WEEK 2: RESPIRATORY TRACT DEFENSE MECHANISMS

Question 1

Why do mucosal surfaces need specialized defensive systems?

Answer 1

Along with the gut, the airways and lungs provide the major point of close contact between the interior of the body and the external environment. As such, they are a prime site for entry of pathogens into the body and so require specialized defensive systems.​

Question 2

State the 3 main types of defenses at the mucosal surfaces.

Answer 2

*Adaptive immunity; antibodies and T- cells
*Innate immunity; Phagocytes and chemical clearance
*Mechanical immunity: mucociliary clearance system

Question 3

State the 3 main components of the Mucociliary clearance system.

Answer 3

Periciliary layer
Mucous layer proper
Cilia

Question 4

Describe how the mucociliary clearance system works.

Answer 4

1.Cilia imbedded in the periciliary fluid with their tips on the mucous layer.
2.Foreign substances trapped on mucous.
3.Cilia beat and clears the pathogens and particles.
4.Coughing and sneezing assist in expelling the mucous containing foreign substances.

Question 5

Describe the mucous layer

Answer 5

*Predominantly water (95% to 97%), ​

*5 to 10 μm thick​

*Low viscosity and highly elastic composed of glycoproteins ​

Question 6

How much mucous should be produced in a day by a healthy person?

Answer 6

*Healthy person ~100 mL/day mucus ​

Question 7

State 4 cell types that contribute to mucous layer.

Answer 7

Goblet cells
Mucous cells
Serous cells (submucosal tracheobronchial glands) ​
Clara cells (are located in the ​epithelium of the bronchioles)​

Question 8

The mucus secreted is not homogeneous – it consists of two layers.
State the two layers.

Answer 8

*The inner layer of mucus overlaying the cilia is a watery sol called the periciliary fluid.

*Overlaying the periciliary fluid is the mucus layer proper
This layer is ‘rowed’ over the periciliary fluid layer by the beating action of the cilia.

NOTE: The mucociliary epithelium does not extend into the alveoli and the smaller bronchioles adjacent to the alveoli.

Question 9

State the functions of the mucous layer.

Answer 9

*Traps foreign substances -the sticky mucus physically traps pathogens as well as innoxious particles ​

*Has antipathogenic activity (to be discussed later)​

Question 10

Describe the sol layer

Answer 10

*Watery, allows free movement of cilia​

*About 5 – 6 mm – close to the length of an extended ​
cilium, though the layer can become deeper during ​
infections

Question 11

How is the periciliary layer fluidity maintained?

Answer 11

The watery periciliary fluid layer is maintained by active ion transport carried out by the columnar epithelial cells .

Cl- ions are secreted by the cells, causing Na+ ions to be absorbed. The increased osmotic pressure immediately above the cells draws water into the layer.

Question 12

Describe cilia.

Answer 12

*Each epithelial cell has about 250 cilia forming its ‘brush border.

*At maximum extension their tips reach the mucus gel layer above.

Question 13

Describe the 2 cilia movements.

Answer 13

*The ‘power stroke’ of the cilia pushes this gel layer across the periciliary fluid. MOVES FORWARD

*The non powered ‘recovery stroke’ of the cilia takes place entirely within the periciliary fluid layer.​ PUSHES BACKWARD

Question 14

Describe the antipathogenic activity of the mucous layer.

Answer 14

*It contains anti-microbials such as oxidants, antimicrobial peptides and protease inhibitors.

*Pathogens gain entry to the body by binding to molecules on epithelial cell surfaces. Often these are glycoproteins or glycolipids found only in specific tissues. Mucus contains similar glycoproteins, which ‘decoy’ many pathogens into binding harmlessly to mucus molecules.

*Mucus also contains a range of antibacterial molecules: examples are lysozyme and antileukoprotease which are antibacterial enzymes, and lactoferrin which complexes iron, depleting the environment of a molecule essential for bacterial survival.

*Additionally, mucus is mildly acid which also disrupts bacterial growth.

*Mucus also contains an antibody, immunoglobulin A (IgA). This antibody is secreted into mucus and is adapted to bind and immobilize pathogens. It recognizes pathogens specifically.

Question 15

Describe what happens to pathogens which avoid mucus trapping -Alveolar space.

Answer 15

*Surfactant proteins A and D; secreted
into alveolar spaces:
- bind to many pathogens
(neutralization + clearance)
- suppress inflammatory & allergic
responses
- promote AM phagocytic activity

*Alveolar macrophages (AM) 95%: kill pathogens

*IgGThey have PRR

Question 16

Why do alveolar macrophages carry PRR?

Answer 16

Alveolar surfaces are patrolled by alveolar macrophages which can phagocytose particles.

These cells are able to kill pathogens which they engulf using special killing mechanisms often involving the use of oxygen free radicals, but these mechanisms are potentially damaging so it is important that they are not deployed against innoxious particles.

Thus, macrophages carry pattern recognition receptors on their surfaces. These recognize pathogens enabling killing responses to be deployed appropriately.

Question 17

Why are alveoli surfaces not covered by mucous?

Answer 17

That is because the mucous is too thick and could distract gaseous exchange.

Question 18

Describe what happens to pathogens which avoid mucus trapping- penetration of the epithelium.

Answer 18

If pathogens penetrate the epithelium the underlying tissue contains dendritic antigen presenting cells, natural killer cells, and T-lymphocytes all of which take part in a coordinated response to them.

