THE IMMUNE SYSTEM

Introduction
• All living things – animals, plants and even bacteria – can act as
hosts for infectious organisms and thus have evolved
mechanisms to defend themselves against infection. Infection
can be by other living things, non-living things (viruses) and
possibly even molecules.
• The immune system is a network of cells, tissues, and organs that
work together to protect the body from infection. In other words
it is a system of biological structures and processes within an
organism that protects against disease.
Introduction contd
• To function properly, an immune system must detect a wide
variety of agents, known as pathogens, from viruses to
parasitic worms, and distinguish them from the organism's own
healthy tissue. Through a series of steps called the immune
response, the immune system attacks organisms and
substances that invade body systems and cause disease.
Infectious Agents
• To understand how the immune system works in infection we
need to know who the aggressors are. Potentially infectious
agents include the following:
 Infectious Agents contd
• Viruses, which are non-living entities. Common examples are
influenza virus, human immunodeficiency virus (HIV) and
herpes simplex virus (HSV, which can cause cold sores or
genital ulcers).
• Bacteria, are single-celled prokaryotic organisms. Examples
include Staphylococcus and Streptococcus that cause acute
infections such as abscesses and sore throats, and
Mycobacteria that cause chronic infections such as
tuberculosis and leprosy.
• Fungi, which are unicellular, such as Candida that causes
thrush, or multicellular.
• Parasites, which are eukaryotic organisms. Some are single-
celled protozoa that cause diseases such as malaria, others are
large, multicellular organisms (metazoa) such as tapeworms.
 HOST DEFENCE
• All organisms possess mechanisms to defend themselves
against infection, and immunity is a specialized form of host
defence
• Immunity from disease is actually conferred by two
cooperative defence systems, called:
Nonspecific, innate immunity
Specific, acquired immunity.
• Nonspecific protective mechanisms repel all
microorganisms equally, while the specific immune
responses are tailored to particular types of invaders. Both
systems work together to thwart organisms from entering
and proliferating within the body. These immune
mechanisms also help eliminate abnormal cells of the body
that can develop into cancer.
NONSPECIFIC, INNATE IMMUNITY

