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					Chapter 43: The Immune System


Our students consider this chapter to be a particularly challenging and important one.
Expect to work your way slowly through the first three concepts. Take particular care
with Concepts 43.2 and 43.3. It is rewarding, however, in Concept 43.4 to put your new
knowledge to work and truly understand the devastation caused by the destruction of
helper T cells by HIV.

Overview: The immune responses of animals can be divided into innate immunity and
acquired immunity. As an overview, complete this figure indicating the divisions of
both innate and acquired immunity.




Concept 43.1 In innate immunity, recognition and response rely on shared traits of
pathogens

1.   We first encountered phagocytosis in Concept 7.5, but it plays an important role
     in the immune systems of both invertebrates and vertebrates. Review the
     process by briefly explaining the six steps to ingestion and destruction of a
     microbe by a phagocytic cell.
•Barriers help an animal to defend itself from the many dangerous pathogens it may
encounter •The immune system recognizes foreign bodies and responds with the
production of immune cells and proteins •Two major kinds of defense have evolved: innate
immunity and acquired immunity

•Innate immunity is present before any exposure to pathogens and is effective from the
time of birth •It involves nonspecific responses to pathogens •Innate immunity consists of
external barriers plus internal cellular and chemical defenses

•Acquired immunity, or adaptive immunity, develops after exposure to agents such as
microbes, toxins, or other foreign substances •It involves a very specific response to
pathogens

•Both invertebrates and vertebrates depend on innate immunity to fight infection
•Vertebrates also develop acquired immune defenses •In insects, an exoskeleton made of
chitin forms the first barrier to pathogens

•The digestive system is protected by low pH and lysozyme, an enzyme that digests
microbial cell walls •Hemocytes circulate within hemolymph and carry out phagocytosis,
the ingestion and digestion of foreign substances including bacteria

Phagocytosis:• A cell engulfs a particle in a vacuole •The vacuole fuses with a lysosome to
digest the particle
1. Internal defenses;
2. Ingestion;
3. Anti-microbial proteins, enzymes;
4. Response;
5. Natural killer cells; and
6. Digestion.
 2.   Explain the role of the Toll receptor in producing antimicrobial peptides.

•White blood cells (leukocytes) engulf pathogens in the body •Groups of pathogens are
recognized by TLR, Toll-like receptors •A white blood cell engulfs a microbe, then fuses
with a lysosome to destroy the microbe •There are different types of phagocytic cells:
1. Neutrophils engulf and destroy microbes
2. Macrophages are part of the lymphatic system and are found throughout the body
3. Eosinophils discharge destructive enzymes
4. Dendritic cells stimulate development of acquired immunity
•Peptides and proteins function in innate defense by attacking microbes directly or
impeding their reproduction
•Interferon proteins provide innate defense against viruses and help activate
macrophages
•About 30 proteins make up the complement system, which causes lysis of invading cells
and helps trigger inflammation
 3.   List the three innate defenses vertebrates share with invertebrates and the two
      defenses unique to vertebrates.
 Three innate defenses vertebrates share with invertebrates:
 1. Barrier defenses, an outer covering of skin, shell, or chemical secretions;
 2. Innate immunity; and
 3. Acquired immunity.
 Two defenses unique to vertebrates:
 Acquired immunity:
 1. Humoral response; and
 2. Cell-mediated response.

   Inflammation can be either local or systemic (throughout the body);
   Fever is a systemic inflammatory response triggered by pyrogens released by
    macrophages, and toxins from pathogens; and
   Septic shock is a life-threatening condition caused by an overwhelming
    inflammatory response

