Microbiology – Introduction to the Immune
System and
Nonspecific Immunity
Chapter 17: Innate Nonspecific Host
Defenses
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I.
Introduction to the Immune System
A. The ability to ward off the pathogens that
produce disease is called
__________________________.
B. Lack of resistance is called
__________________________.
C. Resistance to disease can be grouped into two
broad areas.
1. Nonspecific
immunity – the body’s first line of defense.
a.
Mechanisms that provide general protection against
invasion by a wide range of pathogens.
b.
This resistance is innate (unlearned).
c.
It responds the same to everything – bacteria, viruses,
parasitic worms, etc. are all treated
the same.
d.
This resistance never learns. It
responds the same on
the 1st through the 100th
exposures to the same pathogen.
1) __________________________ – disease-
causing
microorganism
2. Specific
immunity
a.
Dependent upon lymphocytes (a
type WBC or
leukocyte found in the lymphatic
system)
b.
Specific lymphocytes and specific antibodies respond to
specific
antigens
1) __________________________ – anything that
elicits a specific
immune response.
a) Antigens are usually foreign (nonself)
b) Antigens are usually macromolecules such
as proteins
and polysaccharides.
c.
The specific immune system learns through exposure to
pathogens.
1) Memory responses occur much more quickly upon
2nd and
subsequent exposures to that antigen.
2)
Usually responds upon re-exposure before
symptoms of disease set in
D. The body system that carries out specific
immune responses is the
lymphatic
system.
II. Basic terminology & definitions
A.
__________________________ – any change from a state of good
health. Classes of diseases include…
1. Hereditary diseases – e.g. cystic fibrosis;
many genetic
mutations in a certain
gene cause this disease.
2. Dietary diseases – vitamin, mineral, protein
deficiencies;
mental/physical problems
3. Environmental diseases – smog/air pollution;
lung diseases.
Also includes poverty
& host (child) abuse leading to mental illness.
4. Microbial induced diseases
a. Infectious diseases – diseases caused by the
growth of a
microbe
in/on a host.
b. Toxin induced diseases – disease caused by
toxins
produced by microbes,
in which case the living microbe
does not
have to be present in the affected host.
B.
____________________________________ – the organism (species
or strain) responsible for producing
a disease
C.
__________________________ – an association between 2+ different
organisms that has evolved to a
state where they are generally found in
association with each other under
natural condition & where one or both
members of the association benefits
from the relationship
1. e.g. E.
coli in humans
D.
__________________________________ – the organisms normal
found on or in a healthy host most of
the time
E.
__________________________ – a type of symbiosis where an
organism lives on or in a host &
obtains nutrients from that host.
1. A parasite does not necessarily harm the host
& in some cases
their presence is even
beneficial to the host.
a. e.g. Tiny mites live in our eyebrows. These insects
apparently
life off the dead skin cells, oil, & excretions form
our sweat
glands & they do us no apparent harm or good.
2. However, in most cases only one of the
associates truly benefits
from
the association.
a.
e.g. head lice, fleas on your pets, pin worms, etc.
F.
__________________________ – a parasite that causes a disease in
its host
G.
__________________________ – Growth on or in a host. This
growth may or may not harm the host.
H.
__________________________ – An infection with a larger than
single-celled organism.
1. e.g. parasitic worms, pubic & body louse,
etc.
I.
Mutualistic symbiosis – a
situation where 2+ species live in a situation
where
both benefit from the association.
1. In some cases, one or more of the symbiotic
species are totally
dependent on the other.
J.
__________________________ – the ability to cause a disease.
Many organisms are pathogenic under
certain conditions (e.g. the normal
bacteria in our gut, which usually
do us no harm, can become highly
pathogenic under specific
circumstances like getting shot or stabbed in the
gut), but some are almost always
pathogenic (e.g. chicken pox & flu).
K.
__________________________ – the degree of pathogenicity. A
virulent organism is one that
usually produces a violent & severe disease,
often leading to death.
1. Chickenpox & the common cold virus, while
clearly pathogens,
are not considered to be
virulent.
