Download (Innate) Immunity Lecture

The Lymphatic System
Innate Immunity
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Types of Immunity
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Innate (non(non-specific) immunity
Adaptive (specific) immunity
The human body has several different ways that it defends itself against infection by
pathogens. One way of looking at it is that we have three “lines of defense” against
infection. The first line of defense includes physical barriers that try to keep
pathogens out of the body in the first place. The second line of defense are fastacting responses in the body that target all invaders, regardless of whether their
antigens are recognized. The third line of defense is the “immune system” and is
activated when an antigen is encountered that our body has seen before and knows
is bad. The immune system is very effective, but is slow to activate.
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Innate Immunity
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NonNon-specific
No memory cells
“Not me.”
me.”
When talking about immunity, we distinguish between innate (also called
nonspecific) immune responses and adaptive (also called specific) immune
responses. Innate immunity includes all of the body’s general methods of defense.
Basically, any substance in the body that is not recognized as part of the body is
attacked and removed whether or not memory cells have been formed against it.
Innate immunite begins very rapidly once a pathogen is detected, but the response
is usually not as strong as adaptive immune responses. Adaptive immune
responses take time and involve mounting an attack against a specific type of
pathogen that the body has been infected with before.
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Innate Immunity
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Responses:
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Surface barriers
Internal (cells/chemical) responses
Phagocytes
 Natural killer (NK) cells
 Inflammation
 AntiAnti-pathogen proteins
 Fever
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There are several ways that nonspecific immunity works.
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Surface Barriers
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Skin and mucous membranes.
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Physical barrier
Secretions (mucous,
sweat, tears, saliva,
stomach secretions)
Lysozyme
Surface barriers (the skin and mucous membranes) are the body’s first line of
defense against infection. Even without their secretions, they are a very effective
mechanical barrier – very few pathogens can travel through the skin to infect us. In
addition to physically blocking pathogens, though, the skin and mucous membranes
secrete a number of substances that aid in the protection. Just a few examples:
Mucous in the respiratory tract serves to trap and remove pathogens before they
get into the warm, moist lungs.
Sweat, saliva and (especially) stomach secretions are acidic and inhospitable to
most bacteria. The stomach secretions also contain digestive enzymes which digest
bacteria as well as the foods we eat.
Lysozyme is an enzyme found in saliva and tears that breaks down the cell walls of
bacteria. This helps us combat eye infections as well as bacteria in foods – as we
chew our food, saliva mixes with it.
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Internal Responses
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Phagocytes
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Macrophages, microglia,
microglia,
neutrophils
May be aided by
chemical mediators.
Phagocytosis is the destruction of a pathogen by engulfing it through endocytosis
and digesting it with lysosomes. Some common phagocytes include macrophages,
microglia and neutrophils. Macrophages start out in the blood as monocytes, but
when they leave the blood and enter tissues, they grow into very large
macrophages. Macrophages move around through their tissues, patrolling for
pathogens. Microglia are found only in the central nervous system. They aren’t
mobile – they stay in one place and wait for pathogens to come to them. Neutrophils
are fast-acting WBCs that circulate in the blood and are usually the first to respond
to infection. Phagocytes can be attracted and stimulated by chemicals that promote
inflammation.
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Internal Responses
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Natural Killer (NK) cells
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“Pitbulls”
Pitbulls” of the defense system
Cause apoptosis
Enhance inflammatory
response
NK cells are specialized lymphocytes that are especially good at targeting tumor
cells. Since they are tuned to specific antigens, we can think of them as the
“pitbulls” of the defense system. While they cause the death of their target cells,
they work very differently from phagocytes. Instead of engulfing and digesting their
targets, they cause the targets to undergo apoptosis (programmed cell death). In
addition, they enhance the inflammatory response by attracting macrophages and
neutrophils.
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Internal Responses
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Inflammation
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Benefits
Cardinal signs
Stimulus:
TollToll-like receptors
 Mast cells & histamine
 Chemical mediators
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Inflammation is one of the most well-known non-specific responses to infection.
Three major benefits of inflammation include the isolation and destruction of
pathogens (first by neutrophils, then within several hours by macrophages), the
breakdown of damaged tissue, and setting the stage for tissue repair. Inflammation
is always started by a chemical “help!” signal of some kind. This signal can come
from white blood cells that have recognized an invader (via toll-like receptors, mast
cells, etc.) or from damaged tissues itself (such as prostaglandins released when
tissue is damaged). The five cardinal signs of inflammation include redness, heat,
swelling, pain and loss of function.
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Internal Responses
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Inflammation
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Effects:
Vasodilation
 Increased permeability
 Chemotaxis
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The cardinal signs of inflammation are basically side-effects of three important
events. Inflammation causes vasodilation – an increase in size of the blood vessels.
This vasodilation brings more blood to the site of infection, and therefore more
WBCs and plasma proteins. As side effects, the increased amount of blood causes
redness and heat in the affected area. Capillaries near the infection site show
increased permeability. This means that more fluid as well as more WBCs can
cross the capillary wall and enter the tissues. Why more fluid? The extra fluid helps
to dilute any exotoxins (poisons) that have been secreted by bacteria or parasites in
the tissues. Chemotaxis means “moving towards a chemical.” In this context,
inflammation results in WBCs moving towards chemicals that identify the site of
infection (protaglandins, kinins, histamines, complement, etc.)
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This flow chart shows how the effects of inflammation cause the cardinal signs, and
why they are beneficial.
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Internal Responses
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Antimicrobial proteins
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Complement
Enhances inflammation
 Stimulates NK cells
 MAC attack
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Interferons:
Interferons: SOS
signals from virusvirusinfected cells
Complement is a collection of about 20 plasma proteins that normally exists as
inactivated enzymes in the blood. During infection (as part of both specific and nonspecific immunity), though, the complement becomes active. It promotes
inflammation by stimulated NK cells and attracting WBCs to the site of injury. It also
creates MAC (membrane attack complex) protein complexes, which literally punch
holes in the cell walls of bacteria, causing them to lyse.
Interferons are chemical signal molecules secreted by virus-infected cells to “warn”
nearby cells that they have been infected. This causes nearby cells begin producing
antiviral proteins (added protection) and start secreting interferons of their own.
Nothing can be done for the already-infected cells, but this slows or stops the
spread of a viral infection.
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Internal Responses
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Fever
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Pyrogens (from macrophages & lymphocytes)
Effects:
Reduces iron & zinc
 Speeds up repair
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When macrophages and lymphocytes become activated, they secrete (among other
things) pyrogens. The pyrogens circulate to the hypothalamus where they adjust
the body’s temperature set up upwards. This causes the body to increase it’s
temperature (by keeping blood away from the surface, increasing metabolism,
causing shivering, etc.), resulting in a weak, achy, “icky” feeling associated with
being sick. Why would the body do this? One reason is that when body temperature
rises, the liver and spleen sequester iron and zinc, both minerals that bacteria need
in order to reproduce. In addition, the increase in temperature causes a rise in
metabolism, which helps speed up repair and helps WBCs work more efficiently.
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