 4.   In the chart below, list five examples of barrier defenses and how they work.

Barrier Defense                            How the Barrier Repels Pathogens
Skin                                       •The low pH of skin and the digestive system
                                           prevents growth of microbes; and
                                           •In insects, an exoskeleton made of chitin
                                           forms the first barrier to pathogens
Digestive system                           •The low pH of skin and the digestive system
                                           prevents growth of microbes; and
                                           •The digestive system is protected by low pH
                                           and lysozyme, an enzyme that digests
                                           microbial cell walls
Secretions (saliva and tears)              •Many body fluids are hostile to microbes
Reproductive,Respiratory,and Urinary       •Mucus traps and allows for the removal of
mucous membranes                           microbes
Groups of pathogens are recognized by      •All cells in the body (except red blood cells)
                                           have a class 1 MHC protein on their surface
TLR, Toll-like receptors                   •Cancerous or infected cells no longer
                                           express this protein; natural killer (NK) cells
                                           attack these damaged cells
  5.   Explain how Toll-like receptors are used in cellular innate defenses, using TLR3
       and TLR4 as examples.
•All cells in the body (except red blood cells) have a class 1 MHC protein on their surface
•Cancerous or infected cells no longer express this protein; natural killer (NK) cells
attack these damaged cells.
See diagram above for TLR3 and TLR 4

  6.   In the chart below, explain the role of the four phagocytic cells.

Phagocytic Cell Type                           Role in Innate Defense
•A white blood cell engulfs a microbe,
then fuses with a lysosome to destroy
the microbe
Neutrophils                                    –Neutrophils engulf and destroy
                                               microbes
                                               enzymes
Macrophages                                    –Macrophages are part of the
                                               lymphatic system and are found
                                               throughout the body
Eosinophils                                    –Eosinophils discharge destructive
Dendritic cells                                –Dendritic cells stimulate
                                               development of acquired immunity
7.   In the figure below, trace the flow of lymph in four stages. For each stage, explain
     the role of the lymphatic system in innate defense.




8.   Explain the role of the following two antimicrobial compounds.

     Interferon: •Interferon proteins provide innate defense against viruses and
     help activate macrophages
     Complement: •About 30 proteins make up the complement system, which causes
     lysis of invading cells and helps trigger inflammation

9. Use the figure below to explain the three steps of an inflammatory response.
1. •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 phagocytes and
     antimicrobial proteins to enter tissues
2. •Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at
     the site of inflammation
     •Inflammation can be either local or systemic (throughout the body)
     •Fever is a systemic inflammatory response triggered by pyrogens released by
     macrophages, and toxins from pathogens
     •Septic shock is a life-threatening condition caused by an overwhelming
     inflammatory response; and
3. Phagocytosis.
10. What role do natural killer cells play in the immune system?
•All cells in the body (except red blood cells) have a class 1 MHC protein on their surface
•Cancerous or infected cells no longer express this protein; natural killer (NK) cells
attack these damaged cells


11.  It might seem like pathogens have little hope of mounting an infection, but do not
     forget that pathogens are constantly evolving ways to circumvent our immune
     system. As examples, how do the pathogens that cause pneumonia and tuberculosis
     avoid our immune responses?
•Some pathogens avoid destruction by modifying their surface to prevent recognition or
     by resisting breakdown following phagocytosis
•Pneumonia and Tuberculosis (TB) are two such diseases. The outer covering surrounding
     Pneumonia hides its polysaccharide coat. It cannot be defensively recognized. TB
     kills more than a million people a year, because it cannot be broken down by
     phagocytosis..

Concept 43.2 In acquired immunity, lymphocyte receptors provide pathogen-specific
recognition

12. From the first four paragraphs of this concept, summarize where T cells and B
     cells develop, and give an overview of their functions. (Note that they are a type
     of white blood cell known as a lymphocyte.)
•White blood cells called lymphocytes recognize and respond to antigens, foreign
     molecules
•Lymphocytes that mature in the thymus above the heart are called T cells, and those
     maturing in bone marrow are called B cells
•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
•An antigen is any foreign molecule to which a lymphocyte responds
•A single B cell or T cell has about 100,000 identical antigen receptors




13. What is immunological memory, and why is it important?
•Lymphocytes contribute to immunological memory, an enhanced response to a foreign
molecule encountered previously

14. Explain how cytokines help coordinate the innate and acquired immune responses.
•Cytokines are secreted by macrophages and dendritic cells to recruit and activate
lymphocytes

15. The following brief questions will serve as a primer for immune system

    recognition.

a. What is an antigen? •An antigen is any foreign molecule to which a

    lymphocyte responds

b. What is the relationship between an antigen receptor, an antibody, and a

immunoglobin?

