Module 5
Immune and Respiratory Systems
a. Overview of Body Defenses
We can’t really avoid the viruses, bacteria, fungi, protozoa, and parasitic worms
that cause disease. These pathogens are in the air we breathe, the food we eat, and on
everything we touch. This means that our survival depends on having effective defenses
against them. Biologists sometimes portray the body’s anti-infection mechanisms as three
“lines of defense.” This approach can make it easier to remember what each “line” does,
but it is important to remember that all the defenses we will discuss in this function as
parts of a whole.
The first defensive line is the body’s array of physical and chemical barriers to
infection, such as intact skin and the linings of body cavities and tubes. These barriers,
which we discuss further, are not part of the immune system. Instead, the immune system
is a “cellular system” because white blood cells perform most of its core functions. As
you’ll soon see, the immune system’s two interacting arms respond differently to threats.
One is a bit like a community’s “first responder” squad that rushes to the scene of a
mishap. In addition to providing immediate “first aid,” this rapid response mobilizes
reinforcements—appropriate “specialists” that can deal with particular types of threats.
You may remember from that an antigen is something that the body identifies as
nonself and that triggers an immune response. Virus particles, foreign cells, toxins, and
cancer cells all have antigens on their surface. Most antigens are proteins, lipids, or the
large sugar molecules called oligosaccharides. Immunity is the body’s overall ability to
resist and combat something that is nonself.
There are two categories of immune responses. Each of us is born with some
preset responses to infection that are carried out by certain white blood cells and proteins
in blood. These activities are the body’s second line of defense. They are triggered by
chemical cues (such as certain proteins) that are present on or in a variety of pathogens.
The responses begin within minutes and they provide innate immunity.
Innate immune responses are general, rather like a disinfectant that can kill many
different species of bacteria in a bathroom. Even so, innate responses can wipe out many
invaders before an infection sets in. When an innate immune response starts, it also
unleashes the third line of defense, or adaptive immunity. Our adaptive immunity
changes as we go through life. Its responses are tailored to target the particular attackers
that chance to enter the body—a given species of bacteria, a particular virus, a toxin, or
an abnormal cell such as a cancer cell.
In adaptive immunity, huge numbers of white blood cells mount a counterattack
against the invasion. The cells in this “army” all have receptors for a particular antigen
and destroy anything that bears it. Biologists estimate that adaptive immunity can
produce white blood cell armies with receptors for billions of different antigens. This
means that adaptive responses can be mounted against a vast array of potential pathogens.
Adaptive immune responses take a week or so to develop, but they leave behind cells that
“remember” an antigen and protect against it for a long time, perhaps even for life.
As you’ve just read, white blood cells operate in both the innate and adaptive
immune responses. Many circulate in blood, while some enter tissues. All release
substances that help muster or strengthen defense responses. These chemicals include
several types of cytokines, “cell movers” that promote and regulate many aspects of
immunity. Some white blood cells also secrete enzymes and toxins that kill microbes.
Introduced the main white blood cells that circulate in blood. Of the trillions of
these cells in the body, about two-thirds are neutrophils, which are phagocytes.
Eosinophils target parasites, such as worms, that are too big for phagocytosis. They also
play a part in allergies. Basophils release substances from their granules that cause
inflammation.
Three other types of white blood cells perform their functions while in tissues.
Like basophils, mast cells have granules containing chemicals that cause inflammation.
Macrophages are large phagocytes that arise from circulating monocytes. Each one can
engulf as many as one hundred bacteria! Dendritic cells alert the adaptive immune system
when they detect antigens.
Central roles in adaptive immunity are filled by the cells known as lymphocytes.
Most of their activities occur in tissues and organs of the lymphatic system. Those called
B cells and T cells are the white blood cells that can recognize specific antigens. As
you’ll read later in this, cells derived from B cells make the defensive proteins called
antibodies. Some T cells kill abnormal body cells while others help activate B cells.
Many white blood cells circulate in lymph, watery fluid carried in vessels of the
lymphatic system. As the next section describes, this system, which has major roles in
defense, also works with the cardiovascular system in moving substances throughout the
body.
Other things being equal, studies show that in females immune responses to
invading pathogens are stronger than in males. This “turbocharged” immunity has a down
side, however. Females are statistically more likely to develop common autoimmune
disorders, such as multiple sclerosis, lupus, and Hashimoto’s disease (which affects the
thyroid gland). As you will read, in those and other autoimmune disorders, an
overvigilant immune system attacks normal cells or proteins.
Prolonged fatigue, emotional upsets, and other forms of ongoing stress can result
in less effective immune responses. This is because hormones that are produced in
response to stress suppress the chemical triggers that help launch immune responses. The
folk wisdom that you risk getting sick when your “resistance is down” comes from
everyday observations of such biological effects of stress.
b. The Lymphatic System
As you’ve just read, the lymphatic system does several things in the body. It
works with the cardiovascular system by picking up fluid that is lost from capillaries and
returning it to the bloodstream. The lymphatic system’s other key task is defense. As
sketched, the system consists of drainage vessels, lymphoid organs such as the spleen and
lymph nodes, and lymphoid tissues. The tissue fluid that has moved into lymph vessels is
aptly called lymph.
The lymph vascular system consists of lymph capillaries and other vessels that
collect water and dissolved substances from tissue fluid and transport them to ducts of the
cardiovascular system. The lymph vascular system has three functions, which we could
call the “three Ds”— drainage, delivery, and disposal.
To begin with, the system’s vessels are drainage channels. They collect water and
solutes that have leaked out of the blood in capillary beds (due to fluid pressure there)
and return those substances to the bloodstream. The system also picks up fats the body
has absorbed from the small intestine and delivers them to the bloodstream. Finally,
lymphatic vessels transport foreign material and cellular debris from body tissues to the
lymph vascular system’s disposal centers, the lymph nodes.
The lymph vascular system starts at capillary beds where fluid enters the lymph
capillaries. These capillaries don’t have an obvious entrance. Instead, water and solutes
move into their tips at flap like “valves.” These are areas where endothelial cells overlap.
Lymph capillaries merge into larger lymph vessels. Like veins, these vessels have
smooth muscle in their walls and valves that prevent backflow. They converge into
collecting ducts that drain into veins in the lower neck. This is how the lymph fluid is
returned to circulating blood. Movements of skeletal muscles and of the rib cage (during
breathing) help move fluid through the lymph vessels, just as they do for veins.
Several elements of the lymphatic system operate in body defenses. These parts
include the lymph nodes, the spleen, and the thymus. They also include the tonsils and
patches of tissue in the small intestine, in the appendix, and in airways leading to the
lungs.
The lymph nodes are located at intervals along lymph vessels. Before lymph
enters the bloodstream, it trickles through at least one of these nodes. A lymph node has
several chambers where white blood cells accumulate after they have been produced in
bone marrow. During an infection, lymph nodes become battlegrounds where armies of
lymphocytes form and where foreign agents are destroyed. Macrophages in the nodes
help clear the lymph of bacteria and other unwanted substances.
