IMMUNE RESPONSE

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IMMUNE RESPONSE

• Mr. Christ
• Advanced Biology

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Abbreviations SymbolsInformation flows left to
right

• Macrophage T-helper cell B cell Antibodies
• MO TH B Ab
• Key
• - Self Protein MO - Macrophage
• - Foreign Protein TH - T-helper cell
• - Lysosome B - B cell
• Ab - Antibodies
• IL1-interleukin one
• IL2-interleukin two
• BCGF-B cell Growth Factor (AKA IL4)
• BCDF-B cell Differentiating Factor (AKA IL5)

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THIS IS THE RESPONSE TO SPECIALIZED, HUMAN
PATHOGENS. NON-SPECIFIC GERMS ARE EITHER TAKEN
CARE OF BY THE FIVE AREAS OF INNATE EXTERNAL
RESISTANCE, OR THE INFLAMMATORY RESPONSE. BECAUSE
OF THE NATURE OF SPECIALIZED, HUMAN PATHOGENS,
WE NEED THE SPECIFIC ARM OF THE IMMUNE SYSTEM TO
RID US OF THESE PATHOGENS.
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IT IS ESTIMATED THAT ONE IN 1,000 ONE IN
100,000 LYMPHOCYTES IS CAPABLE OF RECOGNIZING A
PARTICULAR ANTIGEN, CIRCULATION GREATLY
INCREASES THE CHANCES OF A MEETING
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PART ONE HUMORAL IMMUNITY INVOLVES ANTIBODIES
CONFERS IMMUNITY IN THE SERUM (HUMORAL PORTION
OF THE BLOOD) BECAUSE ANTIBODIES
ARE GLYCOPROTEINS ANTIBODIES ARE SPECIFIC -
ANTIBODIES FOR CHICKEN POX DO NOT WORK AGAINST
CHOLERA.
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The process often begins in the Lymphatic system
lymph returns Fluids and cells from
intercellular Spaces to the heart. Along the
Lymphatic vessels are the lymph Nodes areas
where white blood Cells lie in waiting. Here
a Macrophage (big eater) starts the Process by
engulfing the bacteria.
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A SECOND ANTIGEN PRESENTING CELL IS THE DENDRITIC
CELL. THESE CELLS ARE EXTREMELY DIFFICULT TO
ISOLATE. THEY PLAY AN IMPORTANT ROLE IN
INGESTING AND PRESENTING EPITOPES FOUND IN MUCUS
MEMBRANES AND OF VIRUSES IN PARTICULAR. IT HAS
BEEN FOUND THAT THESE CELLS MAY HARBOR HIV
VIRUSES AND PRESENT THEM TO TH CELLS.
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MACROPHAGE or DENDRITIC CELL

• Ingests the foreign cell
• Digests it using Lysosomes
• Presents foreign epitopes on its surface along
  with self proteins
• ( self class II)

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F
F
F
F
10
F
F
F
F
F
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F
F
F
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• TH cells bind with the MO. TH work only by
  recognizing foreign and self proteins (class II)
  together. Class two are found on immune system
  cells, class one on body cells. The MO is known
  as an
• antigen presenting cell.

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F
F
F
TH
TH
TH
F
TH
TH
TH
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• The binding action of the MO and TH stimulates
  the MO to release IL1, interleukin one resulting
  in
• Fever
• Stimulation of TH cells to
• A) Release IL2
• B) Build receptors for IL2
• C) Absorb IL2 through the IL2 receptors

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• Net results is an increase in TH clones.
• Cells that absorb IL1,
• build IL2, and IL2 receptors
• divide
• and their offspring can
• absorb IL2 and divide

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F
F
F
TH
TH
TH
F
TH
TH
TH
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F
F
F
TH
TH
TH
TH
F
IL2 RECEPTORS
IL2
TH
TH
TH
TH
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F
F
F
TH
TH
TH
TH
TH
F
TH
IL2
TH
TH
TH
TH
TH
TH
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F
F
F
TH
TH
TH
TH
TH
F
TH
IL2
TH
TH
TH
TH
TH
TH
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F
F
F
TH
TH
TH
TH
TH
F
TH
IL2
TH
TH
TH
TH
TH
TH
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F
F
F
TH
TH
TH
TH
TH
F
TH
IL2
TH
TH
TH
TH
TH
TH
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TH
THESE INCREASE IN
TH
THESE DO NOT INCREASE IN
TH
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• TH cells present Epitopes
• (foreign) to B cells. This
• occurs through random
• collisions, not through A
• conscious seeking out, TH
• cells will bind with B cells with
• Antibody complementary
• to the Epitope.