• Most microorganisms encountered in daily life are

repelled before they cause detectable signs and
symptoms of disease. These potential pathogens, which
include viruses, bacteria, fungi, protozoans, and worms,
are quite diverse, and therefore a nonspecific defence
system that diverts all types of this varied microscopic
horde equally is quite useful to an organism.
• The innate immune system provides this kind of
nonspecific protection through a number of defence
mechanisms, which include the following:
1. Physical Barriers to Infection
• The skin and the mucous membrane linings of the
respiratory, gastrointestinal, and genitourinary tracts provide
the first line of defence against invasion by microbes or
parasites
• Skin
• Human skin has a tough outer layer of cells that produce
keratin. This layer of cells, which is constantly renewed from
below, serves as a mechanical barrier to infection. In
addition, glands in the skin secrete oily substances that
include fatty acids, such as oleic acid, that can kill some
bacteria; skin glands also secrete lysozyme, an enzyme (also
present in tears and saliva) that can break down the outer
wall of certain bacteria.
• Victims of severe burns often fall prey to infections from
normally harmless bacteria, illustrating the importance of
intact, healthy skin to a healthy immune system.
 Mucous Membranes
• Like the outer layer of the skin but much softer, the mucous
membrane linings of the respiratory, gastrointestinal, and
genitourinary tracts provide a mechanical barrier of cells that are
constantly being renewed. The lining of the respiratory tract has
cells that secrete mucus (phlegm), which traps small particles.
Other cells in the wall of the respiratory tract have small hair like
projections called cilia, which steadily beat in a sweeping
movement that propels the mucus and any trapped particles up
and out of the throat and nose.
• Also present in the mucus are protective antibodies, which are
products of specific immunity. Cells in the lining of the
gastrointestinal tract secrete mucus that, in addition to aiding the
passage of food, can trap potentially harmful particles or prevent
them from attaching to cells that make up the lining of the gut.
Protective antibodies are secreted by cells underlying the
gastrointestinal lining. Furthermore, the stomach lining secretes
hydrochloric acid that is strong enough to kill many microbes.
 Defence mechanisms continued
2. Chemical Barriers to Infection
• Some microbes penetrate the body’s protective barriers and enter
the internal tissues. There they encounter a variety of chemical
substances that may prevent their growth. These substances
include chemicals whose protective effects are incidental to their
primary function in the body, chemicals whose principal function
is to harm or destroy invaders, and chemicals produced by
naturally occurring bacteria.
• Chemicals with Incidental Protective Effects
• Some of the chemicals involved in normal body processes are not
directly involved in defending the body against disease.
Nevertheless, they do help repel invaders. For example, chemicals
that inhibit the potentially damaging digestive enzymes released
from body cells which have died in the natural course of events
also can inhibit similar enzymes produced by bacteria, thereby
limiting bacterial growth.
 Defence mechanisms continued
• Another substance that provides protection
against microbes incidentally to its primary cellular
role is the blood protein transferrin.
• The normal function of transferrin is to bind
molecules of iron that are absorbed into the
bloodstream through the gut and to deliver the
iron to cells, which require the mineral to grow.
• The protective benefit transferrin confers results
from the fact that bacteria, like cells, need free
iron to grow. When bound to transferrin, however,
iron is unavailable to the invading microbes, and
their growth is stemmed.
 Defence mechanisms continued
• Antimicrobial Proteins
a. Complement
One group of such proteins is termed complement because it
works with other defence mechanisms of the body,
complementing their efforts to eradicate invaders. Many
microorganisms can activate complement in ways that do not
involve specific immunity. Once activated, complement proteins
work together to lyse, or break apart, harmful infectious
organisms that do not have protective coats.
b. Interferons
• Another group of proteins that provide protection are the
interferons, which inhibit the replication of many—but not all—
viruses. Cells that have been infected with a virus produce
interferon, which sends a signal to other cells of the body to
resist viral growth.
 Continued ….
• All interferons inhibit viral replication by interfering with
the transcription of viral nucleic acid.
• Interferons exert additional inhibitory effects by regulating
the extent to which lymphocytes and other cells express
certain important molecules on their surface membranes
and by stimulating the activity of natural killer cells, which
are described below.
• Proteins From Naturally Occurring Bacteria
• In the small and large intestines the growth of invading
bacteria can be inhibited by naturally gut-dwelling
bacteria that do not cause disease.
• These gut-dwelling microorganisms secrete a variety of
proteins that enhance their own survival by inhibiting the
growth of the invading bacterial species.
Defence mechanisms
continued
3. Cellular Defences
• If an infectious agent is not successfully repelled by the chemical
and physical barriers described above, it will encounter cells whose
function is to eliminate foreign substances that enter the body.
These cells are the nonspecific effector cells of the innate immune
response. They include scavenger cells i.e., various cells that attack
infectious agents directly and natural killer cells, which attack cells
of the body that harbour infectious organisms.
• Some of these cells destroy infectious agents by engulfing and
destroying them through the process of phagocytosis, while other
cells resort to alternative means. As is true of other components of
innate immunity, these cells interact with components of acquired
immunity to fight infection.
Cellular Defences continued
• Scavenger Cells
• All higher animals and many lower ones have scavenger cells—primarily
leukocytes (white blood cells)—that destroy infectious agents. Most
vertebrates, including all birds and mammals, possess two main kinds of
scavenger cells.
a. Granulocytes
