NON SPESIFIK IMMUNITY DEFENSE The human immune system consists
of2 branches: 1) theinnate immune system,which is present at birth
and provides non-specific protection against microbes; and 2)
theadaptive immune system,which provides specific protection
against microbes, but must be acquired over time. The innate and
adaptive immune branches can be further broken down into3 lines of
defensethat work together to protect the body against injury and
infection. Thefirst line of defenseis non-specific and is part of
theinnate immune system. The firstline of defenseconsists of:
1)physical barriers(skin, mucous membranes, cilia); 2)chemical
barriers(saliva, sweat,sebum, tears, lysozyme,digestive enzymes,
lactoferrin, urine); and 3)resident bioflora(beneficial
microbesliving on our skin and in our bodies that help block
infection by disease-causing microbes). Thesecond line of defenseis
also part of thenon-specific, innate immune systemand includes:
1)non-specific immune cells(eosinophils, basophils, neutrophils,
macrophages); 2)chemical mediators(interleukin-1, interferon,
complement); 3)fever; 4)inflammation; and 5)phagocytosis. Thethird
line of defense(see chapter 15) is part of theadaptive or acquired
immune system. This line of defense provides specific, long-term
protection against microbes. The third line of defense includes:
1)T-cells(helper and cytotoxic); 2)B-cells(memory and plasma
cells); and 3)antibodies. All blood cells are born or produced in
thebone marrow. The 3major types of blood cellsareerythrocytes (red
blood cells), thrombocytes (platelets),andleukocytes (white blood
cells). Red blood cells help transport oxygen and nutrients to the
cells of the body.White blood cells(WBCs) defend the body against
infection. The immune system relies upon2 systems for transportof
immune cells and proteins: 1) thecirculatory systemand 2)
thelymphatic system. Thelymphatic systemincludes thethymus, spleen,
tonsils, lymph nodesand other lymph tissues found in the gut
(GALT), skin (SALT), mucosal membranes (MALT), and bronchial tubes
(BALT).T cells mature in the thymus, the spleen filters out damaged
blood cells and microbes, and thelymph nodesserve as
the"headquarters"of the immune system. Leukocytes (white blood
cells) can be classified as: 1)granulocytes(eosinophils,
neutrophils, basophils and mast cells); or
2)agranulocytes(monocytes, macrophages, T-lymphocytes, and
B-lymphocytes). Eosinophilsare granular, non-specific immune cells
that protect againstparasitic infections. Basophilsare granular,
non-specific immune cells found in the blood thatrelease
histaminein response to injury, infection and allergens. Mast
cellsare granular, non-specific immune cells found in the tissues
thatrelease histaminein response to injury, infection and
allergens. Neutrophilsare granular, non-specific immune cells that
patrol the borders of the body and eliminate microbes by
phagocytosis (amateur eaters). Monocytesare agranular, non-specific
immune cells that circulate in the blood and mature into
macrophages when they migrate into tissues. Macrophagesare
agranular, non-specific immune cells that perform the following
functions: 1)phagocytosis(professional eaters); 2) sound chemical
alarm to alert other immune cells; and 3) present information about
the foreign microbes (antigens) to the T cells, which are the
generals of the immune army. Phagocytosisis a second line of
defense process in which foreign materials (microbes) are engulfed
and broken down by neutrophils or macrophages within a digestive
compartment known as the lysosome. Inflammationis a non-specific
response to tissue injury or infection that: 1) walls off damaged
or infected tissue; 2) recruits immune cells to the site of injury
or infection; and 3) clears away microbes or damaged cells so
tissue repair can occur. There are4 signs of inflammation: 1)
rubor; 2) calor; 3) tumor; and 4) dolor. Feveris an increase in
body temperature induced by pyrogens (interleukin-1 and LPS) and
regulated by the hypothalamus, which decreases bacterial cell
growth and increases immune cell activity. Interferonsareanti-viral
proteinsreleased by virally-infected cells that help prevent the
spread of infection to neighboring cells by degrading viral RNA and
blocking production of viral proteins. Complementis a set ofimmune
proteinsthat aid or "complement" immune function. Complement
proteins C3a and C5a induce inflammation. Complement protein C3b
opsonizes or binds to microbial cells marking them for destruction
by phagocytes. Complement proteins C5-C9 form the membrane attack
complex, which forms holes on the surface of targeted microbes and
leads to their lysis. 3 Linesof Immune DefenseThe body utilizes2
types of immunityto defend against microbial
invaders:InnateandAcquired Immunity.Innate immunityis a type of
natural, built-in defense system that provides non-specific
protection against pathogens. Innate immunity includes the1st line
of defense(physical & chemical barriers & resident
bioflora) and the2nd line of defense(inflammation, fever,
phagocytosis and non-specific immune cells).Acquired immunityis a
specific, long-term form of protection that develops over time.
