The Body Defenses
Chapter 12
Immunity is the body’s ability
to resist or eliminate
potentially harmful foreign
materials or abnormal cells.
• The immune system plays a key role in this.
– It defends against invading pathogens, removes “worn-out”
cells, and identifies and destroys abnormal or mutant cells.
– Inappropriate immune responses lead to allergies or
autoimmune responses.
– The primary pathogens are bacteria and viruses. Bacteria
are non-nucleated, single-celled micro-organisms. Viruses
are not cellular, consisting of a nucleic acid enclosed by a
protein coat. Virulent forms of either can cause disease
(pathogenic)
Leukocytes are the effectors of the
immune system. There are five types.
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Neutrophils are highly mobile phagocytes.
Eosinophils secrete chemicals that fight parasites.
Basophils release histamine and heparin.
Monocytes change into macrophages.
B lymphocytes change into plasma cells that make
antibodies. T lymphocytes are responsible for cellmediated immunity.
Most leukocytes arise from stem cells in the bone
marrow. Lymphocytes arise from lymphocyte colonies in
lymphoid tissue.
Lymphoid tissue include the bone marrow, lymph nodes,
spleen, tonsils, adenoids, appendix, and Peyer’s patches
in the digestive tract.
Pathogens in lymph are filtered by lymph nodes.
Lymphocytes serve as macrophages there. The spleen
performs a similar role on the blood. The thymus and
bone marrow process T and B lymphocytes respectively.
Immune responses are either innate
and nonspecific or adaptive and
specific.
• They differ in the timing and selectivity of the defense
mechanism.
• Innate, nonspecific, responses work immediately when the body
is exposed to a threatening agent. They nonselectively defend
against foreign invaders. They provide a first line of defense,
with rapid but limited responses.
• Adaptive, or acquired, immunity specifically targets foreign
material to which the body has already been exposed. The
body has had an opportunity to prepare for attack. This takes
more time.
• Neutrophils and macrophages are important in innate defense,
along with several plasma proteins.
• The responding phagocytic cells are covered with toll–like
receptors. They recognize and bind to pathogenic markers.
Other chemicals are secreted by the phagocytes of the adaptive
immune system.
Innate immunity defenses include
inflammation, interferon, natural
killer cells, and the complement
system.
• Inflammation is a nonspecific response to
foreign invasion or tissue damage.
• Neutrophils and macrophages, phagocytic
specialists, play a major role. Plasma
proteins contribute.
• Inflammation attempts to:
– isolate, destroy, and inactivate the invaders.
– remove debris.
– prepare for subsequent healing and repair.
Inflammation responses are a series
of events.
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Resident macrophages defend against invasive
bacteria during the first hour.
Arterioles, serving the invaded area, dilate.
Histamine is released to increase capillary
permeability in the area. Plasma proteins can
leave the blood and enter the area.
The leakage of plasma proteins and fluid from
the blood causes localized edema in the
injured area. The fluid accumulation causes
swelling, redness, and increased temperature
in the area. The swelling causes pain.
Fibrin formation walls off the area from
surrounding tissues.
Neutrophils or monocytes emigrate from the
blood into the area. They adhere to the inside
surface of capillaries by margination. They
enter the interstitial spaces by diapedesis.
They are guided to the areas where they are
needed by chemotaxis.
Within a few hours of the beginning
of the inflammatory response, there
is leukocyte proliferation.
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Neutrophil numbers may increase four or five times.
Monocytes increase at a slower rate, forming macrophages.
Bacteria are marked for destruction by opsonins. This allows
phagocytes to distinguish among normal and foreign/abnormal cells.
The opsonins are antibodies and one of the activated proteins of the
complement system.
Leukocytes destroy bacteria by phagocytosis.
