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Innate Immunity - Hathairat 02082016
Innate Immunity - Hathairat 02082016
Innate Immunity - Hathairat 02082016
Objectives:
Explain how innate immune system recognizes foreign
substances
Explain components of the innate immune system,
and their functions
Explain functions of the innate immune system
Lecture outline
Overview of innate immunity
Innate recognition
Cell-associated receptors
Soluble molecules
Innate immunity
Innate immunity serves three important functions
Innate immunity is initial response to microbes that prevents,
controls , or eliminate infection of the host by many microbes
Inflammation
Antiviral defense
Non-adaptive
the quality of the reaction to a foreign substance does
not change when the organism encounters this
substance repeatedly
DAMPs
Soluble molecules
Blood
Extracellular fluids
Recruitment and activation of
protein kinases
Activation of transcription factors
Gene transcription
TLR signaling
All TLRs except TLR3 signal through
adaptor protein MyD88
TLR3 signals through TRIF
TLR4 signals through both MyD88
and TRIF
A downstream effect of TLR
signaling through MyD88 is the
activation of the transcription
factor NF-B
A downstream effect of TLR
signaling through TRIF is the
activation of IRF-3 and -7
MyD88; myeloid differentiation primary response gene 88
NOD-Like Receptors
NOD-like receptors (NLRs) are a family
of more than 20 different cytosolic
proteins, some of which recognize
PAMPs and DAMPs
NOD1 & NOD2 recognize
peptidoglycan substructures and
promote innate immune responses
NOD1 diaminopimelic acid (DAP)
NOD2 muramyl dipeptide
Induce the production of
proinflammatory cytokines (IL-1 and
IL-18)
NOD; nucleotide oligomerization domain
RIG-Like Receptors
RIG-like receptors (RLRs) are
cytosolic sensors of viral RNA
that respond to viral nucleic acid
by inducing the production of
the antiviral type I interferons
The two best characterized RLRs
are
RIG-1
MDA5
On binding viral RNA, the RLRs
initiate signaling events that lead
to phosphorylation and
activation of IRF3 and IRF7, as
well as NF-B
Plasma membrane
Circulating proteins
Complement system
Antimicrobial peptides
Cytokines : inflammation (TNF, IL-1)
chemokines (IL-8, MCP-1)
anti-viral (type I interferons)
Exterior defenses
Most infectious agents are prevented from entering the body by physical and
biochemical barriers. The body tolerates a number of commensal organisms,
which compete effectively with many potential pathogens.
Epithelial defenses
Antimicrobial peptides
Short, cationic peptides (most 29-35
amino acids long)
Phagocytes
Neutrophil
Mononuclear phagocyte
Dendritic cell
- Phagocytosis
- Cytokine production :
Pro-inflammatory cytokines (TNF, IL-1)
Phases of phagocytosis
NADPH oxidase
opsonin
Neutrophils
Dendritic cells
A heterogeneous family of cells with long dendrite-like cytoplasmic processes
Constitutively present in lymphoid tissues, mucosal epithelium, and organ
parenchyma
Dendritic cells express more different types of TLRs and cytoplasmic PRRs
than any other cell types
Dendritic cells serve a critical function in adaptive immune responses by
capturing and displaying microbial antigen to T lymphocytes.
TLR signaling induces dendritic cell expression of costimulators and cytokines
that are needed for the activation of nave T cells and their differentiation to
effector T cells
http://www.ucl.ac.uk/~zchabg4/innate.htm
Functions of NK cells
1. NK cells recognize ligands on infected cells or cells undergoing
other types of stress, and kill the host cells.
Functions of NK cells
2. NK cells respond to IL-12 produced by macrophages and secrete
IFN-, which activates the macrophages to kill phagocytosed microbes.
Mast cells
present in the skin and mucosal epithelium
Mast cells express high-affinity Fc receptors
for IgE
Complement system
Consists of about 30 serum and membrane proteins that can
mediate a variety of immune reactions
The active components of complement are generated from
inactive precursors by a cascade of proteolytic reactions
These can be triggered in any of three ways:
Lectin pathway
Classical pathway
Alternative pathway
opsonization
Collectins:
- surfactant protein A (SP-A)
- surfactant protein D (SP-D)
- mannose-binding lectin (MBL)
Ficolins:
- L- , H- , and M-ficolin
C1q, mannose binding lectin, and ficolin can initiate complement activation on
binding to their ligands on cell surfaces
Pentraxins
pentameric plasma proteins
Pentraxins biosynthesis
Acute-phase reactants
Cell 2010;140:771-776
- Vasodilation :
blood flow
diapedesis
Summary
The innate immune system provides the first line of host
defense against microbes
The innate immune system used pattern recognition
receptors to recognize structures called PAMPs and DAMPs
Summary
The two major types of responses of the innate immune
system that protect against microbes are inflammation and
antiviral defense
Molecules produced during innate immune responses
stimulate adaptive immunity and influence the nature of
adaptive immune responses