Acquired immunity represents the3rd line of defenseand is mediated
by specific immune cells (T cells and B cells).Non-Specific
(Innate) ImmunityInnate immunityis a natural defense system present
at birth that provides non-specific protection against a wide range
of pathogens. Although theinnate immunesystem cannot specifically
recognize or remember individual pathogens, it does NOT require
prior exposure to the pathogen in order to be effective against it.
This means it can protect you from microbes that your body has
never encountered before. The innate immune system consists of
the1st and 2nd lines of defense.
Thefirst line of defenseis non-specific and consists of:
1)physical barriers(skin, mucous membranes, cilia); 2)chemical
barriers(saliva, sweat, sebum, tears, lysozyme, digestive enzymes,
lactoferrin, urine); and 3)resident bioflora(beneficial microbes
living on our skin and in our bodies that help block infection by
disease-causing microbes).
1st Line of Defense: Physical Barriers (p. 415-417)Physical
barriers,which include the outer layer of skin (epidermis), cilia,
and mucous membranes, block the entry of pathogens into the body,
much like a castle wall blocks or prevents foreign invaders from
entering the castle.The skin consists of anouter layercalled
theepidermis, which is composed of multiple layers of tightly
packed skin cells that serve as aphysical barrieragainst infection.
As new cells are produced in the layers below, thedead outermost
layers of the epidermis are shed.Any microbes attached to these
dead skin layers are shed along with the dead skin cells. The
dermis, which lies just beneath the epidermis, containscollagen
fibersthat give the skin strength and flexibility. This layer
containssweat glandsthat use salty perspiration to flush microbes
and other contaminants out of the pores. Sweat also contains a
special enzyme calledlysozyme, that breaks down the bacterial cell
wall. In addition to sweat glands, the skin also hassebaceous
glandsthat coat the skin withsebum,which is an oily substance that
contains fatty acids that lower the pH of the skin surface to
inhibit microbial growth.As the dead outermost layers of the
epidermis are shed, any infectious microbes attached to this layer
are also shed from the body. For this reason, you should always
wash your sheets, towels, and other personal clothing items after
you have been ill, as the microbes attached to these dead skin
layers can remain infectious!So, where does all of that dead skin
go? Dead skin cells can be found on our sheets, pillows, clothes,
and even in the dust particles that form in our homes. Dead skin
cells are broken down by dust mites, which are microscopic
parasites that live on our skin, hair, and eyelashes.Mucous
membranesline the respiratory, urinary, gastrointestinal, and
reproductive tracts. Mucous membranes consist of a single layer of
tightly-packedciliated epithelial cells. Neighboringgoblet
cellssecrete a thick, sticky substance calledmucus, which coats the
epithelial cells. Mucus contains lysozyme, which is an enzyme that
breaks down the bacterial cell wall. As bacteria and other debris
become trapped in the thick mucus, cilia sweep it up and out of the
respiratory tract, where it is expelled from the body
bycoughing,sneezing, or evenswallowing!
