Immunology

1. Immunology The study of internal defense systems of humans and other animals

2. Immune System • Body’s internal defense system • Protects against disease-causing organisms and many toxins • Disease causing organisms or pathogens • Certain viruses • Bacteria • Fungi • protozoa

3. Pathogens • Enter our bodies with air, food, water, during copulation and through wounds on our skin • Immune system responds to eliminate them • Immune (latin for safe)

4. Internal Defense • Our internal defense depends on the bodies ability to distinguish self and nonself • What does this mean? • Our bodies are unique and cells have surface proteins different from anyone else’s • The body’s immune system can recognize its own cells, but identifies others as foreign • If the body fails to do this, it results in an autoimmune disease, such as Lupus

5. 1798–Edward Jenner noticed immunity in milkmaids – injected fluid from cowpox blister into skin of patient (orphan or prisoner) 1989- smallpox was eradicated from the world Louis Pasteur 1879- discovered that aged bacterial cultures of Pasteurella lost virulence. Referred to injection of weakened culture a “vaccine” in honor of Jenner 1881- He applied the same technique vs. anthrax….and then rabies Heading towards modern times Pasteur inoculating sheep May 1881

7. Immune Responses (IR) • 2 Main Types: • Nonspecific immune response • Specific immune response

8. Nonspecific IR (innate immunity) • provides general protection against pathogens, parasites, some toxins, drugs and cancer cells • Prevent most pathogens from entering outside barrier and rapidly destroy those that do • Nonspecific examples: • Skin provides outside barrier • Phagocytosis destroys bacteria that invade body

9. Nonspecific IR • An animals first line of defense is its chemical and physical barriers – skin, shell etc. • Microorganisms entering through food are usually destroyed by acid secretions and enzymes in stomach – chemical barrier

10. Nonspecific IR Cont. • Respiratory and reproductive tracts are protected by hair in the nose that filters pathogens and mucous membranes lining that traps pathogens • Once trapped, the pathogens are destroyed by phagocytes • Most invaders that pass the outer barriers are attacked by chemical properties and eliminated quickly

11. Nonspecific IR cont. • In addition to the front-line physical and chemical barriers, nonspecific IR involve • 1. Soluble molecules • 2. Phagocytes • 3. Natural killer cells (NK)

12. 1. Soluble Molecules Mediate IR • Important in immune responses • Include antimicrobial peptides, regulatory peptides, and proteins that destroy pathogens • Two major soluble molecules in nonspecific defense responses • Cytokines • complement

13. Soluble molecules • Cytokines – • Signaling proteins that regulate interactions between cells • Important groups of Cytokines: • Interferons – inhibit viral replication and activate natural killer (NK) cells • Interleukins – help regulate interactions between lymphocytes and other cells of the body • Chemokines – attract, activate, and direct movement of certain cells of the immune system • Tumor necrosis factors (TNFs)– kill tumor cells and stimulate immune cells to initiate an inflammatory response

14. Interferons (soluble mlcs) • Secreted by cytokines cells in response to a virus or parasite • Type I – produced by macrophages (large phagocytic cells) or by fibroblasts (prod. Fibers of connective tissue) • Type I - inhibit viral replication and activate natural killer cells • Type II – prod. as a specific immune response • Type II – enhance activities of other immune cells such as macrophages to destroy tumor cells or host cells that have been infected by viruses • Used by: FDA to treat diseases (hepatitis B & C), genital warts, a type of leukemia, a type of multiple sclerosis

15. Interleukins (soluble mlcs) • Secreted by macrophages and lymphocytes • help regulate interactions between lymphocytes and other cells of the body (widespread of effects) • For example, during infection interleukin-1 can reset the thermostat in the hypothalamus, resulting in fever and its symptoms

16. Chemokines (soluble mlcs) • A large group of cytokines • attract, activate, and direct movement of certain cells of the immune system • Produced in response to infection • Key mediators of the inflammatory response

17. Tumor necrosis factors (TNFs) (soluble mlcs) • Secreted by macrophages and lymphocytes called T-cells • Stimulates immune cells to initiate an inflammatory response • Kill tumor cells • TNFs can be released in large amounts in response to certain infections, which can result in a cascade of reactions that could be potentially fatal • Thus, cytokines can sometimes have harmful effects

