Introduction To The Immune System
Introduction To The Immune System
Introduction To The Immune System
Immune System
Stephen Canfield
Asst. Prof. Medicine
Allergy/Immunology
Prologue:
The Immune System in Health
Defense against invading organisms
Surveillance against malignancy
Orchestrator of tissue repair
Patrol against senescence
Interface with metabolic processes
Body temperature
Fe3+ balance
Body mass
Prologue:
The Immune System in Disease
Too little - immune deficiency
Too much - attack on self
Too long - tissue remodeling
Too vigilent - hypersensitivity
Too effective - graft rejection
Prologue:
Tips on Challenges You Will Face
Details, details, details - new vocabulary
Rules are built on experimental observation
Every rule has an exception
Understanding is evolving
New concepts and new players added every year
Innate
Dermal
and
submucosal
tissues
Adaptive
Reconnaissance specialists
Return invader fingerprints to the central
immune system
Peripheral
tissues
Immune Brain
Uses recon data to build the perfect responder
Remembers the invader for future rapid response
2o Lymphoid
Organs
2o Lymphoid Organs:
LN, Spleen
Mucosa-Associated Lymphoid
Tissue
Cellular
Phagocytes
Natural Killers
Mannose
Flagellin
dsRNA
Release of
soluble fragments
Recruit phagocytes
Phagocytes
Macrophages
Neutrophils (aka: polymorphonuclear leukocytes)
Dendritic Cells
Hematopoietic Lineage
Macrophages
Tissue-resident sentinels
& refuse collectors
Arrayed with sensors:
- PAMP receptors
- Complement Rs
- Antibody Rs
Reorganize cytoskeleton
in response to these inputs:
Seek & Engulf
Sompayrac: How the Immune System Works, 3rd Edition. Copyright 2008 by Blackwell Publishing, Inc.
M as Refuse Manager
Neutrophils
Most abundant blood leukocyte
- 3 million/day exit bone marrow
- production with infection
Neutrophil Chemotaxis
Macrophage/Neutrophil Killing
Phago-lysosome contents
Phagocyte Oxidase oxygen radicals
Inducible NO Synthase nitric oxide
Acid pH
Proteases
Dendritic Cells
Phagocyte with a dual career - reconnaissance specialist
Starts out a tissue-resident sentinel
Constant pinocytosis - small bites
sampling surroundings
B Lymphocytes
Develop in the bone marrow
Each new B cell makes a unique antigen receptor (BCR)
This BCR is also called surface immunoglobulin (Ig),
or antibody
Ag binding by BCR clonal expansion
Some daughter cells become plasma cells: immunoglobulin
secreting factories
Others become memory B cells: long-lived, capable of rapid
response on re-encounter of antigen
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Immunoglobulins
A
Binntig
din en
g
en
tig ing
n
A ind
B
VH
Tetramer
VL
2 H chains + 2 L chains
CH1
Complementarity
Determining
Regions (CDRs)
CL
Interchain disulfides
CH2
CH3
Constant End
Fc Region:
Complement Initiation
Fc Receptor Binding
Determines Ig Class:
IgM, IgD, IgG, IgA, IgE
and effector functions
Immunoglobulin-Antigen Binding
Ag
VH
Ag
VH
VL
VL
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T Lymphocytes
Hematopoietic origin (marrow) but most of
their development occurs in the thymus
Like B cells, T cells:
Utilize a surface Ag receptor (TCR)
Extreme diversity of Ag binding
Ag receptor triggering is required to initiate
clonal expansion
Ag experienced cells produce a long-lived
memory population
T Lymphocytes
Unlike B cells, T cells:
Never secrete their Ag receptor
Cannot bind free antigen molecules - only
peptides of 8-25 amino acids
Require that Ag be presented to them on a
special billboard:
Major Histocompatibility Molecule
Abbas, et al: Basic Immunology, 3rd Edition. Copyright 2008 by Saunders, an imprint of Elsevier,
Inc.
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MHC Class I
antigen
peptide
Expression:
All nucleated cells
Structure:
-chain + 2 microglobulin
Antigenic peptides:
Derived from cells
cytoplasm (generally from
proteins made within the
cell)
Viral Peptides
MHC I
Cytoplasm
Nucleus
Adapted from Janeway, et al: Immunobiology, 6th Edition. Copyright 2005 by Garland Science.
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MHC Class II
Expression:
Antigen presenting cells
(APCs)
Examples - macrophages,
dendritic cells, B cells
Structure
and chains
MHC II
Antigenic peptides
Lysosome
Nucleus
H+
Adapted from Janeway, et al: Immunobiology, 6th Edition. Copyright 2005 by Garland Science.
Peptide/MHC Class I
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IFN-
TH
Recognize Ag peptide
presented by MHC Class
II
Provide essential
activation signals to B
Cells, CD8+ T cells, and
phagocytes
IL-4
TH
Cytokine
CD40L
Contact
soluble - cytokines
surface molecules - CD40LJaneway, et al: Immunobiology, 6th Edition. Copyright 2005 by Garland Science.
CD40
Killing
puncture cell membrane
Induce programmed cell
death or apoptosis
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Adaptive
On first
contact
Immediate response
Receptor
Specificity
Broad classes of
molecules
Ligands
Microbial origin
Potentially any
protein, lipid, or carbo
Memory
None
Long-lived
Recurrent
contact
Same response as
previously
Rapid response
tailored to pathogen
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B Cells
Cytotoxic
Directors
Killers
Antibody Producers
M
Kill
Phagocytes
Neutrophils Dendritic Cells
Wall Off
Summary
1.
2.
The innate arm, the most ancient, is the first to respond. Its cells utilize evolutionarily
conserved pathogen characteristics to recognize danger and act rapidly to tag, engulf,
lyse, or wall off the invader.
3.
The innate system recruits the more highly evolved adaptive system through specialized
reconnaissance experts termed dendritic cells (DCs). These cells engulf bacteria and
virally infected cells, digest the pathogen proteins, and present peptides from these
proteins to naive CD4+ T cells, resulting in their activation and clonal expansion.
4.
5.
6.
T cell direction, required for the optimal immune response, is completely dependent
on the peptides presented. Highly polymorphic MHC genes, and co-dominant
expression of multiple MHC molecules helps ensure that every individual can make a
response to some part of every pathogen.
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