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II. IMMUNE SYSTEM
Immune defenses fall into two categories: nonspecific defenses that guard
against a wide variety of pathogens; and immunity, composed of mechanisms
whereby lymphocytes recognize and destroy specific
pathogens.
NONSPECIFIC DEFENSES
Physical Barriers (p. 764)
Skin (p. 764)
composed mostly of impervious keratin that few pathogens can penetrate.
relatively dry and lacks the nutrients to support microbial growth.
Mucous membranes (p. 764)
The mucous membranes of the digestive, respiratory, urinary, and
reproductive tracts protect them from invasion. Mucus traps microbes and
contains protective chemicals.
Connective Tissue Gel (p. 764)
Hyaluronic acid inhibits the spread of pathogens through connective
tissues. Many pathogens and some snake venom and bacterial toxins overcome
this by producing hyaluronidase.
Chemical Barriers (p. 764)
Certain bodily secretions inhibit the survival of pathogenic
microorganisms. Stomach acid, lactic acid in perspiration, acid in the urethra
and vagina, and lysozyme in tears, saliva, and mucus all serve to deter
pathogens.
Leukocytes and Macrophages (p. 765)
Leukocytes (p. 765)
-Leukocytes fall into five categories.
-Neutrophils are highly mobile, and spend their time wandering the
connective tissue phagocytizing bacteria. Neutrophils also create a
chemical killing zone around themselves, a process that begins with
degranulation. This triggers a respiratory burst, and cells form
superoxide, which is highly toxic when superoxide radicals and hydrogen
ions combine to form hydrogen peroxide. Neutrophils also die in the
attack. High counts of neutrophils are indicative of bacterial infections.
-Eosinophils phagocytize antigen-antibody complexes, allergens, and
inflammatory chemicals. Eosinophils also aggregate around larger parasites
and release enzymes that weaken or destroy them. Allergies and parasitic
infections are marked by eosinophila.
-Basophils secrete the vasodilator histamine and the anticoagulant
heparin, both of which allow greater access for other leukocytes into the
infected area.
-Lymphocytes fall into several functional types. Natural killer (NK) cells
are large
lymphocytes that attack cells of your own body that are infected
by
viruses or have turned cancerous.
-Monocytes are the circulating precursors of macrophages.
Macrophages (p. 765)
-The macrophage system is composed of both wandering macrophages and those
that remain fixed in position.
-Macrophages include the following cell types: histiocytes, reticular
cells, Langerhans cells, microglia, endothelial cells, alveolar
macrophages, and Kupffer cells.
Inflammation (p. 765, Tables 21.1, 21.2)
1. Inflammation is a response to tissue injury, and is characterized by redness,
swelling, heat, pain, and impaired function.
2. The general purposes of inflammation are to limit the spread of the pathogen
and destroy it, to remove the debris of damaged tissue, and to initiate
tissue repair.
3. Pain and Loss of Function (p. 766)
Pain arises from direct injury to nerve endings, their stimulation by
inflammatory chemicals, and by tissue swelling. Bradykinin is a potent
pain stimulus, which is
secreted by basophils and mast cells, and produced
from a plasma protein.
Prostaglandins and bacterial toxins may also
stimulate pain.
Pain is an important signal of tissue damage, and signals the body to rest
the part while it heals.
4. Hyperemia, Swelling, Redness, and Heat (p. 766)
-Bradykinin, histamine, and leukotrienes stimulate vasodilation, which
leads to hyperemia that accounts for the heat of the affected area.
-Heat speeds metabolic activity, thus promoting cell repair.
-Increased blood flow speeds the process of waste removal and tissue
repair.
-Histamine and leukotrienes increase the permeability of blood capillaries
so they release more fluid into tissue, causing swelling. This allows
antimicrobial chemicals in the plasma to enter the area, as well as
increasing lymphatic drainage to remove dead cells and toxins.
-Redness results from capillary permeability and hyperemia.
5. Leukocyte Deployment(p. 767, Fig. 21.13)
-Hyperemia and capillary permeability attract leukocytes to the inflamed
tissue by three mechanisms: margination, which occurs as cell adhesion
molecules within the endothelium make membranes "sticky" and slow the
velocity of leukocytes; by diapedisis, in which leukocytes squeeze through
endothelial cells; and through chemotaxis, because leukocytes are
attracted to bradykinin, leukotrienes, and others.
-Neutrophils are the quickest leukocytes to respond. Damaged tissues
release leukocytosis-promoting factor, which stimulates a quick release of
neutrophils from storage in red bone marrow.
-Basophils provide inflammatory chemicals; eosinophils enter when there
are allergens or parasites; and monocytes arrive later, differentiating
into histiocytes and become the cleanup crew.
-The mixture of tissue fluid, cellular debris, dead and dying neutrophils,
and microbes is called pus.