The spleen is the lymphatic system’s largest organ. It filters blood and also serves
as a holding station for lymphocytes. The spleen has inner chambers filled with soft red
and white tissue called “pulp.” The red pulp is a storage reservoir of red blood cells and
macrophages. (In a developing embryo, the spleen produces red blood cells.) In the white
pulp, masses of lymphocytes are arrayed close to blood vessels. If an invader reaches the
spleen during an infection, the lymphocytes are mobilized to destroy it, just as they are in
lymph nodes.
The thymus is where T cells multiply and become specialized to combat specific
foreign antigens. You will soon be learning more about how these cells function. With
this background on the parts of the lymphatic system, we are ready to look in more detail
at bodily defenses, beginning with those of body surfaces.
c. Barriers to Infection
Normally “friendly” bacteria in the mucosal lining of the digestive tract also help
protect you. In females, lactate produced by Lactobacillus bacteria in the vaginal mucosa
helps maintain a low vaginal pH that most bacteria and fungi cannot tolerate. Any change
in the conditions in which these organisms grow can cause an infection. For example,
some antibiotics can trigger a vaginal yeast infection because they also kill Lactobacillus.
The fungus that causes athlete’s foot may begin to grow between your toes if the skin
there is often moist and warm.
The respiratory system boasts a complex array of defense mechanisms designed
to safeguard the delicate tissues of the lungs from harmful pathogens and airborne
particles. Among these defenses, the mucus layer lining the inner walls of the respiratory
airways plays a pivotal role in trapping and neutralizing potentially harmful invaders.
The mucus layer, produced by specialized cells called goblet cells and
submucosal glands, serves as a physical barrier that traps inhaled particles, including
dust, allergens, and microorganisms, before they can reach the deeper regions of the
lungs. This sticky mucus is composed of water, mucins, glycoproteins, and other
substances that confer its adhesive properties and viscoelastic nature.
Integral to the antimicrobial properties of respiratory mucus are the presence of
protective substances such as lysozyme, an enzyme that exhibits bactericidal activity by
breaking down bacterial cell walls. Lysozyme acts as a first line of defense against
bacterial pathogens, helping to degrade their cell membranes and inhibit their growth and
proliferation within the respiratory tract.
In addition to lysozyme, respiratory mucus contains an array of other
antimicrobial proteins and peptides, including lactoferrin, defensins, and surfactant
proteins, which contribute to the innate immune response against invading
microorganisms. These antimicrobial factors work synergistically to neutralize pathogens
and prevent their colonization and dissemination within the respiratory system.
Complementing the action of mucus and antimicrobial proteins are the
coordinated movements of cilia lining the respiratory epithelium. These microscopic hair-
like structures, known as respiratory cilia, beat in a coordinated fashion to propel mucus
and trapped particles upward and out of the airways in a process called mucociliary
clearance. This "broomlike" sweeping action helps to expel pathogens, debris, and mucus
from the respiratory tract, effectively clearing the airways and maintaining airway
patency.
Impairment of mucociliary clearance or disruption of mucus production and
composition can compromise the respiratory defense mechanisms, increasing the risk of
respiratory infections and respiratory tract diseases such as chronic bronchitis, cystic
fibrosis, and primary ciliary dyskinesia. Environmental factors such as cigarette smoke,
air pollution, and occupational exposures can also impair mucociliary function and
predispose individuals to respiratory infections and inflammatory lung diseases.
Enhancing respiratory mucosal immunity and promoting optimal mucociliary
clearance are important strategies for maintaining respiratory health and preventing
respiratory infections. Strategies to support respiratory health may include maintaining
proper hydration, avoiding exposure to respiratory irritants, practicing good hygiene, and
adopting lifestyle behaviors that support immune function and respiratory wellness.
In summary, the mucus layer and mucociliary clearance system represent integral
components of the innate immune defense mechanisms in the respiratory tract. By
trapping and neutralizing pathogens, clearing mucus, and expelling foreign particles,
these defense mechanisms help to protect the lungs from infection and maintain
respiratory health. Understanding the mechanisms of respiratory mucosal immunity
provides insights into strategies for promoting lung health and preventing respiratory
diseases.
Lysozyme and some other chemicals in tears, saliva, and gastric fluid offer more
protection. Urine’s low pH and flushing action help bar pathogens from the urinary tract.
In adults, mild diarrhea can rid the lower GI tract of pathogens. In children, diarrhea
serves the same function but must be controlled to prevent dangerous dehydration.
d. Innate Immunity
White blood cells and proteins carry out innate immune responses. An extremely
important part of these responses is a set of proteins called the complement system, or
simply complement. These proteins circulate in the blood and tissues. Contact with
antigens or substances leaking from damaged body cells activates them. Then a cascade
of reactions activate ever more complement proteins, until the molecules flood a
damaged area.
Complement proteins coat pathogens. Some also form membrane attack
complexes that create a pore—a hole—in the cell wall or plasma membrane of invading
bacteria. The punctured cell then disintegrates. A complement coating also attracts
phagocytes like macrophages, dendritic cells, and neutrophils to invaded tissues.
Macrophages are usually the first defenders on the scene. They engulf virtually anything
other than healthy body cells. If a macrophage detects an antigen, it releases cytokines
that alert the adaptive immune system that a threat is present
Neutrophils literally blow apart when they come in contact with a particular
combination of complement proteins and other signaling molecules. The “remains” of
each neutrophil, including its granules, form a net that traps nearby invaders.
Activated complement and cytokines from macrophages both trigger the
phenomenon we call inflammation. This is a fast, general response to tissue damage or
infection. In inflammation, mast cells and basophils respond to an antigen or to the
cascade of complement proteins by releasing histamine and other substances. Histamine
is a chemical messenger that makes arterioles in the tissue dilate, so more blood flows
through them.
As a result, the tissue reddens and warms with blood-borne metabolic heat.
Histamine also makes capillaries leak. The narrow gaps between the cells of the capillary
wall become a bit wider, so plasma proteins and phagocytes slip out through them. Water
flows out as well. Due to these and other changes, the tissue balloons with fluid. This
swelling is called edema. The pain that comes with inflammation is due to edema and the
effects of inflammatory chemicals.
The plasma proteins leaking into tissue fluid include blood clotting factors. Clots
can wall off inflamed areas and delay the spread of microbes into nearby tissues. A fever
is a core body temperature above the normal 37°C (98.6°F). Fever develops when
macrophages release cytokines called interleukins, which stimulate the brain to release
prostaglandins. These signaling molecules in turn can raise the set point on the
hypothalamic thermostat, which controls core temperature.
Fevers are not usually harmful. In fact, a fever of about 39°C (100°F) is actually
helpful. Among other benefits, it increases body temperature to a level that is too hot for
many pathogens to function normally. However, a fever that rises above 42°C (107.6°F)
is a medical emergency because it can result in organ damage or death.
e. Overview of Adaptive Defenses
Recognition of self versus nonself: Like the ABO self markers on red blood cells,
all body cells have self markers called MHC markers. (They are named after the genes
that code for them.) MHC markers are some of the proteins that stick out above a cell’s
plasma membrane. T cells have receptors that recognize MHC markers and other self tags
on body cells. These and other receptors also can recognize antigens as nonself.
