chapter 3 the immune system - university of texas at el...

Aguilera Lecture 2010

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Chapter 3Chapter 3

The Immune SystemThe Immune System

Why is the Immune System Important?Why is the Immune System Important?

Why is the Immune System Relevant to HIV?Why is the Immune System Relevant to HIV?


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T LymphocyteLymphocyte Infected by HIV

Brief History of Immunology

ImmunityImmunity- Observation reported in 430 BC afterepidemic in Athens Greece-People that survived diseaselike plague did not get sick again

VariolationVariolation - Practiced in 15th Century (Chinese and Turks)inoculation of people with dried pustules caused by small pox. People still died but ~10 times less frequently

VaccinationVaccination- Edward Jenner (1798). Made observationthat Cowpox which causes a mild disease protectedpeople (milkmaids) from Smallpox

VaccinesVaccines- First produced against other organisms in late 1800s. Louis Pasteur generated vaccines to Fowl Cholera, Anthrax, and Rabies


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Antibodies Antibodies

produced by Bproduced by B--

lymphocyteslymphocytes

TT--lymphocyteslymphocytes

& other white cells& other white cells

Before we talk about the immune system, we have to talk about the circulatory system and blood

Blood is composed of fluids –plasma and cells

Used to transport nutrients and oxygen to tissues/organs

Also removes harmful C02 from system and other waste products

Cells of blood protect against infection by foreign agents

For example:Platelets are needed for wound repair


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Many of the cells in the blood are the critical players in the immune system that protects us from infection from:

(1) viruses-which are sub-cellular agents

(2) bacteria-single cell microorganisms

(3) protozoa- more complex-single cell microorganism –like amoebas

(4) Fungy-complex single or multicellular organism such as yeast and mold

(5) Multicellular organism –large complex multicellularorganisms such as roundworms and tapeworms

The cells of the blood have a limited lifespan of days to weeks depending of the cell type so they need to be constantly replenished by special cells called –“stem cells” that give rise to all blood cells

Stem cells reside in the bone marrow – they make more of themselves as well as differentiate into other cell types

If you kill Stem cells in a human or animal, they become immunodeficient and can die

Differentiation of different cell types requires specific growth factors and a specific micro-environment.


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(1) Red Blood Cells(1) Red Blood Cells or or RBCsRBCs compose the majority of cells of compose the majority of cells of

blood and carry Oxygen and C0blood and carry Oxygen and C022

(2) White Blood(2) White Blood cells (many different kinds)cells (many different kinds) are mostly are mostly

involved in immune surveillanceinvolved in immune surveillance

These cells can be These cells can be specificspecific or or nonnon--specific specific in the way they in the way they

respond to a microbe or foreign agentrespond to a microbe or foreign agent

The cells that are nonThe cells that are non--specific: recognize bacteria and other specific: recognize bacteria and other

invaders noninvaders non--specificallyspecifically-- they interact with and kill bacteria they interact with and kill bacteria

by swallowing them whole by swallowing them whole –– they are called they are called phagocytesphagocytes

((Greek work to eatGreek work to eat)). . Macrophages and Macrophages and monocytesmonocytes eat dead eat dead

or infected cells or infected cells –– found in blood and tissuesfound in blood and tissues--are in pus are in pus

and and neutrophilsneutrophils that kill bacteriathat kill bacteria

Two main types of cells in bloodTwo main types of cells in blood

Other cells such as Mast cells, eosinophils and basophils –help eliminate larger parasites such as

protozoa and worms by releasing toxic substances that kill the invaders

Interestingly, antibodies can help eliminate large organisms by acting as signals for cells to attack

see Fig. 3.4 in booksee Fig. 3.4 in book


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HematopoieticHematopoietic

Stem CellStem Cell

ProgenitorsProgenitors

give rise to give rise to

all Blood cellsall Blood cells

All Blood Cells Come From a Special Cell All Blood Cells Come From a Special Cell

See Fig 3See Fig 3--33

Bone Marrow

B-cells

T-Cells Lymph nodes

Spleen

Thymus

} T+B-cells

Where do lymphocytes come from?Where do lymphocytes come from?

