Innate immunityProperties of innate immunity

Components of innate immunity Epithelial barriersCellular mechanismsHumoral mechanisms

Role of innate immunity in stimulating adaptive immune response

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

Components of innate immunity- epithelial barriers (skin and mucosal membranes)- humoral components (complement, cytokines etc.)- cells (phagocytes, NK cells...)

physical barrierFunctions of epithelia in innate immunty

chemical barrier (production of antimicrobial peptides) physical barrierFunctions of epithelia in innate immunty

intraepithelial lymphocytes - normal bacterial flora chemical barrier (production of antimicrobial peptides) physical barrierFunctions of epithelia in innate immunty

Cells of innate immunityNK cellsDendritic cellsMast cellsNeutrophilsMonocytes/MacrophagesPhagocytosis, inflammationPhagocytosis, inflammation,T-cell activation, tissue repairKilling of infected or tumor cellsEosinophilsInflammationDefense against parasitesPhagocytosis, activation of naive T-cellsCell typePricipal function(s)

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen 2. Recognition of pathogen (macrophages and dendritic cells)- molecular patterns and receptors

Molecular patternsStructures common for certain groups/classes of pathogens essential for their life, replication and/or infectivitystructures of bacterial cell wall (LPS, peptidoglycan, flagellin...)nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...) not present on human cellsExamples:

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen 2. Recognition of pathogen3. Phagocytosis and killing of a pathogen (macrophages)

reactive oxygen species (ROS), nitric oxide (NO) and lysosomal enzymes

Phagocytosis and killing of microbes Pathogen recognition

Zipping of membrane around microbePhagocytosis and killing of microbes

Ingestion of microbePhagocytosis and killing of microbes

Fusion of phagosomewith lysosomePhagocytosis and killing of microbes

Phagocyte activationPhagocytosis and killing of microbes

Killing of microbePhagocytosis and killing of microbeshttp://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_3.html

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen 2. Recognition of pathogen3. Phagocytosis and killing of a pathogen4. Induction of inflammation (macrophages)- production of pro-inflammatory cytokines (TNF, IL-1, chemokines...)

Inflammation inductionProinflammatory cytokinesTNF Tumor Necrosis FactorIL-1 Interleukin-1Chemokines Chemotactic cytokines

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen 2. Recognition of pathogen3. Phagocytosis and killing of a pathogen4. Inflammation induction5. Attraction of cells to infection site- adhesive molecules (selectins and integrins) and chemokines

Leukocytes arrive at the site of infection (extravasation)Weak binding and rollingActivation andfirm bindingEndotheliumTNF & IL-1TransmigrationArrival to the site of infectionSelectinsIntegrinsVarious adhesive moleculesChemokinesMacrophageshttp://www.youtube.com/watch?v=WEGGMaRX8f0

http://www.youtube.com/watch?NR=1&v=DMvixApKzKs

In some inflammatory diseases therapy is directed against proinflammatory cytokines or adhesive molecules(eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis)

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen 2. Recognition of pathogen3. Phagocytosis and killing of a pathogen4. Inflammation induction5. Attraction of cells to infection site6. Pathogen elimination and/or adaptive immunity activation (dendritic cells)- cytokines, costimulatory molecules...

Role of phagocytes in innate immunityOrder of events in infection1. Entry of pathogen 2. Recognition of pathogen3. Phagocytosis and killing of a pathogen4. Inflammation induction5. Attraction of cells to infection site6. Pathogen elimination and/or adaptive immunity activation7. Tissue repair and remodeling (macrophages)- enzymes and cytokines (growth factors, metaloproteinases...)

Role of NK cells in innate immunityKilling of cells infected by intracellular pathogens (eg. viruses) andtumor cellsNK Natural killer

Role of NK cells in innate immunityNK Natural killerKilling of cells infected by intracellular pathogens (eg. viruses) andtumor cellsActivation of macrophages (by IFN-)

NK cell killer functionDepends on balanse of signals by activating and inhibitory receptorsInhibitoryActivating

InhibitoryActivatingNK cell is inhibited

NO KILLINGNK cell killer functionDepends on balanse of signals by activating and inhibitory receptors

InhibitoryActivatingNK cell is activatedKILLINGNK cell killer functionDepends on balanse of signals by activating and inhibitory receptors

InhibitoryActivating activating receptors recognize stress-derrived structures on cells (including infected and malignant cells)- inhibitory receptors recognize MHC class one moleculeNK cell killer functionDepends on balanse of signals by activating and inhibitory receptors

Mechanism of NK cell recognition

Mechanism of NK cell recognition

Apoptosis induction in infected and tumor cellsKilling mechanisms same as in cytotoxic T-cells- Perforin and granzymes- FasL and FasNK cell killer function

complement proteins (8th week seminar)- other plasma proteins (CRP, MBL etc.)- cytokinesHumoral mechanism of innate immunity

Cytokines in innate immunityInflammation induction(TNF, IL-1, chemokines...)

Macrophage and NK cellActivation (IL-12 and IFN-)Antiviral effects (IFN type I, IFN- and IFN-)Differentiation of T-cell subpopulation (eg. IL-12)(eg. INF- in HCV therapy)Cytokines in innate immunityInflammation induction(TNF, IL-1, chemokines...)

Role of innate immunity in stimulation of adaptive immune response

T or B-cells need two signals for activationFirst signal antigen recognitionSecond signal derrived by innate immunity

Thanks for your attention!Questions?

Peptide antibiotics productionj.Innate immunity cells stimulate adaptive immunity by10.Leukocyte migrationi.Bacteria can avoid phagocytosis by9.When a target cell does not express MHC class Ih.IL-12 produced by macrophages stimulates8.Structures that a group of pathogens has in commong.Chemokynes are important for7.NK and T- cellsf.NK cells are activated6. molecules that provide second signale.NK cells5.TNF, IL-1 and other mediatorsd.Macrophages kill phagocytosed microbes by4.Polysaccharide capsule productionc.Macrophages stimmulate inflammation by production of3.Kill our own virus-infected cells b.Epithelial cells provide chemical barrier for pathogens by2.Production of enzymes, ROS and NOa.Receptors on innate immunity cells recognize1.10.____9.____8.____7.____6.____5.____4.____3.____2.____1.____gjdabhifce

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