Specificity: Each B or T cell makes receptors for only one kind of antigen. A
receptor and its antigen fit together, something like a lock and key. B cells make B cell
receptors, and T cells make T cell receptors. Diversity: B and T cells collectively may
have receptors for more than 2 billion different antigens. Memory: Some of the B and T
cells formed during a first response to an invader are held in reserve for future battles
with it.
As you know, lymphocytes arise from stem cells in red bone marrow. Forming B
cells continue developing in bone marrow, but cells that will specialize as T cells travel
via the blood to the thymus gland, where they complete their development. When B and
T cells are mature, most move into lymph nodes, the spleen, and other lymphatic system
tissues. Each cell is studded with its unique receptors and is capable of becoming active
in an adaptive immune response. As you will see, however, activation requires that the B
or T cell meet and recognize the one antigen for which it has receptors.
When a B or T cell does interact with an antigen, the cell divides, the resulting
new cells divide again, and so on until a huge number of identical copies exist. Because
each copy is identical to the “parent” cell, it is called a clone and the copying process is
called clonal expansion. All the cells in the resulting lymphocyte army have exactly the
same receptors, so all recognize the same antigen, but not all will continue down the
same developmental path. Many differentiate into effector cells that can begin destroying
the enemy right away. Others become memory cells. Instead of joining the first battle,
memory cells are set aside. If the threat returns, they will be available to mount a larger,
faster response. Memory cells are what make you “immune” to a given cold or flu virus
once you have recovered from the first infection.
Effector B cells are called plasma cells. Plasma cells make proteins called
antibodies, so the B cell response is called antibody-mediated immune response.
Antibodies target antigens of pathogens and toxins that are outside cells, in blood or
tissue fluid.
Two types of effector T cells form. Cytotoxic T cells kill target cells. Hence the T
cell response is called cell-mediated immune response. Helper T cells release cytokines
that help boost adaptive immune responses. Some of these chemicals are “interleukins”
(meaning between leukocytes) that promote B-cell activity. Others are growth factors that
spur the activity of cytotoxic T cells. Still others serve as a call to arms for neutrophils
and other white blood cells that operate in innate responses.
Even if a T cell encounters an antigen that is a match for its receptors, the antigen
will be “invisible” until it is processed by an antigen-presenting cell. Although
macrophages and B cells may provide this service, the presenter often is a dendritic cell.
First the presenter engulfs a cell or material that includes an antigen. Then enzymes (from
the presenter cell’s lysosomes) cut the antigen into pieces. Some of the pieces then are
joined with MHC markers to form an antigen–MHC complex. This structure is part self
(the MHC marker) and part nonself (the antigen).
The presenter cell displays the complex at its surface. A T cell that has the
receptor for the antigen part of the complex can bind to it—and an adaptive immune
response can get under way. The next two sections explain the steps in the two types of
adaptive immune responses. We look first at how an antibody-mediated immune response
develops, and then at how a cell-mediated response occurs.
f. Antibodies: Defense against Threats outside Cells
Antibodies, also known as immunoglobulins, play a critical role in the adaptive
immune response by recognizing and targeting specific pathogens, toxins, and foreign
substances for elimination from the body. While antibodies themselves do not directly
kill pathogens or destroy toxins, they orchestrate a cascade of immune responses that
ultimately neutralize and eliminate these threats, thereby protecting the body from
infection and disease.
One of the primary functions of antibodies is to facilitate the recognition and
binding of antigens, which are molecular structures present on the surface of pathogens or
toxins. Each antibody molecule possesses a unique antigen-binding site, allowing it to
selectively recognize and bind to specific antigens with high affinity and specificity. This
antigen-antibody interaction serves as a molecular "tagging" mechanism that marks the
invaders for recognition and destruction by other components of the immune system.
Once bound to their target antigens, antibodies can elicit various effector
mechanisms to neutralize or eliminate the pathogens or toxins. One important mechanism
is opsonization, whereby antibodies coat the surface of pathogens, enhancing their
recognition and engulfment by phagocytic cells such as macrophages and neutrophils.
Phagocytosis of antibody-coated pathogens facilitates their internalization and
degradation within phagosomes, effectively removing them from the body.
In addition to opsonization, antibodies can activate the complement system, a
group of plasma proteins that cooperate with antibodies to eliminate pathogens through a
series of biochemical reactions. Antibody binding to antigens triggers the activation of
complement proteins, leading to the formation of membrane attack complexes (MACs)
that puncture the cell membranes of target pathogens, causing cell lysis and death.
Complement activation also promotes inflammation, chemotaxis of immune cells, and
clearance of immune complexes from circulation.
Furthermore, antibodies play a crucial role in antibody-dependent cellular
cytotoxicity (ADCC), a process in which immune cells such as natural killer (NK) cells
recognize and destroy antibody-coated target cells. NK cells express Fc receptors that
bind to the Fc portion of antibodies, allowing them to recognize and lyse cells bound by
antibodies, such as virus-infected cells or cancer cells.
Moreover, antibodies can neutralize toxins and prevent them from exerting
harmful effects on host cells by blocking their binding sites or inhibiting their enzymatic
activity. This neutralization of toxins prevents them from causing tissue damage and
systemic toxicity, thereby limiting the severity of infection or poisoning.
In summary, while antibodies themselves do not directly kill pathogens or destroy
toxins, they serve as indispensable mediators of the immune response by marking
invaders for recognition and elimination by other components of the immune system.
Through opsonization, complement activation, ADCC, and toxin neutralization,
antibodies play a multifaceted role in protecting the body from infection and maintaining
immune homeostasis. Understanding the diverse functions of antibodies is essential for
elucidating the mechanisms of immune defense and developing novel therapeutic
strategies for combating infectious diseases and other immune-related disorders.
When a B cell forms, the genetic mechanisms involved ensure that it has receptors
for only one antigen—such as a particular bacterial or viral protein. If a B cell is
activated, the antibodies that the resulting plasma cells make will target the same antigen.
The typical Y shape of simple antibodies that bind bacteria or viruses. The place where
an antibody can bind an antigen usually is near the tip of the two “arms.” As antibodies
form, they are embedded in a B cell’s plasma membrane so that the two arms stick out.
Antibody-mediated immune responses get under way in the lymphatic system,
especially in lymph nodes and the spleen. Dendritic cells, T cells, and B cells all
participate. Takes you through the basic steps of the response, starting with the point
when a dendritic cell responds to the invasion.
Remember from that dendritic cells serve as antigen “presenters.” A dendritic cell
that detects the invader engulfs it, processes the antigen it bears, and then displays it in an
antigen–MHC complex. When receptors of a responding helper T cell bind to the
complex, the two cells trade signals. The T cell begins to divide, giving rise to effector
and memory helper T cells that have the same antigen receptors. (When you have an
infection, the accumulation of these T cells is what makes your lymph nodes swell.)
Because of the great diversity of antigen receptors, there’s a good chance the
lymph node also contains an inactive B cell with receptors for the invader’s antigen. If so,
the B cell binds to the bacterial antigen and displays it (again, in an antigen–MHC
complex) at the B cell’s surface. This processing activates the B cell. It also allows helper
T cells in the node to recognize and bind to the antigen–MHC complex. Now the T cell
and active B cell can interact. The T cell begins to release cytokines that spur the B cell
to divide. Its descendants become plasma cells or memory B cells.
