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phagocytic
leukocyte
Fighting the
Enemy Within!
Immune / Lymphatic
System
AP Biology
lymphocytes
attacking
cancer cell
lymph
system
2007-2008
Avenues of attack
 Points of entry
digestive system
 respiratory system
 urogenital tract
 break in skin

 Routes of attack
circulatory system
 lymph system

AP Biology
Why an immune system?
 Attack from outside


lots of organisms want you for lunch!
animals are a tasty nutrient- & vitamin-packed meal
 cells are packages of macromolecules

animals must defend themselves against invaders (pathogens)
 viruses
 HIV, flu, cold, measles, chicken pox
 bacteria
 pneumonia, meningitis, tuberculosis
Lyme disease
 fungi
 yeast (“Athlete’s foot”…)
 protists
 amoeba, malaria
 Attack from inside
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
cancers = abnormal body cells
Mmmmm,
What’s in your
lunchbox?
Nonspecific vs. Specific Defenses
 Three cooperative lines of defense have
evolved to counter threats posed by bacteria
and viruses.
 Two of these are nonspecific - that is, they do
not distinguish one infectious agent from
another.
Lines of defense
 1st line: Non-specific barriers

broad, external defense
 “walls & moats”

skin & mucous membranes
 2nd line: Non-specific patrols

broad, internal defense
 “patrolling soldiers”

leukocytes = phagocytic WBC
 3rd line: True immune system

specific, acquired immunity
 “elite trained units”

lymphocytes & antibodies
 B cells & T cells
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Bacteria & insects
inherit resistance.
Vertebrates
acquire immunity.
1st line: Non-specific barriers
 Mechanical Barriers that physically
block pathogens from entering the
body. The skin is the most important
mechanical barrier.
 It is the single most important defense
the body has.
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1st line: Non-specific barriers
 Chemical Barriers destroy pathogens on
the outer body surface, at body
openings, and on inner body linings.
Sweat, mucus, tears, and saliva all
contain enzymes that kill pathogens.
Urine is too acidic for many pathogens,
and semen contains zinc, which most
pathogens cannot tolerate.
In addition, stomach acid kills pathogens
that enter the GI tract in food or water
AP Biology
1st line: Non-specific barriers
 Biological Barriers are living organisms
that help protect the body.
Millions of harmless bacteria live on the
human skin. Many more live in the GI
tract.
The harmless bacteria use up food and
space so harmful bacteria cannot grow.
AP Biology
1st line: Non-specific External defense
 Barrier
 skin
Lining of trachea:
ciliated cells & mucus
secreting cells
 Traps
 mucous membranes,
cilia,
hair,
earwax
AP Biology
1st line: Non-specific External defense
 Elimination
 coughing, sneezing, urination, diarrhea
 Unfavorable pH
 stomach acid, sweat, saliva, urine
 Lysozyme enzyme
 digests bacterial cell walls
 tears, sweat
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2nd line: Non-specific patrolling cells
bacteria
 Patrolling cells

attack pathogens, but don’t
“remember” for next time
 leukocytes
 phagocytic white blood cells
 macrophages, neutrophils,
natural killer cells
Phagocyte & yeast
AP Biology
macrophage
2nd line: Non-specific patrolling cells
 Proteins
 complement system
 proteins that destroy cells
 inflammatory response
 increase in body temp.
 increase capillary permeability
 attract macrophages
AP Biology
Leukocytes: Phagocytic WBCs
 Attracted by chemical signals released by
damaged cells


ingest pathogens
digest in lysosomes
 Neutrophils


most abundant WBC (~70%)
~ 3 day lifespan
 Macrophages

“big eater”, long-lived
 Natural Killer Cells
destroy virus-infected cells
AP Biology & cancer cells

Destroying cells gone bad!
 Natural Killer Cells perforate cells
release perforin protein
 insert into membrane of target cell
 forms pore allowing fluid to
flow in & out of cell natural killer cell
 cell ruptures (lysis)

 apoptosis
vesicle
perforin
cell
membrane
AP Biology
perforin
punctures
cell membrane
cell
membrane
virus-infected cell
Anti-microbial proteins
 Complement system
~20 proteins circulating in blood plasma
 attack bacterial & fungal cells

 form a membrane attack complex
 perforate target cell
extracellular fluid
 apoptosis
 cell lysis
complement proteins
form cellular lesion
plasma membrane of
invading microbe
AP Biology
complement proteins
bacterial cell
Inflammatory response
 Damage to tissue triggers
local non-specific
inflammatory response

