1. Innate immunity Properties of innate immunity Recognition of microbes by innate immune system –structures that are recognized (“molecular patterns”) –receptors that recognize molecular patterns

2. Principle mechanisms of innate and adaptive immunity

3. Principle mechanisms of innate and adaptive immunity

4. 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

5. How does the innate immune system recognize microbes?

6. Structures on pathogens recognized by immune system Antigens INNATE IMMUNITYADAPTIVE IMMUNITY Molecular patterns present only on microbes present both on microbes and non-infectious substances shared by various classes of microbes specific for any particular microbe

7. Receptors of immune system that recognize pathogens T cell and B cell receptors (TCR and BCR) INNATE IMMUNITYADAPTIVE IMMUNITY Pattern recognition receptors encoded in germline (1 gene › 1 receptor) limited diversitygreater diversity encoded by genes produced by somatic recombination of gene segments (more segments › 1 receptor) recognize non-selfrecognize both self and non-self nonclonal distributionclonal distribution

8. Receptors of immune system that recognize pathogens INNATE IMMUNITYADAPTIVE 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

9. Pathogen recognition in innate immunity PATTERN RECOGNITION RECEPTORS (PRRs) (on innate immunity cells) recognize PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPs) (on pathogens)

10. Innate immunity Adaptive immunity Macrophage Dendritic cell Patogens CD4 + T cell PRR PAMP Pathogen recognition in innate immunity

11. 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:

12. 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

13. Christiane Nüsslein-Volhard Nobel prize for medicine 1995 "Das war ja toll!" 1985 Toll-like receptors (TLR)

14. Bruce BeutlerJules Hoffmann Toll-like receptors (TLR) Nobel prize for medicine 2011

15. Cell activation (expression of various proteins) Toll-like receptors (TLR)