Organismal Systems

1. Organismal Systems A Summary of Biological Systems

2. Chemical Defense Systems • Animal and plants have chemical defenses to fight against foreign invaders. • The vertebrate immune system is one of the best studied of these systems.

3. Vertebrate Immune System • The immune system recognizes foreign invaders such as viruses, bacteria, fungi, parasites and other pathogens. • Two major modes of attack have evolved: • Innate Immunity (Nonspecific, Generalized Attack) • Acquired Immunity (Specific, Specialized Attack)

4. “Generalized Attack”: these cells wage an instant campaign of destruction against any pathogen while signaling other cells of the presence of intruders “Specialized Attack”: these cells wage a more specific and enduring attack and are capable of producing lasting immunity against specific invaders.

5. Lines of Defense • The immune system has 3 main lines of defense: • 1st line: Physicalbarriers, chemical barriers, and mechanical barriers. • 2nd line: Phagocytes, complement, inflammation, fever • 3rd line: Cell-mediated and humoral Innate and Nonspecific Acquired and Specific

6. Innate vs. Acquired Immunity • Innate Immunity: is present at birth (before exposure to pathogens), is nonspecificand consists of external barriers plus internal cellular and chemical defenses • Acquired Immunity:develops after exposure to foreign invaders and involves a very specific response to pathogens.

7. Fig. 43-2 Pathogens (microorganisms and viruses) Barrier defenses: Skin Mucous membranes Secretions INNATE IMMUNITY • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells • Rapid response Humoral response: Antibodies defend against infection in body fluids. ACQUIRED IMMUNITY • Recognition of traits specific to particular pathogens, using a vast array of receptors Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. • Slower response

8. A Microbe Invading the Body will Encounter the Following Defenses: • 1st Line of Defense: • Barrier defenses: • Skin: physical barrier prevents entry into body: low pH prevents microbial growth • Mucous membranes of respiratory, urinary, and reproductive tracts: traps microbes, low pH of body fluids is hostile to microbes

9. Once past the 1st line: • 2nd Line of Defense: • White blood cells are the key players in a series of increasingly specific attacks against invading microbes. • White blood cells (leukocytes): engulf a pathogen in the body and trap it within a vacuole. The vacuole then fuses with a lysosome to destroy the microbe (phagocytosis). Many cells are involved in this “Generalized Attack”

10. The Generalized Attack • “On-the-ready” cellsof the generalized attack: • Neutrophils: “eat” pathogens and send out distress signals. • Macrophages: arise from monocytes. They are the “big eaters”. They circulate through the lymph system looking for any foreign invader. Some reside permanently in the spleen and lymph nodes, lying in wait for microbes. • Eosinophils: release destructive enzymes to attack large invaders like parasitic worms. Also involved in the inflammatory response. • Basophils: contain histamines that are released during the inflammatory response. • Dendritic cells: arise from monocytes. They stimulate the development of acquired immunity.

11. Notice that all of the immune cells are derived from a multi-potent cell in the bone marrow known as a Hematopoietic stem cell. (Dendritic cells not shown)

12. Proteins, Complement and Inflammation • The remaining components of the 2nd line of defense do not involve white blood cells. • Peptidesand proteinsattack microbes directly or impede their reproduction. • Example: Interferon proteins provide innate defense against virusesand help to activate microphages.

13. Interferon produced by one infected cell can induce nearby cells to produce substances that interfere with viral reproduction. This limits the cell-to-cell spread of viruses

14. About 30 proteins make up the complement system, which causes lysisof invading cells and helps trigger inflammation

15. Inflammatory Responses • Following an injury, mast cells release histamine, which promotes changes in blood vessels; this is part of the inflammatory response • These changes increase local blood supply and allow more phagocytesand antimicrobial proteins to enter tissues. • Pus (a fluid rich in white blood cells, dead microbes, and cell debris) accumulates at the site of inflammation.