•A single B cell or T cell has about 100,000 identical antigen receptors •All

    antigen receptors on a single lymphocyte recognize the same

    epitope, or antigenic determinant, on an antigen •B cells give rise to

    plasma cells, which secrete proteins called antibodies or
    immunoglobulin

c. How is an epitope related to an antigen? (Look at Figure 43.10.) Epitopes

    are antigenic determinants.
16. In the figure of a B cell below, label the antigen-binding sites, light and heavy
    chains, variable and constant regions, transmembrane region, and disulfide
    bridges.




17. What forms the specific antigen-binding site? (Be sure to note that each B cell
    produces only one type of antigen receptor. For any one cell, all antigen receptors
    or antibodies produced are identical.) Epitopes

18. In the figure of a T cell below, label the antigen-binding site, alpha and beta chain,
    variable and constant regions, transmembrane region, and disulfide bridge.
19. T cells also display only one type of antigen receptor on the surface of the cell.
     Compare and contrast a T cell with a B cell.
•B cell receptors bind to specific, intact antigens
•The B cell receptor consists of two identical heavy chains and two identical light
     chains
•The tips of the chains form a constant (C) region, and each chain contains a variable
     (V) region, so named because its amino acid sequence varies extensively from
     one B cell to another
•Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors
     but lack transmembrane regions that anchor receptors in the plasma membrane
•Each T cell receptor consists of two different polypeptide chains
•The tips of the chain form a variable (V) region; the rest is a constant (C) region
•T cells can bind to an antigen that is free or on the surface of a pathogen
•T cells bind to antigen fragments presented on a host cell
•These antigen fragments are bound to cell-surface proteins called MHC molecules
•MHC molecules are so named because they are encoded by a family of genes called
     the major histocompatibility complex
 20. B-cell receptors recognize and bind to antigens whether they are free antigens
     (like a secreted toxin) or on the surface of a pathogen. Explain the role of the
     major histocompatibility complex (MHC) to T-cell receptor binding.
 •In infected cells, MHC molecules bind and transport antigen fragments to the cell
      surface, a process called antigen presentation
 •A nearby T cell can then detect the antigen fragment displayed on the cell’s surface
 •Depending on their source, peptide antigens are handled by different classes of MHC
     molecules

 21. Explain how an infected host cell uses the MHC molecule to display an antigen.
 •In infected cells, MHC molecules bind and transport antigen fragments to the cell
 surface, a process called antigen presentation

 22. Explain the differences between Class I and Class II MHC molecules, noting
     type of cells that display the molecule, types of diseases involved with each
     molecule, and what type of T cell recognizes the MHC molecules.

MHC     Displayed by?                   Diseases associated with          Recognized by
Class                                   (cancer, viral or bacterial)?     which T
                                                                         cells?
Class •They display peptide             •Class I MHC molecules           To cytotoxic T
I MHC antigens                          are found on almost all          cells
                                        nucleated cells of the body
Class   •Dendritic cells,               •Class II MHC molecules          To cytotoxic T
II      macrophages, and B cells        are located mainly on            cells and helper
MHC     are antigen-presenting          dendritic cells,                 T cells
        cells that display antigens     macrophages, and B cells

 23. Using Figure 43.12 as a guide, label completely the figure below.
24. List three properties of the acquired immune system.
•The acquired immune system has three important properties:
   1. Receptor diversity;
   2. A lack of reactivity against host cells; and
   3. Immunological memory
25. One of the early problems in immunology was trying to understand how an organism
    with a limited number of genes (for humans, about 20,500) could produce a million
    different B-cell protein receptors and 10 million different T-cell protein
    receptors! The answer resulted in a Nobel Prize and a startling exception to the
    notion that all cells have exactly the same DNA. Use the figure below to label and
    explain the four steps involved in producing genetically unique B-cell receptors.