2. Yersinia
pestis, the etiological agent of bubonic plague,
& the
Ebola virus are both considered to be
virulent.
L.
______________________________________ – a mutant of a virulent
pathogen that has lost its ability
to produce a disease.
1. These organisms may be used in the production
of vaccines
M.
_____________________________________ – a normal flora
organism that normally is not a
pathogen, but that becomes pathogenic
when inoculated into the wrong place
or when the host becomes
weakened & immunologically
compromised.
1. Immunologically compromised – a host whose
immune system
is not working to its
full capacity & thus the host’s defenses are
weak.
a. People undergoing chemotherapy for cancer are
immunologically
compromised because the drugs harm the
immune
system.
b. People who are under stress often have a
lowered
immunity
& are more susceptible to catching infections.
III.
Introduction to the Blood
– since many of the immune responses involve
cells of the
blood, a brief introduction to the blood is needed.
A. Whole blood consists of…
1.
Living cells - called formed
elements that are suspended in the
2.
Nonliving fluid matrix - __________________________.
B. Blood Plasma is composed of…
1. 90% H2O
2. 8% plasma proteins (mostly produced by the
liver)
a. These proteins include immunoglobulins –
(a.k.a.
antibodies)
made by plasma cells (a special B cell, which is
a type of
WBC)
3. 2% solutes that include nutrients, gasses,
hormones, wastes,
products of cell
activity, and ions.
C.
Formed Elements of Blood
1. __________________________ (a.k.a. red blood
corpuscles or
RBC’s)
a. What is the function of RBC’s? Transport O2 and CO2
b. They are small cells that are biconcave in
shape.
c.
They lack nuclei and most organelles
1) Therefore, they cannot divide
2) They also can’t make new proteins or repair
themselves
3) Their average life span is 120 days
d. RBC contain mostly hemoglobin
1) Hemoglobin (Hg) is an oxygen-binding pigment
a) Hg is responsible for the transport of most
of
the oxygen in the blood.
b) A Hg molecule consists of 4 globin proteins
bound
to 4 red, iron-containing heme pigments.
i) Heme portion binds oxygen
ii) Globin portion binds carbon dioxide
2. __________________________ (a.k.a. white
blood cells or
WBC’s)
a. Unlike RBC’s, WBC’s have nuclei and are
complete cells
1) WBC’s are usually short-lived and make up
less
than
1% of the total blood volume.
2) They are critical to our defense against
disease.
3) How do they move?
a)
amoeboid movement: using
pseudopodia
b)
diapedesis:
squeeze out between cells of
capillary walls
c) positive chemotaxis: attracted to stimuli
d) phagocytosis:
"cell eating"
b. Granulocytes
are large WBC’s with lobed nuclei and
granules in
their cytoplasm; all are phagocytic
1) __________________________ are the most
numerous
WBC.
a)
They are chemically attracted to sites of
inflammation
b)
They are active phagocytes (digesting
bacteria)
c)
Light pink to blue-black with 2 or more lobes
to nucleus
d)
Release:
i)
prostaglandins (increase permeability)
ii) leukotrienes (attract other
phagocytes)
2)
__________________________ have red
granules
a)
They are relatively uncommon and attack
parasitic worms
b)
They have been implicated in allergic
inflammation response
3)
__________________________: large, granular
cells with purple to blue nuclei
a) Release histamine and heparin that
promote inflammation
b)
Least numerous WBC
c. Agranulocytes lack visibly staining granules
1)
__________________________ have large oval
or kidney bean shaped nucleus
a)
They have amoeboid movement
b)
They become macrophages, eating debris
and pathogens
c)
They attract WBC's and fibroblasts to wall
off infection
d)
They activate T cells
2) __________________________ have large
nuclei,
they are the size of a RBC with a thin
halo of
cytoplasm
a) __________________________: cellular
immunity. They directly attack viral-infected
and tumor cells.