6. Tissue Repair (p. 768)
a. Endothelial cells and platelets secrete platelet: derived growth factor
(PDGF), which stimulates fibroblasts to multiply and synthesize collagen
fibers and matrix.
Antimicrobial Proteins (p. 768)
1. Interferons (p. 768)
a. Interferons are polypeptides secreted by cells that have been invaded
by viruses. They diffuse to neighboring cells and prevent viruses from
attaching to them.
b. Interferons also activate natural killer cells and macrophages, which
destroy infected host cells before they release more viruses.
c. Interferons also stimulate the destruction of cancer cells.
2. Complement(p.768, Figs. 21.14,21.15)
a. The complement system is a group of 20 or more beta globulins of blood
that aid nonspecific resistance and immunity.
b. Complement helps destroy pathogens in three ways: by enhanced
inflammation, by opsonization (making bacteria easier to phagocytize by
coating their surfaces), and through cytolysis (leading to the rupture of
target cells).
F. Fever(p.768, Fig. 21.16, Table 21.3)
I. Fever (pyrexia) can result from trauma, drug interactions, infection,
and other causes.
2. Fever is beneficial in that it promotes interferon activity, elevates
metabolic rate and accelerates tissue repair, and it inhibits the
reproduction of bacteria and viruses.
3. In bacterial infections, macrophages secrete interleukin-l (Il-l),
which may be a pyrogen that stimulates the anterior hypothalamus to
secrete prostaglandin E (PGE). PGE, it turn, stimulates the hypothalamic
thermostat to rise.
4. The elevated temperature stimulates the liver and spleen to harbor zinc
and iron, depriving bacteria of minerals needed for their multiplication.
5. Even though most fevers are beneficial, high temperature can be
dangerous because it causes protein denaturation and cellular dysfunction.
SPECIFIC IMMUNITY (p. 770)
A. The immune system is an array of widely distributed cells that recognize
foreign substances and act to neutralize or destroy them. Two characteristics
that distinguish immunity from nonspecific resistance are specificity and
memory.
Two types of immunity are recognized: humoral (antibody-mediated) immunity
is based on the action of antibodies. Circulating antibodies bind to
bacteria, toxins, and extracellular viruses, "tagging" them for
destruction; and cellular (cell-mediated) immunity is based on the action
of lymphocytes that directly attack foreign cells, cells infected with
viruses or parasites, and cancer cells.
B. Antigens (p. 772, Fig. 21.17)
1. An antigen (Ag) is any molecule that triggers an immune response.
Antigens are generally large, complex molecules, such as proteins,
polysaccharides, glycoproteins, and glycolipids, with structure unique to
each individual. Their uniqueness allows the immune system to distinguish
self from non-self.
2. Some molecules are too small to be antigenic alone. These are called
haptens, and they can stimulate an immune response by binding to a host
macromolecule.
a. Cosmetics, detergents, industrial chemicals, poison ivy, and
animal dander act as haptens and trigger allergies in some people.
C. Antibodies (p. 772, Fig. 21.18, Table 21.4)
I. An antibody (Ab), or immunoglobulin, is a gamma globulin.
2. Its basic structure is composed of four polypeptide chains linked by
disulfide bonds. Two are heavy chains, and two are light chains, all four
of which have a variable region (V region) that give an antibody
uniqueness. The rest of each chain is a constant region (C region).
3. The V regions of a heavy and light chain combine to form an antigenbinding site on each arm.
4. There are five classes of antibodies, named for the structures of their
C regions. These are 19A, IgD, 19E, IgG, and IgM.
D. Passive and Active Immunity (p. 773)
1. When antibodies or lymphocytes are given from one person or source, the
recipient acquires passive immunity. Passive immunity lasts only 2-3
weeks.
2. Active immunity refers to the production of one's own antibodies or
lymphocytes against an antigen. This can be induced by natural exposure or
artificially induced by vaccination, and generally lasts a long time.
E. Lymphocytes (p. 773)
1. The major cells of the immune system are lymphocytes and macrophages.
Macrophages are active in nonspecific resistance but are also crucial in
immunity. Most lymphocytes can be classified as T lymphocytes (T cells) or
B lymphocytes (B cells).
2. T Lymphocytes (p. 774)
a. During fetal development, the bone marrow releases
undifferentiated stem cells into the blood. Some of these colonize
the thymus, where they are stimulated to become T (thymus)
lymphocytes. Under the influence of thymosin, each cell develops
numerous plasma membrane proteins that serve as antigen receptors.
The T cell is now immunocompetent.
b. An immunocompetent T cell divides rapidly, forming a clone of T
cells with identical receptors. All clones yet to encounter an
antigen are called the virgin lymphocyte pool.
c. Clonal deletion leaves only the T cells capable of responding to
foreign antigens, destroying any that are self-reactive.
d. T cells account for 70-80% of the lymphocytes in the blood and in
lymphatic organs.
