The Immune system

1. The Immune system By: Alisa Fay, Rachel Robert, Lindsay Kilday & Kirsten Meisterling

2. Players

3. Stem Cell Lymphoid Stem Cell Myeloid Progenitor Natural Killer B Cell T Cell Neutrophil Eosinophil Monocytes Cytotoxic Helper Suppressor Basophil Mast Cell Mast Cell Plasma Cell

4. Immune System “Players”: Major Cells • Stem Cell: an undifferentiated cell whose daughter cells may differentiate into two different cells • Lymphoid Stem Cell: white blood cell (WBC) of the immune system that is part of the lymph system • Myeloid Progenitor: makes platelets, red blood cells and some WBCs

6. Immune System “Players”: Lymphoid Cells • B Cells: A lymphocyte that matures in the bone marrow and carries out humoral immune response. B Cells have membrane bound antigen receptors. • Plasma Cell: (Activated by B Cells) Secrete antibodies to eliminate certain antigens • Memory Cell: (Activated by B Cells) Remember antigen that caused its formation

7. Plasma Cell The orange part is the endoplasmic reticulum that manufactures, modifies and transports proteins, or antibodies. The cells nucleus is redish-brown and the dark brown dots are mitochondria which provide the cell with energy.

8. Immune System “Players”: Lymphoid Cells • T Cells: A lymphocyte that matures in the thymus and functions in cell mediated response. • TC (Cytotoxic) Cells: Kill infected cells and cancer cells • TH (Helper) Cells: Secrete Cytokines, molecules that are released by one cell as a regulator of a neighboring cell ( B and T cells) • TS(Suppressor) Cells: Probably turn off immune system when antigen is gone. • Memory T Cells: Cells that fight certain previously exposed infections faster and stronger than the first time.

9. T Cell in Action Cytotoxic T Cell (orange) killing a cancer cell (purple).

10. Immune System “Players”: Lymphoid Cells • Natural Killer Cells (NK Cells): Cells that destroy a body’s infected cells, especially the ones that harbor viruses, and aberrant cells, which can form tumors. • “Shake hands” with cell • If cell has no recognizable MHC (identification), then the NK kills it • Attack the membrane of target cell causing it to lysis

12. Immune System “Players”: Myeloid Progenitor Cells • Phagocyte Cells: WBCs that ingest invading particles • Eosinophils • 1.5% WBCs • Limited phagocytic activity, but contain enzymes within cytoplasmic granules • Destroy parasites by positioning themselves on walls and releasing enzymes • Neotrophils • 60-70% of WBCs • Can leave blood and enter infected tissues to destroy microbes, then self destruct • Live only a few days

13. Immune System “Players”: Myeloid Progenitor Cells • Phagocyte Cells: WBCs that ingest invading particles • Eosinophils • 1.5% WBCs • Limited phagocytic activity, but contain enzymes within cytoplasmic granules • Destroy parasites by positioning themselves on walls and releasing enzymes • Neotrophils • 60-70% of WBCs • Can leave blood and enter infected tissues to destroy microbes, then self destruct • Live only a few days

14. Parasite Eosinophil: Above showing the granules which release enzymes and the size. To the right showing a eosinophil attacking a parasite.

15. Neutophil: Leaving the blood to migrate into a tissue and a Neutrophil animation

16. Immune System “Players”: Myeloid Progenitor Cells • Monocytes • 5% WBCs • Very effective phagocytic defense • Monocytes develop into macrophages (big eaters) after migrating into a tissue • Have amoeboid cells that pull in microbes which are then destroyed (by enzymes and reactive oxygen) with macrophages • Some macrophages reside permanently in organs and connective tissue (many reside in lymph nodes and the spleen) • Macrophages secrete hormones called cytokines that call for immune system cells and activate cells involved in tissue repair

17. Immune System “Players”: Myeloid Progenitor Cells • Basophils and Mast Cells • Contain the chemical histamine which aids in the inflammatory response • When these cells are injured in connective tissue, histamine is released • This triggers vasodilation and makes the capillaries “leaky”

18. Monocyte ready to defend against antigens Vasodilation by histamines released by basophils and mast cells

19. Substances COMPLEMENT LYSOZYmE Body tissue INTERFERON Alfha, beta, gamma

20. Substances HISTAMINE INTERLEUKINS contained in basophils and mast cells MHC Chemical signal This can be used as a biochemical fingerprint to each individual.

21. Substances PROSTAGLANDINS Helps cause local vessel dilation. CLOTTING PROTEINS Blood clotting 

22. Substances ANTIBODY PYROGENS Specific protein produced by specialized lymphocytes. ANTIGEN Molecule that sets the body’s thermostat at a higher temperature.