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This binding action results in the release of two
interleukins from the TH cell IL4(BCGF) B cell
Growth Factor, this results in mitosis of B
cells, which soak it up
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IL5(BCDF) B cell differentiating Factor This
results in B cells becoming differentiated
Plasma cells- These are antibody producing cells
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antibody
TH
B
B
TH
B
TH
B
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IL4
B
B
TH
B
NO MATCH NO REACTION
B
TH
B
B
TH
B
B
IL4
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IL4
B
B
TH
B
IL5
PLASMA CELL
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PLASMA CELLS CAN PRODUCE UP TO 10,000 ANTIBODIES
PER SECOND
F
F
B
F
F
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BIOLOGICAL ACTIVITY OF ANTIBODIES
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• AGGLUTINATION ESPECIALLY IGM
• OPSONIZE STIMULATE PHAGOCYTIC CELLS
• TO EAT
• 3. PREVENT VIRAL ATTACHMENT BY BINDING TO
• VIRAL
  EPITOPES
• 4. NEUTRALIZE TOXINS BINDING TO TOXINS
• CHANGES THEIR SHAPE
• 5. ACTIVATE COMPLEMENT COMPLEMENT
• LYSES CELLS COATED W/ AB
• 6. IMMOBILIZE PATHOGENS BY BINDING TO
• CILIA AND FLAGELLA
• 7. DETACH PATHOGENS FOR FLUSHING BY
• BINDING TO PILLI

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• So as B cells divide, some of their offspring
  will soak up BCDF and produce antibodies and some
  will not. Those that do not soak up BCDF are
  called memory cells.
• They remain in circulation for years. Upon
  subsequent exposure to the antigen they are
  specific for, they may soak up BCDF and become
  antibody producing plasma cells.
• This is known as HUMORAL IMMUNITY
• (immunity that arises from fluid not cells)

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SO A SECONDARY RESPONSE IS QUICKER AND MORE
EFFECTIVE BECAUSE THE HOST HAS MORE ANTIGEN
SPECIFIC TH CELLS, B CELLS, AND ANTIBODIES
SPECIFIC FOR THE EPITOPE OF THE ANTIGEN.
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THEREFORE MORE TH CELLS FIND THE MACROPHAGES
SOONER AND MORE B CELLS FIND THE RIGHT TH
CELLS SOONER AND MORE ANTIBODIES ARE PRODUCED
SOONER.
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THAT, COUPLED WITH THE FACT THAT YOU HAVE AB
IN CIRCULATION PRODUCES MEMORY.
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• Each activated
• B cell produces
• 40 to 200
• memory cells,
• which will remain
• in the body
• for years.

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Upon second exposure to antigen, a greater
number of antigen reactive cells will
be available to respond. (both TH cells AND B
cells memory cells)
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www.youtube.com/watch?vhQmaPwP0KRI
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• PART TWO CELL MEDIATED IMMUNITY
• Protection that results from cells, NOT
  protection that results from antibodies. This
  immunity is most important in viral infections as
  well as other intracellular parasites.

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VIRAL INFECTIONS DIFFER FROM BACTERIAL
INFECTIONS, BECAUSE OF THE MANNER IN WHICH
VIRUSES REPLICATE. VIRUSES ARE OBLIGATE
INTRACELLULAR PARASITES. THEY NEED TO
INFECT HOST CELLS WITH THEIR DNA (OR RNA IN THE
CASE OF RETROVIRUSES)
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http//www.hhmi.org/biointeractive/media/viral_lif
ecycle-lg.mov
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http//www.npr.org/templates/story/story.php?story
Id114075029
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VIRUS ATTACHES TO CELL INJECTS ITS DNA
Viruses
Viral DNA
Host cell
Cell nucleus
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Viruses
CELL BEGINS TO BUILD VIRUSES
Viral DNA
Cell nucleus
Host cell
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ANTIBODIES CANNOT GET INSIDE OF CELLS TO BIND TO
VIRUSES. ANTIBODIES ARE NOT COMPLETELY
USELESS AGAINST VIRUSES THOUGH BECAUSE THEY CAN
BIND TO VIRUSES IN CIRCULATION
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VIRAL PAR- TICLES EX- PLODE OUT OF CELL TO
INFECT OTHER CELLS
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• The virus infested cell explodes and viruses
  spill out and infect new cells.
• In order to STOP THE SPREAD OF VIRUSES
  completely, the cells that produce the viruses
  must be destroyed.
• That job is done by the Cytotoxic T cell