release chemical signals
 histamines & prostaglandins

capillaries dilate, become
more permeable (leaky)
 delivers macrophages, RBCs,
platelets, clotting factors
 fight pathogens
 clot formation

increases temperature
 decrease bacterial growth
 stimulates phagocytosis
 speeds up repair of tissues
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Fever
 When a local response is not enough

system-wide response to infection

activated macrophages release interleukin-1
 triggers hypothalamus in brain to readjust body
thermostat to raise body temperature

higher temperature helps defense
 inhibits bacterial growth
 stimulates phagocytosis
 speeds up repair of tissues
 causes liver & spleen to store
iron, reducing blood iron levels
 bacteria need large amounts
AP Biology
of iron to grow
3rd line: Acquired (active) Immunity
 Specific defense with memory
B cell

lymphocytes
 B cells
 T cells

antibodies
 immunoglobulins
 Responds to…

antigens
 cellular name tags
 specific pathogens
 specific toxins
 abnormal body cells (cancer)
AP Biology
Specific Defenses: The 3rd Line of Defense
 While microorganisms are under assault by

phagocytic cells, the inflammatory response,
and antimicrobial proteins, they inevitably
encounter lymphocytes, the key cells of the
immune system.
Lymphocytes generate efficient and selective
immune responses that work throughout the
body to eliminate particular invaders:
 This includes pathogens, transplanted cells,
and even cancer cells, which they detect as
foreign.
Humoral and Cell-Mediated Immunity
 The immune system can mount two types of
responses to antigens: a humoral response and
a cell-mediated response.

Humoral immunity involves B cell activation and
results from the production of antibodies that
circulate in the blood plasma and lymph.
 Circulating antibodies defend mainly against free bacteria,
toxins, and viruses in the body fluids.

In cell-mediated immunity, T lymphocytes attack
viruses and bacteria within infected cells and defend
against fungi, protozoa, and parasitic worms.
 They also attack “nonself” cancer and transplant cells.
 The humoral and cell-mediated immune
responses are linked by cell-signaling
interactions, especially via helper T cells.
B’s and T’s
 The vertebrate body is populated by two

main types of lymphocytes: B lymphocytes
(B cells) and T lymphocytes (T cells).
They are said to display specificity.
 A foreign molecule that elicits a specific
response by lymphocytes is called an
antigen:
 Including molecules belonging to
viruses, bacteria, fungi, protozoa,
parasitic worms, and nonpathogens like
pollen and transplanted tissue or
organs.
bone marrow
Lymphocytes
 B cells


mature in bone marrow
humoral response system
 “humors” = body fluids
 attack pathogens still circulating
in blood & lymph

produce antibodies

mature in thymus
cellular response system
 T cells

 attack invaded cells
 “Maturation”

learn to distinguish “self”
from “non-self” antigens
 if react to “self” antigens, cells
AP Biology
are destroyed during maturation
How are invaders recognized?
 Antigens

cellular name tag proteins
 “self” antigens
 no response from WBCs
 “foreign” antigens
 response from WBCs
 pathogens: viruses, bacteria, protozoa, parasitic worms,
fungi, toxins
 non-pathogens: cancer cells, transplanted tissue, pollen
“self”
AP Biology
“foreign”
B cells
 Attack, learn & remember pathogens
circulating in blood & lymph
 Produce specific antibodies

against specific antigen
Types of B cells
 plasma cells
 immediate production of antibodies
 rapid response, short term release

memory cells
 continued circulation in body
 long term immunity
AP Biology
Antibodies
 One way that an antigen elicits an immune response

is by activating B cells to secrete proteins called
antibodies.
This structure of a lymphocyte’s receptors is
determined by genetic events that occur during its
early development.



As unspecialized cells differentiate into a B or T
lymphocyte, segments of antibody genes are linked
together by a type of genetic recombination in the DNA,
generating a single functional gene for each polypeptide
of an antibody or receptor protein.
This process occurs before any contact with foreign
antigens and creates an enormous variety of B and T cells
in the body, each bearing antigen receptors of particular
specificity.
This allows the immune system to respond to millions of
antigens.
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foreign antigens

tagging “handcuffs”
 “this is foreign…gotcha!”
antigenbinding site
on antibody
antigen
Y
 millions of antibodies respond to millions of
Y

multi-chain proteins
binding region matches molecular shape of antigens
Y
each antibody is unique & specific
Y

