Immune System Ch 31

1. Immune System Ch 31 Advanced Placement Biology in Brandon High School 2013-2014 Teacher: Mrs. Radjewski; Room 224; Upstairs next to Mrs. Spezia in Room 222 Diagonal from the Social Studies Office, otherwise known as the Social Studies Cave with the nasty microwave.

2. Defense against Pathogens • Pathogens • Harmful organisms and viruses that can cause disease • Animals have 2 defensive mechanisms against them to provide immunity • The ability to avoid disease when invaded by a pathogen • Innate immunity • Adaptive immunity

3. Innate Immunity • Nonspecific – used against a wide variety of invasive organisms • Includes barriers such as the skin, which is a 1st line of defense for the body • Also includes phagocytic cells (phagocytes) as a 2nd line of defense for the body • They ingest foreign cells (phagocytosis) • These defenses may be presented all the time, or activated in response from an injury or invasion by a pathogen (if activated, it is rapid) • Most animals have innate immunity

4. Adaptive Immunity • Specific • Distinguishes between substances made by the organism (self) and substances that are not part of the organism (nonself) • Involves antibody proteins that recognize, bind to, and aid in the destruction of specific viruses and bacteria • Typically slow to develop, but long lasting • Only found in vertebrate animals

6. White Blood Cells (WBC’s) • Blood contains 5 billion RBC’s and 7 million WBC’s • Also called leukocytes • Play major role in immune system • Two major kinds • Phagocytes – large cells that engulf pathogens by phagocytosis (involves in innate and adaptive) • Example: macrophages • Lymphocytes – only involved in adaptive • Example: B cells and T cells

8. 4 Major Components of Immune System • Antibodies – proteins that bind specifically to substances identified by immune system as nonself • Binding inactivates and destroys microorganisms and toxins • Can act as a tag on nonself cells, making them easier for immune system to attack • Produced by B cells (type of lymphocyte)

9. 2. Major Histocompatibility Complex (MHC) • Proteins that are self-identifying cells • Play a major role in coordinating interactions between lymphocytes and macrophages (type of phagocyte) • Two classes • MHCI – found on surface on most mammalian cells • MHCII – found on most immune system cells

10. 3. T Cell Receptors • Integral membrane proteins on the surfaces of T cells (type of lymphocyte) • Recognize and bind to nonself substances

11. 4. Cytokines • Soluble signaling proteins released by many cells • Bind to cell surface receptors and alter the behavior of their target cells • They can • Activate and inactivate B cells • Activate and inactivate macrophages • Activate and inactivate T cells

12. 31.2 Innate Defenses are Nonspecific

13. Suppose a bacteria lands on human skin….challenges the bacteria faces: • Physical barrier of the skin • Bacteria can rarely penetrate intact skin • Broken skin increases the risk of infection

14. More challenges… • Saltiness of skin • Bacteria will have a hard time growing • Presence of normal flora • Competition for space and nutrients

15. Pathogen lands on inside nose or another internal organ….defenses it will encounter are: • Mucus • Slippery secretion produced by mucous membranes, which lines various body cavities • Traps microorganisms and will be removed by cilia • Lysozyme • Enzyme made by mucous membranes, that cleave the cell wall of bacteria causing them to burst open

16. More defenses inside nose…. • Defensins • Made by mucous membranes • Peptides of amino acids containing hydrophobic portions that are toxic to bacteria and other pathogens • Insert themselves in plasma membranes of these organisms and make membranes freely permeable to water and all solutes, thus killing the invaders

18. If Bacteria gets into body, 2nd line of defense will begin… • Phagocytes • Recognizes pathogenic cells and then ingest them by phagocytosis

19. 2nd Line of Defense continued… • Natural Killer Cells • Lymphocytes • Can distinguish between healthy cells and those who are infected by viruses or are cancerous • Can initiate apoptosis (programmed cell death) in the target cells