The plasma cells release huge numbers of antibodies into the bloodstream—up to
2,000 each minute. When any of these antibodies binds to an antigen, it marks the invader
for destruction by phagocytes and complement proteins. The memory B cells will be
available to respond quickly to the antigen if it attacks the body another time.
Plasma cells make five classes of antibodies. Collectively they are called
immunoglobulins, or Igs. We abbreviate them as IgM, IgD, IgG, IgA, and IgE. Each type
has antigen binding sites and other sites with special roles.
IgM and IgD serve as the B cell receptors. IgM also is the first antibody secreted
during immune responses and the first one produced by newborns. IgM molecules cluster
into a structure with ten antigen-binding sites. This makes it more efficient at binding
clumped targets, such as agglutinating red blood cells and clumps of virus particles.
IgG makes up about 80 percent of the antibodies in your blood. It’s the most
efficient one at turning on complement proteins, and it neutralizes many toxins. This
long-lasting antibody easily crosses the placenta. It helps protect the developing fetus
with the mother’s acquired immunities. IgG secreted into early milk is also absorbed into
a suckling newborn’s bloodstream.
IgA is the main immunoglobulin in substances secreted by exocrine glands, such
as tears, saliva, and breast milk. It also is in mucus that coats the respiratory, digestive,
and reproductive tracts—areas microbes can easily access. Bacteria and viruses can’t
attach to the cells of mucous membranes when IgA is bound to them. In this way, IgA is
effective in fighting the pathogens that cause salmonella, cholera, gonorrhea, and
influenza.
IgE is involved in allergic reactions, including asthma, hay fever, and hives. IgE
also triggers inflammation after attacks by parasitic worms and other pathogens. When it
binds to an antigen, basophils and mast cells release histamine that causes the
inflammation response.
g. Cell-Mediated Responses: Fighting Threats inside Cells
Many pathogens evade antibodies. They hide in body cells, kill them, and often
reproduce inside them. They are exposed only briefly after they slip out of one cell and
before they infect others. Viruses, bacteria, and some fungi and protozoans all can enter
cells. Cell-mediated immune responses are the body’s weapons against these dangers as
well as against abnormal body cells such as cancer cells.
A simplified version of a cell-mediated immune response to infection by a virus.
Initially, antigens from decaying virus particles in the cell are displayed at the infected
cell’s surface in an antigen–MHC complex. Next, the two cells are linked when a T cell
having receptors for the antigen binds the complex. Together with cytokines, this linking
activates the T cell. The cell now begins dividing, producing active cytotoxic T cells that
can kill virus-infected cells. The response also produces memory cytotoxic T cells.
Cytotoxic T cells release various “killer” substances. Perforins are proteins that
literally perforate the target cell, making holes in its plasma membrane. This “direct hit”
kills the target cell in much the same way that complement membrane attack complexes
do. Cytotoxic T cells also secrete chemicals that cause the target cell to self-destruct. This
genetically programmed cell death is called apoptosis (a-poh-toesis). The term comes
from a Greek word meaning “to fall apart,” and that’s what happens to the cell. As it
disintegrates, its cytoplasm dribbles out, and its DNA and organelles are broken up. After
a cytotoxic T cell has done its defensive work, it disengages from the doomed cell and
moves on.
Other kinds of cells make more general responses. These cells include
macrophages as well as lymphocytes called NK cells (natural killers). NK cells are
present in tissues and organs of the lymphatic system. They can detect and kill virus-
infected body cells and some cancer cells. Helper T cell cytokines stimulate NK cells, but
NK cells don’t need to have an antigen presented to them. Instead, they simply attack any
body cell that has too few or altered MHC markers, or that antibodies have tagged for
destruction. They also kill body cells flagged with chemical “stress markers” that develop
when a cell is infected or has become cancerous.
Cytotoxic T cells cause the rejection of tissue and organ transplants. This is partly
because features of the MHC markers on donor cells differ enough from the recipient’s to
be recognized as antigens. To help prevent rejection, before an organ is transplanted the
MHC markers of a potential donor are analyzed to determine how closely they match
those of the patient. Because such tissue grafts generally succeed only when the donor
and recipient share at least 75 percent of their MHC markers, the best donor is a close
relative of the recipient, such as a parent or sibling, who is likely to have a similar genetic
makeup.
After surgery, the organ recipient receives drugs that suppress the immune
system. The treatment also may include other therapies designed to fend off an attack by
B and T cells. As with Kelly Perkins, the heart transplant patient described in the
introduction, suppression of the immune system means that the patient must take large
doses of antibiotics to control infections. In spite of the difficulties, many organ
recipients survive for years beyond the surgery and lead highly active lives.
Interestingly, not all transplanted tissues provoke a recipient’s immune defenses.
Two examples are tissues of the eye and the testicles. In simple terms, the plasma
membrane of cells of these organs is thought to bear receptors that can detect activated
lymphocytes. Before such a defender can launch an attack, the protein signals the soon-
to-be-besieged cell to secrete a chemical that triggers apoptosis in the approaching
lymphocytes, so the attack is usually averted. Our ability to readily transplant the cornea
—the outer layer of the eye that is vital to clear vision—depends on this mechanism. The
Think Outside the Book feature on this page discusses a disorder for which a cornea
transplant is the only cure.
h. Immunology in Everyday Life
Vaccination (“immunization”) is a way to increase your immunity against a
specific disease. A vaccine is a prepared substance that contains an antigen. A vaccine is
injected into the body or taken orally, sometimes according to a schedule. The first
injection elicits a primary immune response that confers active immunity. A later booster
shot elicits a secondary response, in which more effector cells and memory cells form.
The booster can provide long-lasting protection.
Many vaccines are made from killed or extremely weakened pathogens. For
example, weakened poliovirus particles are used for the Sabin polio vaccine. Worldwide
vaccinations with a weakened relative of the smallpox virus allowed a successful global
effort to eradicate the disease. Other vaccines are made using inactivated forms of natural
toxins, such as the bacterial toxin that causes tetanus.
Today many vaccines are made with genetically engineered viruses. These
harmless “transgenic” viruses incorporate genes from three or more different viruses in
their genetic material. After a person is vaccinated with an engineered virus, body cells
use the new genes to produce antigens, and immunity is established. Examples are the
“flu shots” developed each year to protect against influenza viruses researchers identify
as the major threats during “flu season.”
People who are already infected with pathogens, such as those that cause tetanus,
measles, hepatitis B, and rabies, may be helped by injections of antibodies that confer
passive immunity. A patient receives antibodies that have been purified from another
source, preferably someone whose adaptive immune system already has produced a large
amount of the antibody. The result is “passive” immunity because the recipient’s own B
cells are not producing antibodies or memory B cells. While the helpful effect doesn’t
last long, the injected antibodies may counter the immediate attack.
Vaccines are powerful weapons, but they can fail or have adverse effects. In rare
cases, a vaccine can damage the nervous system or result in chronic immunological
problems. A physician can explain the risks and benefits. Commercially prepared
monoclonal antibodies harness antibodies for medical and research uses. The word
monoclonal (meaning “one clone”) refers to the fact that the antibodies are made by cells
cloned from just a single antibody-producing plasma cell.
