Imunolo Infeksi 1.Fr 14

5/24/2018 Imunolo Infeksi 1.Fr 14

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The Immune System andInfection

the Human and animal Battle against

the Microbe WorldPresented by Patricia A. Lafleur

Harvard - HHMI Summer Outreach Program

12 .5.14 FA. Rantam, Virol & Immunol. 2014


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Genomics Medicine and System Biology

Genetics Gene Protein

Biochemistry Gene Protein

Molecular

Biology

Gene Protein

Functional expression



Expression profile

Model Organisme/

Clinical manifestation

ProteomicsGenomics

Genom Proteome

New

Therapy

New Druge12 .5.14 FA. Rantam, Virol & Immunol. 2014


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Our 1stLine of Defense...

The Integumentary System

Skin

Mucous membranes

Mucous

provides a physical barrier preventingmicrobial access



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The Invaders . . .

Bacteria

Viruses < Click to find out more about

Microbes & Disease >

parasitessuch as fungi,

protista, &

wormsworm trichura.jpg

https://reader003.{domain}/reader003/html5/0302/5a992afe48fc2/5a992b022506

http://www.sdnhm.org/exhibits/epidemic/teachers/background.html

http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html

http://www.sdnhm.org/exhibits/epidemic/teachers/background.htmlhttp://www.sdnhm.org/exhibits/epidemic/teachers/background.htmlhttp://www.sdnhm.org/exhibits/epidemic/teachers/background.htmlhttp://www.sdnhm.org/exhibits/epidemic/teachers/background.htmlhttp://www.sdnhm.org/exhibits/epidemic/teachers/background.html


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Other mechanisms of Defense...

Physiological variables

pH of our environment

temperature of our environment

chemical defenses

nitric oxide, enzymes, proteins, complement

AND the IMMUNE SYSTEM



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Immune System : 2 branches

The Innate Immune system =

a general response to anything other than

recognized self cells

The Adaptive Immune System =

a specific counter-assault against a known

foreign invader [previously recognized]



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Major Concepts -

What Happens during an infection ?

How can immune cells distinguish foreign

invaders from our own cells ?

How can we make 100,000,000 different

antibodies with only 30,000 genes ?



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What Happens during an infection?

Innate Immunity -the troops are called to battle

injury & infection macrophages slip between cells [extravasation]to

arrive

cytokine chemicals attract other troops

[chemotaxis] histamine chemicals dilate blood vessels for easier

access to injury [vasodilation]

< Click on link to view Movie of inflammation > http://www.muhealth.org/~pharm204/inflammation.mov

http://www.muhealth.org/~pharm204/inflammation.movhttp://www.muhealth.org/~pharm204/inflammation.movhttp://www.muhealth.org/~pharm204/inflammation.movhttp://www.muhealth.org/~pharm204/inflammation.mov


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What are macrophages ?

Phagocytic cells - able to

ingest small foreign invaders

neutrophils

monocyte

http://www.mnsfld.edu/~mcb/images/macrophage.gif

they release

cytokines thatenhance the

immune response

http://www.b iology.arizona.edu/imm unology/tutorials/imm unology/graphics/mphage2.gi

http://www.mnsfld.edu/~mcb/images/macrophage.gifhttp://www.mnsfld.edu/~mcb/images/macrophage.gifhttp://www.mnsfld.edu/~mcb/images/macrophage.gifhttp://www.mnsfld.edu/~mcb/images/macrophage.gif


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Mast cells /basophils

release histamine that

dilates blood vessels causes redness

[erythrema],swelling[edema],and heat [fever]

https://reader003.{domain}/reader003/html5/0302/5a992afe48fc2/5a992b063c8b9.jpg12 .5.14 FA. Rantam, Virol & Immunol. 2014


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Your Challenge . . .