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Tcyto -cytotoxic T cells

• Kill cells that have FOREIGN PROTEIN and self
  proteins Class I
• Macrophage shows class II
• Are activated by IL2 and TH cells
• Kill virus infested cells, cancer cells, some
  protozoa, worms, fungi
• (latch on and release enzymes that destroy cells)
• work by lysing on contact (destroying)

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SELF PROTEIN CLASS I
TCYTO
BODY CELL
FOREIGN PROTEIN VIRUS SHELL
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SELF PROTEIN CLASS I
GRANULES OF DIGESTIVE ENZYMES
TCYTO
BODY CELL
FOREIGN PROTEIN VIRUS SHELL
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• ACTIVATION OF THE T CYTO CELL
• OCCURS IN TWO STEPS
• T CYTO CELL INTERACTS WITH
• CELL THAT HAS FOREIGN SELF
• CLASS I - IT IS THEREFORE
• STIMULATED (HAS IL-2 RECEPTORS)
• 2. IL-2 IS SUPPLIED BY ACTIVATED
• TH CELLS ONLY STIMULATED
• T CYTO CELLS CAN ABSORB IL-2
• AND DIVIDE

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SO THE JOB OF RIDDING THE BODY OF VIRUSES GOES
TO THE CYTOTOXIC T CELLS. THEY KILL VIRUS
INFESTED CELLS, CANCER CELLS, AND ANY CELLS
THAT EXPRESS FOREIGN AND SELF CLASS I. THEY KILL
CELLS ON CONTACT. THEY ARE ACTIVATED BY TH CELLS
(USUALLY) THIS IS KNOWN AS CELL MEDIATED
IMMUNITY SINCE IT PRIMARILY INVOLVES CELLS
CYTOTOXIC T CELLS (AKA CD8 CELLS) OR KILLER T
CELLS
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www.youtube.com/watch?v1tBOmG0QMbA
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RESULTS OF A STUDY

• A Mouse was given a vaccine for pneumococcus
• T cells were then removed from the mouse
• T cells were then transferred to second mouse
  (clone)
• second mouse was given dose of pneumococcus to
  check for immunity
• Result NO immunity to pneumococcus

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-Blood was drawn from the mouse -T cells were
found clumped together -scientists concluded that
the vaccine Was too weak, as stronger
antigen Concentrations did confer immunity
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Ts cells were thus discovered

• These cells bind with TH cells and have receptors
  specific for specific TH cell receptors
• Ts cells are activated after TH cells, prevent
  overkill, an overproduction of AB
• AKA T regulatory cells

TH
TS
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Importance of Ts or Tr cells

• The critical role regulatory T cells play within
  the immune system is evidenced by the severe
  autoimmune syndrome that results from a genetic
  deficiency in regulatory T cells.
• Likewise autoimmune disorders may be treated with
  a dose of Ts (or Tr) cells

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• -anti antibodies ALSO
• prevent overkill
• (over production of cells)
• See p.139 Network Hypothesis

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Interferons-

• a. are species specific proteins produced by
  viral infected cells, white blood cells
• b. produce proteins which inhibit viral
  replicationc. three major types alpha, beta,
  gammad. in low concentrations, they stimulate
  cell
• division
• e. in high concentrations, they inhibit cell
• division

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REGULATION OF THE IMMUNE RESPONSE
SO INTERFERONS, ANTI-ANTI- BODIES AND T
SUPPRESSOR CELLS SERVE TO PREVENT OVERKILL AN
OVERPRODUCTION OF ANTI- BODIES AND CELLS.
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TDTH cells-T delayed Type hypersensitivity cells

• Involved in delayed hypersensitivities like
  poison ivy
• Recognize foreign and self (class II like on
  Macrophage) TDTH undergo IL2 mediated clonal
  expansion
• Behave like TH cells, but instead of activating B
  cells.

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TDTH release interleukins that draw neutrophils,
Basophils, and Esinophils to the site. -Takes
12 48 hours typically - This results in
inflammation