Transcript of BIOL 520 Advanced Immunology W2009 Lecture 1 Overview Immunology Lecture 1 Overview Immunology.
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- BIOL 520 Advanced Immunology W2009 Lecture 1 Overview
Immunology Lecture 1 Overview Immunology
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- Immunology Recognition of self and non-self Antigens
Elimination of non-self Exogenous targets Microbes Allergens
Foreign material Endogenous targets Tumors
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- Two Arms of Host Defense Innate immunity Natural immunity
Defense system functional at birth Preformed or available within
hours after infection Pattern recognition Widely present in nature
Adaptive immunity Acquired Available within days Specificity Memory
In higher vertebrates InnateAdaptive
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- Key Players in Immunology InnateAdaptive Cells Phagocytes
Epithelial Cells NK Cells Lymphocytes (B-Ly, T-Ly) Defense Proteins
Complement Antimicrobial (Poly)Peptides Antibodies
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- Most Immune Cells are Found in Blood Granulocytes Monocytes
Lymphocytes Natural Killer Cells
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- Some Immune Cells are Found in the Tissue Mast cells Dendritic
Cells
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- Hematopoiesis Pluripotent Stem Cell Lymphoid Progenitor GEMM
Progenitor Lymphocytes NK-Cells Erythrocytes Megakaryocyte Monocyte
Macrophage Neutrophil Basophil Eosinophil Platelets B-Ly T-Ly
Plasma cell Activated T-cell Dendritic cell
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- Defense Cells Have Specific Tasks Epithelial cells Barrier
(physical, chemical) Communcate Phagocytes Ingest Kill Digest
NK-cells Lyse infected cells or tumor cells B-lymphocytes Produce
antibodies T-helper lymphocytes Strengthen defense cells to improve
their function Regulate immune responses T-killer lymphocytes Lyse
with specificty infected cells or tumor cells
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- Epithelial Cell Defense TLR Microbial Products (LPS, PG, etc)
Antimicrobial Peptides Cytokines TLR: Toll-like receptor (pattern
recognition) LPS: lipopolysaccharide PG: peptidoglycan
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- Opsonophagocytosis 1.Opsonization 2.Attachment 3.Engulfment
4.Phagosome formation 5.Phagolysosome formation 6.Killing and
digestion 1. 2./3. 4. 5. 6.
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- NK Cell Mediated Killing Triggered by two mechanisms Antibody
dependent cytotoxicity Recognition of altered surface molecules
Mediated by: Perforin Pore-forming toxin Permeabilizes target cell
membrane Granzyme Enzyme Induces apoptosis (cell suicide) TNF
Apoptosis Packaged in Granules
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- Recognition of Foreign Material Pattern Recognition Toll Like
receptors TLR1-10 All involved in Immune defense Intracellular
region with homology to IL1 receptor Activated directly by
microbial products not normally found in host Specific antigen
recognition Antigen Receptor B cell receptor antibody molecule T
cell receptor TCR
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- TLRs and Their Ligands Intracellular Extracellular Cytoplasmic
membrane Peptidoglycan TLR2
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- Effects of TLR Activation Cytokine up-regulation and secretion
Pro-inflammatory cytokines Chemokines Reactive oxygen and nitrogen
metabolites Antimicrobial peptide production HBD2 Up-regulation of
surface molecules enhancing adaptive immune responses
Co-stimulatory signals MHC-II Apoptosis Innate Immunity Adaptive
Immunity
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- Basic Structure of an Antibody Molecule 2 light and 2 heavy
chains Disulfide bonds Hinge region N-terminus: variable, antigen
binding C-terminus: constant region, effector function 5 isotypes
IgD, IgM, IgG, IgA, IgE
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- Basic Functions and Distribution of Antibodies Functional
ActivityIgMIgDIgGIgAIgE Neutralization +-++ - Opsonization +-++++-
Sensitization for killling by NK cells --++-- Sensitization of mast
cells --+-+++ Complement activation +++- +-
DistributionIgMIgDIgGIgAIgE Transport across epithelium +--+++-
Transport across placenta ---+++-- Diffusion into extravascular
sites +/- - +++ + mon omer
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- T Cell Receptor 2 chains Connected by disulfide bond Variable
region Constant region Short cytoplasmic tail Mostly and chain Some
specialized T- cells have and chain ( T cells)
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- T-Cell Antigens Short contiguous amino acid (aa) sequence
Processed antigens Antigen must have been unfolded and degraded
Primary aa structure Only when bound to a specialized antigen
presenting molecule (MHC) APC MHC T-Ly
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- TCR Recognizes Antigen Presented by MHC Molecules MHC: major
histocompatibility complex First identified in transplantation
immunology T cells recognize antigen bound to an MHC molecule Two
types of MHC molecules MHC I: presents endogenous peptides Virus
encoded Produced by intracellularly replicating microorganisms
Tumor antigens MHC II: presents exogenous peptides Uptake through
phagocytosis and degradation in phagolysosome MHC I CTL MHC II
TH
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- CTL and MHC ITH and MHC II Apoptosis of Target CellImmune
modulation of target cell TH1, TH2: Activation TH3: Inhibition
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- Immune Cells Interact via Cytokines and Surface Molecules
InnateAdaptive Cells Phagocytes Epithelial Cells NK Cells
Lymphocytes (B-Ly, T-Ly) Defense Proteins Complement Antimicrobial
(Poly)Peptides Antibodies
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- Cytokines Soluble glycoproteins ~ 25 kD Cell to Cell
communication Autocrine, paracrine,endocrine Act by binding to
specific receptors Receptor expression varies Receptors can be
shared by different cells Different cells can respond differently
Interleukins Chemokines Growth Factors Cytokines
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- Antimicrobial Peptides Natural peptide antibiotics Amphiphilic
Cationic Hydrophobic Microbial killing through membrane
permeabilization + + +
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- Complement System of plasma proteins Activates a cascade of
proteolytic reactions and subsequent protein aggregation on the
microbial surface but not on host cell surface Coat microbes with a
substance that is bound by phagocytes (opsonization) Form pores on
microbial surfaces triggering killing Release small peptides that
contribute to inflammation
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- Lymphatic Tissue Central Bone marrow Thymus Secondary Spleen
Lymph nodes GALT (gut associated lymphatic tissue) Tonsils Peyers
patches Appendix Production Interaction with Ag Maturation
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- Thymus Immature T-Cells Mature naive T-Cells Hassalls
corpuscule (Cell destruction?) Bone marrow precursor Blood
stream
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- Lymph Node
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- The Spleen
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- Organization of the Spleen White pulpa Leukocytes arranged
around the blood vessels and sinuses Red pulpa: Blood vessels and
sinuses Marginal Zone Border between white and red pulpa
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- Peyers Patches
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- Time Course of the Immune Response
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- Infection Triggers an Innate Inflammatory Response
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- Dendritic Cells Initiate Adaptive Immune Responses
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- Adaptive Immune Responses Augment Innate Immune Responses
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- References Janeways Immunobiology, 7th edition, 2008 Textbook
of Hematology, McKenzie, 2 nd edition, 1996 Microbiology: An
Introduction; Tortora et al, 8 th edition, 2004 http://www-
medlib.med.utah.edu/WebPath/HEMEHTML/HEMEIDX.htmlhttp://www-
medlib.med.utah.edu/WebPath/HEMEHTML/HEMEIDX.html
http://www.siumed.edu/%7Edking2/erg/smallint.htm Primary
literature: available per request