BIOLOGY. CONCEPTS & CONNECTIONS Fourth Edition. Neil A. Campbell Jane B. Reece Lawrence G. Mitchell Martha R. Taylor. CHAPTER 24 The Immune System

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1 BIOLOGY CONCEPTS & CONNECTIONS Fourth Edition Neil A. Campbell Jane B. Reece Lawrence G. Mitchell Martha R. Taylor CHAPTER 24 The Immune System Modules From PowerPoint Lectures for Biology: Concepts & Connections

2 The Continuing Problem of HIV Acquired immune deficiency syndrome (AIDS) is epidemic throughout much of the world 14,000 people are infected with the AIDS virus every day HIV is the virus that causes AIDS HIV is transmitted mainly in blood and semen Former L.A. Laker Magic Johnson is one of 900,000 Americans who are HIV-positive

3 Our immune system is a specific defense system It backs up several mechanisms of nonspecific resistance HIV attacks the immune system It eventually destroys the body s ability to fight infection

4 NONSPECIFIC DEFENSES AGAINST INFECTION Nonspecific defenses against infection include the skin and mucous membranes, phagocytic cells, and antimicrobial proteins How does our immune system do its job? Human body has an immune system that protects us from pathogens. Pathogen: anything that can cause a disease Ex: virus (flu, cold, hepatitis, HIV), protozoa, bacteria, parasites (mosquito, tick)

5 First pathogens were called germs not really an appropriate term. In biology germ could mean: germ line cell (makes gametes) or germ layers (embryonic development) Were also called microbes not really appropriate term. Microbe is a microscopic organism, not all microbes cause disease Now use pathogen instead. Job of the immune system is to protect us against pathogens.

6 Our immune system is organized into lines of defense. Other systems work together with the immune system to protect us. There are three lines of defense

7 First line of defense External barriers, some types of body fluids and membranes, may also be referred to as walls and moats. 1 st line of defense keeps EVERYTHING OUT, nonspecific type of defense, does not discriminate. What belongs to the 1 st line of defense? Skin, eyelashes, hair, nails, cilia (nose, trachea), mucus, saliva, stomach acid, sweat, membranes (lining) of respiratory and digestive system

8 If the 1 st line of defense fails (is broken), then the second line of defense is activated Second line of defense: this line of defense is supposed to keep pathogens from reaching the blood stream (circulatory system), also nonspecific, does not discriminate.

9 2 nd line of defense uses macrophages which engulf things by phagocytosis, macrophages roam (patrol) the fluid filled spaces between body cells and eat things that have accumulated there, fluid between body cells is called ICF, intercellular fluid or interstitial fluid. The ICF might contain bacteria, viruses or infected body cells. The macrophage uses pseudopodia to engulf the object and destroy it. Figure 24.1A

10 Infected body cells secrete a chemical called interferon and other proteins called complement proteins that protect their neighbors from also becoming infected. VIRUS 1 Viral nucleic acid 6 Antiviral proteins block viral reproduction 2 Interferon genes turned on New viruses mrna 3 Interferon molecules 5 Interferon stimulates cell to turn on genes for antiviral proteins HOST CELL 1 Makes interferon; is killed by virus 4 HOST CELL 2 Protected against virus by interferon from cell 1 Figure 24.1B

11 The inflammatory response mobilizes nonspecific defense forces Inflammatory response: most often how the second line of defense responds. Usually the area where the 1 st line has failed becomes red and swollen (inflamed). Pin Skin surface Swelling Bacteria Chemical signals White blood cell Phagocytes and fluid move into area Phagocytes 1 Tissue injury; release of 2 Dilation and increased leakiness 3 chemical signals such as of local blood vessels; migration histamine of phagocytes to the area Phagocytes (macrophages and neutrophils) consume bacteria and cell debris; tissue heals Figure 24.2

12 How does the inflammatory response work? Break in the first line and pathogens enter Cells at the area of the break release a chemical help signal (chemokine) called histamine Histamine makes the blood vessels (capillaries) dilate, or get bigger. This sends fluid to the infected area, also lets white blood cells leave the blood and go to the infected area. White blood cells phagocytize any pathogens they find, also make the area warmer, release chemicals called pyrogens that increase the temperature slightly to slow down the bacteria

13 Hopefully the second line is successful. May form pus, which is a white, milky fluid that may contain bacteria and white blood cells (probably both dead). Pus forms when the dead white blood cells and bacteria are not absorbed quickly enough by the body. If the second line of defense fails then the third and final line of defense is activated.

