Immune System

1. Immune System AP Biology Chapter 43

2. **ONLY IN VERTS. http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter23/animation__movement_of_oxygen_and_carbon_dioxide.html

3. Pathogens • Everything tries to live! • Viruses • Bacteria • Protists • Fungi

4. Your body fights back • “It’s evolutionarily disadvantageous to die”

5. Two ways to fight • Innate immunity • Defense before any exposure to pathogen • Acquired immunity • Defense builds in response to present pathogen

6. Innate Immunity Part 1

7. Innate Immunity • is present at the time of birth • nonspecific responses to pathogens • Rapid response

8. External Defense • Skin: physical barrier to microbes • Mucous membranes: sweeps (some w/ help of cilia) microbes away • Digestive, respiratory, urinary, & reproductive tracts • Sweat glands: acidic environment on skin • Lysozyme: (in saliva, tears, & cells) digests microbial cell walls

9. FYI • Mucous membranes are the moist linings of the orifices and internal parts of the body that are in continuity with the external surface. They cover, protect, and provide secretory and absorptive functions in the channels and extended pockets of the outside world that are incorporated in the body. This applies to: the whole of the alimentary tract from the mouth to the anus; the respiratory tract from the nose through the larynx, trachea, and bronchial tree leading to the microscopic millions of ‘blind ends’ at the lung alveoli; the urogenital tract — vulva, vagina, uterus, and Fallopian tubes in the female, urethra and bladder in both sexes reaching to the kidneys via the ureters, and the vas deferens and tubules reaching into each testis in the male. The linings of all of these are epithelia and most are known as mucous membranes.Although all these linings are moist, this is by no means everywhere related to the presence of mucus. Actual mucus-secreting cells are scattered among other cells of many mucous membranes, particularly in the intestines and the upper part of the respiratory tract. The lining layers are of varying depth. In the areas which are closest to the transition from the skin — in the mouth, anus, and vagina — there are layers of thin cells, like those of the skin, but without the thickened protective outermost layer. In most other sites there is a single layer which may consist of tall ‘columnar’ cells, flat ‘squamous’ cells, or intermediate ‘cuboidal’ cells — again according to function. Many mucous membranes have glands whose ducts dip from the surface to clusters of secretory cells in the deeper layer of tissue (submucosa).In parts of the genital tracts also, the lining cells are ciliated, assisting movement of an ovum down the Fallopian tube, or movement of sperm along the tubules of the epididymis, from testis to vas deferens. There are glands in the mucous membranes of the Fallopian tubes, uterus, vagina, and vulva, whose secretions all facilitate the reproductive process, from coitus through fertilization to pregnancy; it is the mucosa of the uterus (the endometrium) which thickens and grows new glands monthly in anticipation of possible pregnancy, and which is shed if this doesn't happen, or develops further if it does. In the male, the glands of the mucosa of the genital tract secrete substances which provide an appropriate environment for sperm on their journey from the testes, and the components of the seminal fluid which accompanies them to their potential destination in the female tract.In the urinary tract, the mucous membranes that line the urethra, bladder, and ureters are several cells thick, allowing, especially in the bladder, for expansion; the particular protection required here is against the acidity of the urine. (These linings are in continuity with that of the ‘pelvis’ of the kidney and in turn the ducts and tubules leading to the thin membranes at the glomeruli, which filter the blood.)

10. http://www.wisc-online.com/objects/ViewObject.aspx?ID=AP14704http://www.wisc-online.com/objects/ViewObject.aspx?ID=AP14704 Internal Cellular Defense • Phagocytic cells • Attach to the microbe’s surface receptors or are attracted by signals from damaged tissues (chemitaxis) • Proceed to engulf & destroy microbes with lysozyme & toxic forms of oxygen (react w/ molecules in cell and disrupt things like the membrane) • EX: Macrophages (from monocytes) & neutrophils • Eosinophils help to defend against parasitic worms • Dendritic cells stimulate the development of acquired immunity http://www.youtube.com/watch?v=JnlULOjUhSQ http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/ROS.html

