The Immune SystemThe Immune System

the Human Battle against the Human Battle against

the the

Microbe Microbe WorldWorld

Presented by Patricia A. LafleurPresented by Patricia A. LafleurHarvard - HHMI Summer Outreach Program 2004Harvard - HHMI Summer Outreach Program 2004

Our 1Our 1stst Line of Defense... Line of Defense...

The Integumentary System…The Integumentary System…• SkinSkin• Mucous membranesMucous membranes• MucousMucous

provides a physical barrier provides a physical barrier preventing microbial access preventing microbial access

The Invaders . . . The Invaders . . .

BacteriaBacteria

VirusesViruses < Click to find out more about Microbes< Click to find out more about Microbes

& Disease > & Disease >

parasites parasites such as fungi, such as fungi, protista, & wormsprotista, & 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 Other mechanisms of Defense...Defense...

Physiological variablesPhysiological variables• pH of our environmentpH of our environment• temperature of our environmenttemperature of our environment

chemical defenseschemical defenses• nitric oxide, enzymes, proteins, nitric oxide, enzymes, proteins,

complementcomplement

AND the IMMUNE SYSTEM…AND the IMMUNE SYSTEM…

Immune System : Immune System : 2 2 branchesbranches

The Innate Immune system =The Innate Immune system =• a general response to anything other a general response to anything other

than recognized “self cells”than recognized “self cells”

The Adaptive Immune System =The Adaptive Immune System =• a specific counter-assault against a a specific counter-assault against a

“known foreign” invader [previously “known foreign” invader [previously recognized]recognized]

Major Concepts -Major Concepts -

What Happens during an infection ?What Happens during an infection ?

How can immune cells distinguish How can immune cells distinguish foreign invaders from our own cells ?foreign invaders from our own cells ?

How can we make 100,000,000 How can we make 100,000,000 different antibodies with only 30,000 different antibodies with only 30,000 genes ?genes ?

What Happens during an What Happens during an infection?infection?

Innate Immunity -Innate Immunity - the troops are called to battle… the troops are called to battle…• injury & infectioninjury & infection• macrophages slip between cells macrophages slip between cells [extravasation][extravasation]

to arriveto arrive• cytokine chemicals attract other “troops” cytokine chemicals attract other “troops”

[chemotaxis][chemotaxis]• histamine chemicals dilate blood vessels for histamine chemicals dilate blood vessels for

easier access to injury easier access to injury [vasodilation][vasodilation] • < Click on link to view Movie of inflammation >< Click on link to view Movie of inflammation >

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

What are macrophages ?What are macrophages ?

Phagocytic cells - able to Phagocytic cells - able to ingest small foreign ingest small foreign invadersinvaders• neutrophilsneutrophils• monocytemonocyte• <Click on link to view animation ><Click on link to view animation >• http://www.mnsfld.edu/~mcb/images/macrophage.gifhttp://www.mnsfld.edu/~mcb/images/macrophage.gif

tthey release hey release cytokines that cytokines that enhance the enhance the immune response immune response

http://www.biology.arizona.edu/immunology/tutorials/immunology/graphics/mphage2.gif

Mast cells /basophils Mast cells /basophils • release histamine release histamine

that dilates blood that dilates blood vesselsvessels

• causes redness causes redness [erythrema],[erythrema], swelling swelling [edema],[edema], and heat and heat [fever][fever]

http://www.hhs.gov/asphep/presentation/images/wound.jpg

Your Challenge . . .Your Challenge . . .

You are a macrophage in the You are a macrophage in the following game… following game…

your mission is to phagocytize the your mission is to phagocytize the mumps viruses mumps viruses

use your mouse on the arrows use your mouse on the arrows or or or or

HINT: HINT: antigens are specialized antigens are specialized proteins on cell surfaces that proteins on cell surfaces that provide I.D. recognitionprovide I.D. recognition

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

Summary:Summary:

Macrophages are able to launch the Macrophages are able to launch the first strike…first strike…

more help is needed to overcome more help is needed to overcome rapidly reproducing invaders…rapidly reproducing invaders…

Help from the ADAPTIVE IMMUNE Help from the ADAPTIVE IMMUNE System results in a coordinated System results in a coordinated successful defense !successful defense !

Major players . . . the B lymphocytesMajor players . . . the B lymphocytes

How can antibodies How can antibodies distinguish our self from distinguish our self from foreign invaders?foreign invaders?

Adaptive Immune System - Adaptive Immune System - functionfunction

There are 2 types of lymphocytes:There are 2 types of lymphocytes:

• T lymphocytes T lymphocytes [ T - Helper cells ][ T - Helper cells ] - - help signal immune cells into actionhelp signal immune cells into action

• B lymphocytes B lymphocytes [ B cells ][ B cells ] - make - make special proteins called antibodiesspecial proteins called antibodies

How can antibodies How can antibodies distinguish “self”cells from distinguish “self”cells from foreign invaders?foreign invaders?

Adaptive Immune System - originAdaptive Immune System - origin

There are 2 types of lymphocytes:There are 2 types of lymphocytes:

• 1st Type - 1st Type - T T lymphocytes - lymphocytes - [ T - Helper [ T - Helper cells ]cells ] begin in the begin in the red red bone marrowbone marrowhttp://www.sirinet.net/~jgjohnso/skeletonorg.html

& migrate to the thymus & migrate to the thymus gland ...gland ...

