• The Changes of Lung Immunity under some Pathological Effects

Introduction

In this student essay we explore the changes the lung goes through as one of the most crucial organs in our body in relation to the pathological effects it endures. We will begin by discussing the major defensive function of the alveolar macrophages as they are located on of the major boundary between the body and the outside world. We will then enquire into the immunological role of the two most significant Lung Surfactant Proteinsand discuss the important role Natural Killer Cells have in the adaptive immune response including their role in asthma. In the light of the Ageing Lung we will inquisite the effects it has on the lungs immunity and the heightened risk of infectious diseases. Subsequently we will conclude with an insight into common pulmonary diseases.

Alveolar Macrophages

As we learned in our physiology lectures on immunology, macrophages are derived from monocytes. They have granules filled with digestive enzymes. Alveolar macrophages have an important role in the lung as they fight against bacteria and ingest damaged cells by phagocytosis. They also have a role in adaptive immunity as they present antigens to T-cells. Alveolar macrophages are the first line in defence against microbes and have an important role in the initiation and resolution of inflammation. As a lung ages, the initial response of macrophages to microbes and other inflammatory stimuli is reduced due to inflamm-ageing(Hinojosa, Boyd and Orihuela, 2009)(Metcalf et al., 2015). Their ability to detect pathogens is also hindered due to changes in TLR signalling pathways and elevated negative feedback due to chronic-inflammation.

Efferocytosis is the process in which apoptotic and necrotic cells are removed by phagocyte cells. This process is carried out by macrophages which promote resolution of inflammation. Monocytes and macrophages from aged mice also show reduced phagocytic capacity which decreases their ability to remove microbes from the host in the inflammatory response to infection.(Hinojosa et al., 2014)(Linehan et al., 2014).

Lung Surfactant Proteins Involved in Innate Immunity.

There are two main lung surfactant proteins which have an important role in host defence against infectious and allergic agents. Their defence mechanism includes the killing and clearance of agent by macrophages and neutrophils. These two proteins are SP-A and SP-D.

A surfactant reduces the surface tension at the air/liquid interphase of the lung and is secreted by the epithelial type 2 cells into the alveolar space. SP’s play an important role in surfactant homeostasis. SP-B and SP-C are hydrophobic and they accelerate the absorption of lipids at the air/liquid interphase. (Eggleton and Reid, 1999)Lungs are constantly in danger from a various amount of infectious diseases and allergens so it is important they have a good defence mechanism. It has been known that alveolar macrophages have a very important role in immunity as discussed previously but recent studies show that hydrophilic SP-A and SP-D also have a role in innate immunity of the lung(Wright, 1997)(Crouch, 1998). SP-A and SP-D are caliginous glycoprotein’s and are calcium dependent lectins. They are structurally similar to mannose-binding proteins and bovine conglutinin(Sastry and Alan Ezekowitz, 1993).

Gene-Knockout Studies.

This experiment was performed on mice which made a small complication as mice have a slight variation to humans(Ikegami et al., 1997)(Ikegami et al., 1998)Mice with SP-A knock-out showed an increased inflammation in the lungs but had no major abnormality.Their effectiveness to clear ‘Staphylococcus aurens’ and ‘Pseudomonos aeruginosa’ was decreased.

SP-D knockout mice were more complicated to interrupt as SP-A and SP-B were upregulated. It showed abnormalities of macrophages and type 2 cells. This is a dangerous effect as Type 2 cells secrete the surfactant and if they are damaged the immune system will be disrupted.

Effects on physiology and host defense properties in SP-A-deficient mice

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