1) cytotoxic T cells: destroy foreign
cells in tissues
2) helper T and suppressor T cells:
stimulate
or inhibit the activities of other
lymphocytes
b)
__________________________: humoral
immunity
1)
They become plasma cells, and
produce antibodies (a.k.a.
immunoglobulins)
2) antibodies bind to foreign (non-self)
antigens (surface proteins), marking the
invader for destruction by the immune
system
c) A 3rd, and less common, lymphocyte
is the
large,
granular ________________________
1)
They are nonspecific cells that
interact with virus-infected cells &
some
other abnormal cells, such as cancerous
cells
2) NK’s release ___________________
(a
hole-forming protein) that kills the
targeted,
abnormal body cell
D. __________________________ (a.k.a.
thrombocytes)
1. Platelets are not complete cells, but fragments
of large cells
called megakaryocytes
a. Formation of platelets involves repeated
mitoses of
megakaryocytes
without cytokinesis.
2. Platelets are critical to the clotting
process, forming the
temporary seal when a
blood vessel breaks.
IV. THE LYMPHATIC SYSTEM
A. The functions of the lymphatic system
1. Drains interstitial fluid
a.
The circulatory system leaks plasma into the body tissues
b.
This fluid becomes interstitial fluid
c.
Interstitial fluid is drained from body tissues by the
lympathic
system.
2. Returns leaked plasma proteins to the blood
3. Transports dietary fats, and
4. Protects against invasion by nonspecific
defenses and specific
immune
responses.
B.
The lymphatic system consists of…
1. A fluid called __________________________
a.
Lymph is formed when interstitial fluid drains into
lymphatic capillaries.
2. Lymph capillaries merge to form larger
vessels, called
lymphatic vessels
a.
Lymph vessels convey lymph into and out of structures
called lymph nodes.
3. __________________________ are encapsulated
oval
structures
composed of specialized reticular tissue containing large
numbers
of lymphocytes.
a. Lymph enters a node
b. Within the node, damaged cells, microorganisms,
and
foreign
substances are filtered from the lymph.
1) Macrophages destroy some foreign substances
by
phagocytosis.
2) Lymphocytes bring about the destruction of
others
by
specific immune responses.
c. Lymph exits the node
d.
Lymph nodes are also the site of proliferation of plasma
cells and T
cells.
4. This “cleaned” lymph is then returned to the
circulatory system
where it becomes part of
the plasma
V.
NONSPECIFIC RESISTANCE TO DISEASE
A.
Nonspecific Defense Mechanisms
1. Physical barriers, such as skin and mucous
membranes
2. Secretions, such as mucus, saliva, urine that
flush out microbes
3. Normal floral bacteria
4. Antimicrobial substances in body fluids and
phagocytes
5. Inflammation
6. Physiological defenses, such as fever
B.
First Line of Defense: Surface Barriers – the skin and mucous
membranes
1. Mechanical protection includes the intact
epidermis layer of the
skin,
mucous membranes, the lacrimal apparatus, saliva, mucus,
cilia,
the epiglottis, and the flow of urine. Defecation and vomiting
also
may be considered mechanical processes that expel microbes.
2.
Chemical protection is localized on the skin, in loose connective
tissue, stomach, and vagina.
a. The skin produces sebum, which has a low pH due to the
presence
of unsaturated fatty acids and lactic acid.
b.
Lysozyme is an enzyme
component of sweat that also
has antimicrobial properties.
c. Gastric
juice renders the stomach nearly sterile because
its
low pH (1.5-3.0) kills many bacteria and destroys most of
their
toxins; vaginal secretions also are slightly acidic.
d. Cells are capable of killing pathogens using
a
peroxidase system.
e. Cells can produce an iron-binding protein, lactoferrin,
that
makes Fe unavailable to pathogens. This
limits the
replication
of many pathogens.
3. Competition by normal flora prevents
infection with many
potential pathogens.
C. Second Line of Defense: Internal Defenses
1. The second line of defense involves…
a.
Internal antimicrobial proteins
b.
Phagocytic and natural killer cells
c.
Inflammation
d.
Fever
D. Antimicrobial Proteins – Cytokines. These proteins enhance the innate
defenses by
attacking microorganisms directly or by hindering their ability
to reproduce.
