Beruflich Dokumente
Kultur Dokumente
Immunology
Spring 2007
Prof. Ellen Robey
Prof. Robert Beatty
Prof. Laurent Coscoy
Today’s game-plan
Cellular Immunity
T cells, TCR, development, selection, tolerance, NK cells
Immune Responses
inflammation, allergy, autoimmunity, infection
Course Instructors
Lecturers: GSIs:
Ellen Robey
471 LSA 2-8669
Dina Weilhammer
Office hours: Tues 11-12
Dina@berkeley.edu
Office hours: TBA
Laurent Coscoy
451 LSA 3-4128
Tim Nice
Office hours: TBA
timnice@berkeley.edu
Office hours: TBA
Robert Beatty
176 LSA 2-0671
Office hours: Tues 3-4
Course Components
• Lecture series
• Discussion sections (not required, but highly
recommended)
• Reading: Text (Kuby 6th addition), Journal Articles
• Problem sets (posted on web, these are not graded, but
are to help reinforce what you learn in class)
• Exams-- two mid-terms, plus final exam
Grading
• www.mcb.berkeley.edu/courses/mcb150
• All lecture notes, problem sets, answers will
be posted for viewing or download
• Powerpoint presentations shown in lecture
will be posted for your review
Getting Help!!!
•Web site:
www.mcb.berkeley.edu/courses/mcb150
•Office Hours
Exponential growth
Number of bacteria
Listeria bacteria using the actin cytoskeleton Toxoplasma parasites (red) and dendritic cells
of the host cell to spread from cell to cell. (green) within a mouse lymph node. (Robey
(Portnoy lab) lab)
Pathogens rapidly evolve to avoid the host immune response
Virally encoded
decoy receptors
Overview of the Immune system
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Adaptive
Innate
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Dendritic cells and macrophage: directly kill microbes by phagocytosis and other
mechanisms. They also help to activate T cells (connection between innate and adaptive
immunity)
NK cells are lymphocytes that have characteristics of innate and adaptive immunity.
Overview of the Immune system
Cell-mediated immunity:
Phagocytosis (cellular eating)
cytotoxcity (cellular killing)
Humoral immunity:
complement: group of serum proteins that can directly kill
pathogens.
antibodies: (also called immunoglobulin) proteins secreted
by B cells that bind directly and specifically to pathogens.
Antibodies target pathogens by marking them for destruction by
other components of the immune system.
Macrophage fight microbes by engulfing and
digesting them (phagocytosis or cellullar eating).
A macrophage attempting to
engulf a bacterium Streptococcus
pneumoniae, that is covered with
a slimy coat.
Target cell killing by a cytotoxic
(killer) lymphocyte
DNA rearrangement
(rag1, rag2)
TCR locus:
structure in T cells
transcription
RNA splicing
translation
T cell
Overview of the Immune system
Mediate inflammation
• Pain (dolor)
• Swelling (tumor)
• Heat (calor)
Inflammation occurs when injured tissues release mediators that promote
vasodialation (increased blood flow) and chemotaxis (directed migration)
of leukocytes.
• Vaccination
• Adoptive immunotherapy
• Transplantation
Vaccination: THE major success
Diphtheria
Cases per
100,000
population
Polio
Cases per
100,000
population
Measles
Cases per
100,000
population
year
Treating cancer
Tissue Transplantation
Powerful methods for detecting and
quantitating proteins and cells based on
the highly specific binding of antibodies
(immunoglobulins)
• ELISA: enzyme-linked immunosorbant assay
(measures small amounts of hormones, drugs,
microbes in body fluids)
• Western blot (detects disease associated proteins)
• Flow cytometry (quantifies various cell types in
mixed population-- HIV patients)
Western Blot
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4. Lysosomal enzymes
digest the bacteria.
5. Digested material is
released from cell.
Phagocytes: macrophage,
neutrophils, dendritic cells
Phagocytes use a variety of methods to destroy ingested microbes.
(household bleach)
Macrophage fight microbes by phagocytosis and
production of toxic molecules
A macrophage produces reactive oxygen
species to aid in destruction of the microbe
cell-autonomous defense:
cell produces an immune
response that acts on itself
Apoptosis: Cellular Suicide
Remnants
•Nuclear fragmentation undergo
•Proteolysis phagocytosis
•Blebbing
•Death
Apoptosis versus Necrosis
•Tidy: contents of cells •Messy: contents of cell
degraded from within, released.
producing small cellular
“blebs” •Induced by external insult
eIF2a
dsRNA
or
Kinase interferon
domain
RNA-
binding PKR Phosphorylated Phosphorylated
domain PKR eIF2a
(active) (inactive)
Innate Immunity
Innate immune effector mechanisms
Physical and biochemical barriers (defensins)
Phagocytosis and reactive oxygen
Cell autonomous defenses
Apoptosis
Interferons and PKR
innate adaptive
Receptors that pattern recognition receptors antibodies and T cell antigen receptors (TCR)
Mediate pathogen Toll-like receptors (TLR)
Recognition limited diversity, unlimited diversity
fixed in germline generated by V(D)J recombination