Lacrimal Functional Unit and Host Defense at the Ocular Surface
Lacrimal Functional Unit
The cornea possesses the richest sensory innervation of the body to detect noxious stimuli. The trigeminal sensory neurons (CN V) that innervate the eye vary in their chemical composition and electrophysiological properties, and can be classified according to the stimuli that activate them preferentially: mechan¬ical forces, temperature, or irritant chemicals. Different classes of noxious stim¬uli (mechanical injuries, heat, extreme cold) activate to a different degree the various populations of sensory fibers of the ocular surface and evoke unpleas¬ant sensations of distinct quality .
It is recognized today that the tear film is secreted reflexively from the 'lacrimal functional unit' that is composed of the ocular surface tissues (cornea and conjunctiva, including goblet cells and Meibomian glands), the lacrimal glands (main and accessory), and their interconnecting sensory (CN V) and autonomic (CN VII) innervation . This reflex secretion is initiated by sub¬conscious stimulation of the highly innervated ocular surface epithelia. The human nasolacrimal ducts are integrated in this reflex arc, as shown by recent investigations .
Host Defense at the Ocular Surface
Some defense mechanisms of the innate immune system have already been mentioned above and it is beyond the scope of this chapter to deal with all of them. However, it should be mentioned that the defense of the ocular surfaces presents a unique challenge in that not only must integrity be maintained against microbial, inflammatory and physical assault, but it must be done while minimizing the risk of loss of corneal transparency. This puts severe limitations on the degree to which scarring or neovascularization can occur in the cornea secondary to any infectious, inflammatory, immunological or wound-healing process. The defense system must be equally effective under two extremes of conditions: those found in the open eye and the closed eye environments. Distinctly different defense strategies are utilized in both open and closed con¬ditions. The extraordinary effectiveness of this system is evidenced by the fact that despite continued exposure to a microbe-rich environment, the external ocular surfaces maintain a very low microbial titer and are highly resistant to breaching by all but a few pathogens .
Eye-Associated Lymphoid Tissue as an Entrance Side for
Immunological Events
EALT
The epithelia of the ocular surface, the corneal and conjunctival epithelia, the epithelium of the efferent tear ducts, the Meibomian glands, main and acces¬sory lacrimal glands and lids make up a physiological system that was recently dubbed the lacrimal-ocular surface system (LOS) . The LOS is organized to maintain the clarity of the cornea - a homeostatic set-point. Like the systems that represent epithelial interfaces between the internal and external environ¬ments, i.e., the gastrointestinal, integumentary and respiratory systems, the LOS system collaborates with the innate and adaptive immune system to respond to microbial invasion. The lacrimal glands, conjunctiva and efferent tear ducts constitute one venue of this collaboration area. These tissues are pop¬ulated by IgA-producing plasma cells and their epithelia actively transport secretory IgA into the nascent tear fluid .
Specific secretory immunity depends on sophisticated cooperation between the mucosal B cell system and an epithelial glycoprotein called the secretory component . Initial stimulation of Ig-producing B cells is believed to take place mainly in organized mucosa-associated lymphoid tissue (MALT) . It has become evident that MALT is characterized by considerable region- alization or compartmentalization, perhaps determined by the different cellular expression profiles of adhesion molecules and/or the local antigenic repertoire. Antigenic stimulation of B cells results in the generation of predominantly IgA- synthesizing blasts that leave the mucosae via efferent lymphatics, pass through the associated lymph nodes into the thoracic duct, and enter the circulation. The cells then return selectively to the lamina propria as plasma cells or memory B cells by means of homing mechanisms .
Organized lymphoid tissue in the conjunctiva (conjunctiva-associated lym-phoid tissue - CALT) and efferent tear duct system TALT have
recently been termed collectively EALT . However, aggregated follicles that fulfill the criteria for designation as EALT occur only in somewhat less than a third of conjunctivae and nasolacrimal ducts from unselected cadavers with no known history of disease involving the eye, efferent tear ducts, or nose . In most cases, only lymphocytes and other defense cells are amply present subepithelially, i.e. inside the conjunctiva and efferent tear ducts that do not form aggregated follicles. It is as yet unclear whether special types of bac¬teria, viruses, allergic reactions, or other factors, such as some type of immune deviation, are responsible for the development of EALT in humans. However, when EALT is present, it can provide the basis from which primary low-grade B cell lymphoma of the MALT type may arise.
