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Chapter 24 The Immune System
1) Nonspecific Immunity
a) 1st line f defenses
b) don’t distinguish one microbe from another
c) skin
i)
outer layer, tough, several layers of dead cells
impenetrable by microorganisms (MO’s)
ii) glands of skin secrete acid – inhibit growth
iii) sweat, saliva, tears – contain lysozyme –
enzyme that breaks down cell wall of bacteria
d) mucous membranes
i)
protect digestive and respiratory systems
(1) other protection of these systems
(a)stomach acid
(b) hairs of nostrils
(c)beating cilia of trachea…
e) nonspecific defense cells
i)
cells that confront microbes if they get past skin
or tissues of dig./resp tract
ii) White blood cells
(1) neutrophils and monocytles
both phagocytes
(b) macrophages - “big eaters”
(i) large phagocytes that develop from monocytes
(ii) wander IF looking for and eating bacteria and
virus-infected cells
(c)natural killer cells
(i) attack cancer and infected body cells, especially
ones with viruses
f) protein based
(a)
i)
interferons
(1) interfere with viral reproduction
(2) proteins made by virus-infected cells
(3) help other cells resist viruses
(4) Figure 24.1B
(5) remember, this is not specific
(a)other cells are more resistant to this virus as well as
unrelated ones
(6) resistance is short-term
(7) if these proteins prepare cells for many types of virus,
what should we do?
(a)recombinant DNA technology
ii) complement proteins
(1) complement other defense mechanisms
(2) circulate in inactive form in blood
(3) activated by immune system of microbes
(4) functions
(a)some coat surface of microbes
(i) makes easier for microbes to engulf
(b) some puncture holes in membranes of microbes
(i) why is this a problem?
(c)amplify the inflammatory response
g) inflammatory response – “setting on fire”
i)
major component of non-specific defense
ii) triggered by ANY tissue damage – microbe or
physical (scrape, cut, etc…)
iii) Can see when mosquito bites
(1) reddening around surface (rubor)
(2) swollen (edema)
(3) warmer (calor)
iv) inflammatory response (Figure 24.2) – chain of events
(1) pinprick
(2) damaged cells release chemicals like histamine
(3) chemicals spark various defenses
– induces blood vessels to dilate and
become leakier
(i) increases blood flow to area and increases and
plasma passes out of leaky vessels
(b) other chemicals
(i) attract phagocytes and other WBC’s
(ii) squeeze b/w epithelial cells of vessel (video
starring kinesin)
(c) increased blood to area is what causes redness,
swelling and heat
(4) WBC’s engulf bacteria and dead body cells
(5) many WBC’s die in process
(a)pus = dead WBC’s and leaked fluid from vessels
(b) they are also engulfed
(6) clotting proteins and proteins pass through vessel into
area and form local clots – seal off infected region
v)
inflammatory event can also be widespread (systemic)
(1) MO’s like bacteria or protozoa circulate in blood
(2) toxin from bacteria circulates in blood
(a) bodies response:
(i) WBC’s in blood may increase
(ii) fever – increase in body temp.
1. triggered by toxin itself or certain WBC’s
release chemicals to trigger
2. moderate fevers stimulate phagocytes and
inhibit growth of many MO’s
(3) septic shock
(a)an overwhelming inflammatory response
(b) high fever, low BP
(c)most common cause of death in ICU’s of American
hospitals
h) The lymphatic system – a crucial battleground
i)
lymphatic system
(1) involved in BOTH nonspecific and specific immunity
(2) Consists of
(a)histamine
(a)branching
network of vessels
(b) numerous lymph nodes
(i) sac-like organs chuck full of lymphocytes
(c)tonsils and adenoids
(d) appendix
(e) spleen
(f) bone marrow
(g) thymus
(3) lymph – fluid carried by vessels
(a)similar to IF, but less O2 and nutrients
(4) Functions
(a)return tissue fluid (IF) to circ. system (Fig 24.3B)
(i) The flow scheme (one-way)
1. lymph capillaries are dead ends
2. lymph enters by diffusion
3. travels to larger and larger lymph vessels
4. re-enters veins of circ. system in two places
around shoulders via thoracic and right
lymphatic ducts
(ii) vessels resemble veins
1. have valves
2. depend of movement of skeletal muscles to
move lymph
(b) fight infection
(i) occurs in lymph nodes and other lymphatic organs
(pink labels in 24.3A – know them)
(ii) lymph nodes
1. MO filters
2. packed with lymphocytes and macrophages
a. macrophages will engulf bacteria from sites
of infection nonspecifically
b. lymphocytes may be activated to mount a
specific response
3.
