1. Which type of immunity is present at birth, and which develops over time? 2. Explain the most important antimicrobial proteins in the body. 3. Describe the effects of inflammation in the body, and list the cardinal signs 4. What is the function of complement?
Innate
(Nonspecific) Defenses
Our innate or nonspecific defenses prevent or limit
microorganisms and other environmental hazards from approaching, entering, or
spreading. These defenses are often able to prevent infection by destroy-ing
pathogens, without needing the help of any other defenses. Sometimes, however,
the adaptive immune system is needed to assist the nonspecific defenses.
Nonspecific defenses are the first line of defense and include intact skin and
mucosae. When pathogens penetrate the skin or mucosae, the second line of
defense is activated. This relies on internal defenses, including antimicrobial
proteins and phagocytes. Inflammation is
the most important process in thesecond line of defense. The nonspecific
defenses are classified as mechanical barriers, which cover body surfaces, and
chemical substances, which are involved with invading pathogens.
Also known as physical
barriers, mechanical bar-riers include the skin and the mucous membranes
that line the respiratory system, digestive system, urinary system basement
membranes, and repro-ductive passageways. They protect against certain
infectious agents. The body’s hair, sweat, and mucus also act as mechanical
barriers. The mechanical bar-riers of immunity are ready to act when we are
born. The skin’s keratinized epithelial membrane stops most microorganisms on
the skin from penetrating it. Keratin itself resists many weak bases and acids
as well as toxins and bacterial enzymes. Inside the body, the mucous membranes
function in much the same capacity.
Provided by enzymes and other chemical substances in body
fluids, these include pepsin and hydrochloric acid in the stomach; tears; lysozyme in tears, saliva, breast milk, and
mucus; salt in perspiration; interferons; mucin; defensins; certain lipids in sebum; dermicidin; and complement. Interferons and complement proteins
are the most important antimicrobial pro-teins in the body:
■■ Interferons are small proteins that bind to uninfected
cells and stimulate them to make protective proteins. Interferons are secreted
by infected cells and diffuse to nearby cells, stimulating protein synthesis
that interferes with viral replication. Interferons block viral RNA from
synthesizing proteins and also degrade the viral RNA itself. Interferon-α and
-β also activate NK cells. Interferon-γ, also known as immune interferon, is
secreted by lymphocytes. It activates macrophages and has wide ranging immune
mobilization effects.
■■ Acid mantle components
inhibit bacterial growth. These consist of the acidity of the skin, stomach
secretions, and vagina.
■■ Enzymes such
as lysozyme destroy bacteria. Lysozyme is found in the respiratory mucus,
lacrimal fluid of the eye, and saliva. In the stomach, protein digesting
enzymes kill a variety of different microorganisms.
■■ Mucin is a
substance that forms mucus when dissolved in water. This mucus is thick and
sticky,lining the passageway of the digestive and respiratory systems. It
functions to trap a variety of microorganisms. The mucin of the saliva is
dif-ferent in that it traps microorganisms but washes them from the mouth to
the stomach, where they are digested.
Defensins are
broad-spectrum antimicrobialpeptides secreted from the skin and mucous
membranes. They are produced in much higher quantities when surface barriers
are breached and inflammation develops. They help to control col-onization by
bacteria and fungi in different ways, including disruption of the membranes of
these microorganisms.
■■ Dermicidin found
in eccrine sweat is toxic to bac-teria, similar to the effects of certain
lipids in the body’s sebum.
■■ Complement is a group of proteins in
plasma andother body fluids that interact to cause inflam-mation and phagocytic
activities. Plasma con-tains at least 20 special complement or C proteins that comprise the complement
system, includ-ing proteins C1 through C9; factors called B, D, and P; and also
several proteins that have a reg-ulatory effect. The term complement refers to the way this system “complements” the action
of antibodies. The complement proteins interact in chain reactions or cascades that are similar to those of
the clotting system. Activated com-plement also acts by lysing and killing
certain cells and bacteria. There are additional chemical barriers in the
respiratory tract mucosae. When microorganisms make it past the chemical
barri-ers, the internal innate defenses begin to combat them. Interferons are
not virus-specific, and those
produced against a certain virus protect against other viruses as well. The
interferons are a group of immune modulating proteins with slightly different
effects. They also play an indirect role in fighting cancer. The actions of the
adaptive immune system greatly increase the inflamma-tory response. Most
complement activation also occurs because of this system.
■■ Complement
activation involves the
classical pathway and the alternative pathway. Theclassical pathway
is the fastest and most effec-tive pathway, beginning with binding of
comple-ment protein C1 to an antibody, already attached to its specific
antigen, which may be a bacterial cell wall. When antibody molecules are
absent, the alternative or properdin pathway activates the
complement system. This slow, less effective path-way begins when properdin or factor P, factor B, and factor D interact in the plasma. These
are all various types of complement proteins. This inter-action may be
triggered by exposure to foreign materials. The alternative pathway also ends,
like the
classical pathway, with conversion of inactive C3 protein into activated C3b
protein. The activa-tion of complement results in formation of pores, increased
phagocytosis, and release of histamine.