18. Complement • Complement system leads to the destruction of pathogens • Called this because it “complements” the action of other defense responses • Complement proteins lyse the cell wall of pathogens, coat pathogens and attract WBC to the site of infection • These actions enhance the inflammatory response

19. 2. Phagocytes • Neutrophils (most common type of WBC) and macrophages are the main phagocytes in the body • Phagocytosis when cells engulf microorganisms, foreign matter or other cells • A neutrophil can phagocytize ~20 bacteria before it becomes inactivated and dies

20. Phagocytes • Macrophages – large phagocytes that develop from WBC called monocytes • Phagocytize ~100 bacteria during a life span • Some patrol for damaged cells or foreign matter • Others stay in one place and destroy bacteria as it passes by • For example: air sacs in the lungs contain lg. numbers of macrophages that destroy foreign matter entering with inhaled air

21. 3. Natural Killer (NK) Cells • Lg. granular lymphocytes that originate in the bone marrow • Active against tumor cells and cells infected with some types of viruses • Destroy target cells by specific and nonspecific processes

22. Natural Killer Cells Cont. • Active without prior exposure to target • Has no memory • Generally directed towards damaged cells w/ wrong expressions • Change in surface proteins trigger NK cells • Absence of proteins triggers the NK cells • Can lead to cells self destruction by apoptosis (programmed cell death)

23. Inflammatory Response • Inflammation • Triggered immediately after pathogen invasion or physical injury • 3 main processes: • Vasodilatation – increased blood vessel diameter • Increased capillary permeability – allows fluid & antibodies to leave circulation and enter tissue • Increased Phagocytosis – engulfing of foreign matter, microorganisms and other cells

24. Inflammatory Response • Macrophages and mast cells stationed in the tissues respond rapidly to damaged tissue or infection • Mast cells release histamine, cytokines and other compounds that dilate blood vessels and increase capillary permeability • Begins as a local response, but sometimes the entire body becomes involved (ex. fever)

25. Specific IR (adaptive immunity) • Highly specific • A foreign molecule that elicits an immune response is called an antigen (Ag) • Proteins are the most powerful antigens • Antibodies (Ab) highly specific proteins that recognize and bind to specific antigens

26. Specific IR cont. • Specific IR are directed towards certain Ag and include the production of Ab • Important characteristic of specific IR is immunological memory • Immunological memory – capacity to respond more effectively the second time foreign molecules come around

27. Specific IR • While nonspecific IR responses are destroying pathogens, the body is preparing its specific IR • This takes several days to activate, but once in gear, it is extremely effective • Targeted to destroy specific Ag and have memory • 2 Types: cell-mediated and antibody-mediated immunity

29. Specific Immunity Requires 2 Groups of Cells: • 1. Lymphocytes • 2. Antigen-presenting cells (APCs)

30. Lymphocytes • Principal warriors in specific IR • All lymphocytes develop from stem cells in the bone marrow • 3 main types: • B lymphocytes or B cells –complete dev. in bone marrow • T lymphocytes or T cells - mature in thymus gland • NK cells – as already discussed, NK cells kill virally infected cells and tumor cells

31. B cells • Responsible for Antibody-mediated immunity • Produced in bone marrow (millions each day) • Differentiate in to plasma cells, which prod. Ab • Make specific Ab, neutralize them or mark them for destruction • Some activated B cells become memory B cells which continue to prod. Ab after an infection has been overcome

32. B cells

33. T cells • Responsible for cell-mediated immunity • The thymus gland confers immunocompetence on T cells by making them capable of distinguishing between self and nonself • Bodies cellular soldiers • Travel to the site of infection and attack body cells that are infected by pathogens or foreign cells

34. 3 Types of T cells • TH, helper T cell • Tc, cytotoxic T cell • memory T cells • T cells are distinguished by their T-cell receptor (TCR) which recognizes specific Ag

35. TH, helper cells • Also called CD4 cells because they have a surface glycoprotein designated CD4 on their plasma membrane • Regulatory cells • produce cytokines that activate B,T and phagocytic cells • Memory TH cells