There is mediation of the inflammatory response by phagocytesecreted chemicals. These chemicals include:
nitric oxide (fron macrophages)
lactoferrin (from neutrophils)
histamine (increasing capillary permeability)
kinins (formed from kininogens)
endogenous pyrogen (induces fever development)
leukocyte endogenous mediator (decreases plasma iron)
acute-phase proteins from the liver
Finally the inflammatory
process repairs tissues.
– The repair can be perfect. Cell division replaces
lost cells, replacing the injured area with the same
kind of cells.
– Scar tissue replaces nonregenerative tissues such
as nerve and muscle.
• Salicylates and glucocorticoid drugs suppress
the inflammatory response.
– Salicylates decrease histamine release. They also
reduce fever by inhibiting the production of
prostaglandins.
– Glucocorticoids suppress most aspects of the
inflammatory response.
Interferon transiently inhibits the
multiplication of viruses in most
cells. It interferes with viral
replication.
– It triggers the production of virus-blocking enzymes by
potential host cells. The enzymes remain inactive unless
cells are attacked by viruses.
– Interferon is released nonspecifically from any cell infected
by a virus. It can induce immunity against many different
viruses in many other cells.
– It can bind to and forewarn neighboring cells to viral attack.
Interferon slows cell division. It has anticancer effects.
• Natural killer cells destroy virus-infected cells and
cancer cells on first exposure to them.
– They lyse cell membranes upon first exposure to these cells.
NK cells provide an immediate, nonspecific defense.
Complement punches holes in
micro-organisms.
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The complement system consists of plasma
proteins produced by the liver.
This is a nonspecific response.
It is activated by exposure to particular
carbohydrate chains on the surface of microbes
and to antibodies produced by specific foreign
invaders.
The powerful complement cascade reinforces
other general inflammatory tactics.
C1 of this cascade actives C2 and so forth. C5
through C9 assemble into the membrane attack
complex. This attacks the surface membrane of
micro-organisms.
Complement proteins have additional functions
such as serving as chemotaxins and acting as
opsonins.
Adaptive immune responses are
antibody-mediated (humoral)
immunity and cell-mediated
immunity.
• B cells differentiate and mature in the bone marrow.
• The thymus gland processes T cells that migrate from the bone
marrow.
• B and T cells take up residence in lymphocyte colonies. There
they produce new B and T cells. They occupy different
lymphoid tissues.
• Thymosin is a hormone that maintains T cell lineage.
• An antigen induces an immune response against itself. Their
presence allows B and T cells to distinguish between foreign
invaders (antigenic) and normal cells.
B cells carry out antibodymediated immunity.
• A given lymphocyte has receptors on its surface to recognize
one unique antigen. The TLRs of innate effector cells recognize
generic traits of all microbes.
• Antigens stimulate B cells to convert into plasma cells
• that produce antibodies. A plasma cell produces antibody
molecules that can combine with a specific kind of antigen. All
antibodies eventually enter the blood or lymph.
• The antibody (immunoglobulin) subclasses are:
– IgM - serves as the B cell surface receptor for antigen attachment
– IgG - the most abundant antibody produced in large amounts
– IgE - protects against parasitic worms and is the antibody mediator
for common allergic responses
– IgA - found in the secretions of the digestive, respiratory, and
genitourinary systems
– IgD - on the surface of many B cells with uncertain function
Antibodies are Y-shaped molecules.
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All five classes are composed of five, interlinked
polypeptide chains. Two are long, heavy chains
and two are short, light chains arranged in the
shape of a Y.
They are classified according to properties of
their tail regions.
Characteristics of the arm regions of the Y
determine the specificity of the antibody.
Properties of the tail portion (heavy chains)
determine the functional properties of the
antibody.
An antigen-binding site is on the tip of each arm.
These antigen-binding sites are unique for each
antibody and are responsible for the large variety
of antibody molecules.
The tail of each antibody is constant for all
members of each class. The tail contains binding
sites for particular mediators of antibody-induced
activities.
Antibodies amplify innate
immune responses to promote
antigen destruction.
