acquired immune response mr. christ advanced biology

AcquiredIMMUNE RESPONSE

Mr. Christ

Advanced Biology

Abbreviations & SymbolsInformation flows left to right

Macrophage T-helper cell B cell AntibodiesMO TH B Ab

Key- Self Protein MO - Macrophage- Foreign Protein TH - T-helper cell- Lysosome B - B cell

Ab - AntibodiesIL1-interleukin oneIL2-interleukin twoBCGF-B cell Growth Factor (AKA IL4)BCDF-B cell Differentiating Factor (AKA IL5)

THIS IS THE RESPONSE TO SPECIALIZED,HUMAN PATHOGENS. NON-SPECIFICGERMS ARE EITHER TAKEN CARE OF BYTHE FIVE AREAS OF INNATE EXTERNAL RESISTANCE, OR THE INFLAMMATORYRESPONSE. OVER 70% OF ALL BACTERIAL SPECIES ARE NON-PATHOGENIC.BECAUSE OF THE NATURE OF SPECIALIZED, HUMAN PATHOGENS, WENEED THE SPECIFIC ARM OF THE IMMUNESYSTEM TO RID US OF THESE PATHOGENS.

IT IS ESTIMATED THAT ONE IN 1,000 – ONE IN 100,000 LYMPHOCYTESIS CAPABLE OF RECOGNIZING A PARTICULARANTIGEN, CIRCULATION GREATLY INCREASES THE CHANCES OF A MEETING

PART ONE: HUMORAL IMMUNITYINVOLVES ANTIBODIES – CONFERS IMMUNITY IN THE SERUM (HUMORAL

PORTION OF THE BLOOD)BECAUSE ANTIBODIES ARE

GLYCOPROTEINSANTIBODIES ARE SPECIFIC - ANTIBODIES

FOR CHICKEN POX DO NOT WORK AGAINST CHOLERA.

The process often begins in theLymphatic system – lymph returnsFluids and cells from intercellularSpaces to the heart. Along the Lymphatic vessels are the lymph Nodes – areas where white bloodCells lie in waiting. Here aMacrophage (big eater) starts the Process by engulfing the bacteria.

A SECOND ANTIGEN PRESENTING CELLIS THE DENDRITIC CELL. THESE CELLSARE EXTREMELY DIFFICULT TO ISOLATE.THEY PLAY AN IMPORTANT ROLE IN INGESTING AND PRESENTING EPITOPESFOUND IN MUCUS MEMBRANES AND OFVIRUSES IN PARTICULAR. IT HAS BEENFOUND THAT THESE CELLS MAY HARBORHIV VIRUSES AND PRESENT THEM TO THCELLS.

MACROPHAGE or DENDRITIC CELL

• Ingests the foreign cell or protein – toxin, oil, virus

• Digests it using Lysosomes

• Presents foreign epitopes on its surface along with self proteins

( self class II)

F

F

F

F

F

F

F

F

F

F

F

F

TH cells bind with the MO. TH work only by recognizing foreign and self proteins (class II) together. Class two are found on immune system cells, class one on body cells. The MO is known as an

antigen presenting cell.

F

F

FF

TH

TH

TH

TH TH

TH

The binding action of the MO and TH stimulates the MO to release IL1, interleukin one resulting in:

• Fever (which may denature foreign proteins

• Stimulation of TH cells to:• A) Release IL2• B) Build receptors for IL2• C) Absorb IL2 through the IL2

receptors

Net results is an increase in TH clones. Cells that absorb IL1,- build IL2, and IL2 receptors-divide -and their offspring can absorb IL2 and divide

F

F

FF

TH

TH

TH

TH TH

TH

F

F

FF

TH

TH

TH

TH

TH

TH

THTH

IL2

IL2 RECEPTORS

F

F

FF

TH

TH

TH

TH

TH

TH

THTH

TH

TH

TH

TH

IL2

F

F

FF

TH

TH

TH

TH

TH

TH

THTH

TH

TH

TH

TH

IL2

F

F

FF

TH

TH

TH

TH

TH

TH

THTH

TH

TH

TH

TH

IL2

F

F

FF

TH

TH

TH

TH

TH

TH

THTH

TH

TH

TH

TH

IL2

TH

TH

TH

THESE INCREASE IN #

THESE DO NOT INCREASE IN #

• TH cells present Epitopes

(foreign) to B cells. This

occurs through random

collisions, not through A

conscious seeking out, TH

cells will bind with B cells with

Antibody complementary

to the Epitope.

