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Transcript
Fighting the
Enemy Within!
phagocytic
leukocyte
Immune / Lymphatic
System
AP Biology
lymphocytes
attacking
cancer cell
lymph
system
2007-2008
 Start and review with the
masteringbiology.com Immunology video
 Another good one from McGraw-Hill
 Immune system game by NobelPrize.org
AP Biology
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
AP Biology

cancers = abnormal body cells
Mmmmm,
What’s in your
lunchbox?
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
AP Biology
Bacteria & insects
inherit resistance.
Vertebrates
acquire immunity.
Figure 43.2
Pathogens
(such as bacteria,
fungi, and viruses)
INNATE IMMUNITY
(all animals)
• Recognition of traits shared
by broad ranges of
pathogens, using a small
set of receptors
• Rapid response
ADAPTIVE IMMUNITY
(vertebrates only)
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
• Slower response
AP Biology
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Natural killer cells
Antimicrobial proteins
Inflammatory response
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic cells defend
against infection in body cells.
Development of the key players,
Red & White blood cells
inflammatory
response
Red blood cells
fight
parasites
Leukocytes
Lymphocytes
AP Biology
develop into
macrophages
short-lived phagocytes
60-70% WBC
Figure 43.7
Blood
capillary
Interstitial
fluid
Adenoid
Tonsils
Lymphatic
vessels
Thymus
Tissue
cells
Peyer’s
patches
(small
intestine)
Appendix
(cecum)
Spleen
Lymphatic
vessel
Lymph
nodes
Lymph
node
AP Biology
Lymphatic
vessel
Masses of
defensive cells
1st line: Non-specific External defense
 Barrier
 skin
Lining of trachea:
ciliated cells & mucus
secreting cells
 Traps
 mucous membranes, cilia,
hair, earwax
 Elimination
 coughing, sneezing, urination,
diarrhea
 Unfavorable pH
 stomach acid, sweat, saliva, urine
 Lysozyme enzyme
 digests bacterial cell walls
 tears, sweat
AP Biology
2nd line: Non-specific patrolling cells
bacteria
 Patrolling cells & proteins

attack pathogens, but don’t
“remember” for next time
 leukocytes
 phagocytic white blood cells
 macrophages, neutrophils,
natural killer cells
macrophage
 complement system
 Free-floating proteins that
destroy cells
 inflammatory response
AP Biology
 increase in body temp.
 increase capillary permeability
 attract macrophages
yeast
Leukocytes: Phagocytic WBCs
 Attracted by chemical signals released by
damaged cells
 Neutrophils



most abundant WBC (~70%)
~ 3 day lifespan
phagocyte
 Macrophages


“big eater” phagocyte
long-lived
 Natural Killer Cells

AP Biology
destroy virus-infected cells
& 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
AP Biology
Figure 43.8-1
Pathogen
Mast
cell
Splinter
Macrophage
Signaling
molecules
Capillary
Neutrophil
Red
blood cells
AP Biology
Figure 43.8-2
Pathogen
Mast
cell
Splinter
Macrophage
Signaling
molecules
Capillary
Neutrophil
Red
blood cells
AP Biology
Movement
of fluid
Figure 43.8-3
Pathogen
Mast
cell
Splinter
Macrophage
Signaling
molecules
Capillary
Neutrophil
Red
blood cells
AP Biology
Movement
of fluid
Phagocytosis
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
 antibodies (a.k.a. immunoglobulins)
 T cells
 Responds to…

antigens
 cellular name tags
 specific pathogens
 specific toxins
 abnormal body cells (cancer)
AP Biology
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”
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
Figure 43.20
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)

Engulfed by
Antigenpresenting cell

Stimulates
Gives rise to


B cell
Helper T cell


Cytotoxic T cell
Memory
helper T cells



Antigen (2nd exposure)
Plasma cells
Memory B cells

Memory
cytotoxic T cells
Active
cytotoxic T cells
Secreted
antibodies
Defend against extracellular
pathogens
AP Biology
Defend against intracellular
pathogens and cancer
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
10 to 17 days for full response
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y Y
Y
Y
Y
Y
Y
Y
Y
release antibodies
Y
Y
plasma cells
AP Biology
recognition
Y
Y
Y
Y
Y
Y
Y
Y
macrophage
Y
Y
Y
Y
Y
captured
invaders
Y
memory cells
Y
B cells + antibodies
Y
Y
Y
Y
Y
tested by
B cells
(in blood & lymph)
invader
(foreign antigen)
“reserves”
Y
Y
B cell immune response
clones
1000s of clone cells
Y
Y
multi-chain proteins
binding region matches molecular shape of antigens
each antibody is unique & specific
Y
Y
foreign antigens
tagging “handcuffs”
 “this is foreign…gotcha!”
Y