At one time laboratory mice were the “factories” for making monoclonal
antibodies. Today most monoclonal antibodies are produced using genetically altered
bacteria. Genetically engineered plants such as corn also are being used to make
antibodies that may be both cost effective and safe (few plant pathogens can infect
people). The first “plantibody” to be used on human volunteers prevented infection by a
bacterium that causes tooth decay.
Monoclonal antibodies have become useful tools in diagnosing health conditions.
Because they can recognize and bind to specific antigens, they can detect substances in
the body—a bacterial cell, another antibody, or a chemical—even if only a tiny amount is
present. Uses include home pregnancy tests and screening for prostate cancer and some
sexually transmitted diseases. As you’ll read next, monoclonal antibodies also have
potential uses as “magic bullets” to deliver drugs used to treat certain forms of cancer.
Immunotherapy bolsters defenses against infections and cancer cells by
manipulating the body’s own immune mechanisms. Cytokines that activate B and T cells
are being used to treat some cancers. Monoclonal antibodies are another weapon. For
example, some aggressive breast cancers have telltale HER2 proteins at their surface. The
drug Herceptin is a monoclonal antibody that binds to the proteins and draws a response
from NK cells. The drug can be a double-edged sword, however, because some healthy
body cells also have HER2 proteins, and they are attacked as well.
Monoclonal antibodies also can be bound to poisons to make immunotoxins.
When these substances bind to an antigen on a cancer cell, they enter the cell and block
processes that allow it to survive and multiply. Several experimental immunotoxins have
been tested against HIV, the virus that causes AIDS, but to date none has proven reliably
effective.
Most body cells that become infected by a virus can make and secrete antiviral
cytokines called interferons. When an interferon reaches an uninfected cell, it triggers a
chemical attack that prevents the virus from multiplying. Genetically engineered gamma
interferon is used to treat hepatitis C, a chronic, potentially lethal viral disease that
impairs liver functioning. Some kinds of cells produce beta interferon. This protein has
been approved for the treatment of a type of multiple sclerosis, a disease in which the
immune system mounts an attack on parts of the nervous system.
i. Immune System Malfunctions
In some people, normally harmless substances can provoke immune responses.
These substances are allergens (al-ur-jenz) and the response to them is an allergy.
Common allergens are pollen, various foods and drugs, dust mites, insect venom, and
ingredients in cosmetics. Some responses start within minutes; others are delayed. Either
way, the allergens trigger mild to severe inflammation of mucous membranes and in
some cases other tissues as well.
Some people are genetically predisposed to allergies. Infections, stress, or
changes in air temperature also may cause the reactions. The first time an allergic person
is exposed to a triggering allergen, a primary response sensitizes B cells that produce IgE
antibodies to the trigger. The antibodies attach to mast cells—which, recall, contain
granules containing histamine. The next time the allergen enters the body, a secondary
response occurs. IgE antibodies on mast cells bind it and the mast cells secrete
prostaglandins, histamine, and other substances that fan inflammation. They also cause an
affected person’s airways to constrict, and sometimes trigger the itchy raised welts called
hives. In hay fever, the allergic response produces stuffed sinuses, a drippy nose, and
sneezing. But not all allergies are triggered by antibodies. Skin rashes and other contact
allergies involve a cellmediated response to an allergen.
In food allergies, the immune system registers a particular food as an “invader.”
The most common culprits are shellfish, eggs, and wheat. Depending on the person and
the food involved, symptoms typically include diarrhea, vomiting, and sometimes
swelling or tingling of mucous membranes.
Some allergies, such as to peanuts or bee and wasp stings, can trigger potentially
deadly anaphylactic shock—a whole-body allergic response. Within moments air
passages to the lungs close almost completely. Fluid gushes from dilated blood vessels
throughout the body. Blood pressure plummets, which can cause the cardiovascular
system to collapse. One emergency treatment is an injection of epinephrine. People who
know they are at risk can keep injectable epinephrine on hand.
As their name suggests, antihistamines are antiinflammatory drugs that counteract
the histamine released by basophils and mast cells. Many people use them to relieve
short-term allergy symptoms. In some cases a sufferer may undergo a desensitization
program in which inflammatory responses to one or more allergens are blocked by
treatment that stimulates the patient’s body to make IgG instead of IgE.
Normally, a B or T cell does not have receptors that can “see” a body cell’s MHC
self tags as antigens of an invader. This immunological tolerance is what protects the
body’s own cells from attack by the immune system. In fact, a newly forming B or T cell
that recognizes healthy body cells as foreign undergoes apoptosis and dies. This weeding
out of self-reactive B and T cells goes on throughout a person’s life. When it goes awry,
the result is autoimmunity, in which the immune system generates so-called
autoantibodies—antibodies against normal body cells or proteins. An example is
rheumatoid arthritis (RA). People with RA are genetically predisposed to the disease.
Their macrophages and T and B cells become activated by IgG antibodies associated with
the joints. Immune responses are mounted against their body’s collagen molecules and
also antibodies that have bound to an (as yet unknown) antigen. Inflammation, the
complement system, and malfunctioning repair mechanisms damage joint tissues further.
Eventually the affected joints become immobile.
Another autoimmune disease is type 1 diabetes. This is a type of diabetes mellitus
in which the pancreas does not secrete enough of the hormone insulin for proper
absorption of glucose from the blood. In type 1 diabetes, the immune system attacks and
destroys the insulin secreting cells. A viral infection may trigger the disorder.
A symptom of systemic lupus erythematosus (SLE) is a “butterfly” rash on the
cheeks that extends across the nose. The rash is one sign that the affected person has
developed antibodies to her or his own DNA and other “self” components. Antigen–
antibody complexes accumulate in joints, blood vessel walls, the skin, and the kidneys.
Other symptoms include fatigue, painful arthritis, and in some cases a breakdown of
kidney function. Medicines can help relieve many SLE symptoms, but there is no cure.
Immunodeficiency is a lack of properly functioning lymphocytes— and therefore
the inability to mount normal immune responses. Both T and B cells are in short supply
in the disorder known as severe combined immune deficiency (SCID). SCID usually is
inherited, and infants born with it may die early in life. Lacking adequate immune
responses, they are extremely vulnerable to infections that are not lifethreatening to other
people.
Human Immunodeficiency Virus (HIV) is a retrovirus that specifically targets and
infects certain types of white blood cells, particularly CD4+ T lymphocytes, which play a
central role in coordinating the immune response against pathogens. Upon entering the
bloodstream, HIV binds to CD4 receptors on the surface of CD4+ T cells and other
immune cells, facilitating viral entry and replication within the host cell.
The hallmark of HIV infection is progressive depletion of CD4+ T cells, leading
to profound immunodeficiency and impairment of the body's ability to mount effective
immune responses against infections and malignancies. As the virus replicates and
spreads throughout the body, it gradually undermines the integrity of the immune system,
compromising both innate and adaptive immune functions.
