01 pcvd anne goubie

4TH MERIAL FORUM

HAVE WE GOT PCVD &

SWINE INFLUENZA UNDER

CONTROL?

PCVD

Moderator: Dr François Joisel

• Basics in porcine immunology. Dr. A. Goubier

• PCV2 impact and control on early stage of gestation in sows. Pr G. Sarli

• PCV2 antibody status of gilts before entering swine commercial farms. Dr G. Perreul

A.Goubier_Berlin_2012

Porcine Immunology and vaccinology : back to basics


Porcine Immunology and vaccinology Back to basics

• Immunity: defense strategies

– Physical and chemical barriers

– Innate Immune response

– Adaptative Immune response

– Swine specificities

• Immune memory

• Vaccination strategies

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Immunity

• Oxford Dictionnary

“the ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells”

• Cambridge Dictionary:

«when you are protected against diseases»

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Science photo library

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Physical and chemical barriers

Innate Immunity

Adaptive Immunity

INDUCTION OF AN IMMUNE RESPONSE

Foreign invaders - viruses, bacteria, allergens, toxins and parasites- constantly bombard our body.

Invasion

Inflammation

In

fectio

n

Immunity: Defense strategies against infections


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Tears Blinking

Dessication Desquamation Fatty acids Normal flora Normal flora

Anaerobia Lysozyme Defensins Proteases Diarrhea

Acid pH Vomiting

Mucus Cilia Coughing

Vomiting Saliva

Turbulence Sneezing


Immunity: Defense strategies against infection

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Innate Immunity

Adaptative Immunity



Inflammation

In

fectio

n


Innate Immunity: Pathogens recognition

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1- Identification of abnormal element

?

2- Danger evaluation

1+2 = implementation of Immune defenses

Innate Immunity Pathogens sensing

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TLR4 TLR2

TLR6 TLR1

TLR5

MD2

TLR11

Profilin (Protozoa)

Flagellin (Bacteria)

Enterobacterial LPS (Bacteria)

Mycoplasmal Lipoprotein (Bacteria)

Zymosan Peptidoglycan

(Bacteria, fungi)

Lipoprotein (Bacteria)

TLR7 TLR8 TLR9 TLR3

dsRNA (Virus)

ssRNA (Virus)

CpG DNA (Bacteria,

virus)

NOD2 NOD1

Peptidoglycan component (Bacteria)

PAMPs+ DAMPs = immune system activation

DAMPs: Danger-AMPs = Endogeneous Danger signals recognition

PAMPs: Pathogen-Associated Molecular Patterns = Pathogen recognition


Innate Immunity Implementation of the response

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Tissue

Pathogen entry in the organism: PAMPs

Agression and cell death: DAMPs

Innate Immunity

A.Goubier_Berlin_2012 12

Innate Immunity: Defense Mechanisms

Infection Lysis of pathogens +/- infected cells

Barriers reinforcement

Recruitment and activation of Innate

Immune cells

Eosinophiles

Mastocytes

NK cells

Macrophages

Dendritic cells

Adaptative Immunity


Immunity: Defense strategies against infections

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Innate Immunity

Adaptive Immunity



Inflammation

In

fectio

n

Innate and adaptive Immunity: Sequential and complementary strategies

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• Innate Immunity

– First line of defense immediate

– Able to sense pathogens and danger but invariant

– Do not prevent re-infection

• Adaptive immunity

– Occurs with failure of innate system

Delayed

– Need the innate immunity for activation but custom

– Memory of the infection

Time after infection

Hours Days

0 6 12 1 3 5

CD8

CD8

CD8 CD8

CD8 CD8 CD8

CD4

CD4

CD4

CD4

CD4

CD4

CD4

B B

B B

B

Lymph Nodes

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Messengers between innate and adaptive immunity: The Dendritic Cells

CD8

CD4 B

Blood

Tissue

Lymphatic Vessels

The actors of Adaptive Immunity T CD4+ cells: Conductors of the immune system

Cellules CD4

naïves

TH17

TGFb

+ IL6

IL17 IL6

Neutrophiles and epithelium activation

Anti-microbial peptides production

Inflammation

Defense against extra_cellular bacteria

Treg

TGFb

IL10 TGFb

Regulation of Innate and Adaptive Immunity

TH1

IL12 IFNg

IL2

Activation of macrophages, Cytotoxic T lymphocytes

Inflammation

Defense against virus, intra-cellular bacteria

“cell mediated” Immunity

TH2

IL4 IL4 IL5

IL13

Antibodies production

Barriers reinforcement

Eosinophiles and mastocytes activation

Defense against Helminths

“humoral” immunity


Cytokines production: -IFNg

-TNFa (activation of phagocytic cells and anti-viral effect)

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The actors of Adaptive Immunity T CD8+ lymphocytes: licensed to kill

CMH class I

IL12 CD8

CD8

TC0 CTL

TCR

Killing of infected cells


The actors of Adaptive Immunity B cells: Antibodies factories

B cell

Complement Activation

Lysis of microbes

Phagocytosis of microbes opsonized

with complement fragments

Inflammation

Phagocyte

Microbes and toxines neutralization

Opsonization and phagocytosis of

microbes

Antibody dependent cellular cytotoxicity

NK cells Eosinophiles

Mastocytes Basophiles

Degranulation

From Abbas & Lichtmann, Basic immunology

TH2

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Swine specificities

Swine Immune system characteristics Importance of Innate Immune cells

B cells ( 30%) CD4+ (35-40%) CD8+ (20-25%)

NK (<10%)

ab T cells ( 60%)

B cells ( 25%) CD4+ CD8+

NK cells (15-40%)

gd T cells (15-30%)

ab T cells (25-55%)

CD4+CD8+

Innate Immunity

Adaptive Immunity

Human Mice

Swine Immune system characteristics Adaptive Immune cells specificity

Human

Mice

CD8

T

CD4

T

B

cells

CD8

T

CD4

T

B

cells

CD8

CD4

T

Role? Memory T helper?








• Immune memory


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Immune memory: A guaranty for long-term protection

Characteristics of memory immune response: - Quicker onset - Stronger and longer peak of response - higher affinity for the antigen (better recognition)

Immune memory = protection against re-infections








• Immune memory


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The challenges of vaccination

1.Induce an immune response:

Recognition of abnormal element

+

Danger signal

2.Generating the right type of immunity

3.Eliciting long-term memory

4.Protect throughout life

Adjuvant

Antigen Route

Depot effect

Inactivated

adjuvanted

Modified

Live Vaccine

Viral vectors

DNA

Proteins SC

Mucosal IM

Vaccination

program

One or several shots

Ag targeting

Immunomodulation

Adapted Immune Response

Vaccination strategies


Immunology Basics Conclusions

Defense strategies implemented by the immune system are complex and fine tuned

Vaccination strategies are precisely adapted to the animal and to the infection

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Thanks for your attention!

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01 pcvd anne goubie

Technology

pamps innate immunity

basics immunity

innate immunityimplementation

defense strategies physical

goubier pcv2 impact

immune system activation10

line of defense

immunedefense strategies