1st Line of Defense: Chemical Barriers (p. 417)Chemical
barriers(tears, saliva, sweat,sebum, lysozyme, digestive enzymes,
lactoferrin, urine) help break down or destroy microbial invaders.
Lysozyme, an enzyme found in tears, sweat, mucus, saliva and urine,
acts by destroying the peptidoglycan cell wall of bacteria. Sweat
also contains salt, which creates a hypertonic environment that can
lead to dehydration of microbial cells. Fatty acids found in sebum
contain fatty acids, which give the skin an acidic pH of 5. The
stomach maintains an acidic pH (below 7) and contains digestive
enzymes that can break down microbes that pass through the
gastrointestinal (GI) tract. Bile is found in the intestinal tract,
where it contributes to a basic or alkaline pH (above 7) that
inhibits growth of some microbes. Vaginal and prostrate secretions
containlactoferrin, which is an iron-binding protein that prevents
microbes from attaching to and using free iron to enhance their
metabolism.
Can you answer the questions below?
1st Line of Defense: Resident Bioflora (p. 416-417)Normal
biofloraare beneficial microbes living on our skin and in our
bodies that help block infection by disease-causing microbes.
Resident bioflora provide non-specific protection to the host by
competing with pathogens for nutrients and blocking attachment to
the host, and by secreting toxins (bacteriocidins) that inhibit or
kill microbes. These beneficial microbes also aid in digestion and
absorption of our food.Staphylococcus epidermidisis a normal
resident of the skin andEscherichia coliis a normal resident of the
intestinal tract. Current research also shows that by maintaining a
constant level of beneficial bacteria in our body, we keep the
second line of defense active and ready to fight off infection if
needed. Frequent or chronic antibiotic use can destroy many of the
beneficial bacteria that live in the GI tract, making us more
susceptible to other types of infection.2nd Line of Defense (p.418,
426-438)If pathogens do gain entry into the body, the body's 2nd
line of defense comes into play. Thesecond line of defenseis also
part of thenon-specific, innate immune systemand includes:
1)non-specific immune cells(eosinophils, basophils, neutrophils,
macrophages); 2)antimicrobial chemicals(interleukin-1, interferon,
complement); 3)fever; 4)inflammation; and 5)phagocytosis.Role of
Blood & Lymph in Immune Defense (p. 421-424)Blood consists
ofcellsandplasma,which is a fluid that contains ions, dissolved
gases, nutrients, and proteins involved in inflammation (complement
proteins) and blood clotting. There are 3 major types of blood
cells: 1)erythrocytes(red blood cells); 2)thrombocytes(platelets);
and 3)leukocytes(white blood cells). Erythrocytes transport oxygen
and carbon dioxide gases between the cells and the lungs. The
average adult male has4-6 million red blood cells per microliterof
blood, whereas the average female has4-5 million red blood cells
per microliterof blood. Leukocytes (white blood cells) defend the
body against infection and injury. The average person has
between4500-11,000 per microliter of blood.All blood cells
originate in thebone marrow, within the hollow cavities of the
large bones. In a process calledhematopoiesis, stem cells are used
to produce each of the3 major types of blood cells:
1)erythrocytes(red blood cells), which arise from erythroid stem
cells; 2)thrombocytes(platelets), which arise from myeloid stem
cells; and 3)leukocytes(white blood cells), which arise from both
myeloid and lymphoid stem cells.
White blood cellshave specialized receptors on their surface
that enable them to determine what is"self"and belongs in the body
and what is"non-self"and does not belong. When "non-self" proteins
are encountered, an immune response is mounted to destroy the
foreign (non-self) substance.
Immune Transport: The Circulatory & Lymphatic Systems (p.