• Antibodies can physically hinder antigens.
• By neutralization they prevent harmful chemicals from
interacting with susceptible cells.
• They can bind to foreign cells by agglutination.
• Amplification augments the immune response. Antibodies mark
or identify foreign material, targeting it for destruction. This is
followed by:
• activation of the complement system; This sets of a cascade
leading to the formation of the membrane attack complex. This
is activated by an antibody.
• enhancement of phagocytosis;
• stimulation of killer cells;
• Occasionally an exaggerated antigen-antibody response cause
tissue damage. This is an immune complex disease.
Activated B-cell clones multiply
and differentiate into plasma cells
or memory cells.
• Most are transformed into plasma cells. They produce and
secrete IgG antibodies. Each antibody combines with an
antigen, marking it for destruction.
• During initial contact with a microbial antigen, the antibody
response is delayed. Plasma cells are formed. It reaches its
peak a a couple of weeks by the primary response. After this
peak, antibody concentration decreases.
• A small percentage of the B lymphocytes become memory cells.
The remain dormant and expand a specific clone. Upon
reexposure to the same antigen, they are more ready for
immediate action than the original lymphocytes of the clone.
• This secondary response is quicker, more potent, and longerlasting. This can be induced by disease or vaccination.
The large variety of B cells arises
from the reshuffling of a small set of
gene fragments.
– Each different combination gives rise to a unique B cell
clone.
– The antibody genes of already-formed B cells are highly
prone to mutation, further contributing to variation.
• Active immunity results from exposure to an antigen.
Passive immunity is from the transfer of preformed
antibodies.
– One example of passive immunity is the transfer of IgG
antibodies from mother to fetus.
– Passive immunity gives immediate protection.
– Serum sickness is one drawback to receiving preformed
antibodies.
Blood groups are a form of
passive immunity.
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The ABO blood types are named by the presence of antigens on the
surface of erythrocytes: A, B, AB (both antigens), or O (neither antigen).
The ABO antibody makeup in a person is the opposite, by letter, to the
antigen content:
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antibody A in blood type B
antibody B in blood type A
both antibodies in blood type O
neither antibody in blood type AB
By the transfusion reaction, if the antigen of the donor and antibody of
the recipient match, by letter, the donated red cells can agglutinate in
the blood of the recipient.
For example, the donation of blood type A (antigen) to a person with
blood type B (antibody A) can produce agglutination in the blood of the
recipient.
Blood type O is the universal donor (no ABO antigens).
Blood type AB is the universal recipient (no ABO antibodies)
There are other
blood-group systems.
• A person with the Rh factor is Rh-positive.
• A person without the Rh factor is Rh-negative.
• An Rh negative person can produce anti-Rh
antibodies when first exposed to the Rh
factor. This can occur when an Rh-negative
mother develops antibodies against the
erythrocytes of an Rh-positive fetus. This
condition is called the hemolytic disease of
the newborn.
• There are about 12 minor human erythrocyte
antigen systems.
Lymphocytes respond only to
antigens presented to them by
antigen-presenting cells.
• Macrophages can be an antigen-presenting cells. They cluster
around an appropriate B-cell clone, making the introduction.
• Phagocytosis occurs, processing the raw antigen intracellularly
and presenting the processed antigen, exposing it to the outer
surface of the macrophage’s plasma membrane.
• As a macrophage engulfs and ingests a microbe, it ingests it
into antigenic peptides. Each binds to an MHC molecule.
• The MHC transports the bound antigen to the cell surface,
presenting it to passing lymphocytes.
• Antigen-presenting macrophages secrete interleukin . This
chemical mediator enhances the differentiation and proliferation
of the now-activated B cell clone. Dendritic cells are antigenpresenting cells. Helper T cells help B cells.
T lymphocytes carry out cellmediated immunity.
• They do not secrete antibodies. They bind directly to targets. T
type killer cells release chemicals that destroy these targeted
cells.