20. 2nd Line of Defense continued… • Complement Proteins • 20 different proteins • Once activated, a cascade occurs • One complement protein binds to components on the surface of the invading cell. This binding helps phagocytes recognize and destroy the invading cell • Another protein activates the inflammation response and attracts phagocytes to the site of infection • Finally, other proteins lyse the invading cell

21. 2nd Line of Defense continued… • Interferons • Signalling proteins (cytokines) • Help increase the resistance of neighboring cells to infection • Can bind to receptors on the plasma membrane of uninfected cells, stimulating a signaling pathway that inhibits viral reproduction if the cell near it are infected

22. Inflammation • Response when tissue is damaged because of infection or injury • Redness, swelling, and heat near damaged site • Can be painful • Is important • It isolates the area to stop the spread of the damage • It recruits cells to the location to kill any pathogens • It promotes healing

23. Response to Inflammation • Mast Cells • Adhere to the skin and linings of organs and release numerous chemical signals • Tumor necrosis factor – a cytokine protein that kills target cells and activates immune cells • Prostaglandins – fatty acid derivative that initiates inflammation in nearby tissues • Histamine – amino acid derivative that increases the permeability of blood vessels to white blood cells so they can act in nearby tissues

24. OH NO! A Splinter!! • Damaged tissue attract mast cells, which release histamine that diffuses into the blood vessels • Also tumor necrosis factor is released that diffuses to phagocytes

25. Histamine causes the vessels to dilate and become leaky • Complement proteins leave the blood vessels and attract and activate phagocytes • Tumor necrosis factor stimulates phagocytosis • Blood plasma and phagocytes move into infected tissue from the blood vessels

26. Phagocytosis engulfs bacteria and dead cells • Histamine and complement signaling cease; phagocytes are no longer attracted • A growth factor from platelets stimulates epithelial cell division, healing the wound

27. Following Inflammation • Pus • Mixture of leaked fluid and dead cells (bacteria, WBC’s, and damaged body cells • Normal result of body’s fighting a disease or inflammation • Gradually removed by macrophages

28. Inflammation can cause medical problems • Allergic Reaction • Nonself molecule that is normally harmless, could bind to a mast cell causing the release of histamine and subsequent inflammation (along with itchy, watery eyes and possible rash) • The nonself molecule could come from food or from the environment

29. Inflammation can cause medical problems • Autoimmune Disease • Immune system fails to distinguish between self and nonself • Ends up attacking tissues in own organism’s body • Sepsis • Inflammation does not remain local and extends throughout the body with the dilation of blood vessels • If bp drops during this, it could be lethal

30. In most cases Innate immunity is good enough • But in some cases, when the pathogen is in large numbers, adaptive immunity must take over.

31. 31.3 Adaptive Immunity Response in Specific

32. Key features of Adaptive Immunity • Specific – allows it to focus its responses on pathogens that are actually present • Diverse – enables it to respond to a variety of pathogens • Distinguishes self from nonself– prevents it from destroying self cells • Immunological memory – allows it to respond more effectively in later exposures to the same pathogen

33. Specificity • Reason why its specific is because of B and T lymphocytes • T cell receptors and the antibodies produces by B cells recognize and bind to specific nonselfsubstances called antigens. • This interaction initiates a specific immune response • Each T cell and each antibody-producing B cell is specific for a single antigen

34. Antigens • Have sites that the immune system (antibodies) recognizes called antigenic determinants or epitopes • Usually proteins or polysaccharides • A bacterium can have multiple antigens on them An antigenic determinant is a specific portion of the antigen, like a certain sequence of amino acids

35. Diversity • Pathogens can be: • Viruses • Bacteria • Protists • Fungi • Multicellular parasites • Toxins made by these organisms • Human can respond specifically to 10 million different antigens – by activating lymphocytes • So humans need to generate a vast diversity of lymphocytes that are specific for different antigens

36. Diversity Continued… • Diversity is generated primarily by DNA changes • Each B cell is able to produce only one kind of antibody; thus there are millions of different B cells • There are also millions of different T cells with specific T cell receptors

