phases of infection - lara bücher...2017/06/21  · lecture immunology summer semster 2017| lara...

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Course of Infection 21.06.2017 Lara Bücher FAKULTÄT FÜR BIOCHEMIE Lecture Immunology Summer Semster 2017

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Page 1: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

Course of Infection

21.06.2017

Lara Bücher

FAKULTÄT FÜR BIOCHEMIE

Lecture Immunology Summer Semster 2017

Page 2: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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Course of Infection

▪ Phases of infection – overview timeline

▪ Role of innate immunity response for adaptive response

▪ Cytokines and diffrent T-cell subsets

Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Lehrstuhl für Maschinenelemente und Fördertechnik

Arbeitsgruppe Baumaschinentechnik | Professor Dr. Max Mustermann

Zeile 3

Page 3: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

3Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Phases of Infectionstuhl für Maschinenelemente und Fördertechnik

Arbeitsgruppe Baumaschinentechnik | Professor Dr. Max Mustermann

Zeile 3

Page 4: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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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

Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Phases of Infection

Page 5: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

5Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Phases of Infectionhrstuhl für Maschinenelemente und Fördertechnik

Arbeitsgruppe Baumaschinentechnik | Professor Dr. Max Mustermann

Page 6: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

6Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

▪ innate and adaptive immunity: BOTH ESSENTIAL

Page 7: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

7Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

Innate immune reaction

Page 8: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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▪ 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

Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

Innate immune reaction

Page 9: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

9Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

Innate immune reaction

Page 10: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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▪ 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

Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

Page 11: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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▪ 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

Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

Page 12: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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Adaptive immune reaction

Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Role of innate immunity response for adaptive response

▪ 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

Page 13: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

13Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

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

Page 14: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

14Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

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

Page 15: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

15Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Lehrstuhl für Maschinenelemente und Fördertechnik

Cytokines and diffrent T-cell subsetsustermann

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

Page 16: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

16Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Lehrstuhl für Maschinenelemente und Fördertechnik

Cytokines and diffrent T-cell subsetsustermann

Zeile 3

▪ Influenced by cytokines present during T-cell activation

▪ CD4 + IL-12 + INF-γ TH1-cells

▪ CD4 + IL-4 (+IL6) TH2-cells

Page 17: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

17Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017

Lehrstuhl für Maschinenelemente und Fördertechnik

Cytokines and diffrent T-cell subsetsustermann

Zeile 3

▪ TH1 activation of macrophages (cell mediation)

▪ TH2 activation of B-cells (humoral response)

▪ TH1 and TH2 can regulate each other

Outlook:

Page 18: Phases of infection - Lara Bücher...2017/06/21  · Lecture Immunology Summer Semster 2017| Lara Bücher | 21.06.2017 3 Phases of Infection stuhl für Maschinenelemente und Fördertechnik

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Thanks!

References: Janeway, Immunobiology, 8th, p. 454-470