- Anatomy of the nasal cavity
- Surrounding structures
- Anatomy of the nasal mucosa
- Physiology of the nasal cavity
- Physiology of the nasal mucosa
- Pathophysiological responses of the nasal mucosa in allergic rhinitis
- Genetics and epigenetics of pathophysiological allergic rhinitis responses
The nasal cavity refers to the interior of the nose, or the structure which opens exteriorly at the nostrils. It is the entry point for inspired air and the first of a series of structures which form the respiratory system. The cavity is entirely lined by the nasal mucosa, one of the anatomical structures (others include skin, body encasements like the skull and non-nasal mucosa such as those of the vagina and bowel) which form the physical barriers of the body’s immune system. These barriers provide mechanical protection from the invasion of infectious and allergenic pathogens.
The nasal cavity extends from the external opening, the nostrils, to the pharynx (the upper section of the throat), where it joins the remainder of the respiratory system. It is separated down the middle by the nasal septum, a piece of cartilage which shapes and separates the nostrils. Each nostril can be further divided into roof, floor, and walls. The nasal cavity can be divided into the vestibule, respiratory and olfactory sections.
The nasal vestibule is the dilated area at the nostril opening.
The respiratory section of the nasal cavity refers to the passages through which air travels into the respiratory system. The respiratory section of each nostril contains four conchae (protrusions or bumps) which are also referred to as turbinate bones or lobes and are covered by the nasal mucosa. Underlying these conchae are meatuses (passages to interior body structures). The meatuses of the nasal cavity connect to the paranasal sinuses.
The olfactory receptors (receptors for smell sensations) are found in this section of the nasal cavity. Bowman’s glands are also found in this section of the nasal cavity.
The nasal cavity is surrounded by a ring of paranasal sinuses and meatuses in the nasal cavity connect to these structures. The sinuses develop as outgrowths of, and drain into, the nasal cavity. The mucosa of the sinuses connects to the nasal mucosa.
Nasolacrimal ducts are the ducts which connect the lacrimal (tear) ducts in the eye to the nasal cavity.
For more information about the other sections of the respiratory system and how they work, see Respiratory System.
The nasal mucosa, also called respiratory mucosa, lines the entire nasal cavity, from the nostrils (the external openings of the respiratory system) to the pharynx (the uppermost section of the throat). The external skin of the nose connects to the nasal mucosa in the nasal vestibule. A dynamic layer of mucus overlies the nasal epithelium (the outermost layer of cells of the nasal mucosa).
The initial one-third of the nasal cavity is lined by stratified squamous epithelium (smooth epithelium consisting of flat surfaced cells), several cell layers thick. The outmost layer of squamous cells overlies a layer of proliferative cells (cell which divide and replicate to form new cells) which is attached to a basement membrane, a network of tough fibres which supports the epithelium.
The posterior two-thirds of the cavity is lined with pseudostratified columnar ciliated epithelium (a type of epithelium in which cells arrange themselves in columns and project tiny hairs called cilia) containing goblet cells (mucus producing cells), and which overlies a basement membrane.
The nasal sub-mucosa underlies the basement membrane. This layer is made up of glands which secrete watery substances and mucus, nerves, an extensive network of blood vessels and cellular elements like blood plasma. The entire mucosa is highly concentrated with blood vessels and contains large venous-like spaces; bodies which have a vein-like appearance and swell and congest in response to allergy or infection.
The nasal cavity functions to allow air to enter the respiratory system upon respiration. Structures within the cavity regulate the flow of air and particles it contains. The olfactory region of the nasal cavity regulates the sense of smell.
Conchae (turbinate bones)
The conchae (turbinate bones) of the nasal mucosa expand the total surface area of the mucosa and create turbulence in air entering the respiratory passage. This causes air to swirl as it moves through the nasal cavity and increases contact between infiltrating air and the nasal mucosa, allowing particles in the air to be trapped before entering other parts of the respiratory system (e.g. the lungs).
Bowman’s glands secrete the majority of the mucus which overlies the nerves of the olfactory system. They also secrete the pigment which gives this mucus its yellow colour. Mucus secreted by these glands dissolves odours as they enter the nose, enabling them to interact with the olfactory receptors.
The nasal mucosa plays an important role in mediating immune responses to allergens and infectious particles which enter the nose. It helps prevent allergens and infections from invading the nasal cavity and spreading to other body structures, for example the lungs. The mucus secreted by and which lines the mucosa provides a physical barrier against invasion by pathogens (harmful microorganisms). It is sticky and traps pathogens when they enter the nasal cavity.
Trapping pathogens enables components of the mucus to attack and destroy the microbes. For example, an antibody called IgA prevents pathogenic microbes from attaching to cells of the mucosa and in doing so prevents them from invading the cells. Lysozyme (enzymes which breakdown bacteria) is another component of the nasal mucus. It works to degrade pathogenic microbes. The epithelial or outer cells of the nasal mucosa are constantly being worn away and replaced by new cells from the underlying proliferative (regenerative) layer. This provides additional protection as it ensures that pathogens which do manage to invade the outer cell layer are removed as the epithelial cells are sloughed off.
