Download Janeway`s Immunology

Immunology 2016
BiosE60: Immunology
Course Director
Mihaela Gadjeva([email protected])
TAs
Peter Sage ([email protected])
Vikram Juneja ([email protected])
On-line and on-site education
Lectures-attendance is optional
Sections- attendance is required
Exams-
How do we grade????
55% Final Exam
35% Midterm exam
10% Section
How did it all started?
Edward Jenner invented vaccination in
1796. He introduced a new technique:
inoculation with cowpox to protect against
smallpox
Immune recognition
Effector function
Immune regulation
Immunological memory
Innate and adaptive immunity. The mechanisms of innate immunity provide the
initial defense against infections. Adaptive immune responses develop later and
consist of activation of lymphocytes. The kinetics of the innate and adaptive
immune responses are approximations and may vary in different infections.
Innate Immunity
Adaptive Immunity
Fast
Slow
Limited in specificity Highly diverse
Response to
repeated challenge
is the same as the
initial
Pattern recognition
molecules and
phagocytes
Response is
magnified
Antigen-specific
receptors and
lymphocytes
Key cellular components of the immune system
Neutrophil chasing bacteria
Fenteany et al, 2004, Cytoskeletal remodeling in leukocyte function
“Bonding the Foe”
Resting PMNs
NET-ing PMNs
Innate and adaptive immunity. The mechanisms of innate immunity provide the
initial defense against infections. Adaptive immune responses develop later and
consist of activation of lymphocytes. The kinetics of the innate and adaptive
immune responses are approximations and may vary in different infections.
Where do these cells reside in the body?
Do they migrate, how, and why?
Lymphocyte School System
PreSchool-Kindergarden-LowMiddle-High School
Primary lymphoid organs - sites
where lymphocytes are
generated. These are the bone
marrow and the thymus.
College
Secondary or peripheral
lymphoid organs-sites where
mature lymphocytes are
maintained and adaptive immune
responses are initiated. These are
the lymph nodes, the spleen, and
the mucosal lymphoid tissues.
HIGHLY-ORGANIZED HIGHWAY SYSTEM
Lymph drainage ensures that antigenic material from peripheral sites is
efficiently transported to draining LNs and presented to lymphocytes
that home to the LN from the blood.
The innate system provides an initial discrimination between self and nonself.
Activation of specialized antigen-presenting cells is a necessary first step for
induction of adaptive immunity
Multi-photon imaging allows three-dimensional time-lapse imaging of fluorescent
signals deep below the surface of living tissues, allowing cell migration and cell–cell
interactions to be tracked. The fluorescent images are of slightly lower resolution
compared with those obtained by traditional confocal microscopy.However,multiphoton
imaging has several notable advantages compared with other fluorescence-based
techniques, including: greatly diminished phototoxicity to living cells; reduced
bleaching of fluorescent dyes; the ability to excite several different fluorophores with the
same excitation beam; the phenomenon of second harmonic generation of ultraviolet
photons by collagen fibres,which allows non-invasive imaging of extracellular matrix
components; and deeper tissue penetration (in our hands, the maximal imaging
depth in mouse lymph nodes is ~100 μm for confocal microscopy versus ~400 μm for
multi-photon excitation).
DC Entering Lymph node
a | The microcirculation of the lymph node has been visualized by intravenous injection of a mixture of green and red
fluorescent dextrans. The plasma markers fill all microvessels, which are yellow. The preparation is partly covered by fatty
tissue, which diffracts fluorescent light emitted from the superficial epigastric vein resulting in a ‘bubbly’ appearance. To
identify the different lymphoid compartments, purified fluorescent B cells (green) and T cells (red) were injected
intravenously 20 hours before. After their entry into the lymph node through high endothelial venules (HEVs), the homed
cells segregate. B cells populate the more distal B-cell follicles, whereas T cells remain in the paracortex. b | A higher
magnification of the boxed region in panel a illustrates the relationship of B and T cells and the microcirculation
B cell follicle
T cells and B cells
T cell area in the LN
CD4 T cell - DC interactions
How do cells travel?
Clonal expansion-a
characteristic feature of
immune responses
What are the epitopes?
Antibodies deal with
extracellular forms of
antigens
Summary
Phases of adaptive immune responses. Adaptive immune responses consist of distinct phases, the first
three being the recognition of antigen, the activation of lymphocytes, and the elimination of antigen (the
effector phase). The response contracts (declines) as antigen-stimulated lymphocytes die by apoptosis,
restoring homeostasis, and the antigen-specific cells that survive are responsible for memory. The duration
of each phase may vary in different immune responses. The y-axis represents an arbitrary measure of the
magnitude of the response. These principles apply to humoral immunity (mediated by B lymphocytes) and
cell-mediated immunity (mediated by T lymphocytes).
Specificity, memory, and contraction of adaptive immune responses. Antigens X and Y
induce the production of different antibodies (specificity). The secondary response to
antigen X is more rapid and larger than the primary response (memory). Antibody levels
decline with time after each immunization (contraction, the process that maintains homeostasis). The same features are seen in cell-mediated immune responses.
Summary
Reading material: Chapter 1 Janeway’s Immunobiolog
Key vocabulary: Antigen, Antibody, lymphocytes, innate and adaptive immunity,
pattern recognition receptors, clonal expansion, clonal deletion, sites for primary and
secondary lymphocyte development, structure of lymph nodes, spleen, APC,
immunologic tolerance
Key concepts:
Lymphocytes develop within specific anatomical sites where they acquire signals
that drive their maturation.
Lymphocytes migrate from the central to the peripheral lymphoid sites and this is
associated with their maturation state.
The lymphocytes that have antigen presenting functions migrate to the tissues, where
they are quiescent till infection occurs. After activation these cells migrate to the
draining lymph nodes to induce adaptive immunity
Basic principles of clonal selection hypothesis
Effector mechanisms of the adaptive immunity: Antibodies mediate antigen
neutralization, opsonosation, and ultimately, clearance. Effector T cells facilitate
activation of B cells, macrophages,
ELISPOT
Western Blotting