• Granulocytes are mobile and are attracted to foreign materials by chemical
signals, some of which are produced by the invading microorganisms
themselves, others by damaged tissues, and still others by the interaction
between microbes and proteins in the blood plasma.
• Some microorganisms produce toxins that poison granulocytes and thus
escape phagocytosis; other microbes are indigestible and are not killed
when ingested. By themselves, then, granulocytes are of limited
effectiveness and require reinforcement by the mechanisms of specific
immunity.
b. Macrophages
• The other main type of scavenger cell is the macrophage, the mature form of the
monocyte. Like granulocytes, monocytes are produced by stem cells in the bone
marrow and circulate through the blood, though in lesser numbers. But, unlike
granulocytes, monocytes undergo differentiation, becoming macrophages that
settle in many tissues, especially the lymphoid tissues (e.g., spleen and lymph
nodes) and the liver, which serve as filters for trapping microbes and other
foreign particles that arrive through the blood or the lymph. Macrophages live
longer than granulocytes and, although effective as scavengers, basically provide
a different function.
• Compared with granulocytes, macrophages move relatively sluggishly. They are
attracted by different stimuli and usually arrive at sites of invasion later than
granulocytes. Macrophages recognize and ingest foreign particles by
mechanisms that are basically similar to those of granulocytes, although the
digestive process is slower and not as complete. This aspect is of great
importance for the role that macrophages play in stimulating specific immune
responses—something in which granulocytes play no part
Cellular Defences continued
• Mast cells
• The mast cell is a twin of the basophil, except that it is not a blood cell.
Rather, it is found in the lungs, skin, tongue, and linings of the nose and
intestinal tract, where it is responsible for the symptoms of allergy.
• Natural Killer (NK) Cells
• Natural killer cells do not attack invading organisms directly but instead
destroy the body’s own cells that have either become cancerous or
been infected with a virus. Although similar in outward appearance to
lymphocytes, NK cells contain granules that harbour cytotoxic
chemicals. NK cells recognize dividing cells by a mechanism that does
not depend on specific immunity. They then bind to these dividing cells
and insert their granules through the outer membrane and into the
cytoplasm. This causes the dividing cells to leak and die.
 Nonspecific Responses
•to Infection
The body has a number of nonspecific methods of fighting infection
that are called early induced responses. They include the acute-
phase response and the inflammation response, which can
eliminate infection or hold it in check until specific, acquired
immune responses have time to develop. Nonspecific immune
responses occur more rapidly than acquired immune responses do,
but they do not provide lasting immunity to specific pathogens.
• Non-adaptive immune responses rely on a number of chemical
signals, collectively called cytokines, to carry out their effects. These
cytokines include members of the family of proteins called
interleukins, which induce fever and the acute-phase response, and
tumour necrosis factor-alpha, which initiates the inflammatory
response.
Acute-Phase Response
• When the body is invaded by a pathogen, macrophages release
the protein signals interleukin-1 (IL-1) and interleukin-6 (IL-6) to
help fight the infection. One of their effects is to raise the
temperature of the body, causing the fever that often accompanies
infection.
• Fever is believed to be helpful in eliminating infections because
most bacteria grow optimally at temperatures lower than normal
body temperature.
• In addition to raising body temperature, the interleukins stimulate
liver cells to secrete increased amounts of several different
proteins into the bloodstream. These proteins, collectively called
acute-phase proteins, bind to bacteria and, by doing so, activate
complement proteins that destroy the pathogen.
Continued…..
• The acute-phase proteins act similarly to antibodies but are more
‘democratic’ that is, they do not distinguish between pathogens as
antibodies do but instead attack a wide range of microorganisms equally.
Another effect the interleukins have is to increase the number of
circulating neutrophils and eosinophils, which help fight infection.
• Inflammatory Response
• Infection often results in tissue damage, which may trigger an
inflammatory response. The signs of inflammation include pain, swelling,
redness, and fever, which are induced by chemicals released by
macrophages.
• These substances promote blood flow to the area, increase the
permeability of capillaries, and induce coagulation. The increased blood
flow is responsible for redness, and the leakiness of the capillaries allows
cells and fluids to enter tissues, causing pain and swelling.
Continued…..
• These effects bring more phagocytic cells to the area to help
eliminate the pathogens. The first cells to arrive, usually within
an hour, are neutrophils and eosinophils, followed a few hours
later by macrophages.
• Macrophages not only engulf pathogens but also help the
healing process by disposing of cellular debris which
accumulates from destroyed tissue cells and neutrophils that
self-destruct after ingesting microorganisms.
• If infection persists, components of specific immunity
antibodies and T cells arrive at the site to fight the infection.
SPECIFIC, ACQUIRED IMMUNITY
• It has been known for centuries that persons who contract certain
diseases and survive generally do not catch those illnesses again. For
example smallpox, chicken pox, measles, and mumps, etc.
• There are other infectious conditions, such as the common cold,
influenza, pneumonia, and diarrheal diseases, that can be caught again
and again; these seem to contradict the notion of specific immunity.
• But the reason such illnesses can recur is that many different infectious
agents produce similar symptoms (and thus the same disease). For
example, more than 100 viruses can cause the cluster of symptoms
known as the common cold. Consequently, even though infection with a
particular agent does protect against reinfection by that same
pathogen, it does not confer protection from other pathogens that have
not been encountered.
Acquired immunity contd….
• Acquired immunity is dependent on the specialized
white blood cells known as lymphocytes.

