Course of Infection Lara Bücher. FAKULTÄT FÜR BIOCHEMIE Lecture Immunology Summer Semster 2017

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1 Course of Infection Lara Bücher FAKULTÄT FÜR BIOCHEMIE Lecture Immunology Summer Semster 2017

2 Lehrstuhl für Maschinenelemente und Fördertechnik Arbeitsgruppe Baumaschinentechnik Professor Dr. Max Mustermann Zeile 3 Course of Infection Phases of infection overview timeline Role of innate immunity response for adaptive response Cytokines and diffrent T-cell subsets 2

3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik Arbeitsgruppe Baumaschinentechnik Professor Dr. Max Mustermann Zeile 3 3

4 Phases of Infection Course of a typical acute infection Pathogen replicates, level of infectious agent increases Number of pathogens exceed a certain thredhold dose of antigen innate and nonadaptive response Immunological memory starts to be induced After 4-5 days adaptive response clears infection Dose of antigen falls below the response threshold Response stopps BUT long lasting protection through new antibodies, residual effector cells and immological memory 4

5 Phases of Infection hrstuhl für Maschinenelemente und Fördertechnik Arbeitsgruppe Baumaschinentechnik Professor Dr. Max Mustermann 5

6 Role of innate immunity response for adaptive response innate and adaptive immunity: BOTH ESSENTIAL 6

7 Role of innate immunity response for adaptive response Innate immune reaction 7

8 Role of innate immunity response for adaptive response Innate immune reaction Bactirial infection: inflammed tissue Activation of resident macrophages by bactirial comonents, e.g. LPS LPS acts on Toll-like receptors on the macrophages Activated macrophages secret cytokines and chemokines especially the cytokine tumor nekrosis factor-α (TNF-α) endothelial cell activation widens blood vessels 8

9 Role of innate immunity response for adaptive response Innate immune reaction 9

10 Role of innate immunity response for adaptive response Cytokines cause release of Weibel-Palade bodies Weibel- Palade bodies store IL-8, von Willebrand factor (hemostasis not homeostasis), P-selectin Release of P-selectin Synthesis of E-selectin Selectins (familiy of cell adhesion molecules or CAMs): appearance on endothilial cell surface Binding of leukocytes leukocyte extravasation Attraction of more and more inflammatory cells Response is still nonspecific 10

11 Role of innate immunity response for adaptive response Activation of potential antigen representing cells: dendritic cells Activation, e.g.: Combination of LPS and LPB (lipopolysaccharide binding protein) + binding to CD14 (cell-surface receptor) and TLR-4 (Toll-like receptor) Increased synthesis of MHC class II molecules by dendritic cells Expression of co-stimulatory molecules CD80 and CD86 Possible representation of antigens by CD80 and CD86 Adaptive immune reaction 11

12 Role of innate immunity response for adaptive response Adaptive immune reaction Carrying away antigen representing cells in lymph along with their antigen Entering secondary lymphoid tissue Attraction by chemokines ELC, MIP-ß, SLC (produceed by lymph node stromal and high vascular endothelial cells) Eventually death of dendritic cells - but before: Activation of antigen specific naive T-lymphocytes 12

13 Role of innate immunity response for adaptive response Passing of antigen-specific naive T-lymphocytes through lymph nodes Detection of antigens represented on dendritic cells by T-lymphocytes Division and maturation into effector cells reenter the circulation High efficiency: all naive T-cells trapped in lymph nodes within 2 days after antigen depostion 13

14 Role of innate immunity response for adaptive response NO SENSITISATION of T-cells by infected tissue itself Activation only in peripheral lymphoid organs by antigens brought there by dendritic cells 14

15 Lehrstuhl für Maschinenelemente und Fördertechnik Cytokines and diffrent T-cell subsets ustermann Zeile 3 Diffrentiation of naive CD4 T-cells into 2 major classes of CD4 effector cells: During inital response to antigen in the peripheral lymphoid tissue Development of TH1 or TH2 Decision between macrophage activation or antibody production 15

16 Lehrstuhl für Maschinenelemente und Fördertechnik Cytokines and diffrent T-cell subsets ustermann Zeile 3 Influenced by cytokines present during T-cell activation CD4 + IL-12 + INF-γ TH1-cells CD4 + IL-4 (+IL6) TH2-cells 16

17 Lehrstuhl für Maschinenelemente und Fördertechnik Cytokines and diffrent T-cell subsets ustermann Zeile 3 TH1 activation of macrophages (cell mediation) TH2 activation of B-cells (humoral response) TH1 and TH2 can regulate each other Outlook: 17

18 Thanks! References: Janeway, Immunobiology, 8th, p

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