However, in some individuals abnormal responses of the nasal mucosa occur and immune responses are mounted against allergens which the body does not usually recognise as pathogenic and thus does not usually mount an immune response to. In these individuals the mucosa, which usually functions to protect the body from invading microorganisms, is also thought to play a role in the pathological allergic response referred to as a type 1 hypersensitivity reaction. This type of allergic response is mediated by B cells (antibody producing cells of the immune system), which begin producing immunoglobulin type E (IgE) (discussed further below).
- Provide a physical barrier to the invasion of infectious microorganisms and allergic particles;
- Work in conjunction with mucus glands and cilia to secrete and remove mucus and foreign particles from the nasal cavity.
However, recent evidence suggests the functions of epithelial cells are much broader and that they also regulate immune responses which occur if the physical barrier fails and pathogens infiltrate cells of the nasal mucosa. The epithelium contains antigen-binding proteins (protein chain sections of an antibody that recognise and join to antigens). These proteins are involved in the processes through which allergens are presented to antigen presenting cells. These cells are responsible for introducing pathogens to the T-lymphocyte cells (T cells) which in turn function to mount an immune response to destroy allergens presented to them. Antigen presenting cells capture antigens as they enter the body and present them to naïve T cells. That is; T cells that have not previously encountered, and therefore do not yet recognise as pathogenic, the specific antigen being presented. Thus, antigen-binding proteins in the epithelium catalyse the series of processes through which T cells begin to recognise and respond to allergens.
Epithelial cells also release factors which enhance inflammatory responses. The most important of these factors are cytokines (proteins which regulate the duration and intensity of immune responses). Allergens can directly activate the epithelial cells to produce an inflammatory response, or the epithelial cells may mount such a response in response to T cell recognition of the antigen. Epithelial cells also appear be involved in the IgE-producing processes which perpetuate allergic responses (discussed further below).
Endothelial cells are cells which line the walls of the arteries that feed the nasal mucosa. They are also involved in allergic responses. They primarily function to attract leukocytes (white blood cells) circulating in the blood to the site of inflammation.
Cilia or small hairs which project from the epithelium and line the nasal mucosa create motions which drain mucus from the nasal passage to the throat from where it is swallowed and digested by stomach juices. The activity level of cilia is dependent on temperature and in cold temperatures cilia become less active. Mucus may accumulate in and drip from the nostrils (runny nose) in these conditions. Infectious particles and allergens also impair cilia activity and can lead to symptoms such as a congested or runny nose.
Underlying blood vessels
The thin walled veins on which the nasal mucosa rests function to warm air entering the respiratory passage. Due to the high concentration of blood vessels in the nasal cavity, changes in these blood vessels contribute to nasal congestion. For example, constriction of these blood vessels decreases airway resistance, making it easier for air to enter the respiratory system. The nasal nerves also regulate the congestion response.
Innervation of the nasal mucosa is regulated by the trigeminal and maxillary nerves which also provide sensations to other areas of the face. The trigeminal nerve regulates sensations including touch, pressure and temperature in the nose, while sympathetic and parasympathetic innervation (innervation which controls involuntary movements like constriction and dilation of the blood vessels) occurs via the maxillary nerve. The different types of nerves found in the nasal cavity and mucosa have various functions. For example, constriction of blood vessels which feed the nasal cavity is regulated in part by the sympathetic nervous system, while the parasympathetic nervous system plays a role in regulating secretions of mucus from nasal glands. Other nerves in the nasal cavity influence the dilation of blood vessels, nasal secretions, inflammation and interactions between nerves and the mast cells which mediate allergic responses.
Allergic rhinitis is a response of the nasal passages to specific allergens which is mediated by the antibody IgE. It is amongst the most common allergies in children and adults. It is a type 1 hypersensitivity reaction which occurs when the nasal mucosa becomes sensitised to a specific environmental allergen. Common environmental allergens which cause rhinitis include mites, pollen, animals and fungi.
In individuals with a normally functioning immune system, exposure to particles in the environment such as dust or pollen does not cause an immune response. In allergic individuals, exposure to a specific allergen catalyses an irregular and hypersensitive immune response. It involves systemic (body wide) and localised (in the nasal mucosa) production of IgE antibody which specifically recognises the type of particle (e.g. dust, pollen). IgE is produced by B cells in the nasal mucosa.