Y
 millions of antibodies respond to millions of
Y

Y
Y
Y

Y

Y
Y
 Proteins that bind to a specific antigen
Y
Y
Antibodies
Y
Y
Y
antigenbinding site
on antibody
antigen
Y
Y
Y
Y
variable
binding region
AP Biology
each B cell
has ~50,000
antibodies
Y
Y
Y
Structure of antibodies
Y
s
s
s
light
chain
B cell
membrane
AP Biology
s
s
s
s
s s
s s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
Y
s
Y
s
s
s
Y
s
s
Y
s
variable region
s
Y
s
s
Y
s
Y
Y
antigen-binding site
light
chain
heavy
chains
light chains
antigen-binding
site
heavy chains
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
 Immunoglobulins

IgM
 1st immune response
 activate complement proteins

Antibody levels
Classes of antibodies
invading
Exposure pathogens
to
tagged
with
antigen
antibodies
IgM
IgG
Y
0
macrophage
eating tagged
invaders
2
4
Weeks
IgG
 2nd response, major antibody circulating in plasma
 promote phagocytosis by macrophages

IgA
 in external secretions, sweat & mother’s milk

IgE
 promote release of histamine & lots of bodily fluids
 evolved as reaction to parasites
 triggers allergic reaction

AP Biology
IgD
 receptors of B cells???
6
Figure 43.UN02
Stem cell
Cell division and
gene rearrangement
Elimination of
self-reactive
B cells
Antigen
Clonal
selection
Formation of
activated cell
populations
Memory B cells
Antibody
Plasma cells
Pathogen
AP Biology
Receptors bind to antigens
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
1914 – 1995
Jonas Salk
April 12, 1955
 Developed first vaccine

against polio
 attacks motor neurons
Albert Sabin
1962
oral
vaccine
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
Figure 43.11
Antigenbinding
site
T cell
antigen
receptor
V
V
Variable
regions
C
C
Constant
regions
Disulfide
bridge
 chain
T cell
AP Biology
Transmembrane
region
 chain
Plasma
membrane
Cytoplasm of T cell
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
Figure 43.12
Displayed
antigen
fragment
T cell
T cell antigen
receptor
MHC
molecule
Antigen
fragment
Pathogen
Host cell
(a) Antigen recognition by a T cell
Top view
Antigen
fragment
MHC
molecule
Host cell
AP Biology
(b) A closer look at antigen presentation
Animation: Role of B Cells
AP Biology
© 2011 Pearson Education, Inc.
Right-click slide / select “Play”
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 system & Blood type
blood
type
antigen
on RBC
antibodies
in blood
donation
status
A
type A antigens
on surface of RBC
anti-B antibodies
__
B
type B antigens
on surface of RBC
anti-A antibodies
__
AB
both type A & type B
antigens on surface of
RBC
no antibodies
universal
recipient
O
no antigens
on surface of RBC
anti-A & anti-B
antibodies
universal
donor
Matching compatible blood groups is critical for blood transfusions
A person
AP Biologyproduces antibodies against foreign blood antigens
Animation: Helper T Cells
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
Animation: Cytotoxic T Cells
AP Biology
© 2011 Pearson Education, Inc.
Right-click slide / select “Play”
Figure 43.16
Antigenpresenting
cell
Antigen fragment
Pathogen
Class II MHC molecule
Accessory protein
Antigen receptor
1
Helper T cell


Cytokines
Humoral
immunity
B cell
AP Biology

3
2

Cytotoxic T cell
Cellmediated
immunity
Figure 43.17-1
Cytotoxic T cell
Accessory
protein
Class I MHC
molecule
Infected
cell
1
AP Biology
Antigen
receptor
Antigen
fragment
Figure 43.17-2
Cytotoxic T cell
Accessory
protein
Class I MHC
molecule
Infected
cell
1
AP Biology
Antigen
receptor
Perforin
Pore
Antigen
fragment
2
Granzymes
Figure 43.17-3
Cytotoxic T cell
Accessory
protein
Class I MHC
molecule
Infected
cell
1
AP Biology
Released
cytotoxic
T cell
Antigen
receptor
Perforin
Pore
Antigen
fragment
2
Dying
infected cell
Granzymes
3
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
 HIV
 Helper T cells attacked by virus
 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
Figure 43.22
Histamine
IgE
Allergen
Granule
Mast cell
AP Biology
Figure 43.23
AP Biology
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
Animation: HIV Reproductive Cycle
Right-click slide / select “Play”
AP Biology
© 2011 Pearson Education, Inc.
Helper T cell concentration
(in blood (cells/mm3)
Figure 43.25
Latency
AIDS
Relative anti-HIV antibody
concentration
800
Relative HIV
concentration
600
Helper T cell
concentration
400
200
0
0
AP Biology
1
3
7
8
2
4
5
6
Years after untreated infection
9
10
Review Videos
 Bioflix: Immune response
 Bozeman Biology: Plant and Animal
Defense video
AP Biology