36. Tc, cytotoxic T cells • CD8 expression because they have a glycoprotein designated CD8 on their plasma membrane surface • Recognize and destroy cells w/ foreign Ag on their surfaces – killer T cells • Effector cell that kills virus-infected cells, tumor cells and foreign grafts • For ex: these are cells that recognize a transplant as being foreign and want to fight it • Memory Tc cells

37. Memory T cells • After an infection, both cytotoxic and helper memory T cells remain in the body • Permits rapid IR on second or more exposures to a particular Ag • Memory B cells cont. to produce Ab after the immune system overcomes an infection

38. T cells

39. Antigen-Presenting Cells (APCs) • Display foreign Ag as well as their own surface proteins • *Macrophages • *B cells • *Dendritic cells - located w/in skin & other tissues of the body that interact w/ environment. Specialized to process, transport and present Ag • *All of these are capable of taking an Ag, breaking it down and spitting it out to be recognized by T-cells

41. MHC ProteinsMajor Histocompatibility complex (MHC) • Proteins found on mammalian cells • In transplant patients, if MHC proteins from the donor differ from MHC proteins of the recipient, they may be rejected • MHCI proteins bind epitopes from intracellular pathogens • MHCII proteins bind epitopes from extracellular Ag • *epitope* – is an antigenic determinant – made up of specific sequences of aa, giving an Ag a specific shape recognized by an Ab or TCR

42. MHC 1 • Found on all nucleated cells • “present” to the immune system sm. peptides found in the cytoplasm of cells • Used by the immune system to distinguish normal cells from abnormal cells • Tc (cytotoxic) cells in interact w/ MHC • If peptide is not recognized as self/normal, Tc cell will destroy it

43. MHC II • Found only on antigen-presenting cells (APCs) such as macrophages, B cells and migrating phagocytic cells called dendritic cells • APC phagocytize extracellular Ag such as bacteria and toxins • “Present” these extracellular Ag

44. MHC II cont. • TH (helper) cells interact w/ MHC protein and become activated • Activated TH cells then activate B cells • B cells differentiate into plasma cells • Plasma cells then produce Ab to destroy bacteria

45. Important distinction between MHC Proteins • MHC I proteins bind epitopes from intercellular pathogens while MHC II bind epitopes from extracellular Ag • This ensures the appropriate branch of the immune system is activated for efficient killing of pathogens • MHC I activates cell-mediated IR and kills cells presenting the MHC-I complex, thus destroying intracellular pathogens • MHC II activates the humoral IR, resulting in the production of Ab that are very efficient in destroying extracellular pathogens

46. Cell-mediated immunity vs. Antibody-mediated immunity • In cell mediated immunity, specific T cells are activated; these cells release proteins that destroy cells infected with viruses or other intracellular pathogens • In antibody- mediated immunity, specific B cells are activated; they multiple and differentiate into plasma cells, which produce Ab

47. Cell-Mediated Immunity • Specific T cells are activated by a foreign Ag-MHC complex on the surface of an infected cell • Activated Tc cells multiply, give rise to a clone • Cells migrate to the site of infection and destroy pathogen-infected cells • Activated TH cells give rise to a clone of TH cells, which produce cytokines that activate B cells and macrophages

48. Antibody-Mediated Immunity • B cells are responsible for Ab-mediated immunity • B cells are activated when they combine with an Ag • Once activated, the B cell divides, producing a clone • These cells differentiate and become plasma cells that secrete Ab • Plasma cells stay in lymph tissues, but the Ab are transported to the site of infection by blood or lymph • After the infection has been overcome, memory B cells remain in the tissues

49. Antibody-Mediated Immunity • Plasma cells produce specific Ab, called immunoglobulin's (Ig) • Immunoglobulin's (Ig) or antibodies • specific proteins (produced by plasma cells) • they recognize and bind to specific Ag • An Ab combines w/ a specific Ag to form an Antibody-Antigen complex (Ag-Ab complex) • which may inactivate the pathogen, stimulate phagocytosis or activate the complement system

50. Antibody-Mediated Immunity • Humoral Immunity (another name for Antibody-mediated immunity) • Transferred by serum of an immune individual • Ab produced by B cells • Transfer from individual to individual by serum (passive immunity)