NURSING 2LA2 Lecture Notes - Lecture 3: Complement System, Mast Cell, Innate Immune System

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25 Aug 2016
Department
Module 3: Inflammation & Immunity
Inflammation Part 1
Introduction
Many of the pathological conditions you will encounter are related to the inflammatory process
including meningitis, appendicitis, bursitis, laryngitis, tonsillitis, endocarditis, dermatitis, etc.
When you encounter a condition ending with the suffix “it is”, you will know that inflammation is at
the heart of this disease process.
Human Defense Mechanisms
Inflammation can be specific (and is also called the immune response) or non-specific (also termed the
inflammatory response).
Inflammation can be innate (natural or present at birth) or acquired (evolving over time after birth).
We are all born with the same innate abilities to protect ourselves, but each one of us will vary in our
ability to acquire immunity based on our individual experiences with exposure to pathogens and
foreign antigens over our lifetime.
We will all develop our own unique immune systems, tailored just for us.
We have three types of defense mechanisms:
Natural barriers (our first line of defense) include the epithelial layer of the skin and mucous
membranes lining the gastrointestinal, genitourinary, and respiratory tracts. These are called
natural ‘physical’ barriers which can include mechanical and chemical types.
Mechanical means of ridding the body of pathogens include sloughing, sneezing, coughing,
vomiting, urinating and the cilial action of the respiratory tract. As well, low skin temperatures
discourage the growth of bacteria.
Chemical barriers include mucous, perspiration, saliva, tears, and earwax that trap and kill
microorganisms. Some of these barriers contain enzymes, fatty and lactic acids and
antimicrobial proteins that destroy bacteria. Similarly, our own normal bacterial flora are
capable of producing chemicals to keep pathogens at bay.
Inflammation (our second line of defense) is the primary focus of the module.
Immunity is considered our third line of defense and is an acquired, specific and adaptive ability.
Over time, our immune system develops specific antibodies designed to target specific antigens and
this defense mechanism has memory. This means that upon first exposure to an antigen, our
immune system makes antibodies targeted toward that antigen. Then, upon subsequent exposure
to the same antigen, those antibodies that match the antigen will be called to action to fight off
new infection.
Humoral immunity implies that the response comes from the blood or plasma components. Humoral
response in inflammation involves complement factors while in immunity, it involves the formation
and action of antibodies.
The cellular response refers to a cell-derived process. In inflammation, the involved cells are
neutrophils and macrophages and in the immune response, we are talking about lymphocytes.
Inflammation
Inflammation is the protective response designed to eliminate the initial cause of injury, remove
damaged tissue and generate new tissue.
A similar definition is “the biochemical and cellular response of vascularized tissue to injury; designed
to protect the body from further injury”
It’s important to emphasize the vascularized feature of inflammation to indicate that inflammation
occurs in tissues and organs that are vascularized, or perfused with blood.
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Goals of Inflammation
The goals of inflammation include:
Movement of all the necessary blood and cellular components to the site of injury or insult.
Delivery of nutrients and blood cells to eradicate the offender.
Dilution, confinement and elimination of the offending agents.
Stimulation and facilitation of components of the immune system.
Promotion of healing with generation of new tissue.
There are three major events that occur pretty much simultaneously and include:
The first is an increased metabolic rate. When called upon to fight injury or infection, cells step up
their usual daily routines and increase production of the necessary items for battle. As a result, we
increase our heat production, our oxygen and glucose consumption and our production of wastes.
Secondly, we have dilation of blood vessels to help speed up delivery of the inflammatory
components to the site of injury.
And finally, we have an increased capillary permeability which allows for movement of white cells
(specifically neutrophils), proteins, and nutrients out of the blood vessels and into the tissue where
they can go to work.
Causes of Inflammation
Some of the many causes of inflammation include microbes, immune reactions between antigen and
antibody, trauma, burns, physical or chemical agents and tissue necrosis.
Other causes of inflammation include temperature extremes, oxygen deprivation, nutrient
deprivation, genetic or immune defects, and ionizing radiation.
Acute Inflammation
Acute inflammation is a response to injury or insult that occurs early and quick (minutes to hours).
Any number of stimuli can trigger this response and it is mediated by many factors.
Acute inflammation does not last very long and is self-limiting. It does not take very long to heal.
One of the key features of acute inflammation is its non-specificity. For example, if you stub your toe
today and cut your finger next month, the same processes will occur with the finger as those that
occurred with the toes, regardless of the cause.
The inflammatory system is not terribly particular about where or how the injury occurred – it has a
job to do and goes to work pretty quickly in much the same way every time.
There are two phases of inflammation termed vascular and cellular (discussed later).