16. Fig. 43-8-1 Pathogen Splinter Chemical signals Macrophage Mast cell Capillary Red blood cells Phagocytic cell

17. Fig. 43-8-2 Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Red blood cells Phagocytic cell

18. Fig. 43-8-3 Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Red blood cells Phagocytic cell

19. Symptoms of inflammation include redness, warmth, pain, and swelling. • Inflammation can be either local or systemic (throughout the body) • Feveris a systemic inflammatory response triggered by pyrogensreleased by macrophages, and toxins from pathogens. • Septic shock is a life-threatening condition caused by an overwhelming inflammatory response.

20. Natural Killer Cells • The last component of the innate immune system are the natural killer cells. • All cells in the body (except red blood cells) have a class 1 MHC protein on their surface. (major histocompatibility complex) • Cancerous or infected cells no longer express this protein • Natural killer (NK) cells attack these damaged cells, inhibiting further spread of the virus or cancer.

21. Evading the Innate Immune System • Some pathogens evade the innate immune attack by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis. • Example: Tuberculosis (TB)—these bacterium are resistant to the enzymes inside the lysosomes. Thus, they can hide inside white blood cells without being digested. This disease kills more than a million people per year.

22. Acquired Immunity • The 3rd Line of Defense: • White blood cells called lymphocytes recognize and respond to antigens(foreign molecules). • Lymphocytes that mature in the thymusabove the heart are called T cells, and those that mature in bone marrow are called B cells. • These are the cells involved in the “Specialized Attack”

23. Lymphocytes contribute to immunological memory, an enhanced response to a foreign molecule encountered previously. This is what allows us to develop lifetime immunity to diseases like chickenpox. • The specialized attack usually occurs after being signaled by cells already involved in the generalized attack. • Cytokinesare secreted by macrophages and dendritic cells to recruit and activate lymphocytes.

24. The Specialized Attack • The three stars of this more specialized attack are the B cells, Helper T cells, and Killer T cells (cytotoxic T cells). • B cells mature into plasma cells that generate highly specific antibodiescapable of lasting immunity. • Helper T cells play a central role in coordinating the attack • Killer T cells, once activated, destroy virus-infected cells.

26. B cells and T cells have receptor proteins that can bind to foreign molecules. • Each individual lymphocyte is specialized to recognize a specific type of molecule.

27. Antigen Recognition by Lymphocytes • An antigenis any foreign molecule to which a lymphocyte responds • A single B cell or T cell has about 100,000 identical antigen receptors. • A typical immune response to a virus is seen in the following diagram.

29. From the diagram, we can see that there are two types of specific responses: humoral response (involving B-cells)and cell mediated response (involving cytotoxic T-cells) • The helper T cells can initiate both responses.

30. Antigen Recognition • Recognition of the antigen begins when a macrophage(as seen in the diagram), a B-cell, or a dendritic cell presents the foreign antigen by engulfing the invader, digesting the particle, and then presenting the antigen on the cell’s surface. • MHC molecules (major histocompatibility complex) are used to present the antigens

31. Fig. 43-12 Microbe Antigen- presenting cell Infected cell 1 Antigen associates with MHC molecule Antigen fragment Antigen fragment 1 1 Class I MHC molecule Class II MHC molecule 2 2 T cell receptor T cell receptor 2 T cell recognizes combination (a) Cytotoxic T cell (b) Helper T cell Class II are on macrophages, dendritic cells or B cells. Display to cytotoxic T cells and Helper T cells Class I are found on body cells. Display antigens to cytotoxic T cells

32. Helper T cells then bindto the presented antigen and signalthe production of more T and B cells by releasing cytokines. • This initiates both the humoral and the cell-mediated response.

33. The Humoral Response • In the humoral response, activated B cells give rise to plasma cells, which secrete antibodies or immunoglobulins (Ig) specific to the antigen presented. • Memory B cells also form during the humoral response and persist long after the initial infection ends.

34. Fig. 43-14 Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells

35. The Role of Antibodies • By binding to a pathogen, antibodies can neutralizethe pathogen so that it can no longer infect a host cell. • By binding to a pathogen, antibodies can flagthem so that they are more easily and quickly identified and destroyed by phagocytic cells. • Antibodies, together with proteins of the complement system generate a membrane attack complex and cell lysis.