become swollen and tender when you have an
infection (“swollen glands”) – most obvious in
lymph nodes of neck
a. caused by proliferation of lymphocytes
2) Specific immunity = the immune system
a) used when non-specific fails or in combination
b) defends against invading microbes as well as cancer cells
c) more effective than nonspecific defenses
d) different from nonspecific
i)
ii)
MUST be primed (not always ready to fight)
antigen
(1) foreign substance that primes system
(2) molecule that elicits and immune response
(a)increase # of cells that attack invader
(b) increase # of cells that produce antibodies against
that invader
(3) contraction of antibody-generating
(4) surface molecules of
(a)virus, bacteria, mold spores, cancer cells, pollen,
house dust, foreign transplanted cells, etc…
iii) antibody
(1) protein in blood that attaches to ONE particular kind of
antigen
(2) helps counter its effects
e) highly specific to a specific antigen
f) can “remember” past antigens…it is adaptive
i)
reacts more promptly and vigorously the second time
around – the army of WBC’s is already waiting
ii) chicken pox or rubella (German measles)
(1) cells remember surface molecules on virus
(2) once they see them again, they destroy quick
g) immunity
i)
resistance to specific invaders
ii) usually acquired by natural infection
iii) can also be achieved by vaccination
(1) vaccine
(a)harmless variant of a disease causing microbe
(b) immune system will be primed for the real thing
(i) smallpox, polio, mumps, measles, chicken pox,
influenze
(ii) trying for HIV, but nothing yet…why?
iv) active immunity
(1) body stimulated to produce antibodies
(2) permanent for the most part
v)
passive immunity
(1) fetus obtains antibodies from mother (doesn’t need to
make its own)
(2) travelers sometimes get antibody shots against certain
pathogens
(3) temporary...be able to explain why.
h) lymphocytes mount a dual defense – humoral and cellmediated immunity
i)
lymphocytes
(1) spend most of their time in lymph tissue and organs
(2) produce the immune response
(3) originate in bone marrow
(a)immature lympocytes in marrow have 2 fates
(i) continue to develop there and become a B
lymphocyte (B-cell) – B for Bone
(ii) be carried by blood to thymus and become Tlymphocytes or T-cells – T for Thymus
(b) both types eventually make way to lymph system
ii) humoral immunity (body fluids were once called
“humors”)
(1) Achieved by B-cells
(a)produce antibodies that are secreted and dissolved
into blood (humor)
(b) defends against bacteria and virus in body tissues
(humors)
(c)can
be transferred passively by injecting plasma of
one individual to another
iii) cell-mediated immunity
(1) Achieved by T-cells
(a)cannot be passively transferred with plasma, must
transfer cells
(b) T-cells attack bacterial of viral infected body cells
(c)also work against fungal and protozoa infections, and
cancer cells
(d) promote phagocytes
(e)stimulate B-cells to make antibodies
(i) T-cells are involved in both humoral and cellmediated immunity
iv) antigen-receptors
(1) present on both T-cells and B-cells
(a)can bind a specific type of antigen
(b) B-cells
(i) receptors are parts of Ab they will secrete
(2) every cell recognizes one specific antigen (one cell –
one antigen)
(3) estimated 100 million to 100 billion different B/T cells
(enough to recognize and bind almost any kind of
antigen) – a small population of each kind sits and waits
(a)so we can recognize millions to billions of antigens
(b) many will never encounter the antigen they were
designed for
i) Antigens have specific regions where antibodies bind
i)
antigenic determinants
(1) specific regions on the antigen recognized by the
antibody
(2) antigenic determinant has complementary shape to
antibody
(3) several determinants on a single antigen
(a)more than one type of antibody can bind to it
j) Clonal selection
i)
antigen only activates a “select” number of cells
(those with the proper antigen-receptors)
ii) these cells then proliferate and mature to fight the
infection (Fig. 24.7)
k) initial immune response results in a type of “memory”
i)
first encounter does elicit an immune response
ii) takes two to get the strongest
iii) The two responses (Fig. 24.8A)
(1) The primary immune response
(a)lymphocytes first exposed to antigen
(b) takes several days
(2) secondary immune response
(a) faster and sronger
(b) produce a high level of antibodies
(c)lasts longer than primary
iv) These two responses happen for every new antigen
v)
Fig. 24.8B
(1) cellular events that produce prim. and sec. responses
(2) after clonal selection, clone of activated cells
differentiates into two types
(a)effector cells –
(i) produce Ab’s to combat invader if they are Bcells
(ii) survive only a few days
(b) memory cells
(i) can last decades in lymph nodes, ready to be
activated
(ii) upon a second exposure, memory cells divide
quickly and produce more memory and effector
cells
vi) clonal selection, effector cells, and memory cells are
features of cell-mediated (T-cell) immunity as well.
