BioPharma 03 Innate Immunity

8/9/2019 BioPharma 03 Innate Immunity

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Biotechnolo and Pharmacolo Course To ic 03

Le Van Dong MD., PhD

Deputy Head, Department of Immunology

Vietnam Military Medical University

[email protected]; [email protected]

EDUCATION

INDUSTRY/ TREATMENT

RESEARCH


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Aims

Know key properties of innateimmunity.

Know components made up the

innate immune system.

Understand mechanism(s) by

which the innate immunity use to

protect body.


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Innate immunity and adaptive

Abbas A. K and Lichtman A. H

Basic Immunology 3rd Ed Saunders 2011

First line of defense

Non-specific

Second line of defense

Highly specific with memory


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Pro erties of innate immunit

,

another generation.

ways presen an mme a e y reac

as the microbe enters the body.

Utilize the same mechnism to fight

different microbes (non-specific).

No memory, reaction is not stronger

after each encounterment.


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Components of innate

Epithelia (skin and mucous

.

Phagocytes, NK cell.Plasma proteins, including

complements.

Cytokines.


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Mechnisms of innate immunit

Physical barries of skin and mucous membrane.

Cellular mechanisms: .

Killing by NK cell.

Humoral mechanisms:Lysis by complements.

Cytokines


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Physical and chemical mechanisms

mucous membranes


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Roles of epithelia in innate immunity


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E ithelial Barriers COMMON PORTALS OF ENTRY BY

MICROBES:skin, GI tract, respiratory tract. These 3 portals are lined by continuous

epithelia. These cells also produce peptide

antibiotics. In addition, intraepithelial

l m hoc tes T cell linea e ex ress anti en

receptors of limited diversity common class is

T cells(have and chains which are similar

. Intraepithelial lymphocytesrecognize microbial

trying to breach epithelia.


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a appens w en e p ys ca

and chemical barriers arebreached?


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Cellular mechanismsLeukocyte Players of Innate Immune

Responses


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Cellular mechanisms

Pha oc tosis


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Deployment of phagocyte to the infection site


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How phagocyte get out of the blood


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How do phagocytes recognize microbes?

Mannose

receptorMac-1

Scavenger

receptor

Mannose

receptorMac-1

Scavenger

receptor CD14

Toll like receptor

C FcC Fc

These cell have surface receptor for microbes, that can bind to

.

These receptor recognise unique structure on microbe only (MP).

Receptors for C and Fc to cache C or Ab coated microbe


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Phagocytosis process

NO

Arginine

Inducible nitric

oxide synthaseROI

Oxidase

(INOS)


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How phagocyte capture microbe

Direct

capture with

C coated microbe

(opsonization by C)v a recep or

Y Antibody coated microbe(opsonization by antibody)

(via Fc receptor)


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NK cell kills target cells

ELIMINATING MICROBIAL RESERVOIR


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WhenNKcellkillsothercell?

AL

NO

R

ORMA

Abbas A. K and Lichtman A. H Basic Immunology 2nd Ed Saunders 2004

AB


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Activating and Inhibitory receptors

molecules on stressed cells (viruses, IC bacteria, DNAdamage, malignant transformation, tumour cells) tell NK

to kill.

INHIBITORY RECEPTORSspecific for class I MHCs tellno o .

Viruses have mechanisms which block expression of

.

CTLs but inhibits the inhibitory NK receptors. Thus,NK

cells are still activated and continue to eliminate

v rus- n ec e ce s.


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Injection

Cholaera

Cholaera serum


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+

Fresh serum

+

56 0C

serum Non-

injected

serum

Bordets experiment


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The complement system C

Collection of circulatin membrane associated roteins

(mainly proteolytic enzymes) C activation pathways:

Alternative pathway (innate) is triggered when complement

proteins are activated on microbial surfaces. Microbes dont have

re ulator roteins and cant control it.

Classical pathway(humoral adaptive) is triggered after Abs bind

to microbes and other Ags.

Lectin pathway (innate immunity) activated when mannose-binding lectin binds to terminal mannose residues on microbial

surface glycoproteins (activates proteins of the classical pathway

u s nna e .


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C pathways

Alternative pathway and

innate immunity; Classical

pathway belongs to

Abbas A. K and Lichtman A. HBasic Immunology 2nd Ed Saunders 2004


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Beginning steps

Abbas A. K and Lichtman A. HBasic Immunology 2nd Ed Saunders 2004


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Final steps

3 pathways have

different beginnings but

chare same late steps

and effector functions


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Biolo ical effects of C

pson za on: coa s m cro es,

promotes phagocytosis.

ys s o ac er a: orma on o apenetrates the cell membrane and causes

either l sis or microbial a o totic death.

Chemotaxic: some C fragments arechemoattractants for ha oc tes and

eventually other leukocytes (ie. C5a, C3a).


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ofC

ect

s

a

lef

logi

Bi



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C tokines of Innate Immunit

u - u y u y ,

act on leukocytes (though not all).

e pr nc pa source o cy o nes are

activated dendritic cells and macrophages.

mos pro uce n sma amoun s

bind withhigh affinityto target cells

can act distant from site of secretion

C t ki i


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Cytokines serve various

TNF, IL-1 recuit blood neutrophils and monocytes to

n ec on can a so pro uce rom us orma on,

reduced myocardial contractility, vascular dilation,leakiness andshock.

Septic shock can be produced by disseminated gram-

neg infections. One sees low blood pressure,coagulation, metabolic disturbance in septic shock, one

seeshigh TNF levels.

IL-12 produced by macs and dends in response to LPS,other microbial products.

IFN - produced by NK cells, T cells both innate and

adaptive.


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Macro ha e c tokines



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Other Plasma Proteins

-

opsonizes and activates complement

-

Circulating levels of many plasma proteins

response


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Notes

Extracellularbacteria and fungi combated byphagocytes, complement, acute phase

proteins

n race u ar ac er a an v ruses com a e

by phagocytes, dendritic cells, NK cells

with help fromcytokines

I t i it


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Innate immunity

immunity

Innate immune

responses generate

second signals

(together with antigens)

to activate B and Tlymphocytes.

This microbe-

signal requirementensures no response

to harmless

substances.


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2 signals regulation

signal 1) and moleculesproduced during the innate

immune response (signal 2)

function cooperatively to activate

anti en-s ecific l m hoc tes.

The requirement for microbe-

tri ered si nal 2 ensures that

the adaptive immune response isinduced by microbes and not by

.

Microbes stimulate DC and M to produce


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Microbes stimulate DC and M to produce

second signals that stimulate T

lymphocytes

.

These bind to receptors on nave T cells Ag +.

ALSO DC and M secrete IL-12which stimulates T cell

B lymphocytes recognize C3d on microbes from

alternative athwa

There is a receptor for C3don B cellwhich serves as

costimulator

These second signals not only stimulate


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g y

adaptive immunity but also guide the

response

Intracellular pathogens need to be

eliminated by T cells thus T cells are

s mu a e y -ce cos mu a ors on

dendritic cells and macrophages.

x race u ar pa ogens e. oo -

borne) need to stimulate B cells and

-

stimulators


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Review uestions

. w u y

recognize microbes?

2.How do different components of innate

immunity function to combat different

3.How do innate immune reactions

stimulate adaptive immune responses?

BioPharma 03 Innate Immunity

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