TheseThese Lymphocytes Lymphocytes are sorted are sorted intointo 2 types 2 types

Identification tag is a protein Identification tag is a protein calledcalled Major Histocompatability Major Histocompatability Complex Complex [MHC][MHC]

Self- IDForeign

& in the thymus gland . . .& in the thymus gland . . .

All diversely varying MHC lymphocytes will All diversely varying MHC lymphocytes will wait for a call to action . . .wait for a call to action . . .

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

Self- IDForeign

Saved to be educated… in body defense

Dropped out!

These Lymphocytes will mature These Lymphocytes will mature intointo T-Helper cells T-Helper cells

They function toThey function to stimulate B cells stimulate B cells to activate their attack against the to activate their attack against the invadersinvaders

Adaptive Immune SystemAdaptive Immune System

TThe 2nd type of lymphocyte is:he 2nd type of lymphocyte is:

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

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

When an invader attacks. . When an invader attacks. . ..

An antigen is phagocytized by the B cellAn antigen is phagocytized by the B cell is broken into non-infective piecesis broken into non-infective pieces & attached to the cell’s MHC when processed & attached to the cell’s MHC when processed

through the cell’s machinerythrough the cell’s machinery MHC-antigen complex is placed on the cell MHC-antigen complex is placed on the cell

membrane surface membrane surface where it is recognized by the T Helper cellwhere it is recognized by the T Helper cell <Click on Link to see Antigen Expression process ><Click on Link to see Antigen Expression process > http://www.nature.com/nrm/journal/v2/n3/animation/http://www.nature.com/nrm/journal/v2/n3/animation/

nrm0301_179a_swf_MEDIA1.htmlnrm0301_179a_swf_MEDIA1.html

When help arrives . . .When help arrives . . .

The T-helper cell receptor “docks” The T-helper cell receptor “docks” with the B cell’s MHComplexwith the B cell’s MHComplex

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

Proliferation of cell line

Naïve cell

B cells differentiate B cells differentiate into . . .into . . .

• Antibody producing cells Antibody producing cells [attack [attack mode]mode]

• Memory cells Memory cells [remembers & future [remembers & future protection]protection]Antigen & T-helper cell

memory

antibodies

The RESULT . . . The RESULT . . .

The Antibody producing B cells The Antibody producing B cells mounts a successful attack mounts a successful attack against the invaderagainst the invader

the memory B cells save the the memory B cells save the “recognition ID” for many years in “recognition ID” for many years in preparation for future invasionpreparation for future invasion

How can we make 100,000,000 How can we make 100,000,000 different antibodies with only different antibodies with only 30,000 genes?30,000 genes?

Problem: Problem: • microorganisms easily out-number the total number of microorganisms easily out-number the total number of

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

antibody, there still wouldn’t be enough information to useantibody, there still wouldn’t be enough information to use

Question:Question:• How can such a small amount of How can such a small amount of

information be used for successful information be used for successful antibody diversity ?antibody diversity ?

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

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

same waysame way

b All cells are the same, but function differently All cells are the same, but function differently because they are located in different placesbecause they are located in different places

c All cells have the same genetic material, but different All cells have the same genetic material, but different cells use different active genes to make them cells use different active genes to make them function differentlyfunction differently

Does this same principle apply to antibodies ?Does this same principle apply to antibodies ?

The correct answer is . . .The correct answer is . . .

c All cells have the same genetic material, but All cells have the same genetic material, but different cells use different active genes to make different cells use different active genes to make them function differentlythem function differently

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

<Click for Answer>

SummarySummary

What Happens during an infection ?What Happens during an infection ?

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

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

SummarySummary

How can immune cells distinguish How can immune cells distinguish foreign invaders from our own cells ?foreign invaders from our own cells ?

• By using the invader’s own antigen, By using the invader’s own antigen, immune cells can be produced for specific immune cells can be produced for specific organisms & used to enhance the defense organisms & used to enhance the defense effort effort

• [ as long as the [ as long as the invading organism is the only target ! ]invading organism is the only target ! ]

SummarySummary

How can we make 100,000,000 different How can we make 100,000,000 different antibodies with only 30,000 genes ?antibodies with only 30,000 genes ?• Mixing & matching pieces of genetic Mixing & matching pieces of genetic

material produce huge numbers of antibody, material produce huge numbers of antibody, as well as very specific antibodyas well as very specific antibody

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

For further information . . .For further information . . . Immunology Project Resources –Immunology Project Resources –

Understanding Autoimmune Disease http://www.niaid.nih.gov/publications/autoimmune/work.htmhttp://www.niaid.nih.gov/publications/autoimmune/work.htm

Antibody descriptions [IgG, IgM, IgA] http://sprojects.mmi.mcgill.ca/immunology/Ig_text.htmhttp://sprojects.mmi.mcgill.ca/immunology/Ig_text.htm

Immunology Hyperlinked History & Molecular Movies http://www.bio.davidson.edu/courses/Immunology/Bio307.htmlhttp://www.bio.davidson.edu/courses/Immunology/Bio307.html

Nature Magazine & Immunology http://www.nature.com/nature/view/030102.htmlhttp://www.nature.com/nature/view/030102.html

NCBI Genome Database http://www.ncbi.nlm.nih.gov/http://www.ncbi.nlm.nih.gov/

NCBI Genome Base http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1589796

Immune System Animation Links through Anatomy & Physiology Groups http://science.nhmccd.edu/biol/ap2int.htmhttp://science.nhmccd.edu/biol/ap2int.htm Pier,G. , Lyczak,J., Wetzler,L; Immunology, Infection, and Immunity; American Society for Microbiology

Press,2004,p.12.