3. B Lymphocytes (p. 774)
a. Fetal stem cells also settle into other regions of the body where
they become B lymphocytes. ("B" stands for the bursa of Fabricus, a
lymphatic organ in chickens.) B cells synthesize their antigen
receptors, divide rapidly, and produce immunocompetent clones. Each
clone can react to only one antigen.
b. These clones are evolutionary adaptations to antigens that have
afflicted humans throughout their existence. All an antigen does is
determine which of the preexisting clones is activated.
c. Immunocompetent B cells disperse through the body and colonize
the same organs as T cells, accounting for 20-30% of the body's
lymphocytes.
F. Antigen-Presenting Cells (p. 774)
1. B cells and macrophages also function as antigen presenting cells
(APCs).
2. The role of an APC is to phagocytize an antigen, digest it into
molecular fragments, and "display" some of these fragments on its surface.
Wandering T cells regularly inspect APCs for displayed antigens.
G. Interleukins (p. 774, Tables 21.6,21.7)
1. Interleukins are hormonelike messengers between leukocytes or leukocyte
derivatives. Those produced by lymphocytes are called lymphokines, and
those produced by macrophages are called monokines.
I. Humoral Immunity (p. 775)
A. In humoral immunity, the essential stages are recognition, attack, and
memory.
B. Recognition (p. 775, Figs. 21.19-21.23)
1. The process of recognition involves five steps.
a. Since an antigen is a large molecule with numerous copies
of each antigenic determinant, it binds to several receptors
on a 8 cell and links them together. This capping process
activates the cell.
b. The capped receptors of the 8 cell become drawn into a
cluster, culminating in receptor-mediated endocytosis of the
antigen-receptor complex.
c. The internalized antigen is digested into segments, linked
to MHC proteins, and displayed. This alerts helper T cells to
become active.
d. A helper factor stimulates the B cell to divide repeatedly
into a battalion of identical cells in a process known as
clonal selection.
e. Most cells of a clone differentiate into plasma cells that
can produce antibodies at a rate of2,000 molecules per second.
2. The first time you are exposed to a particular antigen, your
plasma cells produce mainly IgM. In later exposures to the same
antigen, they produce mainly IgG.
3. Antibody Diversity (p. 776)
a. The immune system is thought to be able to produce 2
million different antibodies as a result of somatic
recombination that forms new combinations of DNA base
sequences in somatic cells.
C. Attack (p. 777, Fig. 21.24)
1. Once released by a plasma cell, antibodies use four different
mechanisms to render antigens harmless.
a. Neutralization occurs as antibodies mask sites that bind to
human cells, rendering them harmless.
b. Complement fixation occurs when antibodies bind complement,
then bind with an antigen and expose its complement binding
site. This binds the complement to the antigen, leading to
destruction of the pathogen.
c. Agglutination occurs as antibody molecules bind to several
antigen molecules at once, sticking them together.
d. Precipitation occurs as antibodies interact with antigens,
binding them in groups, and the complex precipitates out of
solution.
D. Memory (p. 779, Fig. 21.25)
1. The primary immune response is generated the first time a person
is exposed to an antigen.
a. During clonal selection, some members of the clone become
memory cells that are long-lived. They are more abundant than
the original virgin lymphocyte pool, and thus are able to
produce a much quicker secondary immune response.
b. The quicker, secondary immune response is also called the
anamnestic response, since often the antigen has little chance
to exert a noticeable effect on the body.
II. Cellular Immunity (p. 779)
A. In cellular immunity, lymphocytes directly attack and destroy foreign
cells and diseased host cells. This involves cytotoxic T cells that carry
out the attack, helper T cells that promote defense mechanisms, suppressor
T cells that regulate the attack, and memory T cells that lie in wait for
the next time the antigen in encountered.
I. Helper T cells have a CD4 glycoprotein on their surface.
Cytotoxic T cells bear a CD8 glycoprotein.
B. Recognition (p. 780)
1. Antigen Presentation (p. 780, Table 21.5)
a. Recognition involves antigen presentation and T cell
activation.
b. T cells respond only to antigen fragments displayed by
APCs, not to free antigens.
c. Both helper and cytotoxic T cells are involved in
surveillance and examine the MHC proteins of all cells.
d. MHC-I {class I) proteins occur on all body cells; MHC-II
{class 11) proteins occur only on the surfaces on APCs,
including B cells, macrophages, and some T cells. A MHC-II
protein displaying an antigen stimulates helper T cells.
e. Cytotoxic T cells respond only to MHC-I proteins, and
helper T cells respond only to MHC-II proteins.