• T cells are clonal and antigen specific. They acquire receptors
for this specificity in the thymus.
• T cells are activated for foreign attack only when on the surface
of a cell that carries foreign and self antigens. Both must be on
a cell’s surface for T cell binding.
• T cells learn to recognize foreign antigens only in combination
with a person’s own tissue antigens. There is a dual antigen
requirement.
• A few days is required before T cells are activated to launch a
cell-mediated attack.
The two types of T cells are cytotoxic and
helper. Helper cells are the most
numerous T cells.
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Cytotoxic T cells secrete chemicals that
destroy target cells. Most frequently they
destroy cells infected with viruses.
There is a clone of these cells specific for
a particular virus. These T cells bind to
the viral antigens and self-antigens on the
surfaces of the viral- infected cells.
The cytotoxic T cells release chemicals
that destroy the attacked cell before the
virus can enter the nucleus and start to
replicate.
Cytotoxic T cells also destroy targeted
cells by releasing perforins. The
exception to this is nerve cells.
Viruses are released from the destroyed
cells. They are destroyed in the
extracellular fluid by phagocytic cells.
Cell division replaces the lost body cells
with healthy cells.
Helper T cells secrete
chemicals that amplify the
activity of other immune cells.
• Cytokines are chemicals (with the exception of
antibodies) secreted by helper T cells. They spur
other immune cells to help ward off the invader.
Examples of cytokines include the B-cell growth
factor, interleukin 2, chemotaxins, and macrophagemigration inhibition factor.
• There are two subsets of helper T cells that augment
different patterns of immune responses by secreting
different types of cytokines.
The immune system is normally
tolerant of self-antigens.
• Tolerance refers to preventing the immune system from
attacking the person’s own tissues. There are at least five
different mechanisms.
• By clonal deletion there is a triggering of the apoptosis of
immature cells that would react with the body’s own proteins.
• By clonal anergy a lymphocyte must receive two specific signals
at the same time for activation. A single signal from a selfantigen turns off a compatible T cell, rendering the cell
unresponsive to further exposure to the antigen.
• By receptor editing, a B cell with a receptor for one of the body’s
own antigens changes its receptor to a nonself version if it
encounters a self antigen.
• B antigen sequestering self molecules are hidden from the
immune system.
• A few tissues have immune privlege.
Autoimmune diseases arise from
a loss of tolerance of selfantigens. There are several
causes.
• The exposure of normally inaccessible antigens
induces an immune attack against them.
• Normal self-antigens can be modified.
• There is an exposure of the immune system to a
foreign antigen almost structurally identical to a selfantigen.
• Some may be related to pregnancy, arising from
lingering fetal cells in the mother’s body after the
pregnancy.
Genes called MHC produce MHC
molecules. These self-antigens are
plasma membrane glycoproteins.
• They vary from one person to another. Their natural function is
to direct the responses of T cells.
• MHC molecules on cells block T cell binding.
• Cytotoxic T cells do not bind to MHC self-antigens in the
absence of a foreign antigen. Therefore, normal body cells are
protected from lethal immune attack.
• T cells become active only when they match a given MHCforeign peptide combination.
• Cytotoxic T cells can respond to foreign antigens only in
association with class 1 MHC glycoproteins.
• Class II MHC glycoproteins, recognized by helper T cells, are
confined to the surface of a few special types of immune cells.
• T cells do bind with MHC antigens present on the surface of
transplanted cells, accounting for their rejection.
By immune surveillance the T cell
system recognizes and destroys
newly arisen, potentially cancerous
tumor cells.
• A tumor consists of a clone of cells identical to the
original mutated cell. A benign tumor does not
infiltrate surrounding tissues.
• Malignant tumors are invasive and cancerous. Their
cells tend to metastasize. If these cells spread
throughout the body, they cannot be removed
surgically.
• Untreated cancer is eventually fatal.
• Most genetic mutations do not lead to cancer.