l) Overview: B-cells are the main warriors of humoral
immunity
i)
effector B-cells = plasma cells
(1) the warriors
(2) secrete ~2000 Ab molecules / second
(3) response subsides as cells die out after 4-5 days
ii) memory B-cells
(1) the reservists
(2) wait around for return of same antigen (could be never)
m)
Antibodies are the weapons of humoral immunity
i)
Antibodies
(1) molecular weapons of defense
(2) Y-shaped (Fig. 24.10)
(3) four polypeptides
(a)two heavy chain
(b) two light chain
(4) each chain has a variable (V) region and a constant (C)
region.
(5) Function
(a)recognize and bind antigen, and in doing so neutralize
it
(6) antigen-binding site
(a)formed by V regions at each tip of each arm of the Y
(b) where antibody binds antigen
(c)must be able to form many different shapes
(i) how would a protein make different shapes?
(ii) have different amino acids
1. this is why it is called the variable (V) region
(7) Tail
(a)formed by C regions
(b) helps with disposal of Ab
(c) five different C regions
(d) each region denotes a different class of Ab
(i) humans and other mammals have 5 classes and
therefore 5 different C regions
n) Antibodies mark antigens for elimination (Fig. 24.11)
i)
antibody binds via weak bonds (H-bonds, ionic, etc..)
to antigen – Ag-Ab complex
ii) Effector mechanisms (Fig. 24.11)
(1) All start with a specific recognition and finish with a
non-specific destruction phase (specific works with
nonspecific)
(2) Types
(a)neutralization
(b) agglutination
(c)precipitation
(d) activation of complement
o) Monoclonal Antibodies (powerful tool in the lab and clinic)
i)
Polyclonal antibodies – coming from many clones
(1) Inject antigen into rabbits
(2) wait some amount of time
(3) remove blood and purify antibodies
(4) Problem:
(a)you get a mixture of all the antibodies
(b) multiple types of antibodies are made against a
single antigen due to multiple antigenic
determinants.
(c)we want a single type of antibody
ii) Monoclonal antibodies – coming from a single clone
(1) all produce identical Ab molecule
(2) harvested from cell cultures rather than animal
(3) Procedure
(a)inject mouse with desired antigen
(b) remove spleen and collect B-cells
(c)fuse B-cells with tumor cells
(i) now each cells can reproduce indefinitely in lab
and produce large amounts of one find of
antibody
(d) grow a colony from one cell and purify antibody
(4) can be used to test for specific bacteria
(5) bind with hormone indicating pregnancy
(6) label them with a dye and you can now “see” if the
hormone is there (home pregnancy test)
(7) herceptin – monoclonal antibody used to treat a form of
breast cancer
(a)bind growth-factor receptor that is present in excess,
shutting it off
(8) attach a cell killing drug to antibody (future) – guided
missile
p) T-cells
i)
B-cells fight the battle outside of our cells
ii) T-cells fight the battle that has entered out cells
iii) respond to antigens presented by our own cells
iv) Two main kinds
(1) cytotoxic T-cells
(a)attack infected body cells
(2) Helper T-cells
(a)help activate cytotoxic T-cells, macrophages and
stimulate B-cells to produce antibodies
(b) antigen-presenting cells (APCs)
(i) macrophages and B-cells
(ii) display foreign antigens on surface
(c)Helper T-cells interact with antigen-presenting cells
(i) activates the Helper T-cell
v)
Process
(1) APC (macrophage) ingests microbe
(2) digests it into pieces
(3) displays pieces on surface bound to one of its own “self
proteins”
(4) Helper T cells recognize and bind self-nonself complex
(a)double-recognition system
(b) recognition depends on T-cell receptors, which can
bind only one type of self-nonself complex
(5) binding triggers a signal transduction pathway in
Helper T cell, activating it
(6) other signals enhance activation
(a)IL-1
(7) Helper T-cell will now secrete IL-2
(a)three
effects of IL-2