11. Lymphatic capillary Interstitial fluid Macrophages are found in spleen, lymph nodes and other parts of lymphatic system. Blood microbes can become trapped by spleen. Interstitial microbes get trapped by lymph nodes. Adenoid Tonsil LE 43-5 Blood capillary Lymph nodes Lymphatic vessel Spleen Tissue cells Peyer’s patches (small intestine) Appendix Lymphatic vessels Masses of lymphocytes and macrophages Lymph node http://www.lymphnotes.com/article.php/id/151/

12. Internal Chemical Defense • A cell is infected with virus • Infected cell secretes interferons • Proteins that when secreted induce nearby cells to produce substances that inhibit viral reproduction • Limit the cell-to-cell spread of viruses in the body

13. Internal Chemical Defense • Proteins in the blood plasma function together to fight infections when they come into contact with foreign substances (bacteria) • These COMPLEMENT proteins are usually inactive, but will activate a cascade of biochemical reactions leading to lysis (bursting) of invading cells http://www.niaid.nih.gov/topics/immuneSystem/immuneCells/Pages/complementSystem.aspx

14. Inflammation (Inflammatory response) • An infected cut in your skin • Basophils (a type of WBC) & Mast cells (found in various tissue in close connection with blood vessels)release histamine, a signaling molecule as an immediate first response • Macrophages in the area may also release cytokines (signal molecules that attract more macrophages) • Histamine triggers capillary dilation (now are more permeable) • Increased blood flow enables more antimicrobial proteins & more phagocytic cells to arrive to destroy microbes • Leads to accumulation of pus (fluid w/ lots of white blood cells, dead microbes, & cell debris) A systemic response from severe tissue damage involves increased production of WBCs & Fever (may speed up chemical rxns). Overwhelming response may lead to septic shock & death.

15. LE 43-6

16. Natural Killer Cells • Body cells normally express surface proteins (Class I MHC markers) • Except RBCs • Viral infected cells and cancer cells can stop expressing these surface proteins • NKcells patrol the body and attack any of these bad cells and induces apoptosis (cell death) • ***Not specific to a particular virus Natural killer (NK) cells are another kind of lethal white cell, or lymphocyte. Like CTLs, NK cells are armed with granules filled with potent chemicals. But CTLs look for antigen fragments bound to self-MHC molecules, whereas NK cells recognize cells lacking self-MHC molecules. Thus, NK cells have the potential to attack many types of foreign cells.

17. Spread of Infectious Diseases • Direct Contact • Person to Person: Infected on touches, coughs on, or kisses someone infected. Also through sexual contact or blood transfusion. • Animal to Person: bites, scratches, or handling animal wastes can be hazardous. • Mother to unborn child: germs can pass through the placenta or be passed along during childbirth. • Indirect Contact • Touching some object that has germs on itself • Droplet transmission (cough/sneeze into air in a 3 foot radius) • Particle transmission (germs remain suspended in air for periods of time and can be breathed in) • Food contamination

18. Decreasing Disease Transmission Risk • Wash hands often • Get vaccinated • Use antibiotics sensibly (when needed & follow directions) • If sick, stay @ home • Prepare & store food properly • Disinfect kitchen & bathroom often • Be safe during “adult activities” • Don’t share personal items (like toothbrush…eww!) • Travel informed (get immunized before foreign trips) • Keep your pets healthy

19. http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__the_immune_response.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__the_immune_response.html Acquired Immunities Part 2 http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/B_and_Tcells.html http://www.biologycorner.com/APbiology/pathology/immunology.html

20. Acquired (Adaptive) Immunity • Develops after exposure to microbe • Immune response is enhanced by previous exposure • Involves a specific response to pathogens • Slower, but specific response • Recognition is by a type of WBC (lymphocytes) http://chemistry.about.com/cs/howthingswork/a/aa011604a.htm http://kidshealth.org/parent/general/body_basics/immune.html#

21. Once the pathogen is inside of cells! When antigens/microbes are available either in the blood or outside of cells in interstitial areas.