14 SPECIFIC IMMUNITY The immune response counters specific invaders Third line of defense: also known as the Immune Response, both 1 st and 2 nd lines of defense have failed, pathogen is now most likely in the blood traveling everywhere in the body. The job of the immune system is to check the labels/antigens on the surface of all cells/objects in the body, if the cells/objects belong they are left alone, if not the immune system responds

15 The 3 rd line of defense is very specific and uses: Lymphatic system: system of vessels and lymph nodes (filters), this system filters fluid called lymph (came from ICF, which came from blood plasma), removes dead cells and cleans the fluid before returning it to the blood.

16 Adenoid LYMPHATIC VESSEL Right lymphatic duct, entering vein Tonsil Lymph nodes Thoracic duct, entering vein VALVE Blood capillary Tissue cells Interstitial fluid Thoracic duct Thymus Appendix Spleen LYMPHATIC CAPILLARY Masses of lymphocytes and macrophages Bone marrow Lymphatic vessels Figure 23.3

17 Lymph nodes contain lots of: Macrophages: clean up the debris that gets caught in the nodes (filtered) Lymphocytes: specific type of WBC, used by immune response, T & B cells Masses of lymphocytes and macrophages Outer capsule of lymph node Macrophages Lymphocytes Figure 23.3C, D

18 Macrophage Figure 24.1x

19 How does an immune response happen? Our immune system responds to foreign antigens. Antigen: label, membrane protein, often a glycoprotein that labels and identifies things Our immune system only recognizes what does not belong in our body (nonself)

20 Vaccination: triggers an immune response by the immune system, contains a weakened or attenuated form of the virus, may make us feel a little ill, but not usually the same way as if we were infected by a full strength virus. Figure 24.4x

21 Immune system uses specific types of white blood cells called lymphocytes to fight and destroy pathogens, 2 types:

22 Lymphocytes mount a dual defense B lymphocytes (B cells): made in and mature in the bone marrow, make antibodies, fight against pathogens found in body fluid T lymphocytes (T cells): made in bone marrow and mature in the thymus gland, destroy infected body cells. Figure 24.5 BONE MARROW Stem cell Immature lymphocytes B cell HUMORAL IMMUNITY OTHER PARTS OF THE LYMPHATIC SYSTEM Via blood Antigen receptors Via blood Lymph nodes, spleen, and other lymphatic organs THYMUS T cell CELL- MEDIATED IMMUNITY Final maturation of B and T cells in lymphatic organ

23 Antigens have specific regions where antibodies bind to them Antibody protein, or immunoglobulin that attaches to a specific antigen on the surface of the pathogen, each antibody has a specific shape and can only recognize a specific antigen. Antibody A molecules Antigen Antigenbinding sites Antigenic determinants Antibody B molecule Figure 24.6

24 Clonal selection musters defensive forces against specific antigens When foreign antigens enter the body they stimulate the immune system to respond. B and T lymphocytes respond by producing many specific cells that respond only to that foreign antigen. The B and T cells produce many identical cells (clones) that can all respond to the antigen. This is called clonal selection.

25 B lymphocyte Figure 24.5x

26 Antigen molecules Variety of B cells in a lymph node Antigen receptor (antibody on cell surface) Cell growth division, and differentiation Clone of many effector cells secreting antibodies Endoplasmic reticulum Antibody molecules Figure 24.7

27 Each B cell contains a unique receptor on its surface Each of those receptors can respond to a different antigen The receptor on the B cell will match the shape of the antibody made by the B cell The antibodies attach to the antigens and label it for destruction by macrophages. The antibodies may form groups of antigens clumped together called agglutination.

