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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



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



IntroductionPhases of Infection




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




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




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



• 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






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





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






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





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






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






12

Overview of CD4 T-cell subsets






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





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



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

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