You are a macrophage in the followinggame

your mission is to phagocytize the mumpsviruses

use your mouse on the arrowsor or

HINT: antigens are specialized proteinson cell surfaces that provide I.D.recognition

http://www.pbs.org/wgbh/nova/aids/immunewave.html

http://www.pbs.org/wgbh/nova/aids/immunewave.htmlhttp://www.pbs.org/wgbh/nova/aids/immunewave.htmlhttp://www.pbs.org/wgbh/nova/aids/immunewave.html


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Summary:

Macrophages are able to launch the firststrike

more help is needed to overcome rapidlyreproducing invaders

Help from the ADAPTIVE IMMUNE Systemresults in a coordinated successfuldefense !

Major players . . . the B lymphocytes12 .5.14 FA. Rantam, Virol & Immunol. 2014


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How can antibodies distinguish our

self from foreign invaders?

Adaptive Immune System - function

There are 2 types of lymphocytes: T lymphocytes [ T - Helper cells ]- help

signal immune cells into action

B lymphocytes [ B cells ]- make specialproteins called antibodies



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How can antibodies distinguish

selfcells from foreign invaders?

Adaptive Immune System - origin

There are 2 types of lymphocytes: 1st Type -

T lymphocytes -[ T - Helper cells ]

begin in thered bone marrow

http://www.sirinet.net/~jgjohnso/skeletonorg.html12 .5.14 FA. Rantam, Virol & Immunol. 2014


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Stem cells in the bone marrow



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T AND B CELLS STEM CELL CULTURE



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COCULTIVATION T CELL STEM CELL AND

HIV PBMC PATIENT



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REAKTIFITAS RESPONS IMUN PBMCs

DENGAN MARKER CD4,CD8,CD14



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M2

M1

B

TH2

NK

NKT

M

DC

DC

B

CDTL8 C

GR1 CD 11b

ma ba eo

TH1

CD4,28,FOXP3

CD8,28

CD4,28

CD4,28

Reactive oxygen, NO, IL-

1b, TNF alfa,, IL-6, 12,23,

tissue destruction, killing

of parasit, tumors resisten

IL-2, TNF- IFN- MIG, IP 10

Tipe II inflamation, tissue

remodelling, angeogenesis,

parasit encapsulation, tumor

promotion, IL 10 TGF beta,

arginase

Mucuc producing cells

IL-15, 18

Differentiation Ig

subtype switching

T regulatory cells

IL-2

IFN-

Endothelial cells

Endothelial cells

IMMUNE

REGULATION

Fedik Abdul Rantam, 2008

IL-4,10,13

IL-4,10,13,IFN-

IFN-

B; B cell, ba:basophil, CTL;cytotoxic cell T,

DC: dendrit cell, Eo:eosinophile, M; monocyte,

Ma; mastcells, M1; macrophage, M2:

macrophage, NK:natural killer cell,

NKT;natural killer T cell, Th; T helper cell .12 .5.14 FA. Rantam, Virol & Immunol. 2014


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& migrate to the thymus gland ...

TheseLymphocytes aresorted into2 types

Identification tag is aprotein called Major

Histocompatability

Complex [MHC]

Self- IDForeign12 .5.14 FA. Rantam, Virol & Immunol. 2014


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& in the thymus gland . . .

All diversely varying MHC lymphocytes will wait

for a call to action . . .

All self MHC cells are destroyed - to removethe chance of friendly fire casualties

Self- IDForeign

Saved to be

educated in

body defense

Dropped out!



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These Lymphocytes will mature into

T-Helper cells

They function tostimulate B cells toactivate their attack against the invaders



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Adaptive Immune System

The 2nd type of lymphocyte is:

B lymphocytes [ B cells]- start in the bonemarrow and circulate through the body

they are called into action when stimulated by

a foreign antigen. . . [ usually a protein fromthe invader]



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When an invader attacks. . .

An antigen is phagocytized by the B cell

is broken into non-infective pieces

& attached to the cells MHC when processedthrough the cells machinery

MHC-antigen complex is placed on the cell

membrane surface

where it is recognized by the T Helper cell

http://www.nature.com/nrm/journal/v2/n3/animation/nrm0301_179a_swf_MEDIA1.html

http://www.nature.com/nrm/journal/v2/n3/animation/nrm0301_179a_swf_MEDIA1.htmlhttp://www.nature.com/nrm/journal/v2/n3/animation/nrm0301_179a_swf__MEDIA1.htmlhttp://www.nature.com/nrm/journal/v2/n3/animation/nrm0301_179a_swf__MEDIA1.htmlhttp://www.nature.com/nrm/journal/v2/n3/animation/nrm0301_179a_swf_MEDIA1.html


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When help arrives . . .