• Location in The Lymphatic System

lymphoid organs
Nature of lymphocytes
• Lymphocytes are the cells responsible for the body’s ability to
distinguish and react to an almost infinite number of different
foreign substances, including those of which microbes are
composed.
• Lymphocytes are mainly a dormant population, awaiting the
appropriate signals to be stirred to action. The inactive
lymphocytes are small, round cells filled largely by a nucleus.
• Although they have only a small amount of cytoplasm
compared with other cells, each lymphocyte has sufficient
cytoplasmic organelles (small functional units such as
mitochondria, the endoplasmic reticulum, and a Golgi
apparatus) to keep the cell alive.
T and B Cells

• Lymphocytes originate from stem cells in the bone marrow;

these stem cells divide continuously, releasing immature
lymphocytes into the bloodstream
• Some of these cells travel to the thymus, where they
multiply and differentiate into T lymphocytes, or T cells. The T
stands for thymus-derived, referring to the fact that these
cells mature in the thymus.
• Once they have left the thymus, T cells enter the bloodstream
and circulate to and within the rest of the lymphoid organs,
where they can multiply further in response to appropriate
stimulation. About half of all lymphocytes are T cells.
Continued…
• Some lymphocytes remain in the bone marrow, where they
differentiate and then pass directly to the lymphoid organs.
They are termed B lymphocytes, or B cells, and they, like T
cells, can mature and multiply further in the lymphoid
organs when suitably stimulated.
• Although it is appropriate to refer to them as B cells in
humans and other mammals, because they are bone-
marrow derived, the B actually stands for the bursa of
Fabricius, a lymphoid organ found only in birds, the
organisms in which B cells were first discovered.
B cells
• B cells work chiefly by secreting substances called
antibodies into the body’s fluids. Antibodies ambush
antigens circulating the bloodstream.
• The job of attacking target cells either cells that have
been infected by viruses or cells that have been
distorted by cancer is left to T cells or other immune
cells.
• Since antibodies circulate through the humours (i.e.,
body fluids), the protection afforded by B cells is called
humoral immunity. They are powerless, however, to
penetrate cells.
B cells mature into plasma cells that
produce antibodies.
B cell continued..
• Each B cell is programmed to make one specific antibody. For example,
one B cell will make an antibody that blocks a virus that causes the
common cold, while another produces an antibody that attacks a
bacterium that causes pneumonia.
• When a B cell encounters its triggering antigen, it gives rise to many
large cells known as plasma cells. Every plasma cell is essentially a
factory for producing an antibody.
• Each of the plasma cells descended from a given B cell manufactures
millions of identical antibody molecules and pours them into the
bloodstream.
• An antigen matches an antibody much as key matches a lock. Some
match exactly; others fit more like a skeleton key. But whenever antigen
and antibody interlock, the antibody marks the antigen for destruction.
 Antibody-Mediated Immune Mechanisms
a) Protective Attachment To Antigens
• Many pathogenic microorganisms and toxins can be rendered harmless by the
simple attachment of antibodies.
• For example, some harmful bacteria, such as those that cause diphtheria and
tetanus, release toxins that poison essential body cells.
• These pathogens bear special molecules that they use to attach themselves to
the host cells so that they can penetrate and invade them. Antibodies can bind
to these molecules to prevent invasion.
• Also susceptible to simple antibody attachment are the many infectious
microbes—including all viruses and some bacteria and protozoans—that live
within the body cells. Antibody attachment also can immobilize bacteria and
protozoans that swim by means of whip-like flagella. In these instances
antibodies protect simply by combining with the repeating protein units that
make up these structures, although they do not kill or dispose of the microbes.
Antibody-Mediated Immune Mechanisms contd

