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)