424-426)Immune cellsmove throughout the body via thecirculatory
system(with vessels that run in opposite directions, like an
interstate) and thelymphatic system(with vessels that run in only
one direction, like a one-way street). Blood and immune cells are
transported quickly through thecirculatory systemvia a pump
(heart), while lymph is moved slowly back toward the heart through
the contraction of skeletal muscles. This dependence on muscle
movement explains why bed- or wheel-chair ridden patients tend to
have swelling or edema of the hands and feet.Lymphoid organsinclude
thethymus(site of T-lymphocyte maturation), thespleen(filters out
damaged red blood cells and pathogens from the blood),lymph
nodes(immune system headquarterswhere white blood cells attack
foreign invaders),tonsils, gut-associated lymphoid tissue (GALT)
which includes the appendix and intestinal Peyer's patch,
mucosal-associated lymphoid tissue (MALT), skin-associated lymphoid
tissue (SALT) and broncial-associated lymphoid tissue (BALT).One of
the functions of the lymphatic system is thereabsorption of
extracellular body fluids, which are returned to the heart via the
lymph vessels. Lymphatic fluid is filtered in the lymph nodes
(immune system headquarters), allowing immune cells within the
nodes to see and respond to foreign cells or antigens. Disruption
of the lymphatic system by parasites, such as the filarial worm
(shown below), can interfere with the reabsorption of extracellular
body fluids and lead to edema or swelling.Leukocytes: Warriors of
the Immune SystemLeukocytes (white blood cells) are microscopic
immune warriors that protect us from injury and infection caused by
invading microbes and disease-causing pathogens. Produced in
thebone marrow, leukocytes (white blood cells) include basophils,
eosinophils, mast cells, neutrophils, monocytes, macrophages and
lymphocytes.T-lymphocytes leave the bone marrow and mature in the
thymus. There are several types of T-lymphocytes produced in the
body-- cytotoxic, helper, memory and suppressor T-cells.
B-lymphocytes are born and mature in the bone marrow. After
activation, B-lymphocytes can become plasma cells that secrete
antibodies or memory cells. Some cells within the lymphatic system
become antigen-presenting cells (APCs). Macrophages are one type of
APC that eat microbial invaders and then display foreign antigens
to the generals of the immune arrmy, the CD4+ T helper cells.
Non-Specific Immune Cells (p. 422-424)Leukocytes (white blood
cells) can be divided into 2 groups based upon their appearance
under the microscope: 1)granulocytes; or 2)agranulocytes.
Granulocytes contain large granules or compartments that store
pre-formed chemicals such as histamine, leukotrienes and
prostaglandins.Granulocytesinclude: eosinophils, neutrophils,
basophils and mast cells. In contrast,agranulocytesdo not appear to
have granules when viewed under a light
microscope.Agranulocytesinclude:monocytes, macrophages,
T-lymphocytes, and B-lymphocytes.
Granulocytes (p. 422-423)Granulocytes account for 75% of all
leukocytes (white blood cells) and contain large granules or
compartments that store pre-formed chemicals such as histamine,
leukotrienes and prostaglandins.Granulocytesinclude: eosinophils,
neutrophils, basophils and mast cells.
Eosinophils (2-4%) are non-specific immune cells (granulocytes)
involved in eliminating allergens and parasites. Eosinophils
primarilyattack parasitic wormsby attaching to their surface.
Eosinophils then release digestive enzymes, such as peroxidase,
lysozyme, and perforin, which act to break down the large parasite
into smaller parts that can be consumed by macrophages.
Eosinophilia, an abnormally high number of eosinophils in the
blood, is often an indication that the patient has a parasitic
infection.Basophils account for 0.5-1% of all leukocytes (white
blood cells). Found circulating in the blood, basophils release
histamine in response to injury, infection and allergic responses.
The release of histamine causes vasodilation of the blood vessels,
which results in increased blood flow and the recruitment of WBCs
into the infected or injured tissue. Although similar in function
to basophils,mast cellsare found in thetissueswhere theyrelease
histaminein response to injury, infection and allergens.Neutrophils
are non-specific immune cells that patrol the borders of our body.