37. Diversity continued… • Antigen binding “selects” a particular B or T cell for proliferation (growth/spreading) • For example, when an antigen fits the surface receptor on a B cell and bind to it, the B cell is activated. It divides to form a clone of cells, (clonal selection) all of which produce and /or secrete antibodies with the same specificity as the receptor • This also applies to T lymphocytes

38. Distinguish self from nonself • The human body contains thousands of different molecules, each with a specific 3D structure capable of generating immune responses • Thus every cell in the body bears a tremendous number of antigens • Hopefully the individuals immune system can recognize it’s own body’s antigens and not attack them

39. Clonal Deletion • Any immature B or T cell that shows the potential to mount a strong immune response against self-antigens undergoes apoptosis within a short time • A failure of clonaldelection leads to an immune response or autoimmunity

40. Autoimmune Diseases • SLE – Systemic Lupus erythrematosis • Their antibodies can cause serious damage when they bind to normal tissue antigens and form large circulating antigen-antibody complexes • They become stuck in tissues and provoke inflammation • Hashimoto’s thyroiditis • Most common in women over 50 • Immune cells attack thyroid tissue, resulting in fatigue, depression, weight gain, and other symptoms

41. Immunological Memory • After responding to a particular type of pathogen once, it will remember that pathogen and will respond faster to same threat in the future • Saves us from repeats of childhood infectious diseases • First exposure – primary immune response • Second exposure – secondary immune response

42. Primary Immune Response • Activated lymphocytes divide and differentiate to produce 2 types of daughter cells • Effector cells – carry out the attack on the antigen • Effector B cells (plasma cells) secrete antibodies • Effector T cells release cytokines • Live only a few days • Memory cells – long lived cells that retain the ability to start dividing on short notice to produce more effector and more memory cells • Memory B and T cells may survive decades

43. Secondary Immune Response • More rapid and more powerful • The memory cells that bind with that antigen proliferate and launch a huge army of plasma cells and effector T cells The principle behind vaccination is to trigger the primary immune response that prepares the body to mount a stronger, quicker secondary response if it encounters the actual pathogen again.

44. 3 phases to adaptive immune response • Recognition – organism discriminates between self and nonself to detect pathogen • Activation – The recognition event leads to a mobilization of cells and molecules to fight the invader • Effector phase – mobilized cells and molecules destroy the invader

45. A T cell with a specific receptor binds to an antigen presenting cell. The T cell then makes cytokines, which stimulate other cells to divide

46. T cell that binds to the antigen on the antigen presenting cell is stimulated to form a clone The specific B cell that binds the antigen is stimulated to form a clone. T cells bind to and destroy cells bearing the antigen B cells form specific antibodies that bind to free antigens

47. 31.4 Adaptive Humoral Response involves specific antibodies

48. Humoral Response • Basis is B cells • Billions of B cells survive the test of clonal deletion and are released from the bone marrow into the circulatory system • Remember it has a receptor protein on its cell surface that is specific for a particular antigen • It gets activated by antigen binding to this receptor and then after stimulation from a T cell, it produces a clone of plasma cells that make antibodies as well as memory cells

49. This B cell makes an antibody that binds this specific antigen Each B cell makes a different specific antibody and displays it on its cell surface The specific antigen also binds to a T cell, which stimulates the B cell to divide, resulting in a clone of cells Potential Secondary Immune Response – a few cells develop into non-secreting memory cells that divide at a low rate. Primary immune response – some cells develop into plasma cells (effector B cells) that secrete the same antibody as the parent cell

50. Antibodies • Also called immunoglobulins • Two of the polypeptides are identical light chains and two are identical heavy chains • Held together by disulfide bonds • Each chain has a • Constant region – amino acid sequence determines the general structure and function (class) of the immunoglobulin • Variable region – amino acid sequence is different for each specific immunoglobulin. • There are 2 antigen binding sites, making the antibody bivalent. – This allows the antibodies to form large complexes with the antigens