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Immunity
Innate & Adaptive
Immunity
• Innate: response to attack is always the
same
–
–
–
–
Mechanical mechanisms
Chemical mediators
Cellular response
Inflammatory response
• Adaptive: response to attack improves
with each exposure
– Specific
– Has memory
Innate immunity
• Mechanical mechanisms
– Skin & mucus membranes form physical
barriers to prevent entry
– Tears, saliva, urine wash away pathogens
from surface or body or dilute invading army
of pathogens
Innate immunity
• Chemical mediators: Some prevent entry
to cells, kill bacteria, or produce
inflammation
– Complement proteins
• ~ 20 in plasma
• normally inactive; activated by combining with
parts of bacterial cells or antibodies
• Leads to chain rxn activation of neighboring
compliments & inflammation, phagocytosis, or lysis
Innate immunity
• Chemical mediators
– Interferons protect against viral infection
• Virus-infected cells place interferons on their
surface (SOS signal)
• These bind to neighboring cells & stimulate
neighbors to produce antiviral proteins
• Intiviral proteins inhibit production of new viral
RNA
• Some interferons activate macrophages and NKC
Innate immunity
• Cellular mechanisms
– WBC & derivatives are most important
cellular components
• Attracted to invading bacteria and
microorganisms through chemotaxis
– Phagocytic cells (who are these?)
– Inflammatory cells (…and these?)
– Natural Killer Cells (NKC)
White Blood Cells
Innate immunity
• Phagocytic cells
– Neutrophils
• Small; first to enter infected tissue from blood;
ingest, then die --> pus accumulation
– Macrophages
• Monocytes leave blood & enlarge; arrive after
neutrophils; do most eating & cleanup
• Also hang out at “entry points” (gate-keepers)
Innate immunity
• Natural Killer Cells (NKC)
– 15% of all lymphocytes are NKC
– Recognize tumor cells or virus-infected cells
(generalist killers)
– No memory; non-specific
– Kill via chemical release (cell membrane lysis)
Innate immunity
• Inflammatory cells: activated through
innate or adaptive immunity; release
histamine & pyrogens
– Basophils
• Motile WBC; enter infected tissue
– Mast cells
• Non-motile; Located in lymph organs at “points of
entry”
– Eosinophils
• Release enzymes that reduce inflammation (control)
Inflammation is useful!
• Local inflammation: Redness, heat, swelling
– caused by increased blood flow & vascular permeability
– Chemicals and swelling activate pain receptors
• Systemic inflammation
– Red marrow increases neutrophil production
– Pyrogens stimulate fever by increasing heat production
& conservation
– Vascular permeability increases
Adaptive immunity
• Lymphocytes
– Origin & development
– Activation & multiplication
• Antibody-mediated
• Cell-mediated
Adaptive immunity
• Antigens stimulate adaptive immune response
– Self
– Foreign
• MHC molecules display antigens
• Lymphocytes
– Origin & development
– Activation & multiplication
• Types of Adaptive Immunity
– Antibody-mediated
• B cells; produce cells that make antibodies
– Cell-mediated
• T cells; cytotoxic & helper T cells
Antigens
• Foreign
– Components of bacteria, viruses, and their
chemical byproducts
– Pollen, animal hair, foods produce allergic
response (overreaction of immune system)
• Self
– Produced by our bodies
• Recognize tumor antigens
B & T-cells (Lymphocytes)
• Contain antigen receptors in their cell
membranes
• We each have thousands of different
populations of B & T-cells, each with
unique antigen receptors
• Cells are stimulated by binding of antigens
to their unique receptors
Cell
Development
Bone
marrow
Stem cell
• Red marrow
produces:
– Pre B-cells:
released into
bloodstream
– migrate to lymph
organs
Thymus
Via
blood
Immature
lymphocytes
Antigen
receptor
Antigen
receptor
B cell
– Pre T-cells:
migrate to thymus
& mature there
• Mature T-cells
migrate to lymph
organs
T cell
Via
blood
Lymph nodes,
spleen, and
other lymphatic
organs
Final maturation
of B and T cells in
lymphatic organ
Activation & multiplication
• Macrophages present
antigens
– Phagocytize invaders, process
& display antigens (with help of
MHC molecules)
• MHC/Antigen complex binds
to receptors on B or T-cells
• T-cells auto-stimulate
– Produce cytokines (peptides;
e.g. interleukin) that upregulate growth & division
B cell activation
• Antibody-mediated
• B-cells can also
phagocytize & process
antigens
– same antigen that stimulated
a Th
• Th binds to B-cell
• Interleukins are produced
– stimulate B-cell division &
proliferation
– Daughter (plasma) cells
produce antibodies
Effects of Antibodies
• Direct
– Antibodies bind antigens = inactivation
• Indirect
– Activate Complement cascade
• Inflammation (mast cells and basophils release
histamine)
• Chemotaxis (attracts white blood cells)
• Phagocytosis or lysis (macrophage eats antibody &
antigen
Binding of antibodies to antigens
inactivates antigens by