Fever is the elevation of body temperature that reduces iron
in the blood, which inhibits bacterial and fungal reproduction; fever also causes
increased phagocy-tosis by macrophages. Fever is a systemic response to
invading microorganisms. Exposure of leukocytes and macrophages to foreign
substances causes the release of pyrogens, which
cause the hypothalamus to raise the body temperature. As a result of fever, the
spleen and liver keep iron and zinc away from the rest of the body somewhat so
they cannot be used to sup-port bacterial growth. Cells are repaired more
quickly because fever increases their metabolic rate. Active macrophages release
a cytokine that is called endoge-nous
pyrogen or interleukin-1, which
produces a fever.
Inflammation is a tissue response to injury or infection
that may include four cardinal signs:
redness, swelling, heat, and pain. Infected cells attract white blood cells,
which engulf them. Impaired function
is a fifth occur-rence that many experts consider to be the fifth car-dinal
sign of inflammation. When functions such as movement become impaired, the
injured area may be temporarily forced to rest so it can heal. Masses of
leu-kocytes, bacterial cells, and damaged tissue may form a thick fluid called pus. The body may react to inflam-mation by forming a network
of fibrin threads where the infection is centered. This closes off the infected
area to inhibit the spread of pathogens. An
inflam-matory response is triggered when mast cells releasehistamine,
serotonin, and heparin. The inflammatory response is a tissue-level reaction
and is therefore related to the tissues and integumentary system. The inflammatory
response helps to dispose off pathogens and cell debris, triggers the adaptive
immune system to act, and prepares the body to repair damaged tis-sues.
Neutrophils squeeze through capillary walls in response to inflammatory
signals. This movement is called diapedesis.
Inflammatory chemicals may be released by injured tissue
cells, stressed tissue cells, and immune cells. They can also be formed by mast cells. The strong inflam-matory chemical
known as histamine is
released by mast cells. Macrophages are able to recognize invaders and trigger
a chemical response by using surface mem-brane or toll-like receptors. Additionally, inflammatory chemicals such as kinins, prostaglandins, and com-plement help
to dilate localized arterioles and causeadditional leakage from localized
capillaries. They may cause leukocytes to be attracted to an injured area for
additional inflammatory actions.
The redness and heat of inflammation are caused by
vasodilation. Local hyperemia occurs
when local arterioles dilate, which means that there is congestion in the area
with blood. Fluid containing clotting fac-tors and antibodies, known as exudate, leaks from the blood into the
tissue spaces, causing local swelling or edema.
This condition increases pain by pressing on nearby nerve endings. Bacterial
toxins that are released also contribute to pain. Released prostaglandins and
kinins contribute to sensitizing effects, and pain relief by aspirin or other
anti-inflammatory drugs is based on the inhibition of prostaglandin synthesis.
Injured tissues attract neutrophils and monocytes, which
engulf and digest particles such as pathogens and cell debris; monocytes
influence the development of macrophages that attach to blood and lymphatic
vessels. Neutrophils, along with eosinophils, are termed micro-phages because of their smaller size. Together, thesevarious
phagocytic cells make up the mononuclearphagocytic
system to remove foreign particles fromthe lymph and
blood. Neutrophils are the most abun-dant and begin to engulf invaders when
they find infectious material in the body tissues. Macrophages are larger in size, mostly derived from monocytes, and
provide most phagocytic activities. Both free and fixed types of macrophages
exist, which are similar in struc-ture and function. The free macrophages
search tissue spaces for invaders or cellular debris. Fixed macro-phages live
permanently inside certain organs, such as the liver’s stellate macrophages. All the various phago-cytes are collectively
called the monocyte macrophagesystem or reticuloendothelial system.
Natural
killer (NK) cells patrol the blood and lymphas part of immunologic surveillance. They are able to lyse
and kill both cancer and viral cells before acti-vation of the adaptive immune
system. They are part of the cells known as large
granular leukocytes and have wider actions against pathogens than the
lymphocytes of the adaptive immune system. They detect generalized
abnormalities, such as when cell-surface proteins known as major histocompatibility
complex (MHC) are lack-ing. However, they are not phagocytic and kill by
con-tacting target cells directly, in the same way as cytotoxic T cells
kill. Cytotoxic T cells secrete a poisonous lympho-toxin
that kills target cells. The inflammatory response isincreased by strong chemicals
secreted by NK cells. NK cells recognize abnormal cells, adhere to them, and
use their Golgi apparatus to produce perforins, which are proteins that diffuse to the target cell. The
perforins cre-ate holes or pores in the target cell’s membrane, resulting in
lysis of the abnormal cell. NK cells attack cancer cells and those infected
with viruses. The plasma membranes of cancer cells contain tumor-specific antigens, which the NK cells use to find
them. Some cancer cells can destroy NK cells, via a process of either avoiding
their detection or neutralizing body defenses. This process is called immunological escape.
A final form of innate, nonspecific defense is speciesresistance. For example, a human
may be resistantto certain diseases that affect other species of animals. A
pathogen effective against a dog, for example, may be unable to survive in a
human. In reverse, humans can be infected with measles, gonorrhea, mumps, and
syphilis, none of which affects other animal species.
1. Which type of immunity is present at birth, and which
develops over time?
2. Explain the most important antimicrobial proteins in the
body.
3. Describe the effects of inflammation in the body, and list
the cardinal signs.
4. What is the function of complement?
Related Topics
TH 2019 - 2023 pharmacy180.com; Developed by Therithal info.