1.
__________________________ are small regulatory proteins
essential for communication between
cells.
a. Cytokines are important to …
1) the development of the inflammatory response
2) the development of fever
3) the development of specific immune responses.
b. They include…
1) Interferons
2) Interleukins
3) Colony-stimulating factors
4) Tumor necrosis factors
5) Complement
2. __________________________ (IFNs) are produced and
released by body cells infected with viruses.
a. IFNs diffuse to uninfected neighboring cells
and binds to
surface
receptors
b. Neighboring, uninfected cells, are induced to
synthesize
antiviral
proteins that interfere with or inhibit viral replication.
c. Other effects of IFNs…
1) Enhance the activity of phagocytes and
natural
killer
(NK) cells
2) Inhibit cell growth
3) Suppress tumor formation
3.
__________________________ – 18+ different cytokines
produced by leukocytes. Their functions include…
a. Inducing fever
b. Signaling for the release of PMN’s
(neutrophils) from
bone
marrow
c. Attracting WBC’s (leukocytes) to areas of
inflammation
d. Inducing the proliferation of lymphocytes (T
and B cells)
4.
_______________________________________ – direct
immature cells into appropriate
maturation pathways to produce
needed cell lines.
a. Myeloid
stem cells (in bone marrow) can be directed to
become
mature granulocytes (basophils,
eosinophils, or
neutrophils)
and monocytes (which can become
macrophages
and dendritic cells).
b. Lympoid stem cells
(in lymph nodes) can be directed to
become
mature lymphocytes (T cells, B
cells, and natural
killer
cells).
c. Megakaryoblasts will be directed to become
megakaryocytes
which will become the platelets.
5.
_________________________________________________
a.
Mast cell granules store tumor necrosis factor alpha. Its
release…
1) Induces fever
2) Recruits neutrophils to areas of inflammation
3) It is also antiviral
6. __________________________ - A group of about
20 proteins
present
in blood plasma and on cell membranes.
a. These proteins “complement” or enhance
certain
immune,
allergic, and inflammatory reactions.
b. Complement mainly acts on foreign cells by
punching
holes
in their membranes to cause their lysis & death.
c. Complement works in concert with the specific
antibodies
that
“point out” the cells to be attacked
1) The antibodies act as the “finger” to
identify a
target
cell
2) Complement acts as the “hit man” that kills
the
targeted
cell.
d. Complement plus antibodies also designate which
cells
are
to be engulfed by the phagocytic cells.
1) This is called opsonization.
e. Complement can cause a serious allergic
response
known
as anaphylactic shock.
E. Natural Killer Cells and Phagocytes
1. Natural
killer (NK) cells are lymphocytes that lack the
membrane
molecules that identify T and B cells.
a.
NKs are able to lyse and kill cancer cells and virally
infected cells before the adaptive
immune system has been
activated.
b. NK cells can release perforins.
1) Perforins insert
into the plasma membrane of cells,
causing
them to become leaky.
2) Cytolysis (death) occurs
c. NKs can also bind to target cells and inflict
damage by
direct
contact.
2. Phagocytes confront microorganisms that
breach the external
barriers.
a. __________________________ occurs in several
steps:
1)
chemotaxis – the phagocyte is attracted to nonself
antigens
exposed on bacteria surfaces or virally
infected
body cells
2)
attachment
3)
ingestion through endocytosis
4)
fusion of resulting vacuole with lysosome produces
a
phagolysosome
5)
killing within phagolysosome due to lethal
oxidants
contained within the lysosome
6)
breakdown of dead materials
a)
The phagocyte will present the resulting,
processed nonself
antigens together with self
antigens to alert the specific
immune system to
respond.
7)
exocytosis of the resulting debris.
b. Phagocytic cells include…
1) Macrophages
- the main phagocytes of the body.
2) Neutrophils
- the first responders
a) They become phagocytic when they
encounter
infectious material.
3) Eosinophils
which are weakly phagocytic
a) They are important in defending the body
against
parasitic worms.
