Post on 01-Sep-2019
Date: Mo 05.06.19
Immune response to pathogens
Immunologie
Michelle Koci
Immune Response to Pathogens
Michelle Koci | 05.06.19
Content
1.) Phases of Infection
2.) Role of innate immune response for adaptive response
3.) Cytokines and different T cell subsets in response to different
pathogens
4.) Summary
Immune Response to Pathogens
Michelle Koci | 05.06.191
1. Establishment of infection
• Infectious agent colonizes the host
and it replicates
• Innate response is initiated
immediately
2. Inductive phase
• Number of antigens exceeds the
threshold level
• Adaptive response is initiated
3. Effector phase
• Effector cells and molecules start to clear the infection
4. Memory phase
• Level of antigen below the threshold
• Residual effector cells, antibody, and immunological memory provide lasting protection against
reinfection
IntroductionPhases of Infection
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.192
IntroductionPhases of Infection
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Course of Infection
3
First contact through epithelial
surface or mucosal surface
→ Focus of infection has to
be established
Local innate immune response
contain the infection
• Antigen-presenting dendritic
cells migrate to lymphatics
Initiation of the adaptive immune response
• Activation of naive T cells and antigen producing B cells
Clearance of infection by specific antibody and effector T cells
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Course of InfectionImportance of innate and adaptive immune response
4
• Natural deficiencies in non-adaptive immune
defences are rare
→ Innate and adaptive immune system
necessary for effective host defence
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Role of innate immune response for
adaptive response
5
1. Inflammation of tissue
• Activated macrophages secrete cytokines and chemokines → recruit neutrophils,
monocytes, and other leukocytes
→ Signals the presence of infection
2. Activation of antigen-presenting dendritic cells
• Dendritic cells migrate away from infected tissue to the lymph nodes
→ Initiate adaptive immune response by
• Activation of naive T cells and B cells resulting in proliferation and differentiation
• Migration of the activated effector T cells to the infected tissue
Innate
response
Adaptive
responseDendritic cell
Immune Response to Pathogens
Michelle Koci | 05.06.19
• different cytokines are released depending on the microorganism that influences the
behaviour of innate immune cells and antigen presenting cells
→ Cytokines can specific direct the differentiation of naive CD4 T-cells
Classes of CD4 T effector cells: TH17, TH1, TH2, and regulatory subsets
• T-cell subsets influence the effector response (e.g. extend of macrophage activation,
recruitment of eosinophil/neutrophil, classes of antibody)
Cytokines and different T cell subsets in
response to different pathogens
6
→ Orchestrate different
immune functions
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
7
Infection by extracellular bacteria and fungi leads
to the generation of TH17 cells
Recognition of a pathogen
Secretion of IL-6 and IL-23
Differentiation to TH17 cells
Migration to the site of infection
Activation of dendritic cells (e.g.
dectin-1)
Stimulation by pathogen antigen
Release of IL-7 family Secretion of cytokines
IL-6 and chemokines
CXCL8 and CXCL2
Recruitment of neutrophils
Secretion of G-CSF
and GM-CSF
Increase neutrophil and macrophage
production and the differentiation of
monocytes
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
8
Infection by extracellular bacteria and fungi leads
to the generation of TH17 cells
• Cytokine environment prevents false immune
response to self antigens or commensal
microorganisms
• Absence of infection: only TGF-β is produced
→ Inhibits proliferation and differentiation of TH1
and TH2
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
9
Activation of the TH 1 response
• Induction by viruses or bacterial and protozoan pathogens that survive inside
the macrophages
Infection via virus:
• Activation of cytotoxic CD8 T-cells → recognize virus infected-cells
• Stimulation of IgG antibody production → neutralize virus particles
Infection via bacterial or protozoan pathogens:
• Activation of macrophages → destroy pathogen
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
10
Activation of the TH1 response
• Development of TH1 cells by IL-12 and IFN-γ
→ IFN-γ inhibits the proliferation of TH2 cells
• NK cells and CD8 T-cells also activated by virus
infection → produce abundant IFN-γ
• Macrophages and dendritic cells produce IL-12
triggered by TLR signalling
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
11
Activation of the TH 2 response
• Mechanism of the development of TH2 response is
less clear
→ Activated in the presence of IL-4
• Helminths and other extracellular parasites induce
differentiation
• iNKT cells, basophils, and mast cells are IL-4
producers
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
12
Overview of CD4 T-cell subsets
Murphy, K. and Weaver, C. (2017) Immunology Janeway ’ S 9 Th Edition
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
12
Cross regulation
• Differentiation into different CD4
T-cell subsets is regulated by
cross regulation
• TH17: + IL-6, IL-23, and TGF-β
- IL-4 and IFN-γ
• TH1: + IL-12, IFN-γ
- IL-4 and IL-10
• TH2: + IL-4
- IFN-γ
Immune Response to Pathogens
Michelle Koci | 05.06.19
Cytokines and different T cell subsets in
response to different pathogens
13
• Appropriate choice of the CD4 T-cells is important
for the clearance of infection
• Infection by L.major requires TH1 response and
activation of macrophages
• C57BL/6 mice: production of TH1 cells
→ infection is eliminated
• BALB/c mice: production of TH2 cells
→ unable to activate macrophages
→ fail to kill L. major
• Memory T cells in BALB/c produce IL-4
→ addition of IL-4 antibody eliminates the pathogen
Immune Response to Pathogens
Michelle Koci | 05.06.19
Summary
14
• Four different phases of infection
→ Innate immune system starts immediately whereas the adaptive
immune system develops
→ Both are necessary for an effective immune response
• Dendritic cells are the bridge between the innate and adaptive immune
response
• Cytokines can specific direct the differentiation of naive CD4 T-cells in
response to pathogens
• Differentiation into different CD4 T-cell subsets is regulated by cross
regulation as well
→ Appropriate choice of the CD4 T-cells is important for the clearance of
infection