Lacrimal Functional Unit
The cornea possesses the richest sensory innervation of the body to detect noxious stimuli. The trigeminal sensory neurons (CN V) that innervate the eye vary in their chemical composition and electrophysiological properties, and can be classified according to the stimuli that activate them preferentially: mechan¬ical forces, temperature, or irritant chemicals. Different classes of noxious stim¬uli (mechanical injuries, heat, extreme cold) activate to a different degree the various populations of sensory fibers of the ocular surface and evoke unpleas¬ant sensations of distinct quality .
It is recognized today that the tear film is secreted reflexively from the 'lacrimal functional unit' that is composed of the ocular surface tissues (cornea and conjunctiva, including goblet cells and Meibomian glands), the lacrimal glands (main and accessory), and their interconnecting sensory (CN V) and autonomic (CN VII) innervation . This reflex secretion is initiated by sub¬conscious stimulation of the highly innervated ocular surface epithelia. The human nasolacrimal ducts are integrated in this reflex arc, as shown by recent investigations .
Host Defense at the Ocular Surface
Some defense mechanisms of the innate immune system have already been mentioned above and it is beyond the scope of this chapter to deal with all of them. However, it should be mentioned that the defense of the ocular surfaces presents a unique challenge in that not only must integrity be maintained against microbial, inflammatory and physical assault, but it must be done while minimizing the risk of loss of corneal transparency. This puts severe limitations on the degree to which scarring or neovascularization can occur in the cornea secondary to any infectious, inflammatory, immunological or wound-healing process. The defense system must be equally effective under two extremes of conditions: those found in the open eye and the closed eye environments. Distinctly different defense strategies are utilized in both open and closed con¬ditions. The extraordinary effectiveness of this system is evidenced by the fact that despite continued exposure to a microbe-rich environment, the external ocular surfaces maintain a very low microbial titer and are highly resistant to breaching by all but a few pathogens .
Eye-Associated Lymphoid Tissue as an Entrance Side for
Immunological Events
EALT
The epithelia of the ocular surface, the corneal and conjunctival epithelia, the epithelium of the efferent tear ducts, the Meibomian glands, main and acces¬sory lacrimal glands and lids make up a physiological system that was recently dubbed the lacrimal-ocular surface system (LOS) . The LOS is organized to maintain the clarity of the cornea - a homeostatic set-point. Like the systems that represent epithelial interfaces between the internal and external environ¬ments, i.e., the gastrointestinal, integumentary and respiratory systems, the LOS system collaborates with the innate and adaptive immune system to respond to microbial invasion. The lacrimal glands, conjunctiva and efferent tear ducts constitute one venue of this collaboration area. These tissues are pop¬ulated by IgA-producing plasma cells and their epithelia actively transport secretory IgA into the nascent tear fluid .
Specific secretory immunity depends on sophisticated cooperation between the mucosal B cell system and an epithelial glycoprotein called the secretory component . Initial stimulation of Ig-producing B cells is believed to take place mainly in organized mucosa-associated lymphoid tissue (MALT) . It has become evident that MALT is characterized by considerable region- alization or compartmentalization, perhaps determined by the different cellular expression profiles of adhesion molecules and/or the local antigenic repertoire. Antigenic stimulation of B cells results in the generation of predominantly IgA- synthesizing blasts that leave the mucosae via efferent lymphatics, pass through the associated lymph nodes into the thoracic duct, and enter the circulation. The cells then return selectively to the lamina propria as plasma cells or memory B cells by means of homing mechanisms .
Organized lymphoid tissue in the conjunctiva (conjunctiva-associated lym-phoid tissue - CALT) and efferent tear duct system TALT have
recently been termed collectively EALT . However, aggregated follicles that fulfill the criteria for designation as EALT occur only in somewhat less than a third of conjunctivae and nasolacrimal ducts from unselected cadavers with no known history of disease involving the eye, efferent tear ducts, or nose . In most cases, only lymphocytes and other defense cells are amply present subepithelially, i.e. inside the conjunctiva and efferent tear ducts that do not form aggregated follicles. It is as yet unclear whether special types of bac¬teria, viruses, allergic reactions, or other factors, such as some type of immune deviation, are responsible for the development of EALT in humans. However, when EALT is present, it can provide the basis from which primary low-grade B cell lymphoma of the MALT type may arise.
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