophils are an essential part of the innate immune response and participate in the first line of defense against the invaders. They are among the cells which first accumulate at the site of infection.
The neutrophils always scan the blood and tissues for the invader. On encountering an invader, they destroy it through phagocytosis and intracellular degradation, release of granules or formation of neutrophil extracellular traps. These leucocytes contribute in inflammation as well. They also play a major role in events like hematopoiesis, angiogenesis, fibrogenesis and repair of tissue injury.
Neutrophils can produce a variety of chemokines and cytokines (see fig 4) which modulate all its functions.
c. Basophils:
Basophils constitute less than 1% of the circulating granular leukocytes. Their nucleus may have 2-3 lobes (fig 5). They differentiate in the bone marrow and enter the circulation as mature, functionally active cells. Basophils are capable of chemotaxis and are recruited into tissues during inflammatory reaction. Basophils (contains acidic components) get stained by basic stains (e.g. hematoxylin gives it blue colouration).
When activated, basophils degranulate and release histamine, proteoglycans (e.g. chondroitin and chondroitin sulphate), and several proteolytic enzymes (e.g. elastase and lysophospholipase). They also secrete lipid mediators (such as leukotrienes and prostaglandins), express cysteinyl leukotriene receptors, produce several important cytokines (IL-3, IL-4, IL-6, IL-9, IL-13, IL-25), chemokines, GM-CSF and express activation-related membrane markers.
Basophilic cells play an important role in chronic allergy inflammation, regulation of Th2 cell function and immune cell memory. They are potent antigen-presenting cells of Th2 cells and involved in the Th2 cytokine-mediated inflammation. Basophils are also involved in the induction of Th2 response in cases helminth parasites and allergens.
Basophils have high-affinity receptors for immunoglobulin E (IgE) termed as FcϵRI. When IgE bound to an allergen, attaches itself to FcɛRI receptor the basophils get activated. These activated basophils release of inflammatory mediators and contribute in immediate hypersensitivity and inflammatory reactions.
(Just for info: Read this paper titled ‘Signalling through the high-affinity IgE receptor FcɛRI.)
d. Mast cell:
Mast cells were first described by Ehrlich in 1878. Mast cells are granulocytes and have a large number of granules. They are not polymorphonuclear but have round nucleus.
Mast cells do not usually circulate in the blood stream but are localized in connective tissues (mostly around the blood vessels) and beneath epithelial surfaces (like the GI and respiratory tracts, and skin). They mature in the tissues in which they get localized.
Like basophils, one of the pro-inflammatory mediators in the granules of mast cells is histamine. Their granules contain most of the body’s histamine. The mast cells residing in connective tissues generally contain more histamine than basophils. Histamine is released when the body encounters a toxic substance or on detecting an injury. It causes nearby blood vessels to dilate allowing more blood to reach the site of the injury or infection.
Mast cells play a central role in inflammatory and immediate allergic reactions. During asthma and inflammatory bowel disease, they get concentrated in lungs and gastrointestinal tract respectively . They release pro-inflammatory mediators (such as histamine), proteases, chemotactic factors, cytokines and metabolites of arachidonic acid. (that act on the vasculature, smooth muscle, connective tissue, mucous glands and inflammatory cells).
Mast cells surface (like basophils) have FcɛRI receptors. When IgE bound to an allergen, attaches itself to FcɛRI receptor of the mast cell, the mast cell gets activated and release cytokines, eicosanoids and their secretory granules, which are proinflammatory and immunoregulatory in nature.
Mast cells interact directly with bacteria and appear to play a vital role in host defense against pathogens. These cells play an active role in diseases such as asthma, rhinitis, middle ear infection and pulmonary fibrosis. They also play a crucial role in the initiation of the allergic reactions by inducing IgE synthesis and Th2 differentiation.
(Mast cells and basophils play similar roles in acquired and innate immunity. These two are the predominant cells participating in the allergic reactions and subsequent tissue repair.)
(Just for info: Read this post about the roles of mast cells and basophils in the acquired immunity)
2. Monocytes/macrophage:
The other types of cells derived from myeloid progenitor are the monocytes/macrophages, which will be discussed in the next post, along with the cells derived from cells derived from lymphoid progenitor.
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High Pressure Liquid Chromatgraphy (HPLC).
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References:
Muniz et al (2013) Functional Extracellular Eosinophil Granules: A Bomb Caught in a Trap.Int Arch Allergy Immunol. 162:276–282.
Kovalszki and Weller (2016) Eosinophilia. Prim Care 43(4): 607–617.
Shah et al (2017). Neutrophils. Kelley and Firestein’s Textbook of Rheumatology (Tenth Edition) 1: 169-188.e3. 10.1016/B978-0-323-31696-5.00011-5.
Siraganian (1998) Basophils. Encyclopedia of Immunology (Second Edition) Pages 332-334.
Aminab (2012) The role of mast cells in allergic inflammation. Respiratory Medicine 106 (1): 9-14.
Rosales (2018) Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? Front. Physiol https://doi.org/10.3389/fphys.2018.00113.
Tecchio et al. (2014) Neutrophil-Derived Cytokines: Facts Beyond Expression. Front Immunol. 5: 508.
Lee et al. (2012). Human versus mouse eosinophils: “That which we call an eosinophil, by any other name would stain as red”. The Journal of allergy and clinical immunology. 130: 572-584.
Chirumbolo (2012) State-of-the-art review about basophil research in immunology and allergy: is the time right to treat these cells with the respect they deserve? Blood Transfus. 10 (2): 148–168.
Georgin-Lavialle et al. (2012). Mast cell leukemia. Blood 121(8): 1285-1295.
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