TH

TH

TH

B

B

B

B

Antibody – only Fab portion is exposed, Fc regionOf anti-body is

embedded

This binding action results in the release of two

interleukins from the TH cell*IL4(BCGF) B cell Growth

Factor, this results in mitosis of B cells, which

soak it up

*IL5(BCDF) B cell differentiating Factor

This results in B cells becoming differentiated

Plasma cells- These are antibody

producing cells

TH

TH

TH

B

B

B

B

antibody

TH

TH

TH

B

B

B

B

IL4

IL4

B

B

B

B

NO MATCH NO REACTION

TH B

IL4

B

B

IL5

PLASMA CELL

B

F

F

F

F

PLASMA CELLS CAN PRODUCE UP TO 10,000 ANTIBODIES PER SECOND

BIOLOGICAL ACTIVITY

OF ANTIBODIES

1. AGGLUTINATION – ESPECIALLY IGM2. OPSONIZE – STIMULATE PHAGOCYTIC CELLS TO EAT3. PREVENT VIRAL ATTACHMENT – BY BINDING TO VIRAL EPITOPES4. NEUTRALIZE TOXINS – BINDING TO TOXINS

CHANGES THEIR SHAPE5. ACTIVATE COMPLEMENT – COMPLEMENT

LYSES CELLS COATED W/ AB6. IMMOBILIZE PATHOGENS – BY BINDING TO

CILIA AND FLAGELLA7. DETACH PATHOGENS FOR FLUSHING – BY BINDING TO PILLI

1. Agglutination: clumping

2. Opsonization – candy coating

3. Prevent viral attachment

4. Neutralize toxins by binding to active site

5. Activate complement

6. Bind to cilia and flagella

7. Detach pilli

- So as B cells divide, some of their offspring will soak up BCDF and produce antibodies and some will not. Those that do not soak up BCDF are called memory cells.

- They remain in circulation for years. Upon subsequent exposure to the antigen they are specific for, they may soak up BCDF and become antibody producing plasma cells.

- *This is known as HUMORAL IMMUNITY*- (immunity that arises from fluid not cells)

Each activated

B cell produces

40 to 200

memory cells,

which will remain

in the body

for years.

Upon second exposure to antigen, a greater number of antigen

reactive cells will beavailable to respond.

(both TH cells AND B cells– memory cells)

THEREFORE MORE TH CELLS FIND THE

MACROPHAGES SOONER AND MORE

B CELLS FIND THE RIGHT TH CELLS SOONER

AND MORE ANTIBODIES ARE PRODUCED

SOONER.

SO A SECONDARY RESPONSE IS QUICKER

AND MORE EFFECTIVE BECAUSE THE HOST

HAS MORE ANTIGEN SPECIFIC TH CELLS,B CELLS,

AND ANTIBODIES SPECIFIC FOR

THE EPITOPE OF THE ANTIGEN.

THAT, COUPLED WITH THE FACT THAT YOU HAVE AB IN CIRCULATION PRODUCES

MEMORY.

www.youtube.com/watch?v=hQmaPwP0KRI

PART TWO: CELL MEDIATED IMMUNITY:

Protection that results from cells, NOT protection that results from antibodies. This immunity is most important in viral viral infectionsinfections as well as other intracellular parasitesintracellular parasites.

VIRAL INFECTIONS DIFFER FROM BACTERIAL INFECTIONS, BECAUSE OFTHE MANNER IN WHICH VIRUSES REPLICATE.VIRUSES ARE OBLIGATE INTRACELLULARPARASITES. THEY NEED TO INFECTHOST CELLS WITH THEIR DNA – (OR RNAIN THE CASE OF RETROVIRUSES)

http://www.hhmi.org/biointeractive/media/viral_lifecycle-lg.mov

http://www.npr.org/templates/story/story.php?storyId=114075029

Viruses

Cell nucleus

Host cell

Viral DNA

VIRUS ATTACHES TO CELLINJECTS ITS DNA

Viruses CELL

BEGINS TO BUILD VIRUSES

Cell nucleus

Host cell

Viral DNA

ANTIBODIES CANNOT GET INSIDE OF CELLS TO BIND TO VIRUSES.

ANTIBODIES ARE NOT COMPLETELY USELESS AGAINST VIRUSES THOUGH BECAUSE THEY CAN BIND TO VIRUSESIN CIRCULATION

VIRAL PAR-TICLES EX-PLODE OUT OF CELL TO INFECTOTHER CELLS

The virus infested cell explodes and viruses spill out and infect new cells. In order to STOP THE SPREAD OF VIRUSES completely, the cells that produce the viruses must be destroyed.