4) Mast
cells – these cells look like macrophages,
but
are in the body tissues, not the circulatory
systems
a) They have the ability to bind with, ingest,
and
kill a wide range of bacteria.
F.
__________________________ occurs any time the body tissues are
injured by physical trauma, intense
heat, irritating chemicals, or infection
by viruses, fungi, or bacteria.
1. The four cardinal signs of acute inflammation
are…
a.
b.
c.
d.
2. Substances that contribute to inflammation
are histamines,
kinins,
prostaglandins, leukotrienes, and complement.
3. The three basic stages of inflammation are…
a. __________________________ - chemicals cause
dilation
of surrounding blood vessels. This leads
to
increased
blood flow to the area increased permeability.
1)
Vasodilation results in clotting factors and
antibodies leaving the plasma to
enter the tissues.
b. Phagocyte
migration - soon after inflammation
begins,
the
damaged site is invaded by neutrophils and
macrophages.
1)
Phagocytes engulf damaged tissue and microbes
2)
Eventually, the phagocytes die.
3) This forms a pocket of dead phagocytes and
damaged tissue and fluid called pus.
4)
Pus must drain out of the body or it accumulates in
a confined space, causing an abscess.
c. Tissue
repair.
G.
Physiological Changes contribute to body defense
1. Fever - an abnormally high body temperature.
a. Fever is a systemic response to infection
from bacteria
(and their
toxins) and viruses.
b. Fever is caused by pyrogens
that act on the
hypothalamus
to increase body temperature.
c. The high body temperature inhibits some
microbial
growth
d. Fever speeds up body reactions that aid
repair.
2. Changes in Iron Availability. Iron is
made less available to
Microorganisms,
hindering their replication.
3. Changes in Protein and Carbohydrate
Metabolism. Host
protein and carbohydrate metabolism is
increased to meet the
demands of the active
immune response.
VI. Nonspecific defense mechanisms of the body’s
weak spots – where our
fragile
body is actually open to the cold, cruel microbial world around us.
A.
Skin – tough, dry, salty,
oily, rich in fatty acids & urea, low in nutrients
(lots of dead, empty cells), &
thick.
1. Sweat glands secrete a mixture of salt &
fatty acids that inhibit
many microbes
2. The skin is host of normal flora organisms
that are antagonistic
to potential pathogens.
a. Normal flora eat up
potential nutrients on the skin surface
b. To
wash or not to wash? Washing our
skin helps to
remove
transient (potentially disease-causing) organisms.
1) However, our obsession with cleanliness also
washes
away the acid mantle of our skin that helps
prevent
infection with disease-causing organisms.
(Cure
– weak solution of apple cider vinegar sprayed
on
after bath or shower.)
2) Further, the use of antimicrobial soaps kills
much
of
the good, normal flora & can help produce
antimicrobial
resistant “super bugs”.
B.
Mouth & Gastrointestinal
tract
1. The mouth
– harbors a host of microbes that live more or less
permanently, on the
inside surface & in the nooks & crannies of the
mouth tissues. These microbes are symbiotic & usually do
us little
harm as long as we
remain healthy.
a. Some of these species do us harm by
contributing to the
production
of cavities, but many are beneficial because they
out-compete
harmful microbes that otherwise would live in
our oral
cavity & do us harm in the process.
b. Mouth microbes have evolved elaborate systems
for
sticking to
things (e.g. pili)
c. In addition, there is a continuous flow of
fluid (saliva)
through the
mouth which flushes loose microbes into
the
stomach.
2. The stomach
– contains a strong acid, hydrochloric acid.
Many
microbes are killed by
this acidic environment & digested by the
proteolytic enzymes in
the digestive system.
a. It is important to thoroughly chew food in
order to expose
potential
pathogens to this acid bath.
b. Some bacteria can live & thrive in this
low pH
environment. E.g. Helicobbacter pylori,
the cause of
stomach
ulcers & stomach cancers. This needs
to be taken
into account
when treating stomach ulcers.