22. Antigens & Antibodies • Antigens: any foreign molecule that is specifically recognized by lymphocytes & elicits a response • Can be attached to pathogens surface or secreted into blood/interstitial fluid • B cells & T cells recognize antigens using antigen receptors. • B cells sometimes change into plasma cells that secrete a soluble form of the antigen receptor called an ANTIBODY, or immunoglobulin (Ig). • Epitope: the part of the antigen that binds to specific receptor or antibody.

23. Antibody Diversification • Due to genetic recombination & alternative splicing, the genes coding for variable regions of the antibody produce an unlimited variety. • Therefore there is no viral disease for which humans cannot produce antibodies. http://outreach.mcb.harvard.edu/animations/antibody.swf

24. B lymphocytes (aka military intelligence group) • Recognize intact microbes (antigens), engulf/digest them, and then display parts of antigen on cell surface • Then clonal selection occurs • B cell then differentiates & divides into clone plasma cells that secrete the specific antibodies, and clone memory cells (long-lived cells that can respond rapidly due to second exposure) • Develop & mature in Bone marrow • Y shaped surface receptor

25. Antigen molecules B cells that differ in antigen specificity Antigen receptor LE 43-12 Antibody molecules Clone of plasma cells Clone of memory cells http://outreach.mcb.harvard.edu/animations/commoncold.swf

26. Antibody-Mediated (Humoral) Immune Response • Macrophage, dendretic cell, or B cell phagocytize a pathogen in blood or tissue fluid. Then display the antigens on the surface using class II MHC markers. • B cell will either activate itself or a helper T cell will bind to AnitigenPresentingCells and release cytokines to stimulate B cells to activate. • B cell activation causes differentiation into Plasma (immediate antibody secreting cells) & memory (long term protection for 2nd+ exposures) cells. • Antibodies flow through fluid and attach to corresponding antigens. This can neutralize pathogens (not allow them to bind to host cells), promote quicker phagocytosis (opsonization), or activate the complement system causing cell to lyse.

28. http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation__ige_mediated__type_1__hypersensitivity__quiz_1_.htmlhttp://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation__ige_mediated__type_1__hypersensitivity__quiz_1_.html

29. T Lymphocytes (aka soldiers that act on the intel report) • MHC molecules bring microbe fragments to the cell membrane of an infected cell (Cancer, viral, or some intracellular bacteria=ex.Chlamydia trachomatis) • T cells recognize small antigen fragment and help to destroy the problem cells/microbes • Helper T cells react to APCs (macrophages typically) which then releases cytokines “interleukins” (which will clone the helper T cells into plasma & memory versions) to activate B cellshumoral response & cytotoxic T cellscell mediated response • Cytotoxic T cells find the targeted cells and induce apoptosis • Develop in bone marrow, but mature in the Thymus http://www.ncbi.nlm.nih.gov/books/NBK27101/

30. MHCs • Major histocompatibility complexes produce a host cell protein that will “present” antigen fragments on the surface of an infected cell. • Class I MHC: found on all nucleated body cells, used to display parts of antigens on infected cells enhanced binding/interaction with CD8 protein. • Recognized by Cytotoxic T cells (CD8) • Release perforin (makes holes in membranes) that allows chemicals to go inside the cell and induce apoptosis leading to cell death • Class II MHC: found on APCs: macrophages, B cells, & dendritic cells (another phagocytic cell) after breaking down a pathogen, enhanced binding/interaction with CD4 protein • Recognized by Helper T cells (CD4)

31. The “Pores” allow granzymes access to the inside of the cell to quickly induce apoptosis!

32. Cell Mediated Immune Response • If body cells are displaying incorrect class I MHCs or displaying antigens with correct MHCs then T cells act fast. • Cytotoxic T cells take out these body cells causing cell death • If APCs phagocytize foreign substances, the antigens presented can activate helper T cells that can help initiate the humoral response, but also stimulate cytotoxic T cells to search & destroy already infected cells. • During this process both helper & cytotoxic T cells will differentiate into active & memory cells.