That job is done by the Cytotoxic T cell

Tcyto -cytotoxic T cells• Kill cells that have FOREIGN PROTEIN and

self proteins Class Iself proteins Class I• Macrophage shows class II• Are activated by IL2 and TH cells• Kill virus infested cells, cancer cells, some

protozoa, worms, fungi(latch on and release enzymes that destroy cells)work by lysing on contact (destroying)

TCYTOBODY CELL

SELF PROTEIN – CLASS I

FOREIGN PROTEIN – VIRUS SHELL

TCYTOBODY CELL

SELF PROTEIN – CLASS I

FOREIGN PROTEIN – VIRUS SHELL

GRANULES OF DIGESTIVE ENZYMES

ACTIVATION OF THE T CYTO CELLOCCURS IN TWO STEPS:

1. T CYTO CELL INTERACTS WITH CELL THAT HAS FOREIGN & SELF CLASS I - IT IS THEREFORE STIMULATED (HAS IL-2 RECEPTORS)2. IL-2 IS SUPPLIED BY ACTIVATED TH CELLS – ONLY STIMULATED T CYTO CELLS CAN ABSORB IL-2 AND DIVIDE

SO THE JOB OF RIDDING THE BODY OF VIRUSES GOES TO THE CYTOTOXIC T CELLS. THEY KILL VIRUS INFESTED CELLS,CANCER CELLS, AND ANY CELLS THATEXPRESS FOREIGN AND SELF CLASS I.THEY KILL CELLS ON CONTACT. THEYARE ACTIVATED BY TH CELLS (USUALLY)THIS IS KNOWN AS CELL MEDIATED IMMUNITY SINCE IT PRIMARILY INVOLVESCELLS – CYTOTOXIC T CELLS (AKA CD8 CELLS) OR KILLER T CELLS

BB TcytoTcyto

humoral Cell-mediated

www.youtube.com/watch?v=1tBOmG0QMbA

RESULTS OF A STUDY• A Mouse was given a vaccine for

pneumococcus• T cells were then removed from the mouse• T cells were then transferred to second

mouse (clone)• second mouse was given dose of

pneumococcus to check for immunity• Result – NO immunity to pneumococcus

-Blood was drawn from the mouse-T cells were found clumped together-scientists concluded that the vaccineWas too weak, as stronger antigenConcentrations did confer immunity

Ts cells were thus discovered• These cells bind with TH cells and have

receptors specific for specific TH cell receptors

• Ts cells are activated after TH cells, prevent overkill, an overproduction of AB

TH TS

•-anti antibodies ALSO

prevent overkill

(over production of cells)

Network Hypothesis

Niels Jerne proposed that cells and molecules of the immune system not only recognize foreign substances, but also recognize, respond to and are regulated by each other. It followed that we should regard the immune system as a network of interacting cells and antibodies.

Interferons-

• a. are species specific proteins produced by viral infected cells, & white blood cells

• b. are proteins which inhibit viral replicationc. three major types: alpha, beta, gammad. in low concentrations, they stimulate cell

divisione. in high concentrations, they inhibit cell

division

REGULATION OF THE IMMUNE RESPONSE

SO INTERFERONS, ANTI-ANTI-BODIES AND T SUPPRESSOR CELLS SERVE TO PREVENT OVERKILL – AN OVERPRODUCTION OF ANTI-BODIES AND CELLS.

HYPERSENSITIVITIES

Also known as allergies:Fall into four categories, We will address the two majorTypes – Immediate (aka type I And Delayed (aka type IV)

Immediate or type I

Involve IgE antibodies, When released, they bind To mast cells.

Mast cells were first described by Paul Ehrlich in 1878. Their unique staining characteristics and large granules, led him to the incorrect belief that they

existed to nourish the surrounding tissue.

so he named them Mastzellen (from German Mast, meaning "fattening", as of animals)We now know that they are immuneSystem cells that IgE antibodies bind to ( the Fc region of the IgE)

If the allergen binds to the Fab region of the IgE,

then the mast cell releases:

histamine – which causes blood vessels to dilate, and

makes the blood vessels more permeable

The mast cells also release heparin, which thins the blood

by preventing clots, which allows cells and fluids to flow into and out of the blood and

lymph.

Delayed or type IV hypersensitivities:

TDTH cells-T delayed Type hypersensitivity cells

• Involved in delayed hypersensitivities like poison ivy

• Recognize foreign and self (class II like on Macrophage) TDTH undergo IL2 mediated clonal expansion

• Behave like TH cells, but instead of activating B cells……….

TDTH release interleukins that draw neutrophils, Basophils, and Esinophils to the site.

- This results in inflammation