b) Activation Of The Complement System

• The complement system is made up of about 25 proteins
that work together to “complement” the action of
antibodies in destroying bacteria. Complement also helps to
rid the body of antibody-coated antigens (antigen-antibody
complexes).
• Complement proteins, which cause blood vessels to
become dilated and then leaky, contribute to the redness,
warmth, swelling, pain, and loss of function that
characterize an inflammatory response.
T Cells
• Unlike B cells, T cells do not recognize free-floating antigens. Rather,
their surfaces contain specialized antibody-like receptors that see
fragments of antigens on the surfaces of infected or cancerous cells.
• T cells contribute to immune defences in two major ways: some direct
and regulate immune responses; others directly attack infected or
cancerous cells.
• Because this second type of acquired immunity depends on the direct
involvement of cells rather than antibodies, it is called cell-mediated
immunity
• Helper T cells, or Th cells, coordinate immune responses by
communicating with other cells. Some stimulate nearby B cells to
produce antibody, others call in microbe-gobbling cells called
phagocytes, still others activate other T cells.
• Killer T cells—also called cytotoxic T lymphocytes or CTLs—
perform a different function. These cells directly attack other
cells carrying certain foreign or abnormal molecules on their
surfaces. CTLs are especially useful for attacking viruses
because viruses often hide from other parts of the immune
system while they grow inside infected cells.
Fig a) Some T cells are helper cells, others are
killer cells. b) Killer cell makes contact with target
cell, trains its weapons on the target, then strikes.
Continued….
• In most cases, T cells only recognize an antigen if it is carried on the
surface of a cell by one of the body’s own major histocompatibility
complex (MHC) molecules. MHC molecules are proteins recognized by T
cells when distinguishing between self and non-self. A self MHC molecule
provides a recognizable platform to present a foreign antigen to the T
cell.
• Although MHC molecules are required for T-cell responses against foreign
invaders, they also pose a difficulty during organ transplantations.
Virtually every cell in the body is covered with MHC proteins, but each
person has a different set of these proteins on his or her cells.
• If a T cell recognizes a non-self MHC molecule on another cell, it will
destroy the cell. Therefore, doctors must match organ recipients with
donors who have the closest MHC makeup. Otherwise the recipient’s T
cells will likely attack the transplanted organ, leading to graft rejection.
PROPHYLACTIC IMMUNIZATION
• Prophylactic immunization refers to the artificial establishment of
specific immunity, a technique that has significantly reduced
suffering and death from a variety of infectious diseases.
• There are two types of prophylactic immunization: passive
immunization, in which protection is conferred by introducing
preformed antibodies or lymphocytes from another individual
whose immune system was stimulated by the appropriate antigen,
and
• active immunization, in which protection results from the
administration of a vaccine, with dead or harmless living forms of an
organism or with an inactivated toxin, that stimulates the immune
system to produce lymphocytes and antibodies against that
organism or toxin.
Passive Immunization
• It is sometimes the case that an infectious organism or a poisonous
substance can have such a rapid deleterious effect that the victim
does not have time to develop an immune response spontaneously.
• At such times passive immunization with preformed antibodies can
provide life-saving assistance in combating the pathogen or poison
• This situation may arise in victims of poisonous snakebites or
botulism, as well as in those in whom such infections as diphtheria,
tetanus, or gas gangrene have progressed to the point at which
bacterial toxins have been absorbed into the bloodstream. It is also
the case with bites from a rabid animal, although active
immunization is begun at the same time, since the spread of the
rabies infection to the central nervous system is relatively slow.
Passive Immunization continued

