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Innate Immunity Mechanisms
Innate Immunity Mechanisms
Mechanical Barriers/surface secretion:
Innate Immunity Mechanisms
Soluble Mediators
Innate Immunity Mechanisms
Cellular Defense Mechanisms
Compare and contrast:
Innate and Adaptive immunity
Inflammation
Buildup of Immunity
The Acute Phase Response
Black Bile & Medieval Bleeding
"Danger Signals" activate innate cells
PAMPS bind to Receptors called PRRs
“Pattern Recognition Receptor”
Some Danger Signals Include
TLR4 (Toll-like Receptor 4) recognizes:
Location of pathogen-associated molecular patterns (PAMPs)
TLR (toll-like receptor) Ligands
TL4 recognizes
TLR5 recognizes
TLR3 recognizes
TLR7 & TLR8 recognize
TLR9 recognizes
TLR Signaling
Two Core signaling proteins:
MyD88 and TRIF
(core TLR signaling proteins)
TLRs in the pathogenesis of Human Disease
TLR4: D299G Mutation Results in
NEMO Mutation: (several polymorphisms) results in
IkBa: S321 Mutation results in
IRAK4: stop codons 287, 293 Mutation results in
CARDs (Caspase Recruitment Domain- containing proteins) in human disease:
CARD9 deficiency mutation
Cytokines
The cytokines of innate immunity:
Cytokine
IL10
Cytokine
TNF
Cytokines
TNF1alpha and TNF2beta
Chemokines and Chemokine Receptors
Chemokine Subfamily: HIV Co-receptors
Main receptor?
What is complement?
Four principles of complement activation
Complement involves a “proteolytic activation cascade”
What are the 3 pathways of initiation?
Classical (antibody required)
Alternative (innate)
Lectin (innate)
All three pathways of complement converge at?
C3 Convertase can split into:
C3a and C5a
C3b
C5b, C6, C7, C8, and C9
or C5b-C9
The Classical Pathway involves 3 Stages
Stage 1:
The Classical Pathway involves 3 Stages
Stage 2:
The Classical Pathway involves 3 Stages Stage 3:
What do C5a and C3a do?
C5b triggers formation of the Membrane Attack Complex
MAC (Membrane attack complex) is MOST effective against:
The Alternative pathway
Alternative Pathway
*Factor D, Factor B, Properdin*
The Lectin Pathway
(MB Lectin)
Complement Regualtion
Complement Regulation
(1) liability of?
(2) Sialic acid inactivates?
(3) Regulatory proteins?
Complement receptors mediate other functions:
-- immune complex clearing
-- chemotaxis
-- opsonization
How does C3b cause opsonization by phagocytic cells?
RBCs and CR1 play major role in immune complex clearance
Complement and Medicine
BUILDUP OF IMMUNITY
Macrophage Killing Mechanisms
Neutrophil (PMNs) Mechanisms