Y
 Proteins that bind to a specific antigen

Y
Antibodies
Y
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variable
binding region
AP Biology
each B cell
has ~50,000
antibodies
Structure of antibodies
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s
light
chain
s
s
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s
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s
s s
s s
s
s
light
chain
s
s
heavy
chains
B cell
membrane
AP Biology
s
s
s
s
s
s
s
s
Y
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s
s
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s
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s
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s
variable region
s
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s
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s
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s
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antigen-binding site
What do antibodies do to invaders?
neutralize
invading pathogens
tagged with
antibodies
macrophage
eating tagged invaders
AP Biology
Y
capture
precipitate
apoptosis
First Exposure to antigen:
 The selective proliferation and differentiation of
lymphocytes that occur the first time the body is
exposed to an antigen is the primary immune
response.
 About 10 to 17 days are required from the initial
exposure for the maximum effector cell
response.
 During this period, selected B cells and T cells
generate antibody-producing effector B cells,
called plasma cells.
 While this response is developing, a stricken
individual may become ill, but symptoms of the
illness diminish and disappear as antibodies
and plasma cells clear the antigen from the
body.
Secondary Response
 A second exposure to the same antigen at
some later time elicits the secondary
immune response.
This response is faster (only 2 to 7 days), of
greater magnitude, and more prolonged.
 In addition, the antibodies produced in the
secondary response tend to have greater
affinity for the antigen than those secreted
in the primary response.

10 to 17 days for full response
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release antibodies
Y
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plasma cells
AP Biology
recognition
Y
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macrophage
Y
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captured
invaders
Y
memory cells
Y
B cells + antibodies
Y
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tested by
B cells
(in blood & lymph)
invader
(foreign antigen)
“reserves”
Y
Y
B cell immune response
clones
1000s of clone cells
Active Immunity
 Immunity conferred by recovering from an
infectious disease such as chicken pox is
called active immunity because it depends on
the response of the infected person’s own
immune system.



Active immunity can be acquired naturally or
artificially, by immunization, also known as
vaccination.
Vaccines include inactivated toxins, killed microbes,
parts of microbes, and viable but weakened
microbes.
These no longer cause disease, but they can act as
antigens, stimulating an immune response, and
more important, immunological memory.
Vaccinations
 Immune system exposed
to harmless version of pathogen

stimulates B cell system to produce
antibodies to pathogen
 “active immunity”
rapid response on future exposure
 creates immunity
without getting
disease!

 Most successful
against viruses
AP Biology
Polio epidemics
1994:
Americas polio free
AP Biology
Passive immunity
 Obtaining antibodies from another
individual

maternal immunity
 antibodies pass from mother to baby across
placenta or in mother’s milk
 critical role of breastfeeding in infant health
 mother is creating antibodies against pathogens baby
is being exposed to
 Injection
injection of antibodies
 short-term immunity

AP Biology
What if the attacker gets past the B
cells in the blood & actually infects
(hides in) some of your cells?
You need trained assassins to recognize
& kill off these infected cells!
Attack
of the
Killer T cells!
T
AP Biology
But how do T cells
know someone is
hiding in there?
2007-2008
How is any cell tagged with antigens?
 Major histocompatibility (MHC) proteins



proteins which constantly carry bits of cellular
material from the cytosol to the cell surface
“snapshot” of what is going on inside cell
give the surface of cells a unique label or
“fingerprint”
MHC protein
Who goes there?
self or foreign?
T or B
cell
MHC proteins
displaying
self-antigens
AP Biology
How do T cells know a cell is infected?
 Infected cells digest some pathogens

MHC proteins carry pieces to cell surface
 foreign antigens now on cell membrane
 called Antigen Presenting Cell (APC)
 macrophages can also serve as APC
 tested by Helper T cells
infected
cell
WANTED
MHC proteins displaying
foreign antigens
TH cell
T cell with
antigen receptors
AP Biology
T cells
 Attack, learn & remember pathogens hiding in
infected cells


recognize antigen fragments
also defend against “non-self” body cells
 cancer & transplant cells
 Types of T cells

helper T cells
 alerts rest of immune system

killer (cytotoxic) T cells
 attack infected body cells

memory T cells
 long term immunity
AP Biology
T cell attacking cancer cell
T cell response
APC:
infected cell
recognition
helper
T cell
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recognition
Y
Y
helper
T cell
AP Biology
Y
clones
Y
APC:
activated
macrophage
stimulate
B cells &
antibodies
Y
or
helper
T cell
helper
T cell
Y
interleukin 1
activate
killer T cells
Y
helper
T cell
killer
T cell
Attack of the Killer T cells
 Destroys infected body cells
binds to target cell
 secretes perforin protein