Finally, acute inflammation will have one of two outcomes – healing or chronic inflammation.
Cells Involved in Inflammation
Normally, cells float within our blood vessels continuously and harmoniously.
In response to inflammation though, each cell type springs into action to perform a very specific
function.
There are numerous biochemical mediators released from mast cells, plasma proteins, and dying cells
which trigger the production of adhesion molecules on the surface of many cells.
Adhesion molecules cause these cells to stick, or adhere to the endothelium.
Let’s look at each of the cell types involved in the inflammatory response.
Endothelial Cells: These cells line the walls of blood vessels and normally maintain very close contact
with each other. The space between them is very tight, limiting the movement of cells and particles
across the vessel wall. In addition to this traffic control function, endothelial cells also:
Produce antiplatelet and antithrombotic agents to prevent formation of clots
Produce both vasoconstrictors and vasodilators to regulate flow
Regulate leukocyte extravasation through the use of adhesion molecules
Regulate immune cell proliferation through secretion of colony stimulating factors
Participate in the repair process through angiogenesis and formation of an extracellular matrix
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Platelets: These cells also referred to as thrombocytes and they circulate passively until activated by
products of tissue degradation like collagen, thrombin, and platelet activating factor. Their primary
role is one of hemostasis (stops blood flow – don’t want to keep bleeding) or the stemming of blood
flow. Once activated, they produce potent inflammatory mediators which result in increased vascular
permeability, chemotaxis, adhesive and proteolytic properties of the endothelium.
Neutrophils: These cells represent one type of granulocyte (so named because enzyme containing
lysosomal granules are found within their cytoplasm) and are considered the chief phagocytic
leukocytes. Early in the inflammatory response (about 90 minutes to 6-12 hours post injury), these
cells are attracted to the site of injury by chemotactic factors. On their surface are found a number of
different receptors each designed to recognize and interact with certain substances such as bacterial
glycoproteins, microbes, cytokines, and chemokines. Because of their lysosomal enzymes, they are
called upon to destroy invaders and remove subsequent debris. Once they themselves die off, they
become exudate, or pus. In the presence of inflammation, neutrophils are released from bone marrow
and the neutrophil count will rise. They are relatively short-lived because they are incapable of
division, and when they die off, they release macrophage chemotactic factor to attract macrophages
to the site of injury. In the presence of severe inflammation, as demand for neutrophils increases, the
bone marrow can’t quite keep up and releases immature neutrophils called bands. When the band
count is elevated on a CBC, we then know that the bone marrow is overworked and trying valiantly to
keep up with an on-going inflammatory process. Main purpose – kill invaders and eat up the debris
Monocytes/Macrophages: Like the neutrophils, monocytes are also leukocytes derived from bone
marrow, but contain larger and fewer lysosomes than their counterparts. They too, express receptors
that interact with a variety of substances. Typically, monocytes exit the circulation in response to
inflammation and take up residence in various tissues as the more mature macrophage. Monocytes
then, are considered to be an immature form of macrophage.
Macrophages are named according to their tissue location – some examples include Kupffer cells in the
liver, alveolar macrophages in the lung, microglia in the brain. Macrophages arrive at the site of
inflammation a little later than the neutrophils (about 24-48 hours post injury). Eventually, they
replace the neutrophils as they die off. Macrophages are often associated with chronic inflammation
as they are somewhat sluggish.
Monocytes/macrophages differ somewhat from neutrophils in other ways too. They produce very
potent vasoactive mediators (prostaglandins, leukotrienes, platelet activating factor, inflammatory
cytokines and growth factor) and they engulf more material than neutrophils. Their lifespan is 3-4x
longer than neutrophils and they also interact with the immune system.
Macrophages are responsive to lymphokines from T cells which enhance their efficacy and work with
the immune system by processing and presenting antigens to the lymphocytes and by stimulating
growth and differentiation of granulocytes and monocytes in the bone marrow and substances that
promote wound healing.
Eosinophils: They are granulocytes with many lysosomes. They contain biochemical mediators of
inflammation and are especially prominent in the allergic response and hypersensitivity disorders. As
well, they are particularly good at tackling parasitic infections. Like their counterparts, eosinophils
circulate in the blood until they are needed to response to insult or injury. Then, they migrate to the
tissues where they modulate release of inflammatory mediators and degrade vasoactive molecules,
controlling the vascular effects of histamine and serotonin.
Basophils: They are very similar in function to eosinophils. They too, produce lipid mediators and
cytokines to induce the inflammatory response. They too, are important in the allergic and
hypersensitivity reactions. They also interact with the immune system in that they bind to IgE through
receptors on their cell surface. This action triggers the release of histamine and vasoactive agents.
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