Circulatory System Is Very Circulatory System Is Very

Important to Immune SystemImportant to Immune System



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Antibody are our Antibody are our

““smart bombssmart bombs””

Have region that Have region that

specifically specifically

interacts with interacts with

foreign particles foreign particles

called antigenscalled antigens


BB--lymphocytes are antibody factorieslymphocytes are antibody factories



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Y Y

Y

Antibodies against Antibodies against

bacteria or foreign moleculesbacteria or foreign molecules

enhance destruction by enhance destruction by

macrophages/macrophages/monocytesmonocytes


Y

Y

Y

Antibodies to Antibodies to

parasites help parasites help

white cells to white cells to

recognize and recognize and

destroydestroy

Antibodies

•• Receptor that evolved to combat disease

•• each antibody recognizes only one specificantigen

•• An antigen is a chemical or moleculethat induces or elicits an immune response-such as the production of a spec. antibody


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•• Theoretically, antibodies can be

produced to just about any foreign substance

An antibody can distinguish one proteinfrom another by a single amino acid difference

•• Antibodies are highly specificfor example:

BindingBinding

site resemblesite resemble

Enzyme bindingEnzyme binding

sitessites


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AmountAmount

of specificof specific

AntibodyAntibody

Exposure to AntigenExposure to Antigen

DaysDays10 20 30 40 50 10 20 30 40 50

A second exposure to the same antigen induces a faster & strongeA second exposure to the same antigen induces a faster & stronger response r response

PrimaryPrimary

SecondarySecondary



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Antibodies are important tools

•• Protein identification

•• Localization of proteins in cells

•• Cell isolation

•• Protein purification

•• Gene cloning

•• Therapy against diseases and venoms

B-Cell

Specific

Ligand /Antigen

Each B cell Produces a Single Type of Antibody

To produce the billions of different

antibodies necessary to combat disease,billions of antibody genes must have evolved to encode this information

This theory was based on the idea of

One Gene = One Protein

Would need more genes than coded for in the genome


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1987 Nobel Prize

Susumu Tonegawa

Demonstrated that the variable region and the constant Demonstrated that the variable region and the constant

regions were regions were ““rearrangedrearranged”” in Bin B--cell tumors (myelomas)cell tumors (myelomas)

Variable Region Gene RearrangementVariable Region Gene Rearrangement

V J JV D

~50 ~10~ 200s

J

V J CµEnh

~~~~~~~~~~~~~~~~~~~~~~~~

VDJCµµµµ mRNASee Fig 3See Fig 3--1010


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Lymphocyte-specific gene rearrangements is mediated by a specific enzyme complex

Deleted DNA

enzymes

T cells have similar receptors as B cells T cells have similar receptors as B cells ––related to antibodiesrelated to antibodies



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CD4 positiveCD4 positive

TT--Helper CellHelper CellTH

foreign antigenforeign antigen

Hormones Hormones

called cytokinescalled cytokines

Antigen Stimulated TAntigen Stimulated T--Helper Cells are Essential for a Helper Cells are Essential for a

Functional Cellular and Functional Cellular and HumoralHumoral Immune ResponseImmune Response


Fig 3Fig 3--18/1918/19

Y

Because Macrophages eat microbes and otherBecause Macrophages eat microbes and other

things, they are excellent processors of antigensthings, they are excellent processors of antigens

segments of microbe are sent to surfacesegments of microbe are sent to surface


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T-cell Antigen Receptor

CD4orCD8

Antigen Presenting Cells

MHC I or IIMHC I or II

self or foreign peptideself or foreign peptide

TT--cellcell

Macrophages are excellent

CytotoxicCytotoxic TT--Cell (CTL)Cell (CTL)

MHC IKill only virusinfected cellsdue to peptidepresented by Class I MHC

peptide

TCR

Like “Smart Bombs” T cells hit only specific targetsCan also kill cancerous cells (tumors) if express abnormal proteins


chapter 3 the immune system - university of texas at el...

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