The IgE antibodies produced inhabit immune system cells called mast cells and basophils which would not normally consider the particles (e.g. dust, pollen) as antigens. When IgE inhabits the mast cells and basophils it sensitises them to the specific type of particle (antigen). With future exposure to the antigen, sensitised individuals experience an abnormal and pathological inflammatory response and often also experience a similar reaction to unrelated allergens like tobacco smoke. Mast cells, which form part of the immune system and mediate the inflammatory response, are abundant in the nasal mucosa of sensitised (allergic) individuals, but not in non-allergic individuals. In these individuals (unlike in non-allergic individuals) mast cells in the nasal mucosa function to:
- Increase the production and secretion of inflammatory cytokines in response to exposure to the allergen to which they have become sensitised; and
- Catalyse synthesis of IgE by B cells in response to allergen. B cells do not normally produce IgE; they only do so in the pathological response of allergic rhinitis and other type 1 hypersensitivity reactions.
Basophils, which release cytokines as well as other inflammatory factors called histamines, are normally not present in the nasal mucosa; however, they are evident in the nasal mucosa of individuals affected by allergic rhinitis. The more basophils that are found in the nasal mucosa, the greater the severity of allergic symptoms of allergic rhinitis.
Eosinophils, a type of white blood cell, are recruited from bone marrow to infiltrate the nasal mucosa. These cells contain numerous inflammatory factors, including a range of cytokines. They are more highly concentrated in the nasal secretions of individuals undergoing allergic reaction. The function of T helper cells, which regulate normal immune function, is also impaired in individuals affected by allergic rhinitis.
Early phase immune response
The inflammatory response of the nasal mucosa in allergic rhinitis can be separated into early and late phases. The early phase is mast cell-regulated and characterised by infiltration of the nasal mucosa by the allergen (e.g. pollen), following which IgE (antibody) receptors on sensitised mast cells recognise and link with the allergen. This causes mast cells to degranulate (rupture) and release factors which cause inflammation, including histamine (the key mediator of allergic rhinitis), tryptase and prostaglandins.
The early phase of the inflammatory response occurs immediately after exposure to an allergen and causes symptoms including sneezing, rhinorrhoea, itching and nasal congestion. Symptoms occur because histamine stimulates the trigeminal nerve (for sneezing) or the nasal mucus glands (for nasal secretions). They typically persist for 2–3 hours. Histamine, in conjunction with prostaglandins and other factors, stimulate blood vessel changes which result in nasal congestion, and may persist for up to 24 hours.
Late phase immune response
The late phase immune response occurs 4–8 hours after allergen exposure, and involves other pro-inflammatory factors including eosinophils, basophils and T cells which release cytokines including interleukin (IL)-4 and -5. IL-4 is a switch factor for IgE synthesis; it causes B cells to produce IgE. IL-5 is a growth factor for eosinophils and its release stimulates the release of more eosinophils from the bone marrow where they are produced. Individuals affected by allergic rhinitis preferentially produce T cells which secrete IL-4 and IL-5 (as opposed to T cells which do not produce these ILs). In turn, IL-4 and IL-5 are thought to cause the preferential production of IgE which occurs in allergic responses.
Cytokines also help produce molecules which facilitate the infiltration of eosinophils, basophils and T lymphocytes to the nasal mucosa. Cytokines help these cells bind to nasal mucosa cells and induce or continue its inflammatory response. Nasal blockage and hyper-reactivity (sensitisation) of the nasal passage occur as a result of the late-phase response.
Secondary immune response (perpetuation of allergic response)
Some cytokines also promote the survival of inflammatory cells in the nasal mucosa. This in turn promotes prolonged IgE synthesis in B cells and causes a secondary immune response which influences how the individual responds when they are exposed to the allergen in the future. Exposure to an allergen and the associated inflammatory response have a threshold-lowering effect in relation to future exposure; affected individuals become more sensitive to the allergen with increasing exposure. The late phase is responsible for perpetuating the inflammatory response and the threshold lowering effect, sometimes referred to as the ‘priming’ effect.
Systemic immune response
The pathophysiological response which characterises allergic rhinitis also induces systemic (whole body) circulation of inflammatory factors which may infiltrate tissues at other sites. Inflammatory factors associated with allergic rhinitis are particularly likely to infiltrate the connecting systems, the upper and the lower airways. Allergic rhinitis often affects individuals who also experience other allergic conditions including asthma, atopic dermatitis and rhinosinusitis. As the mucosa of the nasal cavity and sinuses are continuous, infection or allergy of the nasal mucosa can spread easily to the sinuses.
Allergic rhinitis is an atopic (genetic) condition which often runs in a family. Those with a family history of the disorder have a greater likelihood of experiencing the condition themselves. Some evidence suggests that irregular IgE responses and sensitisation to specific environmental allergens is genetically determined, although the genetic components of the allergic rhinitis are not well understood. Specific genes which might pass on the irregular IgE response trait have not been identified.
Epigenetic mechanisms (mechanisms not directly changing the DNA), particularly prenatal (in the womb) and early life exposure to environmental allergens, are also thought to play a role. Transient environmental exposures are known to influence the function of genes. Maternal factors (e.g. exposures of the mother during pregnancy) are also known to influence the likelihood of allergy in the offspring.
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