 punctures cell membrane of infected cell
 apoptosis
vesicle
Killer T cell
Killer T cell
binds to
infected
cell
infected cell
AP Biologydestroyed
cell
membrane
perforin
punctures
cell membrane
target cell
cell
membrane
Immune response
pathogen invasion
antigen exposure
skin
free antigens in blood
antigens on infected cells
macrophages
(APC)
humoral response
alert
B cells
Y
Y antibodies
cellular response
alert
T cells
memory
T cells
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Y
Y antibodies
AP Biology
Y
Y
Y
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Y
helper
T cells
memory
B cells
Y
plasma
B cells
skin
cytotoxic
T cells
HIV & AIDS
 Human Immunodeficiency Virus

virus infects helper T cells
 helper T cells don’t activate rest of immune system:
killer T cells & B cells
 also destroys helper T cells
 AIDS: Acquired ImmunoDeficiency Syndrome
infections by opportunistic
diseases
 death usually from
 “opportunistic” infections

 pneumonia, cancers
AP Biology
HIV infected T cell
AIDS
The HIV virus fools helper T-cells
into thinking its proteins are
“self,” and so is able to infect the
cells that trigger specific
immunity.
The virus forces T-cells
to make more viruses,
killing the T-cells when
the new viruses burst
out.
AP Biology
NATURAL COURSE OF HIV/AIDS
AP Biology
Stage 1 - Primary
 Short, flu-like
illness - occurs
one to six weeks
after infection
 Mild symptoms
 Infected person
can infect other
people
AP Biology
Stage 2 - Asymptomatic
 Lasts for an average of ten years
 This stage is free from symptoms
 There may be swollen glands
 The level of HIV in the blood drops to
low levels
 HIV antibodies are detectable in the
blood
AP Biology
Stage 3 - Symptomatic
 The immune system deteriorates
 Opportunistic infections and cancers
start to appear.
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Stage 4 - HIV  AIDS
 The immune
system weakens
too much as CD4
cells decrease in
number.
AP Biology
Opportunistic Infections associated with AIDS
CD4<500
 Bacterial infections
 Tuberculosis (TB)
 Herpes Simplex
 Herpes Zoster
 Vaginal candidiasis
 Hairy leukoplakia
 Kaposi’s sarcoma
AP Biology
Opportunistic Infections associated with AIDS
CD4<200
 Pneumocystic carinii
 Toxoplasmosis
 Cryptococcosis
 Coccidiodomycosis
 Cryptosporiosis
 Non hodgkin’s
lymphoma
AP Biology
HEALTH CARE FOLLOW UP OF HIV
INFECTED PATIENTS
For all HIV-infected individuals:
 CD4 counts every 3–6 months
 Viral load tests every 3–6 months and 1 month following a change in










therapy
PPD
INH for those with positive PPD and normal chest radiograph
RPR or VDRL for syphilis
Toxoplasma IgG serology
CMV IgG serology
Pneumococcal vaccine
Influenza vaccine in season
Hepatitis B vaccine for those who are HBsAb-negative
Haemophilus influenzae type b vaccination
Papanicolaou smears every 6 months for women
AIDS Prevention
 HIV is a fragile virus that cannot live
outside the human body for more than
a few minutes.
 Preventing HIV spread comes down to
preventing exposure to body fluids of
an infected person.
AP Biology
How to protect yourself…
AP Biology
Helping the immune system
 Medical science has
created to systems for
augmenting the
human immune
system:
Antibiotics (NOT the
same as antibodies)
 Vaccines

AP Biology
How antibiotics work
 Antibiotics help destroy

bacteria (but not viruses).
Antibiotics work in one of
several ways:
Slowing bacteria
reproduction.
 Interfering with bacterial
cell wall formation.

AP Biology
Antibiotic myths
 Antibiotics are not antibodies.
 Antibiotics do not weaken our immune
system. They help it by weakening
bacteria.
 Humans do not become “immune” to
antibiotics.
 Bacteria that resist antibiotics and are not
completely destroyed may multiply,
producing more antibiotic-resistant
bacteria.
AP Biology
Immune system malfunctions
 Auto-immune diseases

immune system attacks own molecules & cells
 lupus
 antibodies against many molecules released by normal
breakdown of cells
 rheumatoid arthritis
 antibodies causing damage to cartilage & bone
 diabetes
 beta-islet cells of pancreas attacked & destroyed
 multiple sclerosis
 T cells attack myelin sheath of brain & spinal cord nerves
 Allergies

over-reaction to environmental antigens
 allergens = proteins on pollen, dust mites, in animal
AP Biology
saliva
 stimulates release of histamine
It’s safe
to Ask Questions!
AP Biology
2009-2010