Acquired Immunodeficiency Syndrome (AIDS) represents the advanced stage of
HIV infection, characterized by severe immune suppression and susceptibility to
opportunistic infections, tumors, and other complications. The development of AIDS
typically occurs when the CD4+ T cell count falls below a critical threshold (usually
<200 cells/mm³) or when certain AIDS-defining illnesses or conditions manifest in HIV-
infected individuals.
The pathogenesis of HIV/AIDS is multifaceted and involves intricate interactions
between the virus, the immune system, and host factors. HIV employs various strategies
to evade host immune defenses and establish persistent infection, including rapid
mutation rates, viral latency, and evasion of immune surveillance mechanisms. The virus
also induces chronic immune activation and inflammation, contributing to immune
dysfunction and progressive CD4+ T cell depletion.
The clinical course of HIV/AIDS varies widely among individuals and is
influenced by factors such as viral virulence, host genetics, coexisting infections, and
access to healthcare. Early stages of HIV infection may be asymptomatic or present with
nonspecific symptoms such as fever, fatigue, and lymphadenopathy. As the disease
progresses, however, opportunistic infections, malignancies, and autoimmune disorders
may develop, heralding the onset of AIDS.
Opportunistic infections associated with AIDS encompass a diverse spectrum of
pathogens, including bacteria, viruses, fungi, and parasites, which take advantage of the
weakened immune defenses in HIV-infected individuals. Common opportunistic
infections include Pneumocystis jirovecii pneumonia (PCP), Mycobacterium avium
complex (MAC) infection, cytomegalovirus (CMV) retinitis, and cryptococcal
meningitis, among others.
In addition to opportunistic infections, individuals with AIDS are at increased risk
of developing AIDS-defining malignancies, such as Kaposi sarcoma, non-Hodgkin
lymphoma, and invasive cervical cancer, as well as non-AIDS-related complications,
including cardiovascular disease, neurocognitive impairment, and metabolic disorders.
Despite significant advancements in antiretroviral therapy (ART) and HIV/AIDS
management, the global burden of HIV/AIDS remains substantial, with millions of
people living with HIV worldwide. Prevention efforts, including widespread HIV testing,
access to ART, behavioral interventions, and pre-exposure prophylaxis (PrEP), play a
crucial role in reducing HIV transmission and improving outcomes for individuals living
with HIV/AIDS.
In summary, HIV infection leads to immune dysfunction and the development of
AIDS, a complex syndrome characterized by severe immunodeficiency and increased
susceptibility to opportunistic infections, malignancies, and other complications.
Understanding the pathogenesis, clinical manifestations, and management of HIV/AIDS
is essential for effective prevention, diagnosis, and treatment of this global public health
challenge.
j. The Respiratory System: Built for Gas Exchange
Your lungs and airways make up your respiratory system . During quiet breathing
(as while reading), air typically enters and leaves the system by way of the nose. Hairs at
the entrance to the nasal cavity and in its ciliated epithelial lining filter out large particles,
such as dust, from incoming air. The air also is warmed in the nose and picks up moisture
from mucus.
A septum (wall) of bone and cartilage separates the nasal cavity’s two chambers.
Channels link the cavity with paranasal sinuses above and behind it (which is why nasal
sprays can relieve mucus-clogged sinuses). Tear glands produce moisture that drains into
the nasal cavity. Crying increases the flow, which is why your nose runs when you cry.
From the nasal cavity, air moves into the pharynx. This is the entrance to both the
larynx (an airway) and the esophagus (which leads to the stomach). Nine pieces of
cartilage form the larynx. One of these, the thyroid cartilage, is the Adam’s apple.
The flaplike epiglottis, attached to the larynx, points up during breathing. When
you swallow, the larynx moves up so that the epiglottis partly covers the opening of the
larynx. This helps prevent food from entering the respiratory tract and causing choking.
From the larynx, air moves into the “windpipe” or trachea (tray-kee-uh). Press
gently at the lower front of your neck, and you can feel some of the bands of cartilage
that ring the tube, adding strength and helping to keep it open. The trachea branches into
two airways, one leading to each lung. Each airway is a bronchus (brong-cuss; plural:
brong-kee). The epithelial lining of bronchi includes mucus-secreting cells and cilia.
Just above the larynx, horizontal folds of an elastic mucous membrane form the
vocal cords. When you exhale, air rushes through the glottis, a gap between the cords that
opens to the larynx. Air moving through it makes the cords vibrate. By controlling the
vibrations we can make sounds. Using our lips, teeth, tongue, and the soft roof of the
mouth (the soft palate), we can form these sounds into vocalizations such as speech.
Your lungs are cone-shaped organs separated from each other by the heart. The
left lung has two lobes, the right lung three. The lungs are located inside the rib cage
above the diaphragm, a broad sheet of muscle between the thoracic (chest) and abdominal
cavities. The lungs are soft, spongy, and elastic and don’t attach directly to the chest wall.
Instead, each lung is enclosed by a pair of thin membranes called pleurae (singular:
pleura). This arrangement is a little like a fist pushed into an inflated balloon. A lung
occupies the same sort of position as your fist, and the pleural membrane folds back on
itself (as the balloon does) to form a closed pleural sac. A narrow intrapleural space
(intra- means “between”) separates the membrane’s two facing surfaces. A thin film of
lubricating fluid in the space reduces chafing between the membranes.
Inside each lung, the bronchi narrow as they branch and form “bronchial trees.”
These narrowing airways are bronchioles. Their narrowest portions deep in the lungs are
respiratory bronchioles. In each lung, about 150 million tiny air sacs bulge out from their
walls. Each sac is an alveolus (plural: alveoli). Alveoli are where gases diffuse between
the lungs and blood capillaries. Together the millions of alveoli provide a huge surface
area for this exchange of gases. If they were stretched out as a single layer, they would
cover the body several times over—or the floor of a racquetball court!
k. Respiration 5 Gas Exchange
Gas exchange in the body relies on the tendency of oxygen and carbon dioxide to
diffuse down their respective concentration gradients—or, as we say for gases, their
pressure gradients. When molecules of either gas are more concentrated outside the body,
they tend to move inside and vice versa.
At sea level air is about 78 percent nitrogen, 21 percent oxygen, 0.04 percent
carbon dioxide, and 0.96 percent other gases. Atmospheric pressure there is about 760
mm Hg, as measured by a mercury barometer. Each gas accounts for only part of the total
pressure exerted by the whole mix of gases. Oxygen’s partial pressure is 21 percent of
760, about 160 mm Hg. Carbon dioxide’s partial pressure is about 0.3 mm Hg.
Meeting the metabolic needs of a large, active animal such as a human requires
extremely efficient gas exchange. Various factors influence the process. To start with,
gases enter and leave the body by crossing a respiratory surface of thin, moist epithelium.
The surface must be thin—at most, one or two cells thick—because gases only diffuse
rapidly over short distances. The respiratory surface must be moist because gases can’t
diffuse across it unless they are dissolved in fluid. The thin walls of the millions of
alveoli in the lungs meet these requirements.
The exchange of gases, namely oxygen and carbon dioxide, between body cells
and the surrounding tissue fluid is a fundamental process essential for cellular
metabolism and homeostasis. This exchange occurs via diffusion across the walls of
capillaries, facilitated by the intricate network of blood vessels comprising the
cardiovascular system.
