Download Innate immunity

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
- are not enhanced upon repetead contact with pathogen (no memory)
- react predominantly to infectious agents
- first line of defense
- stimulate and shape adaptive imunity
How does the innate immune system
recognize microbes?
Structures on pathogens recognized by immune system
INNATE IMMUNITY
Molecular patterns
ADAPTIVE IMMUNITY
Antigens
shared by various classes
of microbes
specific for any particular
microbe
present only on microbes
present both on microbes and
non-infectious substances
Receptors of immune system that recognize pathogens
INNATE IMMUNITY
ADAPTIVE IMMUNITY
Pattern recognition receptors
T cell and B cell receptors
(TCR and BCR)
limited diversity
greater diversity
encoded in germline
(1 gene › 1 receptor)
encoded by genes produced by somatic
recombination of gene segments
(more segments › 1 receptor)
recognize non-self
nonclonal distribution
recognize both self and non-self
clonal distribution
Receptors of immune system that recognize pathogens
INNATE IMMUNITY
ADAPTIVE IMMUNITY
Pattern recognition receptors
T cell and B cell receptors
(TCR and BCR)
identical receptors on all
cells of the same lineage
clones of lymphocytes with
distinct specificities express
different receptors
Pathogen recognition in innate immunity
PATTERN RECOGNITION RECEPTORS (PRRs)
(on innate immunity cells)
recognize
PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPs)
(on pathogens)
Pathogen recognition in innate immunity
Dendritic
cell
Patogens
CD4+
T
cell
PAMP
PRR
PAMP
Macrophage
PRR
Innate immunity
Adaptive
immunity
Molecular patterns
Structures common for certain groups/classes of pathogens
- essential for their life, replication and/or infectivity
- not present on human cells
Lipoproteins
Flagellin
Examples:
structures of bacterial cell wall (LPS, peptidoglycan, flagellin...)
nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...)
Pattern recognition receptors
On/in the cell
On the membranes
(Toll-like receptors, TLRs)
- on plasma membrane
- on endosomal membrane
In cytosol
In Circulation
Plasma protiens that recognize molecular patterns (MBL, CRP...)
Toll-like receptors
(TLR)
"Das war ja toll!"
1985
Christiane Nüsslein-Volhard
Nobel prize for medicine 1995
Toll-like receptors
(TLR)
Bruce Beutler
Jules Hoffmann
Nobel prize for medicine 2011
Toll-like receptors
(TLR)
Cell activation
(expression of various proteins)