Always on the lookout for foregin invaders, neutrophils are the 1st
cells to arrive at the site of injury or infection. The primary
function of the neutrophil is to eat and digest invading microbes
by phagocytosis (amateur eaters). Although neutrophils account for
55-65% (25 billion cells) of all white blood cells (WBCs), they are
short-lived and only survive 3-8 days before dying and forming pus.
Substances that induce pus formation are calledpyogens.For
example,Streptococcuspyogenes, causes the formation of white
nodules at the back of the throat.Non-Specific Immune Cells:
Agranulocytes (p. 423-424)Agranulocytesdo not appear to have
granules when viewed under a light microscope.Agranulocytesinclude:
monocytes, macrophages, dendritic cells, T-lymphocytes, and
B-lymphocytes.
Monocytes & Macrophages (p. 432-433)Monocytesare agranular,
non-specific immune cells that circulate in the blood andmature
into macrophageswhen they migrate into tissues.Macrophagesperform 3
important functions within the non-specific immune system:
1)phagocytosis(professional eaters); 2)release chemical
messengersto alert other immune cells; and 3)present
informationabout the foreign microbes (antigens) to the T cells,
which are the generals of the immune army.
Macrophages that migrate into specific tissues are named for
their location in the body. For example,alveolar macrophagesare
found in the lungs,Kuppfer cellsare found in the liver,dendritic
cellsare found in the skin and mucous membranes, andmicrogliaare
found in the brain.
Chemical Messengers: Cytokines & Interleukins (p.
428-429)Immune cells communicate usingchemical
messengerscalledcytokines. Cytokines are small, regulatory proteins
essential for communication between cells. Cytokines are produced
by many types of cells including, monocytes, macrophages,
lymphocytes, fibroblasts, mast cells, platelets, and endothelial
cells. Cytokines have several different functions within the body:
1) they can mediate non-specific immune reactions such as
inflammation, fever, and phagocytosis; 2) they regulate the growth
and activation of the specific immune system lymphocytes; 3)
stimulate hematopoiesis in the bone marrow; amd 4) they can either
expand (vasodilate) or constrict (vasoconstrict) blood
vessels.Interleukinsare a special class of cytokine that allow
immune cells (leukocytes) to communicate with each other and the
rest of the body. For example,interleukin-1 (IL-1)is produced by
macrophages in response to infection. This chemical messenger
activates the hypothalamus and induces fever.Histamineis a
vasoactive chemical messenger produced by mast cells and basophils,
that causes vasodilation and increased vascular
permeability.Leukotrienesalso increase vascular
permeability.Prostaglandins,which can be produced by most body
cells, can trigger inflammation and pain.
2nd Line of Defense: Fever (p. 431-432)Feveris an increase in
body temperature induced by endogenous (interleukin-1, IL-1) or
exogenous (Lipopolysaccharide found on Gram-negative bacterial
cells) pyrogens. Fever is induced when chemical messengers such as
IL-1 stimulate the hypothalamus to raise body temperature. Fever
acts to slow down microbial metabolism while, at the same time,
ehances immune cell function.
What Causes Chills?If the thermostat (hypothalamus) has been set
by the pyrogen (interleukin-1 or LPS) at 102F, but the blood
temperature is only at 99F, then the muscles are stimulated to
contract or shiver to produce heat. At the same time, vessels in
the skin constrict (become smaller) and the piloerector muscles in
the skin cause "goosebumps" to form. In contrast, when the
thermostat is reset to 98.6F, but the blood is still at 102F, the
body will cause the vessels to dilate (expand) and the body will
sweat in an attempt to release heat and lower the body's
temperature.2nd Line of Defense: Inflammation (p.