28 B cells are involved in the Humoral Response, when the 3 rd line becomes active (immune response) Humoral body fluid: inside the body, body fluid could be ICF or blood B cells respond to antigens in the body fluid Antigens bind to the B cells with the correct receptor B cells (with attached antigen) are then activated by Helper T Cells.

29 Activated B cells can become: Plasma (effector) cells: make antibodies that can attach to antigen Memory cells: remember the pathogen (antigen), can respond in the future if infected with same pathogen (antigen) again

30 Fig (TE Art) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Invading microbe Interleukin-1 Helper T cell Antigen Macrophage T cell receptor MHC-II protein Memory cell Processed antigen Processed antigen Helper T cell Plasma cell Interleukin-2 Plasma cell B cell B cell receptor (antibody) B cell Antibody Microbe marked for destruction

31 There are 2 types of immune responses Primary immune response: 1 st time the antigen/pathogen infects you, takes the immune system: 7-10 days to find the pathogen/antigen 7-10 days to get rid of pathogen/antigen Secondary immune response: takes 1-3 days to find and destroy the pathogen/antigen. This quick response is because of the memory cells left behind. Can immediately become plasma cells in the future.

32 initial immune response results in a type of memory Figure 24.8A

33 When memory cells are activated by subsequent exposure to an antigen, they mount a more rapid and massive secondary immune response Unstimulated lymphocyte First exposure to antigen FIRST CLONE Memory cells Second exposure to antigen Effector cells SECOND CLONE More memory cells New effector cells Figure 24.8B

34 Overview: B cells are the main warriors of humoral immunity Triggered by a specific antigen, a B cell differentiates into an effector cell The effector cell is called a plasma cell The plasma cell secretes antibodies

35 PRIMARY RESPONSE (initial encounter with antigen) Cell growth, division, and differentiation Antigen Antigen receptor on a B cell Antigen binding to a B cell Clone of cells Plasma cell Antibody molecules Memory B cell SECONDARY RESPONSE (can be years later) Cell growth, division, and further differentiation Later exposure to same antigen Larger clone of cells Plasma cell Antibody molecules Memory B cell Figure 24.9

36 Antibodies are the weapons of humoral immunity An antibody molecule Figure 24.10A

37 An antibody molecule has antigen-binding sites that attach to the specific antigen. Antigen-binding sites Light chain Heavy chain Figure 24.10B

38 Antibodies mark antigens for elimination Antibodies may block harmful antigens on microbes clump bacteria or viruses together precipitate dissolved antigens activate complement proteins

39 Binding of antibodies to antigens inactivates antigens by Neutralization (blocks viral binding sites; coats bacterial toxins) Virus Agglutination of microbes Bacteria Precipitation of dissolved antigens Activation of complement Complement molecule Bacterium Antigen molecules Foreign cell Hole Enhances Phagocytosis Leads to Cell lysis Macrophage Figure 24.11

40 Connection: Monoclonal antibodies are powerful tools in the lab and clinic Antibodies can be used for specific types of testing, also use mice to produce the antibodies (monoclonal antibodies) Antigen injected into mouse B cells (from spleen) Tumor cells grown in culture Tumor cells Cells fused to generate hybrid cells Antibody Single hybrid cell grown in culture Figure 24.12A Hybrid cell culture, producing monoclonal antibodies

41 These cells are useful in medical diagnosis Example: home pregnancy tests They are also useful in the treatment of certain cancers Testing for blood types Figure 24.12B

42 Blood types Blood type Antigen present Antibodies made A A antigen Anti B antibodies B B antigen Anti A antibodies AB A & B antigens No blood type antibodies O No blood type antigens Anti A & Anti B antibodies Can get from Can give to A, O A, AB B, O B, AB Universal Recipient O AB Universal donor

43 Human RBCs have an extra antigen on their surface called the Rh Factor, if you have it then you have a + blood type, if you don t have it they you have a - blood type.

