BACTERIAL STRATEGIES FOR OVERCOMING INNATE AND

ADAPTIVE IMMUNE RESPONSES

BYSOUPARNA MUKHERJEE 131001777004 ANKITA KUNDU 131001009009

Mathias W.Hornef, Mary Jo Wick,Mikael Rhen and Staffan Normack.University of Goteborg,SwedenMTC,Stockholm,Sweden

REVIEW PAPER FOCUS

To discuss how pathogens avoid the various hindrances of the immune system. To understand their strategical interference with the various immune responses--the innate and the adaptive immune responses. To examine the various steps taking place during the course of infection. To reveal the complex interference between the pathogens and the higher organisms. To explain questions and issues related to the strategies of interference.

WHAT IS THE PURPOSE OF THIS REVIEW PAPER??

ANSWER IS-

INTRODUCTION

• Usually invading pathogens get hindrance while entering human body due to their INNATE and ADAPTIVE IMMUNITY RESPONSE.

• But some pathogens-

sAvoid host recognition

sDampen the subsequent immune activation through sophisticated interactions with host responses

sGet benefit from inflamatory reactions

WHAT IS INNATE AND ADAPTIVE IMMUNITY??

Complement Cascade

Alternative pathway

Phagocytes

Neutrophils

Macrophages

Natural Killer CellsEosinophils

SkinMucous Membrane

SalivaFlushing action of urine and tearsStomach Acid

ADAPTIVE

T-Cell Immunity(Cell Mediated Immunity)

B-Cell Immunity(Humoral Immunity)

THCTLs Ts TD Plasma Cells Memory

Cells

Antibodies

Second exposure

Classical Pthway(Complement Cascade)

HOW CAN BACTERIA ESCAPE ALL THESE????

WHAT ARE THEIR STRATEGIES??

WANT TO KNOW?

SCROLL DOWN

MECHANISMS/STRATEGIES USED BY THE PATHOGENS

The mechanisms pathogens use to follow to overcome immune responses are-

i- Attachment to colonization of body surfacesii- Evasion of immune recognition by mucosal surfacesiii- Resistance to antibacterial effectors on epithelial surfacesiv- Strategies for invading and crossing the equilibriumv- Escape from phagocyte responsesvi- Resistance to humoral defense mechanismsvii- Bacterial interference with cytokine secretionviii- Bacterial interference with antigen presentationix- Inhibiting T and B cell effector functions

ATTACHMENT AND COLONIZATION OF BODY SURFACE BY THE PATHOGENS IN HIGHER

ORGANISMSvImmunology Strategies-sBacteria is excluded by-i-skin(≈4m2)ii-mucous membranesiii-acid environment of

stomachiv-Ciliary movement in

URTv-Continuous flushing

with urine of lower urinary tract

vBacterial Strategies-sMotility and attachment factors are essential to withstand mechanical removal.-----------------------------------------------lBordetella pertusis-qcauses whooping cough.qParalyzes ciliary clearance function of respiratory tract by release of cell wall constituents that induce nitric oxide mediated ciliostasis.-----------------------------------------------lPseudomonas aeruginosa & Staphylococcus epidermis-qProduces biofilm that shield bacteria from hostile environment.

Evasion of immune recognition by VULNERABLE mucosal surfaces

VImmunology strategies-

S Vulnerable mucosal surfaces are covered with an array of opsonizing factors such as antibodies.

S They immobilize and remove approaching bacteria.

VBacterial Strategies-

S Proteolytic degradation of secretory immunoglobulin

eg-Haemophilus influenzaS Steric shielding or

modification of exposed PAMPs(pathogen associated molecular patterns) helps to avoid innate recognition.

Resistance to antibacterial effectors on epithelial surfaces

1.Prevention of Opsonization2.Colonization of host surfaces.3.Toxin secretion paralyzes the host defense.4.Toxin secretion disrupts it’s mucosal integrity.5.Microbial recognition and host responses-such as secretion of antimicrobial peptides.6.Chemokine production.7.Can be impaired by modification of pattern molecule presentation or interference with intracellular signaling or cell trafficking8. Escape from phagosome along with inhibition of intracellular recognition.9. Microbe induced cell uptake.10.Persistense in modified endosomes.

BACRETIAL DEFENSE AGAINST PHAGOCYTES

1. Bacterial Defense Strategies against phagocyte engulfment include the induction of programmed cell death as well as inhibition of uptake by translocated effector proteins2. Effector proteins can also be used to down regulate other host cell nuclear responses.4. Should Phagocytosis occur bacteria can escape from the endosome into the host cell cytosol.5. Interfere with endosome trafficking as well as maturation of phagosome.6.The subcellular localization of defense factors..

BACTERIAL DEFENSE STRATEGIES AGAINST ADAPTIVE IMMUNE RESPONSE

1.Strategies include the induction of immunosuppressive cytokines such as IL-10,IL-6 and TGF-ß.2.Inhibition of pro-inflamatory cytokine production and surface expression of costimulatory molecules such as CD86.3.By antigen presenting cells(APC).Interference with bacterial uptake.4.Phagosome mutation.5.Antigen processing.6.MHC class I and II expression.7.Lead to diminished antigen presentation..Inhibiting tyrosine phosphorylation of the T and B cell receptors.8.Activates the inhibitory CEA-CAM I receptor on T cells.9.Further decreases effector cell function.Certain bacteria can also induce regulatory T cells(formerly called suppressor T cells) that dampen the immune response.10.Induce T cell apoptosis by enhancing FasL expression on T cells.

THE RESEARCH STUDY OF PARVEEN GOYAL AND HAN REMAUT (VIB/VRIJE UNIVERSITEIT BRUSSEL) NATURE, SEPTEMBER, 2014

Bacteria are particularly ingenious when it comes to survival strategies. They often create a biofilm to protect themselves from a hostile environment, for example during treatment with antibiotics. A biofilm is a bacterial community that is surrounded by a protective slime capsule consisting of sugar chains and “curli”. Scientists at VIB and Vrije Universiteit Brussel have for the first time created a detailed three-dimensional image of the pores through which the curli building blocks cross the bacterial cell wall, a crucial step in the formation of the protective slime capsule. In addition to the fundamental insights provided by this work, the new results could in the long-term also result in many useful applications.

Parveen Goyal (VIB/VUB): “Based on the structure of the secretion channel, we are able for the first time to build a model of how bacteria can cross this barrier.”

Han Remaut (VIB/VUB): “By determining the three-dimensional structure, it is now possible to develop small molecules that fit like a stopper in the pore of the transporter. This inhibits the excretion of the curli building blocks and can prevent the formation of curli fibers and unwanted biofilms during infections or in industrial installations.”

WHAT ELSE CAN COME UP FROM THIS TYPE OF RESEARCH

Many bacteria are actually quite good at GROUP COMMUNICATION!

And new research suggests that we might be able to disrupt that “group communication” in ways that could make agriculture safer without the use of traditional pesticides.

The basic idea is that use of a synthetic compound (for instance, a halogenated furanone) might allow us to prevent the bacteria from sensing the signaling compounds being emitted by their neighbors. This, in turn, would keep them from becoming virulent, without having to resort to using harsh chemicals to completely wipe out the bacteria!

REVIEW PAPER FORMULATED QUESTIONS

The hypotheses that have been proposed are:-

Will the current knowledge of the strategies of bacterial interference with innate and adaptive immune system will help us to prevent and treat infectious diseases?

Do the pathogens directly/indirectly interfere with the immune system and what is their extent of interfering strategies?

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