Imunolo Infeksi 1.Fr 14

The Immune System and
Infection
the Human and animal Battle against
the Microbe World
Presented by Patricia A. Lafleur
Harvard - HHMI Summer Outreach Program
12 .5.14 FA. Rantam, Virol & Immunol. 2014
Genomics Medicine and System Biology
Genetics Gene
Protein
Biochemistry
Gene
Protein
Molecular
Biology
Gene Protein
Functional expression
Expression profile
Model Organisme/
Clinical manifestation
Proteomics Genomics
Genom Proteome
New
Therapy
New Druge
Our 1
st
Line of Defense...
The Integumentary System
Skin
Mucous membranes
Mucous

provides a physical barrier preventing
microbial access

The Invaders . . .
Bacteria

Viruses
< Click to find out more about
Microbes & Disease >

parasites
such as fungi,
protista, &
worms
worm trichura.jpg
http://www.hhs.gov/asphep/presentation/images/bacteria.jpg
http://www.sdnhm.org/exhibits/epidemic/teachers/background.html
http://www.skidmore.edu/academics/biology/plant_bio/lab13.FUNGI.html
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
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]
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 ?

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

What are macrophages ?
Phagocytic cells - able to
ingest small foreign invaders
neutrophils
monocyte
<Click on link to view animation >
http://www.mnsfld.edu/~mcb/images/macrophage.gif

they release
cytokines that
enhance the
immune response

http://www.b iology.arizona.edu/immunology/tutorials/immunology/graphics/mphage2.gi
f
Mast cells /basophils
release histamine that
dilates blood vessels
causes redness
[erythrema], swelling
[edema], and heat [fever]

http://www.hhs.gov/asphep/presentation/images/wound.jpg
Your Challenge . . .
You are a macrophage in the following
game
your mission is to phagocytize the mumps
viruses
use your mouse on the arrows or or

HINT: antigens are specialized proteins
on cell surfaces that provide I.D.
recognition
http://www.pbs.org/wgbh/nova/aids/immunewave.html

Summary:
Macrophages are able to launch the first
strike
more help is needed to overcome rapidly
reproducing invaders
Help from the ADAPTIVE IMMUNE System
results in a coordinated successful
defense !
Major players . . . the B lymphocytes

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 special
proteins called antibodies

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 the
red bone marrow
http://www.sirinet.net/~jgjohnso/skeletonorg.html
Stem cells in the bone marrow
T AND B CELLS STEM CELL CULTURE
COCULTIVATION T CELL STEM CELL AND
HIV PBMC PATIENT
REAKTIFITAS RESPONS IMUN PBMCs
DENGAN MARKER CD4,CD8,CD14
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.
& migrate to the thymus gland ...
These Lymphocytes are
sorted into 2 types

Identification tag is a
protein called Major
Histocompatability
Complex [MHC]
Self- ID Foreign
& in the thymus gland . . .
All diversely varying MHC lymphocytes will wait
for a call to action . . .

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

Self- ID
Foreign
Saved to be
educated in
body defense
Dropped out!
These Lymphocytes will mature into
T-Helper cells

They function to stimulate B cells to
activate their attack against the invaders
Adaptive Immune System
The 2nd type of lymphocyte is:

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

they are called into action when stimulated by
a foreign antigen. . . [ usually a protein from
the invader]

When an invader attacks. . .
An antigen is phagocytized by the B cell
is broken into non-infective pieces
& attached to the cells MHC when processed
through the cells machinery
MHC-antigen complex is placed on the cell
membrane surface
where it is recognized by the T Helper cell
<Click on Link to see Antigen Expression process >
http://www.nature.com/nrm/journal/v2/n3/animation/nrm0301_179a_swf_MEDIA1.html
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
B cells differentiate into . . .
Antibody producing cells [attack mode]
Memory cells [remembers & future
protection]
Antigen & T-helper cell
memory
antibodies
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 future
invasion
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 ?

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 differently
because they are located in different places
c All cells have the same genetic material, but different
cells use different active genes to make them
function differently
Does this same principle apply to antibodies ?
The correct answer is . . .
c All cells have the same genetic material, but
different cells use different active genes to make
them function differently

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

<Click for Answer>
Summary
What Happens during an infection ?

The immune system activates a multitude of
characters to defend the body in a variety of
ways.

Several players work together, feedback
systems enhance or suppress functions as
changes occur

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 ! ]

Summary
antibodies with only 30,000 genes ?
Mixing & matching pieces of genetic material
produce huge numbers of antibody, as well as
very specific antibody

The immune system is well equiped to
defend the human body against the daily
onslaught of microorganisms . . . If
everything goes as planned . . .

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=158979
6

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.


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