Within the body, cells continuously consume oxygen and produce carbon dioxide
as byproducts of cellular respiration, a process that generates energy in the form of
adenosine triphosphate (ATP). To meet the metabolic demands of tissues, oxygen must
be delivered efficiently to cells, while carbon dioxide must be removed from the cellular
environment to prevent its accumulation, which can lead to acidosis and impaired cellular
function.
The cardiovascular system plays a crucial role in facilitating the transport of gases
between the lungs, where oxygen is acquired and carbon dioxide is expelled, and the
tissues, where oxygen is utilized and carbon dioxide is produced. Oxygen-rich blood,
carried by arteries, is pumped from the heart to peripheral tissues, where oxygen diffuses
from capillaries into the tissue fluid and subsequently into cells. Concurrently, carbon
dioxide diffuses out of cells into the tissue fluid and then into capillaries, where it is
transported back to the lungs for elimination during exhalation.
The process of gas exchange is governed by concentration gradients, with oxygen
moving from areas of higher partial pressure (such as arterial blood) to areas of lower
partial pressure (such as tissue fluid and cells), while carbon dioxide moves in the
opposite direction. This passive diffusion of gases across cell membranes and capillary
walls is facilitated by the lipid solubility of oxygen and carbon dioxide, allowing them to
dissolve and diffuse freely through biological membranes.
Factors such as tissue metabolism, blood flow, and the affinity of hemoglobin for
oxygen influence the rate and efficiency of gas exchange in the tissues. For example,
during periods of increased metabolic activity, such as exercise, oxygen delivery to
tissues is augmented by vasodilation of arterioles and increased blood flow, enhancing
oxygen diffusion and uptake by cells.
In addition to oxygen and carbon dioxide, other gases such as nitrogen and
volatile organic compounds may also participate in gas exchange processes within
tissues, albeit to a lesser extent. These gases may have physiological roles in cellular
signaling, vasodilation, and immune responses, contributing to tissue homeostasis and
function.
Disruption of gas exchange processes can occur in various pathological
conditions, such as respiratory disorders (e.g., chronic obstructive pulmonary disease,
pulmonary edema) or cardiovascular diseases (e.g., heart failure, peripheral artery
disease), leading to impaired oxygen delivery, tissue hypoxia, and metabolic dysfunction.
Understanding the mechanisms of gas exchange and their regulation is essential for
elucidating the pathophysiology of these disorders and developing therapeutic
interventions to restore tissue oxygenation and function.
In summary, the cardiovascular system serves as a conduit for the transport of
gases between the lungs and tissues, facilitating the exchange of oxygen and carbon
dioxide necessary for cellular metabolism and physiological function. The dynamic
interplay between blood flow, tissue perfusion, and gas diffusion ensures the maintenance
of tissue oxygenation and metabolic homeostasis, essential for overall health and well-
being.
Two factors affect how many gas molecules can move into and out of lung alveoli
in a given period of time. The first is surface area, and the second is the partial pressure
gradient across it. Diffusion occurs faster when the surface area is large and the gradient
is steep. The millions of alveoli in your lungs provide a huge surface area for gas
exchange. As we see next, the interaction between hemoglobin and oxygen helps
maintain a steep gradient that in turn helps bring oxygen into the lungs.
l. Science Comes to Life: Breathing at High Altitude and Underwater
In environments where there is less oxygen than normal, such as at high altitude
or underwater, the rules of gas exchange change. For instance, the partial pressure of
oxygen falls the higher you go. A person who isn’t acclimatized to the thinner air at high
altitude can become hypoxic—meaning that tissues are chronically short of oxygen.
Above 2,400 meters (about 8,000 feet), the brain’s respiratory centers trigger
hyperventilation— faster, deeper breathing—to compensate for the oxygen deficiency.
High-altitude environments present unique challenges to individuals with
preexisting heart disease or respiratory conditions, such as asthma, due to the reduced
availability of oxygen and changes in atmospheric pressure. The physiological responses
to high altitude, including hypoxia (low oxygen levels) and hypobaric hypoxia (reduced
atmospheric pressure), can exacerbate symptoms and complications in vulnerable
populations, leading to adverse health effects and increased risk of cardiovascular and
respiratory events.
For individuals with heart disease, which impairs the function of the
cardiovascular system, the decreased oxygen availability at high altitudes can exacerbate
underlying ischemic heart conditions, such as coronary artery disease (CAD) and angina
pectoris. Angina, characterized by chest pain or discomfort resulting from inadequate
oxygen supply to the heart muscle (myocardium), may be precipitated or intensified by
the combination of hypoxia and increased cardiac workload associated with altitude
exposure.
At higher elevations, the reduced partial pressure of oxygen in the air leads to
lower arterial oxygen saturation levels and decreased oxygen delivery to tissues,
including the myocardium. This mismatch between oxygen supply and demand can
trigger myocardial ischemia and anginal symptoms in susceptible individuals, particularly
during physical exertion or emotional stress. The combination of reduced oxygen
availability, increased cardiac output, and systemic vasoconstriction further compromises
myocardial perfusion and exacerbates ischemic symptoms in individuals with
compromised coronary circulation.
Respiratory conditions, such as asthma, pose additional challenges for individuals
ascending to high altitudes, where the air is thinner and oxygen levels are lower. Asthma
is characterized by airway inflammation, bronchoconstriction, and increased mucus
production, which can be exacerbated by environmental factors such as cold, dry air and
altitude-related hypoxia. At high altitudes, individuals with asthma may experience
worsened respiratory symptoms, including wheezing, coughing, chest tightness, and
dyspnea (shortness of breath), due to the combined effects of hypoxia and airway
hyperresponsiveness.
The decreased oxygen tension at high altitudes can lead to bronchial smooth
muscle constriction and airway narrowing, further impeding airflow and exacerbating
bronchoconstriction in individuals with asthma. Additionally, the cold, dry mountain air
may irritate the airways and trigger bronchospasm and mucus production, contributing to
respiratory distress and exacerbating asthma exacerbations.
Furthermore, the increased respiratory effort required to compensate for altitude-
induced hypoxia can exacerbate respiratory fatigue and worsen symptoms in individuals
with preexisting lung conditions. The decreased oxygen saturation in arterial blood can
also impair oxygen delivery to peripheral tissues and organs, exacerbating hypoxemia
and respiratory distress in susceptible individuals.
In summary, high-altitude environments pose significant challenges for
individuals with heart disease and respiratory conditions, exacerbating symptoms and
increasing the risk of cardiovascular and respiratory complications. The combination of
reduced oxygen availability, increased cardiac workload, and airway hyperresponsiveness
can lead to worsened anginal symptoms, respiratory distress, and exacerbations of
underlying health conditions at high elevations. Understanding the physiological effects
of altitude on cardiovascular and respiratory function is essential for mitigating risks and
ensuring the safety of individuals with preexisting health conditions during travel or
residence at high altitudes.
When engaging in activities such as swimming or diving, the human body
encounters a unique challenge when it comes to extracting oxygen from water, as
opposed to air. Unlike aquatic animals equipped with gills, which efficiently extract
dissolved oxygen from water to sustain respiration, humans lack specialized respiratory
adaptations for underwater gas exchange. As a result, the ability of individuals to remain
submerged without access to supplemental oxygen is limited, primarily due to the
inability to extract dissolved oxygen directly from water.
