acquired immune response mr. christ advanced biology
TRANSCRIPT
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)
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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.
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FF
TH
TH
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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
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IL2
IL2 RECEPTORS
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IL2
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THTH
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IL2
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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
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B
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B
antibody
TH
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IL4
IL4
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NO MATCH NO REACTION
TH B
IL4
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IL5
PLASMA CELL
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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.
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
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
