Host Defence In The Lung Flashcards
Why are lung susceptible to infection?
Pores of Kohn
Alveolar surface area is the size of a tennis court
The air is not always sterile
During inflammation the skin ma become, hot, red, swollen and painful what causes this?
Red and hot are due to vasodilation, more blood flow to the area to bring antibodies, neutrophils etc. More blood = red and also more heat.
Swollen = due to the vasodilation more fluid (exudate) may fill the area.
Pain = due to inflammatory mediators
What happens during an Inflammatory response?
Release of histamine from capillaries cause vasodilation of the capillaries.
This vasodilation results in more blood plasma carrying antibodies, platelets etc to the area.
The release of cytokines lead to biochemical cascades such as the complement and coagulation cascade.
Neutrophils, but also monocytes and other leukocytes are also attracted to the area. They phagocytose bacteria and damaged cells.
There will be presentation of antigens by APC’s
There will also be apoptosis of neutrophils by macrophages as they will host damaged tissues etc.
Is inflammation good?
It is a double edge sword:
Defence against infection
But many people die from disease caused by inflammatory responses.
What are some common diseases that van be caused by inflammatory responses?
COPD = Chronic obstructive pulmonary disease. They are a group of conditions that damage alveoli and lead to inflammation.
ARDS = acute respiratory distress syndrome = rapid onset of widespread inflammation.
Caused by water and neutrophils filling the alveoli. - due to sepsis, lung infection.
Bronchiectasis = one or more of the bronchi are widened leading to increased mucus production, which increased the chance of an infection and an infection can cause the bronchi to widen further etc etc.
Asthma = inflammation of the conducting system often triggers by allergens.
What is acute inflammation?
Acute inflammation is a short-term process occurring in response to tissue injury, usually appearing within minutes or hours. It is characterized by five cardinal signs: pain, redness, immobility (loss of function), swelling and heat.
How do we recognise pathogens we have never seen before?
with pattern recognition receptors (PRRs).
They are found on lots of cells.
They recognise pathogen or damaged associated molecular patterns.
What is a toll-like receptor?
One of the best known PAMP’s is lipopolysaccharide. This specific component of bacteria is recognised by Toll like receptor TLR4
So Toll receptors are a type of receptor that recognise PAMP’s
What is an alveolar macrophage?
Mononuclear phagocyte found in alveoli of the lungs. They ingest small inhaled particles and also neutrophils etc. They degrade them and then present any antigens on their surface.
They consist of 93% of pulmonary macrophages.
They are long lived and arise from monocytes
Neutrophils
% of WBC
How many produced per minute?
Overview of structure
70% of WBC pop
80 mil each minute
Contains granules
Primary - myeloperoxidase, elastase etc
Secondary - receptors, lysozyme, collagenase
How do neutrophils function overview?
ID the threat - use of receptors for bacteria structures, host mediators (cytokines) or host opsonins (mark the antigen) - antibodies
Activation - stimulus response coupling
Adhesion -
Migration - ability to detect a concentration gradient and move along it
Phagocytosis - engulf in phagosome - form phagolysosome
Bacteria killing - lysosomal enzymes - cathepsins and elastase as well as reactive oxygen species - destroys the bacteria.
Apoptosis - programmed cell death - the neutrophils are destroyed by alveolar macrophages.
Reactive oxygen species are…
and produced by?
By a membrane enzyme complex - NADPH oxidase
What are cytokines?
Cytokines are molecules that are used for cell signaling, or cell-to-cell communication. Cytokines are similar to chemokines, wherein they can be used to communicate with neighboring or distant cells about initiating an immune response. Cytokines are also used to trigger cell trafficking, or movement, to a specific area of the body.
What are macrophages?
Macrophages: Macrophages, commonly abbreviated as “Mφ”, are efficient phagocytic cells that can leave the circulatory system by moving across the walls of capillary vessels. The ability to roam outside of the circulatory system is important, because it allows macrophages to hunt pathogens with less limits. Macrophages can also release cytokines in order to signal and recruit other cells to an area with pathogens.
What are mast cells?
Mast cells are found in mucous membranes and connective tissues, and are important for wound healing and defense against pathogens via the inflammatory response. When mast cells are activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade. Mediators, such as histamine, cause blood vessels to dilate, increasing blood flow and cell trafficking to the area of infection. The cytokines released during this process act as a messenger service, alerting other immune cells, like neutrophils and macrophages, to make their way to the area of infection, or to be on alert for circulating threats.