36. Fig. 43-21 Viral neutralization Opsonization Activation of complement system and pore formation Bacterium Complement proteins Virus Formation of membrane attack complex Flow of water and ions Macrophage Pore Foreign cell

37. The Cell-Mediated Response • In the cell-mediated response, cytotoxic T- cells target intracellular pathogens which B-cells cannot recognize. • Antibodies are not used. • Cytotoxic T-cells and Natural Killer cells detect and destroy altered or infected body cells. • Memory T-cells are also generated.

38. Fig. 43-16 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) Stimulates Gives rise to + Engulfed by Antigen- presenting cell + + + B cell Helper T cell Cytotoxic T cell + + Memory Helper T cells + + + Antigen (2nd exposure) Memory Cytotoxic T cells Active Cytotoxic T cells + Plasma cells Memory B cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells.

39. Primary and Secondary Responses • The first exposure to a specific antigen represents the primary immune response. • During this time, plasma cells are generated, T cells are activated, antibodiesand memory B and T cells are produced. • In the secondary immune response, memory cells facilitate a faster, more efficient response.

40. Fig. 43-15 Primary immune response to antigen A produces antibodies to A. Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. 104 103 Antibody concentration (arbitrary units) Antibodies to A Antibodies to B 102 101 100 0 7 14 21 28 35 42 49 56 Exposure to antigen A Exposure to antigens A and B Time (days)

41. Lymphocyte Development • The acquired immune system has three important properties • Receptor diversity—our cells have an amazing ability to rearrange genes to generate over 1 million different B cells and 10 million different T cells. • A lack of reactivity against host cells—as lymphocytes mature, any that exhibit receptors specific for the body’s own molecules are destroyed by apoptosis. • Immunological memory—there is an increase in cell number and behavior triggered by the binding of antigen that allows the immune system to “remember attackers”

42. Active and Passive Immunity • Active immunity develops naturally in response to an infection. • It can also develop following immunization, also called vaccination. • Passive immunity provides immediate, short-term protection • It is conferred naturally when antibodies cross the placenta from mother to fetus or from mother to infant in breast milk. • It can be conferred artificially by injecting antibodies into a non-immune person

43. Immune Rejection • Cells transferred from one person to another can be attacked by immune defenses • This complicates blood transfusions and organ transplants. • MHC molecules are different from person to person and this difference stimulates most organ rejections. • Successful transplants try to match MHC tissue types and utilize immunosuppressive drugs.

44. Blood Groups • Antigens on red blood cells determine whether a person has blood type A (A antigen), B (B antigen), AB (both A and B antigens), or O (neither antigen) • Antibodies to nonself blood types exist in the body • Transfusion with incompatible blood leads to destruction of the transfused cells • Recipient-donor combinations can be fatal or safe

45. Disruptions ofImmune System Function • Allergies: exaggerated responses to certain antigens called allergens • Anaphylactic shock: an acute, allergic, life-threatening reaction that can occur within seconds of allergen exposure

46. Autoimmune Diseases: the immune system loses tolerance for self and turns against certain molecules of the body. • Examples: Lupus, rheumatoid arthritis, and multiple sclerosis.

47. Acquired Immunodeficiency Syndrome (AIDS): • Caused by human immunodeficiency virus(HIV) • Infects Helper T-cells • Impairs both the humoral and the cell-mediated immune responses. • HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA. • People with AIDS are highly susceptible to opportunistic infections and cancersthat take advantage of an immune system in collapse.

48. Cancer: The frequency of certain cancers increases when the immune response is impaired. • Two suggested explanations are: • Immune system normally suppresses cancerous cells • Increased inflammation increases the risk of cancer.

49. Eliminating Wastes and Obtaining Nutrients • Organisms have a variety of mechanisms for obtaining nutrients and eliminating wastes. • These mechanisms all contribute to maintaining homeostasis in living things.

50. Removal of Nitrogen Waste • All animals must regulate the amount of, and composition of, their body fluids. • Examples: • Sponges: have no excretory organs,: nitrogen waste diffuses out across the body wall. • Flatworms: have a tubular excretory organ that delivers nitrogen waste in the form of ammonia to a special pore in the body surface. • Insects: convert ammonia to uric acidto reduce water loss. • Vertebrates: have a urinary system with two kidneys that filters the blood and adjusts its solute concentration.