(i) makes helper T-cell itself grow and divides
1. producing both memory T-cells and more
Helper T-cells of this specific type
2. positive feedback
(b) stimulates cytotoxic T-cells
(c)helps activate B-cells
vi) cytotoxic T-cells are only ones to kill other cells
(1) once activated, C T-cells recognize cells same way as H
T-cells
(2) self-nonself complex on an infected cell is like a red
flag
(3) Once bound, C T-cell produces perforin
(4) perforin makes holes in infected cells membrane
(5) another T-cell proteins enters hole and triggers
apoptosis (programmed cell death)
q) C T-cells may prevent cancer
i)
people with immune deficiencies often susceptible to
cancer
ii) if surface proteins are changed in a significant way,
they may be able to be recognized by T-cells
r) Immune system depends on out molecular fingerprints
i)
immune system needs to recognize self from nonself
ii) Two sets of self proteins (molecular fingerprints) –
called the majorhistocompatability complex (MHC)
because it is important in organ donor typing.
(1) Class I proteins
(a)on all nucleated cells
(2) Class II proteins
(a) found on only a few types of cells
(i) B-cells, Activated T-cells, macrophages
(3) genes at six loci determine the fingerprint proteins
(a)there
are hundreds of alleles for each gene loci
(b) almost impossible for any two people (except
identical twins) to have matching sets of selfproteins
(i) organ transplants – find donor with most similar
MHC’s
(ii) combine with anti-rejection meds like
cyclosporine, which suppresses cell-mediated
immunity
(iii)Use stem cells of person to produce their own
organ (future)
3) Disorders of the immune system
a) autoimmune diseases
i)
immune system turns against self
(1) systemic lupus erythromatosus (lupus)
(a)B-cells make antibodies against many molecules
including histones and DNA
(2) Rheumatoid arthritis
(a) antibodies against joints of bones
(3) insulin-dependent diabetes
(a) cells of pancreas targeted by cell-mediated response
(4) multiple sclerosis
(a)T-cells react against myelin
ii) most medications either suppress immunity or just
alleviate symptoms
b) immunodeficiency diseases
i)
people that lack one or more components of the
immune system
(1) severe combined immunodeficiency (SCID) – rare
congenital disease (born with it)
(a)T-cell and B-cells are absent or inactive
(i) stem cells (future)
(ii) gene therapy (future) if it is a single gene
(2) Hodgkin’s disease
(a)type
of cancer of the lymphcytes
(b) can suppress immune system
(3) AIDS
c) Stress may affect our immune system
d) allergies
i)
overreaction to certain environmental antigens
ii) allergens
(1) antigens that cause allergies
(a)proteins of surface of pollen, proteins on animal hair,
proteins on surface of tiny mites, etc…
(b) allergic to cats and dogs? most people who are are
allergic to their salivary proteins, which is on their
fur from licking
iii) can occur in many parts of body (nasal passages,
bronchi, digestive tract, skin, etc…)
iv) can be quick
(1) few molecules of allergen can cause a reaction in
minutes
v)
symptoms
(1) sneezing, coughing, wheezing, upset stomach, and
itching
vi) Two stages of an allergic reaction (Fig. 24.17)
(1) Sensitization
(a)allergen causes B-cells to secrete special kind of
antibody that in turn attach to mast cells and cause
mast cells to release histamine
(2) Later exposure to same allergen
(a)allergen binds directly to antibodies bound to mast
cell releasing histamines immediately
vii) Antihistamines
(1) interfere with histamine action and gives temp. relief
viii) anaphylactic shock
(1) very dangerous type of allergic reaction
(2) very sensitive to allergen (venom of bee sting)
(a)mast cells release histamine very suddenly
blood vessels dilate very quickly (swelling)
(c)blood pressure drops (shock) – potentially fatal
(3) epinephrine – hormone that can counter anaphylactic
shock
(b)
4)