• Physicians use passive immunization as temporary

protection for persons traveling to countries where
hepatitis B is prevalent.
• Passive immunization provides antibodies to persons
who suffer from B-cell deficiencies and are therefore
unable to make antibodies for themselves (see
immune system disorder: Immune deficiencies).
• Also, passive immunizations of anti-Rh antibody can
prevent erythroblastosis fetalis.
Active Immunization

• Medical workers have long helped the body’s immune system

prepare for future attacks through vaccination. Vaccines consist of
killed or modified microbes, components of microbes, or
microbial DNA that trick the body into thinking an infection has
occurred.
• An immunized person’s immune system attacks the harmless
vaccine and prepares for subsequent invasions.
• Vaccines remain one of the best ways to prevent infectious
diseases and have an excellent safety record. Previously
devastating diseases such as smallpox, polio, and whooping cough
have been greatly controlled or eliminated through worldwide
vaccination programs.
DISORDERS OF THE IMMUNE SYSTEM
•Allergic Diseases
• The most common types of allergic diseases occur
when the immune system responds to a false alarm.
In an allergic person, a normally harmless material
such as grass pollen or house dust is mistaken for a
threat and attacked.
• Allergies such as pollen allergy are related to the
antibody known as IgE. Like other antibodies, each
IgE antibody is specific; one acts against oak pollen,
another against ragweed.
•Autoimmune Diseases
• Sometimes the immune system’s recognition apparatus breaks down,
and the body begins to manufacture T cells and antibodies directed
against its own cells and organs.
• Misguided T cells and autoantibodies, as they are known, contribute to
many diseases. For instance, T cells that attack pancreas cells contribute
to diabetes, while an auto anti body known as rheumatoid factor is
common in people with rheumatoid arthritis.
• No one knows exactly what causes an autoimmune disease, but
multiple factors are likely to be involved. These include elements in the
environment, such as viruses, certain drugs, and sunlight, all of which
may damage or alter normal body cells.
• Hormones are suspected of playing a role, since most autoimmune
diseases are far more common in women than in men. Heredity, too,
seems to be important. Many people with autoimmune diseases have
characteristic types of self marker molecules.
• Immune Complex Diseases
• Immune complexes are clusters of interlocking antigens and antibodies.
Normally, immune complexes are rapidly removed from the
bloodstream. Sometimes, however, they continue to circulate, and
eventually become trapped in the tissues of the kidneys, the lungs, skin,
joints, or blood vessels. There they set off reactions with complement
that lead to inflammation and tissue damage.
• Immune complexes work their mischief in many diseases. These include
malaria and viral hepatitis, as well as many autoimmune diseases
• Immunodeficiency Disorders
• When the immune system is missing one or more of its components, the
result is an immunodeficiency disorder.
• Immunodeficiency disorders can be inherited, acquired through
infection, or produced unintentionally by drugs such as those used to
treat people with cancer or those who have received transplants.
• Immunodeficiency Disorders continued..
• Temporary immune deficiencies can develop in the wake of common virus
infections, including influenza, infectious mononucleosis, and measles.
Immune responses can also be depressed by blood transfusions, surgery,
malnutrition, smoking, and stress.
• Some children are born with poorly functioning immune systems. Some
have flaws in the B cell system and cannot produce antibodies. Others,
whose thymus is either missing or small and abnormal, lack T cells. Very
rarely, infants are born lacking all of the major immune defenses. This
condition is known as severe combined immunodeficiency disease or SCID.
• AIDS is an immunodeficiency disorder caused by a virus (HIV) that infects
immune cells. HIV can destroy or disable vital T cells, paving the way for a
variety of immunologic shortcomings. HIV also can hide out for long
periods in immune cells. As the immune defenses falter, a person with
AIDS falls prey to unusual, often life-threatening infections and rare
cancers.
• Cancers of the Immune System
• The cells of the immune system, like other cells, can
grow uncontrollably, resulting in cancer. Leukemias
are caused by the proliferation of white blood cells,
or leukocytes. The uncontrolled growth of
antibody-producing plasma cells can lead to
multiple myeloma. Cancers of the lymphoid organs,
known as lymphomas, include Hodgkin’s disease.