immune response to infection - ruhr-uni-bochum.de · response protects often long lasting against...

Immune response to infection

Dr. Sandra Nitsche ([email protected] ) 20.06.2018

1

Course of acute infection

2

Typical acute infection that is cleared by an adaptive

immune reaction

1. invasion of pathogen

2a. expansion of pathogen

2b. reaches threshold

activation of adaptive

immune mechanisms

2c. Reaction of innate

immune system

2d. Memory response is

started

3. 4-7d adaptive immune

reaction (e.g. effector t-

cells, antibodies) eliminate

the infection

4a. antigen amount under

threshold

4b. Immune reaction stops

4c. Immunological memory

response protects often

long lasting against new

infection with same

pathogen

Protection against infection – stages of infection

3

1. Attachment on epithelial cells and infection

2. local, innate immune reaction dampen the infection

3. expansion of microorganism to lymphatic system

4. adaptiv immune response eliminate the pathogen

Time course of infection in

normal/immunodeficient indiviuum

4

Duration of infection in

immunocompromised and

healthy mice/humans is

depended on the immune

status.

Red: without innate

immune reaction

Green: with innate but

without adaptive immunity

Yellow:

immunocompetent

mice/human

Mac: macrophages

PMN: polymorphonuclear

leukocytes

T: T-cells

B: B-cells

Balance of T-cell development by

cytokines produced by DCs

5 Aus: Murphy, Travers, Walport, Janeway Immunologie, 7. Aufl. © Spektrum Akademischer Verlag 2010

TH17: T-helper cells Typ 17

-> high TGF-ß, low IL-6 and IL-23

Treg: regulatory T-helper cells

-> high TGF-ß, high IL-6 and IL-23

Early infection phase triggers

differentiation from naïve CD4-

cells to TH17 cells and not to Treg

IL-17 and IL-17F were produced

by TH17 cells to induce chemokine

production in e.g. epithelial cells

for recruitment of neutrophils to

the side of infection

Cells without antigen contact stay

naive

T cell differentiation influenced by cytokines


Viral infection (and some

intracellular bacterial infections)

triggers DC´s (production of IL-12)

and NK cells (production of IFN-γ)

which both cause TH1

-> IFN-γ IL-2 TNF-β

IL-4 produced by NK-T-cells or

other cells triggered by helminth or

other pathogens cause TH2 profile

of the naïve CD4-T-cell

-> IL-4 IL-5 IL-13

T cells produce cytokines for regulation of

other subsets


Treg produce TGF-β which dampen the differentiation to TH1, TH2 or TH17

In case of an infection: DC´s produce IL-6 -> TH17 upregulated and Treg is

depressed (TGF-β down)

TH1 or TH2 cytokine (IL-10; IFN-γ) dampens TH17 and regulation of subsets by

downregulation of the other subset of helper T cells

Infection may trigger TH1 polarization via

TLR-pathways


- Infection may trigger to a TH1-polarisation via signaling pathways

by Toll-like receptors

- Adaptor protein MyD88 is a central component by signal

transduction of toll-like receptors

- KO-mice could not respond to T.gondii with IL-12, IFN-γ and TH1

reaction profile so they died 2 weeks after infection

Manipulating the CD4 T-cell subsets by

cytokines in early stages of infection


Cytokine milieu is responsible for the

development of naïve T cells to

differentiate into

TH1(IL-4, Il-5, IL13)

or

TH2 (IFN-γ, IL-2, TNF-β) cells

Influence by blocking antibodies

(cytokines or receptors)

Change of surface molecules on effector T cells


Effector T cells change their surface

molecules for binding on endothelial

cells in the lymph node

L-Selectin in naïve T cells binds to

CD34

After differentiation in the lymph node

integrine VLA-4 and LFA-1 are

upregulated and bind to VCAM-1 or

ICAM-1 respectively on endothelial cells

CD45RO fasten the specific antigen

stimulation up

Usage of chemokines for migration


Lymphocytes which are at the dermis binds to E-Selectin

(via CLA) and CCL17 (via CCR4) in the endothelium

Lymphocyte at the cell surface (ceratinocyt) binds via

CCL27 to CCR10 as receptor

Cytokines IL-12 and IL-23 share subunits


- Both cytokines augment the activity and

proliferation of the CD4 subsets that

express receptors for them

- TH1-cells express IL-12R

- TH17-cells express IL-23R

- Mice deficient in p40 lack expression of

both of there cytokines and show an

immune deficiencies in both TH1- and

TH17 activity

CD8 T cell activation by APCs


Activated DC´s during infection

express B7 and other co-

stimulatory molecules and

activate naïve CD8-T cells and

via Peptid-MHC-I-complex for

proliferation of the Cytotoxic-T-

lymphocyte (CTL) (left)

Activated DC´s also produce

IL-12 and IL-18 and stimulate

naïve CD8-t cells to produce

IFN-γ

IFN-γ activates macrophages

to eliminate intracellular

bacterial or helps other cell

types for an antiviral reaction

Antigen specific T– and B- cells can

interact at the peripheral lymphatic tissue


Different strategies to clear primary infection


Protective immunity (immunological memory)


After first infection with the pathogen where are pathogen

specific antibodies and effector-T cells are generated the

immunity based on immunological memory response to

secondary infection reacts immediately (often without any

symptoms of infection)

18 https://youtu.be/zQGOcOUBi6s

Das Immunsystem erklärt - Bakterien Infektion Kurzgesagt – In a Nutshell

https://youtu.be/zQGOcOUBi6s

https://www.youtube.com/channel/UCsXVk37bltHxD1rDPwtNM8Q




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