44 T cells mount the cell-mediated defense and aid humoral immunity T lymphocytes (T cells) are responsible for destroying infected body cells Helper T cells and cytotoxic T cells are the main effectors of cell-mediated immunity Helper T cells also stimulate the humoral responses Helper T cells are the on switch for the immune response

45 Cell-mediated immunity: responsible for finding and destroying infected body cells An antigenpresenting cell (APC) first displays a foreign antigen and one of the body s own self proteins to a helper T cell Activates a helper T cell Microbe 2 1 APC 3 Macrophage (will become APC) Antigen from microbe (nonself molecule) Self protein Self protein displaying antigen 4 Helper T cell T cell receptor Binding site for self protein Binding site for antigen Figure 24.13A

46 Helper T cell turns activates: B cells turns them into plasma cells and memory cells T cells turns them into cytotoxic T cells that destroy any body cell that displays a foreign antigen Self protein displaying an antigen T cell receptor Interleukin-2 stimulates cell division Cytotoxic T cell Cell-mediated immunity (attack on infected cells) APC Helper T cell Interleukin-2 activates other T cells and B cells Interleukin-1 activates helper T cell B cell Humoral immunity (secretion of antibodies by plasma cells) Figure 24.13B

47 Cytotoxic T cells bind to infected body cells and destroy them by making them lyse. Macrophages then clean up the debris 1 Cytotoxic T cell binds 2 Perforin makes holes 3 to infected cell in infected cell s membrane Infected cell is destroyed INFECTED CELL Foreign antigen Hole forming Perforin molecule Cytotoxic T cell Figure 24.13C

48 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. MHC-II protein Fig (TE Art) Processed viral antigen Virus Interleukin-1 Helper T cell Macrophage MHC-I protein Antigenpresenting cell T cell receptor that fits the particular antigen Viral antigen Cytotoxic T cell Proliferation Interleukin-2 Infected cell destroyed by cytotoxic T cell

49 Cytotoxic T cells may help prevent cancer Cytotoxic T cells may attack cancer cells The surface molecules of some cancer cells are altered by the disease Killer T cells can only attack and destroy body cells if they display foreign (nonself) antigens Figure 24.14

50 The immune system depends on our molecular fingerprints The immune system normally reacts only against nonself substances It generally rejects transplanted organs The cells of transplanted organs lack the recipient s unique fingerprint of self proteins

51 DISORDERS OF THE IMMUNE SYSTEM Connection: Malfunction or failure of the immune system causes disease Autoimmune diseases The system turns against the body s own molecules Immunodeficiency diseases Immune components are lacking, and infections recur Physical and emotional stress may weaken the immune system

52 Connection: Allergies are overreactions to certain environmental antigens Allergies: hypersensitive to something in the environment called an allergen which causes the release of LOTS of histamine. B cell (plasma cell) Histamine Antigenic determinant Mast cell Allergen (pollen grain) B cells make antibodies Antibodies attach to mast cell Allergen binds to antibodies on mast cell Histamine is released, causing allergy symptoms SENSITIZATION: Initial exposure to allergen LATER EXPOSURE TO SAME ALLERGEN Figure 24.17

53 Allergy-causing spores Figure 24.17x

54 Histamine can cause itching (hives) sneezing, runny nose, runny eyes. Extreme allergic reactions may cause anaphylaxis, also known as anaphylactic shock. Caused by a TREMENDOUS release of histamine, swelling in throat that blocks airway, may be able to stop with an epipen that contains epinephrine (adrenaline). May be caused by nuts, bee and/or wasp stings MSG

55 Arthritis X-ray Figure 24.16x

56 Connection: AIDS leaves the body defenseless AIDS: acquired immune deficiency syndrome, caused by a virus (HIV) that attacks Helper T cells and cripples the immune system So far, AIDS is incurable Drugs and vaccines offer hope for the future Lots of different strains (over 20) Virus hides/incubates and is difficult to find Currently treated with antiviral drugs Practicing safer sex could save many lives

57 HIV on a lymphocyte Contracted through body fluid Exchanges such as: Breast milk Vaginal secretions Semen Blood Figure 24.18x1

58 HIV budding collage Figure 24.18x2

59 AIDS posters Figure 24.18x3

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