Neutralization
Virus
Agglutination
of microbes
Precipitation of
dissolved antigens
Activation of
complement system
Complement
molecule
Bacteria
Antigen
molecules
Bacterium
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
Hole
Antibody production
• Differs following first and second
exposure to antigen
– First exposure = primary response
• B-cells bind antigen; produce plasma cells (produce
antibodies) and memory B-cells
• Response time = 3-14 days; disease symptoms
develop; SLOW
Fig. 24-7aa-1
Primary immune
response
B cells with
different
antigen
receptors
1
Antigen receptor
(antibody on cell
surface)
Fig. 24-7aa-2
Primary immune
response
B cells with
different
antigen
receptors
1
Antigen receptor
(antibody on cell
surface)
2
Antigen
molecules
Fig. 24-7aa-3
Primary immune
response
B cells with
different
antigen
receptors
1
Antigen receptor
(antibody on cell
surface)
2
Antigen
molecules
3 First exposure
to antigen
Cell activation:
growth,
division, and
differentiation
Fig. 24-7aa-4
Primary immune
response
1
B cells with
different
antigen
receptors
Antigen receptor
(antibody on cell
surface)
2
Antigen
molecules
3 First exposure
to antigen
Cell activation:
growth,
division, and
differentiation
Antibody
molecules
4
First clone
Endoplasmic
reticulum
Plasma (effector) cells secreting antibodies
Fig. 24-7aa-5
Primary immune
response
1
B cells with
different
antigen
receptors
Antigen receptor
(antibody on cell
surface)
2
Antigen
molecules
3 First exposure
to antigen
Cell activation:
growth,
division, and
differentiation
Antibody
molecules
4
First clone
5
Endoplasmic
reticulum
Plasma (effector) cells secreting antibodies
Memory cells
Antibody production
• Differs following first and second
exposure to antigen
– Second exposure = secondary response
• Memory cells quickly induce plasma cells to
produce antibodies
• Time to antibody production is reduced
• More plasma cells & antibodies produced
• RAPID response, no disease symptoms = immunity
Fig. 24-7aa-6
Antigen
molecules
6 Second exposure
to same antigen
Secondary
immune
response (May
occur long after
primary immune
response.)
Antibody
molecules
Endoplasmic
reticulum
Second clone
Plasma (effector) cells secreting antibodies
Memory cells
Fig. 24-7b
Second exposure
to antigen X,
first exposure
to antigen Y
Secondary immune
response to
antigen X
First exposure
to antigen X
Primary immune
response to
antigen X
Antibodies
to Y
Antibodies
to X
0
7
14
21
Primary immune
response to
antigen Y
28
35
Time (days)
42
49
56
Cell-mediated immunity
• Cytotoxic T cells (Tc)
• Effective against viruses, bacteria
• Infected cells display antigens, and Tc
binds to MHC/antigen combo
– Stimulates production of more Tc
– Costimulation by Th which were stimulated by
macrophage display of antigens
Fig. 24-11b
Self-nonself
complex
B cell
T cell
receptor
Interleukin-2
stimulates
cell division
5
3
2
Helper
T cell
Interleukin-1
stimulates
helper T cell
Interleukin-2
activates B cells
and other T cells
7
4
Antigen-presenting
cell
6
Humoral
immune
response
(secretion of
antibodies by
plasma cells)
Binding Binding
site for site for
antigen self protein
Cytotoxic
T cell
Cell-mediated
immune
response
(attack on
infected cells)
Fig. 24-12-1
1 Cytotoxic T cell binds
to infected cell
Self-nonself
complex
Infected cell
Foreign
antigen
Perforin
molecule
Cytotoxic
T cell
Fig. 24-12-2
1 Cytotoxic T cell binds
to infected cell
Self-nonself
complex
Infected cell
Foreign
antigen
Perforin
molecule
Cytotoxic
T cell
2 Perforin makes holes in
infected cell’s membrane
and enzyme enters
Hole
forming
Enzyme that
can promote
apoptosis
Fig. 24-12-3
1 Cytotoxic T cell binds
to infected cell
Self-nonself
complex
Infected cell
Foreign
antigen
Perforin
molecule
Cytotoxic
T cell
2 Perforin makes holes in
infected cell’s membrane
and enzyme enters
Hole
forming
Enzyme that
can promote
apoptosis
3 Infected cell
is destroyed
Show “Immune Response”
Mcgraw Hill
Th stimulate both immune
responses
B cell
Self-nonself
complex
Macrophage
Microbe
Interleukin-2
stimulates
cell division
T cell
receptor
5
3
1
2
6
Helper
T cell
Interleukin-2
activates B cells
and other T cells
7
4
Self protein
Antigen from microbe
(nonself molecule)
Antigen-presenting
cell
Interleukin-1
stimulates
helper T cell
Humoral
immune
response
(secretion of
antibodies by
plasma cells)
Binding
site for
antigen
Binding
site for
self protein
Cytotoxic
T cell
Cell-mediated
immune
response
(attack on
infected cells)
Acquiring Adaptive immunity
Antigens, Antibodies & Vaccines
• Inject host with inactive or attenuated virus
(usually bits & pieces aka antigens)
• Host immune cells grab antigens & stimulate
other cells (B cells) to engineer antibodies to
bind to antigens
Antigens, Antibodies & Vaccines
• B cells “remember” how to make this antibody
forever
• On subsequent infection, live virus is mobbed by
antibodies, targeted for termination and eaten
by macrophages