Acquired IMMUNE RESPONSE Mr. Christ Advanced Biology

Abbreviations & Symbols Information flows left to right MacrophageT-helper cell B cell Antibodies MO TH B Ab Key - Self Protein MO - Macrophage - Foreign Protein TH - T-helper cell - LysosomeB - B cell Ab - Antibodies IL1-interleukin one IL2-interleukin two BCGF-B cell Growth Factor (AKA IL4) BCDF-B cell Differentiating Factor (AKA IL5)

THIS IS THE RESPONSE TO SPECIALIZED, HUMAN PATHOGENS. NON-SPECIFIC GERMS ARE EITHER TAKEN CARE OF BY THE FIVE AREAS OF INNATE EXTERNAL RESISTANCE, OR THE INFLAMMATORY RESPONSE. OVER 70% OF ALL BACTERIAL SPECIES ARE NON-PATHOGENIC. BECAUSE OF THE NATURE OF SPECIALIZED, HUMAN PATHOGENS, WE NEED THE SPECIFIC ARM OF THE IMMUNE SYSTEM TO RID US OF THESE PATHOGENS.

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

PART ONE: HUMORAL IMMUNITY INVOLVES ANTIBODIES – CONFERS IMMUNITY IN THE SERUM (HUMORAL PORTION OF THE BLOOD) BECAUSE ANTIBODIES ARE GLYCOPROTEINS ANTIBODIES ARE SPECIFIC - ANTIBODIES FOR CHICKEN POX DO NOT WORK AGAINST CHOLERA.

The process often begins in the Lymphatic system – lymph returns Fluids and cells from intercellular Spaces to the heart. Along the Lymphatic vessels are the lymph Nodes – areas where white blood Cells lie in waiting. Here a Macrophage (big eater) starts the Process by engulfing the bacteria.

A SECOND ANTIGEN PRESENTING CELL IS THE DENDRITIC CELL. THESE CELLS ARE EXTREMELY DIFFICULT TO ISOLATE. THEY PLAY AN IMPORTANT ROLE IN INGESTING AND PRESENTING EPITOPES FOUND IN MUCUS MEMBRANES AND OF VIRUSES IN PARTICULAR. IT HAS BEEN FOUND THAT THESE CELLS MAY HARBOR HIV VIRUSES AND PRESENT THEM TO TH CELLS.

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 F F 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 F F TH

F F F F IL2 IL2 RECEPTORS

F F F F TH IL2

F F F F TH IL2

F F F F TH IL2

F F F F TH IL2

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 B B B B Antibody – only Fab portion is exposed, Fc region Of 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 B B B B antibody

TH B B B B 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 IGM 2.OPSONIZE – STIMULATE PHAGOCYTIC CELLS TO EAT 3. PREVENT VIRAL ATTACHMENT – BY BINDING TO VIRAL EPITOPES 4. NEUTRALIZE TOXINS – BINDING TO TOXINS CHANGES THEIR SHAPE 5. ACTIVATE COMPLEMENT – COMPLEMENT LYSES CELLS COATED W/ AB 6. IMMOBILIZE PATHOGENS – BY BINDING TO CILIA AND FLAGELLA 7. 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 be available 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: viral infections intracellular parasites Protection that results from cells, NOT protection that results from antibodies. This immunity is most important in viral infections as well as other intracellular parasites.

VIRAL INFECTIONS DIFFER FROM BACTERIAL INFECTIONS, BECAUSE OF THE MANNER IN WHICH VIRUSES REPLICATE. VIRUSES ARE OBLIGATE INTRACELLULAR PARASITES. THEY NEED TO INFECT HOST CELLS WITH THEIR DNA – (OR RNA IN THE CASE OF RETROVIRUSES)

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Viruses Cell nucleus Host cell Viral DNA VIRUS ATTACHES TO CELL INJECTS 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 VIRUSES IN CIRCULATION

VIRAL PAR- TICLES EX- PLODE OUT OF CELL TO INFECT OTHER 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 self proteins Class IKill cells that have FOREIGN PROTEIN and self 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)

TCYTO BODY CELL SELF PROTEIN – CLASS I FOREIGN PROTEIN – VIRUS SHELL

TCYTO BODY CELL SELF PROTEIN – CLASS I FOREIGN PROTEIN – VIRUS SHELL GRANULES OF DIGESTIVE ENZYMES

ACTIVATION OF THE T CYTO CELL OCCURS 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 THAT EXPRESS FOREIGN AND SELF CLASS I. THEY KILL CELLS ON CONTACT. THEY ARE ACTIVATED BY TH CELLS (USUALLY) THIS IS KNOWN AS CELL MEDIATED IMMUNITY SINCE IT PRIMARILY INVOLVES CELLS – CYTOTOXIC T CELLS (AKA CD8 CELLS) OR KILLER T CELLS

B Tcyto 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 vaccine Was too weak, as stronger antigen Concentrations 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 replication c. three major types: alpha, beta, gamma d. in low concentrations, they stimulate cell division e. 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 major Types – 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 Their unique staining characteristics and large granules, led him to the incorrect belief that they existed to nourish the surrounding tissue.Paul Ehrlich

so he named them Mastzellen (from German Mast, meaning "fattening", as of animals)We now know that they are immuneGerman System 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