Question 19

Describe how GAMMA DELTA T CELLS what happens to pathogens which avoid mucus trapping- penetration of the epithelium.

Answer 19

GAMMA DELTA T CELLS
They recognize pathogens directly, rather than pathogens which have been processed by other cells, as the ab- receptor does. In many ways the gd -cells behave like innate immune system cells and their receptor behaves like a pattern recognition receptor. ​

gd T-cells can secrete similar cytokines to those produced by antigen specific T-cells but they actually seem to be able to damp down the inflammatory response which the antigen specific T-cells normally provoke.

Question 20

Describe how natural killer cells act on pathogens which avoid mucus trapping- penetration of the epithelium.

Answer 20

NATURAL KILLER CELLS

These cells are so called because they have cytotoxic activity similar to cytotoxic T-cells but do not have a specific surface recognition molecule. Instead they recognise and react to cells which display little or no major histocompatibility antigens on their surfaces.​

Often cells which have become transformed into cancer cells have reduced amounts of surface protein, so natural killer cells are able to detect and kill cancer cells. ​

Some viruses also prevent the cell they infect from displaying MHC antigens on the cell surface. They do this because MHC antigens display viral peptides on the cell surface so that it can be recognized by cytotoxic T-cells as an infected cell. Natural killer cells recognize and kill viral infected cells which evade the cytotoxic T-cell response in this way

Question 21

Describe how dendritic antigen presenting cells act on pathogens which avoid mucus trapping- penetration of the epithelium.

Answer 21

Pathogens which cross the alveolar and bronchial epithelium can be picked up by dendritic antigen presenting cells, which recognise them using PRRs. These cells are large with a surface area increased by long dendritic extensions. They form the bridge between the innate and specific immune response. ​

They patrol the body surfaces, recognising any pathogens which have gained entry across the epithelia. At this stage they are phagocytic. They engulf the pathogen killing it using reactive oxygen and nitrogen species as macrophages do.​

Dendritic cells then move into the secondary lymphoid tissues. Here they process the pathogen and present peptides derived from it on the cell surface. The antigens presented in this form are recognised by T-cells – both CD8 +ve (cytotoxic T-lymphocytes) and CD4+ve (helper T-lymphocytes) which are stimulated to clone.​

Dendritic cells also secrete cytokines including the antiviral interferon molecules, but also including several potent inducers of inflammation.

Question 22

Describe IgG, asthma and allergy relations.

Answer 22

It is very uncommon and difficult to detect in the blood, but it can bind to receptors on the surface of tissue mast cells. Here it forms an antigen specific receptor on the mast cell surface. When the mast cell encounters an antigen which IgE recognises it is stimulated to degranulate, releasing inflammatory mediators and producing a local inflammatory response.​

In normal situations this is thought to be a defense against eukaryotic parasites, but IgE can often be produced against innoxious antigens like grass pollen or animal dander. In this situation breathing in these antigens can provoke a local inflammatory response involving bronchoconstriction, excessive mucus secretion and mucosal swelling – all the symptoms of an asthma attack.

Question 23

Describe what happens in cystic fibrosis.

Answer 23

Cystic Fibrosis is an autosomal recessive disease caused by a mutation which inactivates the Cl- active transport channel protein. In lung epithelium this prevents Cl- transport and prevents formation of the periciliary fluid layer.

Cillia are unable to beat properly, since they are now having to beat in the mucus gel layer, and the normal mucus flow in the airways does not occur.

Sufferers have repeated lung infections and require intensive physiotherapy to clear their lungs.

Question 24

Describe what happens in COPD.

Answer 24

Excessive quantities of dust particles can damage the ciliated epithelium, and chronic exposure may destroy it.

Large quantities of smaller particles can accumulate in the lower reaches of the airways beyond the ciliated area and may eventually compromise gas exchange.

Long term exposure to large quantities of dust can produce permanent damage to the lungs resulting in chronic obstructive pulmonary disease (COPD).

MAIN CAUSE: Tobacco smoking, burning fuel for cooking in poorly ventilated area.

Question 25

In COPD, less air flows in and out of the airways because of …

Answer 25

*The airways and air sacs lose their elastic quality.
*The walls between many of the air sacs are destroyed.
*The walls of the airways become thick and inflamed.
*The airways make more mucus than usual, which can clog them.

Question 26

Describe EMPHYSEMA and CHRONIC BRONCHITIS

Answer 26

*Emphysema is a condition in which the air sacs in the lungs are destroyed, leading to less oxygen entering the blood.

*Chronic bronchitis is inflammation of the lining of the bronchial tubes, which results in daily cough and mucus production.

Question 27

Name the diseases caused by the following dust particles inhalation:
*Coal, graphite and man made
*Silica
*Asbestos

Answer 27

*Carbon worker’s pneumoconiosis
*Silicosis/ Potter’s rot
*Asbestosis

Question 28

Describe IgG, asthma and allergy relations.

Answer 28

It is very uncommon and difficult to detect in the blood, but it can bind to receptors on the surface of tissue mast cells. Here it forms an antigen specific receptor on the mast cell surface. When the mast cell encounters an antigen which IgE recognises it is stimulated to degranulate, releasing inflammatory mediators and producing a local inflammatory response.​

In normal situations this is thought to be a defense against eukaryotic parasites, but IgE can often be produced against innoxious antigens like grass pollen or animal dander. In this situation breathing in these antigens can provoke a local inflammatory response involving bronchoconstriction, excessive mucus secretion and mucosal swelling – all the symptoms of an asthma attack.