3. The small
intestine – full of digestive enzymes & detergents
(bile) that agreeably
digest microbes as well as hamburger & pizza.
a. Even though the small intestine may be full
of nutrients,
the
absorption system of the healthy body is so efficient that
these
nutrients are absorbed from the intestine so rapidly
that
residential microbes have little to live on.
b. Further, the intestines are anaerobic, so
obligate aerobes
are
unable to grow there even if they should survive the trip
through
the stomach.
4. The large
intestine – is a different story. It
collects & processes
undigested material that
passes through the small intestine.
Bacteria, including some
very nasty potential pathogens, grow
robustly on this debris
& yet they rarely manage to invade the body.
a. The wall of the large intestine is coated
with a protective
mucous layer
that separates the contents from direct contact
with the
cells lining the large intestine.
b. Epithelial cells of the mucosal epithelium
lining body
channels
that sometimes communicate with air (e.g. the gut,
lungs,
urogenital tract, etc.) secrete antibiotic peptides
(defensins) that
kill bacteria by membrane disruption.
c. The normal flora of the large intestine
evolved to live on
the
available food supply in the anaerobic conditions found
there. Feces are approximately 40% bacteria by
weight.
1) One problem with antibiotics taken by mouth
is
that
they may upset the natural microbial balance &
allow
unusual microbes to establish themselves in our
mouth, intestinal tract, or
bowel. This often results in
intestinal
problems (e.g. excess gas & diarrhea) until
the
original mix of microbes is again established.
C. Genitourinary
Tract – this region of the body is a rich source of
infection for
obvious reasons.
1.
The urinary tract
a. The urine is a good nutrient for many
microbes.
b. The kidneys provide numerous nooks and
crannies
where
microbes can hide form the body’s defense systems.
c. Sexual activity significantly increases the
exposure to
potential
pathogens.
d. The efficiency of our nonspecific immune
system is
shown
by the fact that we don’t suffer more urogenital
infections
than we do.
1)
Microbes are prevented from reaching the bladder
& kidneys mainly due to the
vigorous flushing of urine
out of the body through the urethra.
2)
Because the urethra in women is shorter than in
men, bladder infections are more
common in women.
3)
People subject to frequent bladder infections
should drink lots of water & should
urinate soon after
sex to wash out potential pathogens
that may have
entered the urethra during
intercourse.
2. The vaginal area
a. Normally the vagina is acidic due to the
growth of
lactobacilli
that produce lactic & acetic acid. Also
there is a
continuous
outward flow of mucus that expels microbes from
the
vagina. Further, the entry to the
reproductive organs is
blocked by a
mucous plug much of the time.
b. However, the vaginal lining is thin &
easily damaged by
unsuitable
physical activity, including the improper use of
sanitary
napkins. Its rich blood supply makes it
an easy
entry point
for pathogens.
c. Damage to the vaginal lining is a major reason why
women are
more likely to become infected with HIV from
fewer
exposures.
3. The anal area
a. It is continually exposed to fecal microbes
that should not
be
introduced into the blood or tissue.
b. Such introduction is usually prevented by a
mucous
covering
over the delicate anal membrane lining.
c. Anal penetration by foreign objects is very
dangerous
because
these delicate membranes are easily torn & begin
bleeding. This explains why sexually transmitted
diseases
(STD’s) are
so readily contracted through anal intercourse.
D.
Respiratory tract – the
lungs, with their large surface area &
numerous small chambers, offer a
rich source of nutrients & a great
potential for concealing pathogens.
1. Everyday we breathe in hundreds of liters of
air contaminated
with dust, pollen, and
microbes, yet rarely do we get lung infections.
2. The nose is designed so that the turbulent
flow of air throws
particulate matter onto
the sticky mucous lining where much of it
adheres.
3. Particles trapped in mucous in the nose &
lungs are moved by
the beating of cilia
that line the air passages into the throat where
they are swallowed.
4. Cells lining the air passages also secrete defensins that punch
holes in the membranes
of many bacteria & destroy them.
5. Sneezing & coughing expels material out
of the air passages.