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Innate immunity
• Properties of innate immunity
• Recognition of microbes by innate immune system
– structures that are recognized (“molecular
patterns”)
– receptors that recognize molecular patterns
Principle mechanisms of innate and adaptive immunity
Principle mechanisms of innate and adaptive immunity
Mechanisms of innate immunity
- phylogenetically older
- exist before or react immediately after contact with pathogen
- first line of defense
- are not enhanced upon repetead contact with pathogen (no memory)
- react predominantly to infectious agents
- stimulate and shape adaptive imunity
How does the innate immune system recognize microbes?
Structures on pathogens recognized by immune system
Antigens
INNATE IMMUNITY ADAPTIVE IMMUNITY
Molecular patterns
present only on microbespresent both on microbes and
non-infectious substances
shared by various classesof microbes
specific for any particularmicrobe
Receptors of immune system that recognize pathogens
T cell and B cell receptors(TCR and BCR)
INNATE IMMUNITY ADAPTIVE IMMUNITY
Pattern recognition receptors
encoded in germline(1 gene › 1 receptor)
limited diversity greater diversity
encoded by genes produced by somatic recombination of gene segments
(more segments › 1 receptor)
recognize non-self recognize both self and non-self
nonclonal distribution clonal distribution
Receptors of immune system that recognize pathogens
INNATE IMMUNITY ADAPTIVE IMMUNITY
T cell and B cell receptors(TCR and BCR)
Pattern recognition receptors
clones of lymphocytes with distinct specificities
express different receptors
identical receptors on all cells of the same lineage
Pathogen recognition in innate immunity
PATTERN RECOGNITION RECEPTORS (PRRs)
(on innate immunity cells)
recognize
PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPs)
(on pathogens)
Innate immunity
Adaptive immunity
Macrophage
Dendritic cell
PatogensCD4
+T cell
PRR
PRR
PAMP
PAMP
Pathogen recognition in innate immunity
Molecular patterns
Structures common for certain groups/classes of pathogens
- essential for their life, replication and/or infectivity
structures of bacterial cell wall (LPS, peptidoglycan, flagellin...)
nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...)
- not present on human cells
Lipoproteins
Flagellin
Examples:
Pattern recognition receptors
On the membranes(Toll-like receptors, TLRs)
- on plasma membrane
- on endosomal membrane
Plasma protiens that recognize molecular patterns (MBL, CRP...)
In cytosol
On/in the cell
In Circulation
Christiane Nüsslein-Volhard
Nobel prize for medicine 1995
"Das war ja toll!" 1985
Toll-like receptors(TLR)
Bruce Beutler Jules Hoffmann
Toll-like receptors(TLR)
Nobel prize for medicine 2011
Cell activation(expression of various proteins)
Toll-like receptors(TLR)