Immune surveillance depends on the
interplay of cytotoxic T cells, NK
cells, and macrophages plus
interferon. They attack and destroy
cancer cells.
• NK cells are the first line of defense against cancer.
• Cytotoxic T cells probably defend against virus-induced cancers.
• Macrophages clear away the remains of dead cells and engulf
and destroy cancer cells intracellularly.
• Some cancer cells can avoid these immune mechanisms. Some
cancer cells have counter-productive blocking antibodies that
interfere with T cell function.
• The immune system is regulated by the endocrine and nervous
systems by negative feedback loops.
• For example, cortisol mobilizes the body’s store of metabolic
fuel. Lymphocytes and macrophages are responsive to bloodborne signals.
Abnormal functioning of the
immune system can lead to
immune diseases.
• Immune deficiency diseases result from insufficient immune
responses. The immune system does not respond adequately
to foreign invasion.
• For example, in severe combined immunodeficiency both B and
T cells are lacking.
• In HIV a virus invades and incapacitates helper T cells.
• Inappropriate adaptive immune attacks cause reactions the
harm the body. They include autoimmune responses, in which
the immune system turns against the body. Another example is
immune complex diseases, which damage tissues by violent
reactions.
• The third example is allergies.
An allergy is the acquisition of an
inappropriate specific immune
reactivity (hypersensitivity) to a
normally harmless environmental
substance.
• Hypersensitivity can be immediate (within about 20 minutes
after exposure to an allergen) or delayed, occurring a day or so
after exposure. The difference is due to different mediators
involved.
• Triggers for hypersensitivity include pollen grains, bee stings,
penicillin, certain foods, molds, dust, feathers, and animal fur.
• Allergens bind to and elicit the synthesis of IgE antibodies.
Their tail portions are attached to mast cells and basophils.
These cells produce and store inflammatory chemicals such as
histamine.
• Chemical mediators include histamine, SRS-A, and eosinophil
chemotactic factor
Other facts on allergies
include:
• Symptoms of immediate hypersensitivity vary.
Usually the reaction is localized to the body site
where the IgE-bearing cells first contact the allergen.
Examples include hay fever, asthma, and the hives.
• Antihistamines block some of these reactions.
Adrenergic drugs and cortisol are often used.
• Anaphylactic shock occurs when large amounts of
chemical mediators enter the blood. Circulatory
failure and bronchiolar constriction occur.
• Immediate hypersensitivity is similar to the responses
elicited from parasitic worms.
• Delayed hypersensitivity is a T cell-mediated immune
response. Allergens from poison ivy can produce
The most obvious external
defense is the skin.
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The skin is a barrier for the passage of most
materials into the body.
It consists of an outer protective epidermis
and an inner connective tissue dermis.
The epidermis consists of numerous layers
of epidermal cells. It lacks a blood supply
and has an outer, protective keratinized
layer.
The dermis has an abundance of blood
vessels and specialized nerve endings. The
blood vessels are involved in temperature
regulation.
Exocrine glands of the skin include sweat
glands and sebaceous glands. Sweat
glands are involved in temperature regulation
for the body. The sebum from sebaceous
glands protects the body surface.
The hypodermis is a subcutaenous layer. It
is mainly adipose tissue.
Specialized cells in the
epidermis produce keratin and
melanin.
• They participate in immune defense.
• Melanocytes produce the pigment melanin. It
absorbs harmful UV rays.
• Keratinocytes secrete the protective protein, keratin.
• Langerhans cells are antigen-presenting cells.
• Granstein cells inhibit skin-activated immune
responses.
• The skin synthesizes vitamin D.
Protective measures in body
cavities include:
• Secretions in the oral cavity (saliva) and the
pH of the stomach are examples of protective
measures in the digestive system.
• The genitourinary system protects through
mucous secretions and its pH.
• The respiratory system has nasal hairs,
adenoids, the mucous escalator, and alveolar
macrophages for protection.