2. T Cell Activation (p. 780)
a. CD4 and CD8 proteins are cell adhesion molecules that bind
a T cell to a target cell during antigen presentation. They
are also linked to a second-messenger system that triggers
clonal selection in the T cell.
b. Clonal selection requires costimulation, whereby an A PC
and a T cell communicate through interleukins.
C. Attack (p. 780)
1. Helper T Cells (p. 781, Fig. 21.26)
a. When a helper T recognizes a MHC-antigen complex, it
secretes a variety of, lymphokines that attract neutrophils
and promote inflammation.
b. One of the lymphokines, macrophage-activating factor (MAP),
enhances the phagocytic activity of macrophages.
2. Cytotoxic T Cells (p. 781, Figs. 21.27,21.28)
a. Cytotoxic (killer) T cells are the only T lymphocytes that
directly attack and kill other cells.
b. When a cytotoxic T cell recognizes a complex of antigen and
MHC-I protein, it "docks" on that cell and delivers a lethal
hit.
c. Cytotoxic T cells degranulate and release perforin that is
inserted into the enemy plasma protein. The perforin gradually
polymerizes and creates holes in the energy cell.
d. Other ways that cytotoxic T cells kill include release of
lymphotoxin that destroys the target cell's DNA, and tumor
necrosis factor that kills cancer cells.
3. Suppressor T Cells (p. 783)
a. Suppressor T cells release lymphokines that inhibit T cell
and B cell activity.
D. Memory(p.783,Tables21.6,21.7)
1. On first exposure to a pathogen, this constitutes the primary
response. Following clonal selection, some T cells become memory
cells.
2. Upon second exposure to a pathogen, memory cells mount a quick
attack called the T cell recall response.
III. Immune System Disorders (p. 784)
A. Hypersensitivity (p. 784)
1. Hypersensitive people produce antibodies to substances that most people
tolerate, such as pollen or bee stings. Such substances are called
allergens.
2. Type I (acute) hypersensitivity is the most common form and begins
within seconds of exposure, and subsides within 30 minutes.
a. Anaphylaxis is a variant of type I in which the allergen contacts
an 19E molecule associated with mast cells and basophils. The cells
release inflammatory chemicals that cause edema, mucus production,
and congestion, as well as cramps, vomiting and diarrhea.
b. Asthma is a local anaphylactic reaction to inhaled allergens.
Allergen exposure can cause massive release of histamine, which
triggers spasmodic contraction of the bronchioles, and wheezing.
Asthma can be deadly in severe cases.
c. Anaphylactic shock is a systemic response from injection of an
allergen into the bloodstream (bee sting or penicillin). Bronchiolar
constriction, circulatory shock, and sometimes death, result.
3. Type II (antibody-dependent cytotoxic) hypersensitivity occurs when IgG
or IgM binds to antigens on cells and lyses them, as is the case in a
transfusion reaction.
4. Type III (immune complex) hypersensitivity, also mediated by IgG or
IgM, stems from the formation of large amounts of antigen-antibody complex
throughout the body. These complexes can be trapped under the endothelium
of blood vessels and trigger intense inflammation.
5. Type IV (delayed) hypersensitivity occurs 12 to 72 hours after
exposure. It occurs when APCs display antigens to helper T cells in the
lymph nodes. Cosmetics and poison ivy haptens are common culprits.
B. Autoimmune Diseases (p. 785)
1. Autoimmune diseases are failures of the immune system to distinguish
self from foreign antigens.
2. The immune system produces autoantibodies that attack the body's own
tissues as a result of cross-reactivity (some foreign antigens are similar
to those of the body, causing antibodies to direct their attack against
the body), to abnormal exposure of self-antigens to the blood, or to
changes in the structure of self-antigens.
C. Immunodeficiency Diseases (p. 786, Fig. 21.29)
1. In immunodeficiency diseases, the immune system fails to respond
vigorously enough.
2. Severe combined immunodeficiency disease (SCID) is a congenital
deficiency of both T and B cells. Children with SCID are highly vulnerable
to opportunistic infections and must live in protective enclosures.
3. Acquired immunodeficiency diseases are contracted after birth, such as
acquired, immunodeficiency syndrome, or AIDS (p. 787, Figs. E.I , E.2).
i. The human immunodeficiency virus (HIV) was first isolated in 983.
It invades helper T (CD4) cells, along with macrophages,
neutrophils, and brain cells.
ii. Since HIV targets CD4 cells, nonspecific defenses, humoral
immunity, and cellular immunity are hampered. At first, antibodies
against HIV are produced, helping the CD4 count to return to near
normal. Eventually, as the virus replicates, more CD4 cells are
destroyed.
iii. Most people with AIDS die of opportunistic infections.
iv. Transmission of my can be prevented by not sharing intravenous
needles, and protected sexual intercourse.
v. Treatment involves a variety of new drugs, each with adverse side
effects.