In aquatic environments, oxygen is present in dissolved form within the water
column, originating from the process of atmospheric diffusion, photosynthesis by aquatic
plants, and mechanical agitation of water surfaces. However, the concentration of
dissolved oxygen in water is substantially lower than that in air, typically ranging from a
few to several milligrams per liter depending on factors such as temperature, salinity, and
water turbulence.
Unlike gills, which are highly specialized structures evolved by fish and other
aquatic organisms for efficient gas exchange in water, the human respiratory system is
adapted for extracting oxygen from air. The respiratory tract of humans is equipped with
structures such as the lungs, bronchi, and alveoli, which facilitate gas exchange between
air and blood during respiration. When submerged in water, the respiratory surfaces of
the lungs are inaccessible, preventing the uptake of oxygen from the surrounding water.
Individuals trained to dive without the use of oxygen tanks, a practice known as
freediving or breath-hold diving, rely on their body's oxygen reserves to sustain aerobic
metabolism during submersion. Freediving techniques typically involve maximizing
breath-holding capacity, optimizing oxygen utilization, and minimizing oxygen
consumption to prolong dive times and enhance underwater performance.
During a freedive, individuals engage in preparatory breathing exercises, breath-
holding techniques, and mental focus to reduce oxygen consumption and increase
tolerance to hypoxia (low oxygen levels). By slowing the metabolic rate, conserving
oxygen, and enhancing oxygen transport and utilization, experienced freedivers can
extend their breath-hold times and explore underwater environments with remarkable
skill and efficiency.
However, even with training and physiological adaptations, the duration of
breath-hold dives is inherently limited by factors such as individual physiology, diving
depth, water temperature, and physical exertion. The mammalian diving reflex, a
physiological response triggered by submersion in water, helps to conserve oxygen and
prolong breath-holding ability by reducing heart rate, peripheral vasoconstriction, and
metabolic rate. Despite these adaptations, most trained freedivers can only remain
submerged for a few minutes before needing to resurface for air.
In summary, while humans lack the ability to extract oxygen directly from water
like aquatic animals with gills, trained individuals can enhance their breath-holding
capacity and underwater endurance through specialized techniques and physiological
adaptations. Freediving offers a unique opportunity to explore underwater environments
and push the limits of human performance, albeit within the constraints of our terrestrial
respiratory physiology. Understanding the challenges and limitations of underwater
respiration underscores the remarkable adaptations and capabilities of both humans and
aquatic organisms in their respective environments.
Deep divers risk nitrogen narcosis or “raptures of the deep.” This condition
develops because water pressure increases the deeper you go, and at about 45 meters (150
feet) dangerous amounts of nitrogen gas (N2 ) start to become dissolved in tissue fluid
and move into cells. In brain cells the nitrogen interferes with nerve impulses, and the
diver becomes euphoric and drowsy. If a diver ascends from depth too quickly, the falling
pressure causes N2 to enter the blood faster than it can be exhaled, so nitrogen bubbles
may form in blood and tissues. The resulting pain (especially in joints) is called ”the
bends” or decompression sickness.
m. Breathing: Air In, Air Out
Breathing ventilates the lungs in a continuous in/out pattern called a respiratory
cycle. Ventilation has two phases. First, inspiration—or inhalation—draws a breath of air
into the airways. Then, in the phase of expiration, or exhalation, a breath moves out.
In each respiratory cycle, the volume of the chest cavity increases, then decreases.
At the same time, pressure gradients between the lungs and the air outside the body are
reversed. To understand how this shift affects breathing, it helps to remember that air in
your airways (oxygen, carbon dioxide, and the other atmospheric gases) is at the same
pressure as the outside atmosphere. Before you inhale, the pressure inside all your alveoli
(called intrapulmonary pressure) is also the same as that of outside air.
The basic respiratory cycle As you start to inhale, the diaphragm contracts and
flattens, and external intercostal muscle movements lift the rib cage up and out. As the
chest cavity expands, the lungs expand too. At that time, the air pressure in alveoli is
lower than the atmospheric pressure. Fresh air follows this gradient and flows down the
airways, then into the alveoli. If you take a deep breath, the volume of the chest cavity
increases even more because contracting neck muscles raise the sternum and the first two
ribs.
During normal, quiet breathing, expiration is passive. The muscles that contracted
to bring about inspiration simply relax and the lungs recoil, like a stretched rubber band.
As the lung volume shrinks, the air in the alveoli is compressed. Because pressure in the
sacs now is greater than the outside atmospheric pressure, air follows the gradient and
moves out of the lungs.
If your lungs must rapidly expel more air—for instance, when you huff and puff
while working out—expiration becomes active. Muscles in the wall of the abdomen
contract, pushing your diaphragm upward, and other muscle movements reduce the
volume of the chest cavity even more. Add to these changes the natural recoil of the
lungs, and a great deal of air in the lungs is pushed outward.
A negative pressure gradient outside the lungs contributes to the respiratory cycle.
Atmospheric pressure is a little bit higher than the pressure in the pleural sac that wraps
around the lungs. The pressure difference is enough to make the lungs stretch and fill the
expanded chest cavity. It keeps the lungs snug against the chest wall even when air is
being exhaled, when the lung volume is much smaller than the space inside the chest
cavity. As a result, when the chest cavity expands with the next breath, so do the lungs.
About 500 milliliters (two cupfuls) of air enters or leaves your lungs in a normal
breath. This volume of air is called tidal volume. You can increase the amount of air you
inhale or exhale, however. In addition to air taken in as part of the tidal volume, a person
can forcibly inhale roughly 3,100 milliliters of air, called the inspiratory reserve volume.
By forcibly exhaling, you can expel an additional expiratory reserve volume of about
1,200 milliliters of air.
Vital capacity is the maximum volume of air that can move out of the lungs after
you inhale as deeply as possible. It is about 4,800 milliliters for a healthy young man and
about 3,800 milliliters for a healthy young woman. As a practical matter, people rarely
take in more than half their vital capacity, even when they breathe deeply during
strenuous exercise. At the end of your deepest exhalation, your lungs still are not
completely emptied of air; another roughly 1,200 milliliters of residual volume remains.
How much of the 500 milliliters of inspired air is available for gas exchange?
Between breaths, about 150 milliliters of exhaled “dead” air remains in the airways. Thus
only about 350 (500 2 150) milliliters of fresh air actually reaches the alveoli each time
you inhale. An adult typically breathes at least twelve times per minute. This rate of
ventilation supplies the alveoli with 4,200 (350 3 12) milliliters of fresh air every 60
seconds—about the volume of soda pop in four 1-liter bottles.
When food “goes down the wrong way” and enters the trachea (instead of the
esophagus), it’s impossible to inhale or exhale normally. A choking person can suffocate
in just a few minutes. The Heimlich maneuver can dislodge material from the trachea by
elevating the diaphragm. This reduces the chest volume, forcing air up the trachea. With
luck, the air will rush out with enough force to eject the item.