33. Although MHC molecules are required for T cell responses against foreign invaders, they also create problems during organ transplantations. Virtually every cell in the body is covered with MHC proteins, but each person has a different set of these proteins on his or her cells. If a T cell recognizes a nonself-MHC molecule on another cell, it will destroy the cell. Therefore, doctors must match organ recipients with donors who have the closest MHC makeup. Otherwise the recipient’s T cells will likely attack the transplanted organ, leading to graft rejection. http://outreach.mcb.harvard.edu/animations/cellmediated.swf NO

34. http://classes.midlandstech.edu/carterp/Courses/bio225/chap17/Adaptive_Immunity3.htmlhttp://classes.midlandstech.edu/carterp/Courses/bio225/chap17/Adaptive_Immunity3.html

35. Field Trip • Buses leaving EHS 7am in the student parking lot! • Meaning you need to be here by 6:45 AM

36. Primary vs Secondary Immune Response • Primary response is performed by B & T cells that are the plasma clones. These fight upon immediate first exposure. • Secondary response includes memory B & T cells that can react fast and some of which can undergo clonal selection into more plasma & future memory cells.

38. Self vs. Nonself • As lymphocytes are maturing their antigen receptors are tested for self-reactivity (to see if they match up with specific body molecules…not good). • If they are self-reactive they are made to undergo apoptosis • If they only react to foreign molecules they are good to go. http://outreach.mcb.harvard.edu/animations/cellmediated.swf

40. Active vs Passive Immunity • Active immunity: results from exposure to a particular microbe. • Can develop from vaccinations where antigens are introduced into the body through immunization (weakened, dead, or parts of microbes). • Leads to rapid & strong secondary response when exposed to real thing • Passive immunity: when antibodies are transferred from mom to baby (but only last as long as the antibodies…a few months, hence why they are given immunizations). • Can also be done when antibodies from immune animals are transferred to nonimmune animals, example is antivenom for snake bites http://www.wellness.com/reference/allergies/newborn-immune-system

41. Blood Transfusion Example • Blood cells have antigens (A,B,O) • Immune system destroys foreign antigens

42. True universal Donor is? • True universal recipient is?

44. Allergies • Antigens called allergens bind to antibodies connected to mast cells • Once bound histamine is released • Leads to typical allergy symptoms: sneezing, runny nose, teary eyes • Anaphylactic Shock • Too much histamine, blood pressure drops, can die in mins. • Epinephrine pen constricts blood vessels, increase heart rate, decrease histamine release & reduces swelling in the throat (so as not to suffocate)

45. Autoimmune Diseases • Immune system turns against beneficial molecules in the body (loss of self-tolerance) • Ex: Multiple sclerosis • T cells destroy myelin sheath of neurons • Causes nerve signals to slow or even stop • Lots of problems associated with it including paralysis

46. Immunodeficiency Diseases • Inability of immune system to protect the body against pathogens • Ex: AIDS • Major loss of T cells • Can’t stop HIV from further infecting T cells • Makes individuals way more susceptible to infections & cancers that are normally defeated http://news.softpedia.com/news/HIV-and-AIDS-Explained-to-You-75646.shtml

47. Together these mechanisms constitute the clonal selection hypothesis (e) "According to this hypothesis, embryos contain many different lymphocytes, each genetically programmed to recognize a particular antigen and make antibodies to destroy it. If a lymphocyte encounters and recognizes that antigen after development is complete, it divides repeatedly to produce a clone, a group of identical progeny cells that make the same antibody. If, during embryonic development, it encounters its programmed antigen as part of a normal host substance (self), the lymphocyte is somehow destroyed or inactivated. This mechanism removes lymphocytes that can destroy host tissues and thereby creates tolerance for self. It also selects for survival [of] lymphocytes that will protect the host from foreign antigens." (f)See Figure 17.5, Clonal selection hypothesis "Humoral immunity depends first on the ability of B lymphocytes to recognize specific antigens and second on their ability to initiate responses that protect the body against foreign agents. The most common response is the production of antibodies that will inactivate an antigen and lead to destruction of infectious organisms." http://www.youtube.com/watch?v=HUSDvSknIgI http://www.mansfield.ohio-state.edu/~sabedon/black17.htm#specific_immunity