426-431)Inflammationis a non-specific response to tissue injury or
infection that limits the spread of pathogens, removes damaged
cells or tissues, destroys pathogens, and stimulates tissue
repair.4 Signs of InflammationInflammation is characterized by 4
signs: rubor, calor, tumor, and dolor.
Inflammation begins when injured or infected tissuesrelease
chemical distress signals, such ashistamine, that
causevasodilation. Vasodilation leads toincreased blood flowand
therecruitment of non-specific immune cellsto the site of injury.
Non-specific immune cells migrate in response to the chemical
distress signal released by infected or injured cells via a process
called chemotaxis and leave the blood vessel to enter the tissue
viadiapedesis.
Steps in Inflammation1. Mast cells release chemical messengers
(histamineandleukotrienes) in response to tissue injury or
infection. These factors create a"chemical trail"for the immune
cells to follow to the site of injury or infection via a process
calledchemotaxis.2.Histaminecauses vasodilation or expansion of the
blood vessels. This causes redness (rubor) and increased heat
(calor) in the affected region.Leukotrienesmake the blood vessel
walls more permeable or leaky.
3. Neutrophils & macrophages crawl out of the blood vessels
by diapedesis. This causes swelling (tumor) in the affected
tissue.Neutrophilsandmacrophagesremove microbes or damaged tissue
by phagocytosis (eating) and pus is formed.
4. Tissue damage is repaired and scars can form if fibroblasts
are involved.Inflammation can either be acute or chronic.Acute
inflammationis a localized response that develops immediately upon
injury and lasts for a short period of time. Acute inflammation is
typically beneficial and results in the destruction of microbes and
tissue repair.Chronic inflammationis a more slow-progressing form
of inflammation that persists for a longer period of time (months
to years). Chronic inflammation can cause damage to surrounding
host tissues.
Bothsteroidal(corticosteroids) andnon-steroidal
anti-inflammatory drugs (NSAIDs)can be used asanti-inflammatory
drugsto reduce pain and swelling. NSAIDS, which include drugs like
aspirin and ibuprofen, prevent prostaglandins from being
synthesized. They achieve this by inhibiting the cyclooxygenase
(COX) enzyme. In contrast, other products, such as Tylenol
(acetaminophen) can be used to reduce pain (analgesic), but cannot
reverse the effects of inflammation.2nd Line of Defense:
Phagocytosis (p. 432-434)Phagocytosis involves: 1) chemotaxis; 2)
attachment to the microbe; 3)endocytosis; 4)fusion with a lysosome;
5) digestion of the microbe; 6) formation of residual waste; and 7)
release of waste by exocytosis.
Antimicrobial Secretions: Interferon (p. 434-435)Non-specific
immune cells produce and secrete a variety of antimicrobial
substances including interleukins, lactoferrins, peroxides, free
radical, lysins, complement and interferon. These substances act to
destroy the invading microbe or inhibit microbial metabolism.
Interferon is ananti-viral cytokineproduced by virally infected
cells that helps prevent the spread of infection to neighboring
cells.Antimicrobial Secretions: Complement (p.
435-438)Thecomplement systemis a series of 9 blood proteins that
are activated in response to microbial invasion. When activated,
these proteins either bind to pathogens or antibody-pathogen
complexes to target them for destruction by phagocytosis or form a
membrane attack complex to lyse the invading cell. Complement
proteinsC3a & C5ainducechemotaxisandinflammation. Complement
proteinC3bcoats or opsonizes the surface of microbes to enhance
phagocytosis (cellular eating) by macrophages. Complement proteins
C5-9 form themembrane attack complex (MAC)and induce lysis of the
microbe.
Preview of Specific Immunity (Chapter 15)The3rd line of
defenseinvolves the activation of thespecific or acquiredimmune
system. Once activated, the specific immune system mounts a defense
that is specific to the invader, global, and long-lasting. The
specific immune response is mediated by B- and T-lymphocytes, which
work together but utilize different mechanisms to destroy the
microbial invader. Only B- or T-cells