Upload
dwi-wahyu-rochmawati
View
16
Download
0
Embed Size (px)
DESCRIPTION
Imunologi
Citation preview
5/24/2018 Imunolo Infeksi 1.Fr 14
1/34
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
5/24/2018 Imunolo Infeksi 1.Fr 14
2/34
Genomics Medicine and System Biology
Genetics Gene Protein
Biochemistry Gene Protein
Molecular
Biology
Gene Protein
Functional expression
Functional expression
Functional expression
Expression profile
Model Organisme/
Clinical manifestation
ProteomicsGenomics
Genom Proteome
New
Therapy
New Druge12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
3/34
Our 1stLine of Defense...
The Integumentary System
Skin
Mucous membranes
Mucous
provides a physical barrier preventingmicrobial access
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
4/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
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.html5/24/2018 Imunolo Infeksi 1.Fr 14
5/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
6/34
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]
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
7/34
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 ?
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
8/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
http://www.muhealth.org/~pharm204/inflammation.movhttp://www.muhealth.org/~pharm204/inflammation.movhttp://www.muhealth.org/~pharm204/inflammation.movhttp://www.muhealth.org/~pharm204/inflammation.mov5/24/2018 Imunolo Infeksi 1.Fr 14
9/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
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.gif5/24/2018 Imunolo Infeksi 1.Fr 14
10/34
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
5/24/2018 Imunolo Infeksi 1.Fr 14
11/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
http://www.pbs.org/wgbh/nova/aids/immunewave.htmlhttp://www.pbs.org/wgbh/nova/aids/immunewave.htmlhttp://www.pbs.org/wgbh/nova/aids/immunewave.html5/24/2018 Imunolo Infeksi 1.Fr 14
12/34
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
5/24/2018 Imunolo Infeksi 1.Fr 14
13/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
14/34
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
5/24/2018 Imunolo Infeksi 1.Fr 14
15/34
Stem cells in the bone marrow
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
16/34
T AND B CELLS STEM CELL CULTURE
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
17/34
COCULTIVATION T CELL STEM CELL AND
HIV PBMC PATIENT
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
18/34
REAKTIFITAS RESPONS IMUN PBMCs
DENGAN MARKER CD4,CD8,CD14
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
19/34
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
5/24/2018 Imunolo Infeksi 1.Fr 14
20/34
& 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
5/24/2018 Imunolo Infeksi 1.Fr 14
21/34
& 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!
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
22/34
These Lymphocytes will mature into
T-Helper cells
They function tostimulate B cells toactivate their attack against the invaders
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
23/34
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]
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
24/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
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.html5/24/2018 Imunolo Infeksi 1.Fr 14
25/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
26/34
B cells differentiate into . . .
Antibody producing cells [attack mode]
Memory cells [remembers & future
protection]Antigen & T-helper cell
memory
antibodies
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
27/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
28/34
How can we make 100,000,000 different
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
5/24/2018 Imunolo Infeksi 1.Fr 14
29/34
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
5/24/2018 Imunolo Infeksi 1.Fr 14
30/34
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 >
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
31/34
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
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
32/34
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 ! ]
12 .5.14 FA. Rantam, Virol & Immunol. 2014
5/24/2018 Imunolo Infeksi 1.Fr 14
33/34
Summary
How can we make 100,000,000 different
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
5/24/2018 Imunolo Infeksi 1.Fr 14
34/34
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