Angela Mitchell
BIO422
2013
mitcheam@email.unc.edu
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Recognize that invaders are present
◦ Recognize that these are different than self
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Recruit more cells/factors to fight invaders
Kill the invaders
Block any toxins produced by the invaders
Learn from past encounters to increase future
effectiveness
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Antigen: the molecule recognized by the
response
The epitope is the specific part of the antigen
recognized
Each adaptive immune cell can only recognize
one epitope
Figure 24.2
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Can an antigen have more than one epitope?
◦ Yes, almost always
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Can an epitope have more than one antigen?
◦ No (almost always…)
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You found two adaptive immune cells that
respond to pilin. Are these cells specific for
the same epitope?
◦ No necessarily: they could respond to two different
epitopes on the same antigen
Cellular Immunity
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Main cells are T cells
Useful against
intracellular pathogens
Humoral Immunity
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B cells and antibodies
Useful against
extracellular microbes
and toxins
T cell Mediated Immunity
CD8+
CD4+
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T cell receptor
Recognizes small parts of proteins
“presented” on MHC molecules
MHC is present on antigen presenting cells
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MHCI is present on all nucleated cells
◦ CD8+ cytotoxic T cells recognize MHCI
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MHCII is present on professional antigen
presenting cells  pAPCs
◦ CD4+ helper T cells recognize MHCII
Figure 24.20
Figure 24.21
Figure 24.21
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Professional antigen presenting cells
Dendritic cells, macrophages, and B cell
Offer activating signals to T cells—primes for
activity, causes proliferation
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Cytotoxic T cells: CD8+ T cells
◦ Recognize antigens on MHCI
◦ Releases granules to kills target cells
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Helper T cells: CD4+ T cells
◦ Recognize antigens on MHCII
◦ Secrete cytokines to activate other cells
◦ Two major types: Th1 and Th2
Death of cells
infected with
virus or
cytoplasmic
bacteria,
cancer cell,
etc.
Th1 cells: activate
phagocytes
Th2 cells: activate B cells
What do cytotoxic T cells recognize?
A.
B.
C.
D.
E.
Exogenous peptides on MHCI
Endogenous peptides on MHCI
Exogenous peptides on MHCII
Carbohydrates on bacteria cells
Endogenous peptides on MHCII
T helper 1 cells (Th1) are important for defense
from…
A.
B.
C.
D.
E.
Extracellular pathogens
Fungi only
Viruses only
Cytoplasmic pathogens
Phagocytosed/Endosomal pathogens
Epitopes and Antigens
MHCI and MHCII
Activation of T cells
Figure 24.2
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Every T cell has a different T cell receptor
specific to a different epitope
◦ Your body can make about 10^18 different T cell
receptors
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Developmental processes kill T cells that
cannot recognize your MHC and that
recognize self peptides
Initial T cell recognition of a peptide without
an innate immune response (inflammation)
does not activate the T cell
Croft. 2003. Nat Rev Immun. 3: 609.
Death of cells
infected with
virus or
cytoplasmic
bacteria,
cancer cell,
etc.
Th1 cells: activate
phagocytes
Th2 cells: activate B cells
Cell Type
Cytotoxic T cell
Th1 Helper T cell
Th2 Helper Tcell
Type of MHC
MHCI
MHCII
MHCII
Location of MHC
All nucleated cells
Professional
antigen presenting
cells
Professional
antigen presenting
cells
Location of antigen
Endogenous—
within the
cytoplasm of the
cell
Exogenous—
present in the
phagosome
Exogenous—
present in the
phagosome
Type of epitope
Small linear peptide
Small linear peptide
Small linear peptide
Response to initial
recognition
Proliferate and
activate to effector
Proliferate and
activate to effector
Proliferate and
activate to effector
Activated cell
Granules—
recognizing epitope perforins,
releases
granzymes
Cytokines
Cytokines
Which…
Activate phagocytes
(WBC) to kill
phagocytosed
microbes
Activate B cells to
proliferate, produce
antibodies, and
develop memory
Kill the target cell
B cell Mediated Immunity
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Defense from extracellular pathogens and
toxins
Recognize antigen in native form
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B cell receptor (BCR)
recognizes antigen
◦ Membrane bound
antibody
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Th2 cells help
activation and are
required for memory
B cell differentiates to
plasma cell, which
produces antibodies
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Immunoglobulins (Ig)
“Y” shaped proteins
4 polypeptides linked by
disulfide bonds
◦ Two identical heavy chains
◦ Two identical light chains
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Has variable and constant
regions
Variable regions are
responsible for
recognizing the epitope
Figure 24.7
Functional Activity
IgM
IgD
IgG
IgA
IgE
Neutralization
+

++
++

Phagocytosis
+

+++
+

Natural killer cell
killing


++


Mast cell activation


+

+++
+++

+++
+

Complement activation
Location
BCR &
Serum
BCR
Serum &
(minor) tissue
Mucus & Mast
tissue
cells
Basophile activation?
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B cells recognize _____ with membrane
bound_____.
A.
B.
C.
D.
E.
Peptides only
Whole antigens
Peptides only
Carbohydrates only
Whole antigens
MHCs
MHCs
Antibodies
TLRs
Antibodies
Secondary responses to
infection
Vaccination
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Small populations of B and T cells retained
from first exposure
Survive for a long time
Begin faster than first response
Stronger than first response
Vaccinations take advantage of memory
responses
Figure 24.13
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Deliberate induction of an immune response
to a pathogen by introducing a dead or nonpathogenic (attenuated) form of the pathogen
Vaccination began with Edward
Jenner (around 1796)
◦ Observation that people exposed
to cowpox did not get smallpox
◦ Exposed a boy to cowpox
(vaccinia) and the boy did not
get sick with smallpox
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When you’re exposed to a pathogen for the
second time, your innate and adaptive
immune responses will be
A. Innate and adaptive both faster and stronger
B. Adaptive faster and stronger but innate only
faster
C. Innate and adaptive both faster only
D. Innate the same, adaptive both faster and
stronger
E. Innate the same, adaptive faster only
The roles of IgE and mast cells
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Symptoms or disease caused by immune
activation by a normally harmless antigen
(known as an allergen)
Allergies are mediated by IgE and mast cells
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50% of people in developed countries have
allergies
◦ There are less allergies in the developing world.
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Some families have high rates of allergies
Environmental factors: the hygiene
hypothesis
◦ Lower levels of childhood disease, especially
parasite infections
◦ Immune system is not “trained” correctly
◦ Therefore, the immune system responds
inappropriately to harmless antigens
Nature Reviews Immunology 2001 (1) 69-75
A
B
C