23. Process: Fighting an Infection

24. 1. Chemotaxis • When the epithelium of the skin is damaged, chemicals are sent into the bloodstream by the invading bacteria and tissues • These molecules, called chemokines, attract phagocytic cells to the infected area • Chemotaxis is the process of phagocytic cells migrating to the source of the chemical attractant

25. 2. Vasodilation • When the chemokines are released, vasodilation, the widening of the arteries, also occurs • Increases the blood flow to the infected area, carrying the needed white blood cells • Causes the redness and heat as the white blood cells work to cure the infection

27. Inflammation: redness pain swelling heat

28. 3. Diapedesis • When the white blood cells get to the infected area in the bloodstream, they undergo the process of diapedesis • The cells move through the epithelium of the capillaries and into the surrounding interstitial fluid to destroy the invaders

29. 3. Diapedesis • When the white blood cells get to the infected area in the bloodstream, they undergo the process of diapedesis • The cells move through the epithelium of the capillaries and into the surrounding interstitial fluid to destroy the invaders

30. 2. chemokines sensed by neutrophils/monocytes 1. damaged cell releases chemokines 3. monocytes squeeze out of capillaries (diapedesis) 4. monocytes (and/or macrophages) start to engulf pathogen (phagocytosis)

31. 4. Phagocytosis • When the phagocytic cells get to the invaders, they go through the process of phagocytosis to finally eliminate the bacteria

32. 4. Phagocytosis • When the phagocytic cells get to the invaders, they go through the process of phagocytosis to finally eliminate the bacteria

33. The Pseudopodia on the macrophages attach to polysaccharides on the microbes surface to pull it in.

34. Once the microbe is in the cell, the lysosome comes to destroy it • The lysosome in the cell can kill the microbe in one of two ways: • Generating toxic forms of oxygen • Releasing enzymes that digest microbial components

35. Clotting Cascade • When the skin’s epithelium is damaged, a series of reactions occur to stop the bleeding • The cascade follows two pathways: extrinsic and intrinsic and then finishes in the final common pathway http://www.hopkinsmedicine.org/hematology/Coagulation.swf

36. -Definition: large amount of fluid beneath the skin; swelling -Homeostasis maintains the amount of interstitial fluid around the body - Too much fluid causes swelling as well as poor removal of fluid Edema

37. How it starts-- Leaky Capillaries Two types of pressure measured in the capillaries: - hydrostatic pressure: causes water to filter into surrounding tissues - oncotic pressure: pulls water back into the vessel from the tissues Together the two pressures maintain homeostasis of fluid levels in the body

38. Most leakage occurs in the capillaries due to there semi-permeable membrane Factors that increase leakage of fluid 1. increase of hydrostatic pressure in vessel 2. decrease of oncotic pressure in vessel 3. increase in vessel wall permeability

39. Humoral Immunity What is it? Transformation of B-cells into plasma cells that can then produce and secrete antibodies B-cells = -created in the bone marrow -circulate through blood and lymph -changes into a clone of plasma cells to secret a specific antibody -also can change into a clone of memory cells to make antibodies after first encounters

40. 1st Antigen Exposure • Antigen is engulfed by macrophage • -Macrophage stimulates Helper T-Cell • -Helper T-Cells stimulate B-Cells and Cytotoxic T-Cells • -B-Cells turn into plasma and memory cells • -Plasma cells secret antibodies into blood; memory b-cells are “stored” until their specific antigen shows up again (2nd exposure) • -Cytotoxic t-cells turn into active cytotoxic t-cells and memory t-cells • - Cytotoxic t-cells go and kill the antigen; memory t-cells are also stored until their specific antigen shows up again (2nd exposure)

42. Cellular Immunity What is it? Ability for antibodies to recognize a foreign organism, known as antigens, and destroy it Advantage Allows for a person’s body to destroy of antigen faster before the antigen, which could be harmful to a person, causes damage Types of WBC’s (antibodies) 

43. Cellular vs. Humoral Immunity -Humoral immunity is the first stage the builds the memory b-cells for cellular immunity. -Cellular immunity depends on the cells that are made during b-cell and cytotoxic t-cell transformation into memory cells -Memory cells are formed with specific antibody receptors that bind to a specific antigen

44. Clonal Selection Definition -The selection of a lymphocyte by an antigen which activates the lymphocyte stimulating it to divide and diferentiate. Two Types: Effector cells --plasma cells--make antibodies--short lived Memory cells --long lived White blood cells fighting a antigen

45. the antibody (Ab) protein hypervariable region (hundreds of billions of possible shapes) constant region (same for all antibody molecules) (aka Fc region)

46. a simpler way to show the antibody molecule hypervariable region (hundreds of billions of possible shapes) constant region (same for all antibody molecules) (also called Fc region)

47. Ab are incredibly SPECIFIC • each one will bind ONLY to its matching antigen. • this shows 14 different antibody molecules. • in reality there would be MANY BILLIONS of different antibodies.

48. antigens (Ag) • any foreign object that our immune system can react with • protein, virus, bacterial cell, toxic molecule, pollen grain, polysaccharide, etc • here, there are 8 shown • in reality there are hundreds of billions • any ONE bacterial cell might have hundreds or thousands of antigenic proteins on its surface

49. Antigens and Antibodies must make an EXACT MATCH • if they don’t match – no triggering, no sticking • if they DO match – they stick together strongly • if they DO match – triggers something to happen • what DOES happen when they match?

50. another way to show the antibody molecule... http://www.nwfsc.noaa.gov/hab/habs_toxins/marine_biotoxins/detection/elisa.html