The T-helper cell receptor docks with the

B cells MHComplex

B cells proliferate . . .Antigen & T-helper cell

Proliferation of

cell line

Nave

cell



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B cells differentiate into . . .

Antibody producing cells [attack mode]

Memory cells [remembers & future

protection]Antigen & T-helper cell

memory

antibodies



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The RESULT . . .

The Antibody producing B cells

mounts a successful attack against the

invader

the memory B cells save the recognition

ID for many years in preparation for futureinvasion



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antibodies with only 30,000 genes?

Problem:

microorganisms easily out-number the total number

of genes on the human genome if only one gene was responsible for coding for one

antibody, there still wouldnt be enough information

to use

Question:

How can such a small amount of information

be used for successful antibody diversity ?12 .5.14 FA. Rantam, Virol & Immunol. 2014


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Consider the following . . .What is true about the different cells of the body?

Which Statement is most correct ?a All cells in the body are the same and function the

same way

b All cells are the same, but function differentlybecause they are located in different places

c All cells have the same genetic material, but differentcells use different active genes to make themfunction differently

Does this same principle apply to antibodies ?12 .5.14 FA. Rantam, Virol & Immunol. 2014


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The correct answer is . . .

c All cells have the same genetic material, but

different cells use different active genes to makethem function differently

< Click on Animation Link to learn how gene segments are combined toproduce a large number of diverse antibodies >



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Summary

What Happens during an infection ?

The immune system activates a multitude ofcharacters to defend the body in a variety of

ways.

Several players work together, feedbacksystems enhance or suppress functions as

changes occur



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Summary

How can immune cells distinguish foreign

invaders from our own cells ?

By using the invaders own antigen, immune

cells can be produced for specific organisms &

used to enhance the defense effort

[ as long as the invading organism is the

only target ! ]



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Summary


antibodies with only 30,000 genes ?

Mixing & matching pieces of genetic materialproduce huge numbers of antibody, as well as

very specific antibody

The immune system is well equiped todefend the human body against the daily

onslaught of microorganisms . . . If

everything goes as planned . . .12 .5.14 FA. Rantam, Virol & Immunol. 2014


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For further information . . .

Immunology Project Resources

Understanding Autoimmune Disease

http://www.niaid.nih.gov/publications/autoimmune/work.htm

Antibody descriptions [IgG, IgM, IgA]

http://sprojects.mmi.mcgill.ca/immunology/Ig_text.htm

Immunology Hyperlinked History & Molecular Movies

http://www.bio.davidson.edu/courses/Immunology/Bio307.html

Nature Magazine & Immunology

http://www.nature.com/nature/view/030102.html

NCBI Genome Database

http://www.ncbi.nlm.nih.gov/

NCBI Genome Base

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796

Immune System Animation Links through Anatomy & Physiology Groups

http://science.nhmccd.edu/biol/ap2int.htm

Pier,G. , Lyczak,J., Wetzler,L; Immunology, Infection, and Immunity; American Society for Microbiology

Press 2004 p 12
http://www.niaid.nih.gov/publications/autoimmune/work.htmhttp://sprojects.mmi.mcgill.ca/immunology/Ig_text.htmhttp://www.bio.davidson.edu/courses/Immunology/Bio307.htmlhttp://www.nature.com/nature/view/030102.htmlhttp://www.ncbi.nlm.nih.gov/http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796http://science.nhmccd.edu/biol/ap2int.htmhttp://science.nhmccd.edu/biol/ap2int.htmhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796http://www.ncbi.nlm.nih.gov/http://www.nature.com/nature/view/030102.htmlhttp://www.bio.davidson.edu/courses/Immunology/Bio307.htmlhttp://sprojects.mmi.mcgill.ca/immunology/Ig_text.htmhttp://www.niaid.nih.gov/publications/autoimmune/work.htm

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Imunolo Infeksi 1.Fr 14