26. Explain how the body develops self-tolerance in the immune system.
•Antigen receptors are generated by random rearrangement of DNA
•As lymphocytes mature in bone marrow or the thymus, they are tested for self-
reactivity
•Lymphocytes with receptors specific for the body’s own molecules are destroyed by
apoptosis, or rendered nonfunctional

27. Define the following terms.
    In the body there are few lymphocytes with antigen receptors for any
    particular epitope
    •The binding of a mature lymphocyte to an antigen induces the lymphocyte to
    divide rapidly
    Effector cells••Two types of clones are produced: short-lived activated
    effector cells and long-lived memory cells
    Memory cells: •Two types of clones are produced: short-lived activated
    effector cells and long-lived memory cells
    Clonal selection: •This proliferation of lymphocytes is called clonal selection

    28. The blue in the Figure 43.14 explains the four events in clonal selection.




29. Graphs similar to the one below have been seen on several AP Biology exams. It
    depicts the primary and secondary immune response. The first arrow shows
    exposure to antigen A. The second arrow shows exposure to antigen A again, and
    also antigen B. Label this graph and then use it to explain the difference between
    a primary and secondary immune response.
Concept 43.3 Acquired immunity defends against infection of body cells and fluids

30. Explain fully the function of the two divisions of acquired immunity.

     Humoral immune response: •Acquired immunity has two branches: the humoral
     immune response and the cell-mediated immune response
     •Humoral immune response involves activation and clonal selection of B cells,
     resulting in production of secreted antibodies
     Cell-mediated immune response: •Cell-mediated immune response involves
     activation and clonal selection of cytotoxic T cells
     •Helper T cells aid both responses

31. Helper T cells play a critical role in activation of both T cells and B cells. In full
    detail, label and explain the three steps involved using Figure 43.17. This is an
    important step!
32. Explain the role of dendritic cells and macrophages in starting a primary and
     secondary immune response.
•The first exposure to a specific antigen represents the primary immune response
•During this time, effector B cells called plasma cells are generated, and T cells are
     activated to their effector forms
•In the secondary immune response, memory cells facilitate a faster, more efficient
     response

33. •Cytotoxic T cells are the effector cells in cell-mediated immunity.

34. What must occur for a cytotoxic T cell to become activated?

•Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction
between a target cell and a cytotoxic T cell
•Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and
makes it an active killer
•The activated cytotoxic T cell secretes proteins that destroy the infected target cell

35. Completely label the diagram below. Then carefully explain (944 in Campbell’s)
    the three primary steps that occur as a cytotoxic T cell destroys a target cell.
36. How is B-cell antigen presentation unique?
•The humoral response is characterized by secretion of antibodies by B cells
•Activation of B cells is aided by cytokines and antigen binding to helper T cells
•Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells
of humoral immunity

37. Completely label the diagram below. Then carefully explain (944 in Campbell’s) the
three primary steps that occur in B cell activation.
38. What is the difference between plasma cells and memory cells produced from the
activation of B cells?
Plasma cells: Secrete antigens; and
Memory cells: keep the antigens of the parent

39. Explain how monoclonal antibodies are used in home pregnancy kits.
•The five major classes of antibodies, or immunoglobulins, differ in distribution and
function
•Monoclonal antibodies are prepared from a single clone of B cells grown in culture


40. Why is the antibody response to a microbial infection polyclonal?
•Polyclonal antibodies are the products of many different clones of B cells following
exposure to a microbial antigen

41. Explain these three ways antibodies can dispose of antigens.
    Viral neutralization: •Neutralization occurs when a pathogen can no longer infect a
    host because it is bound to an antibody
    Opsonization: •Opsonization occurs when antibodies bound to antigens increase
    phagocytosis
    Activation of complement:•Antibodies together with proteins of the complement
    system generate a membrane attack complex and cell lysis

42. Using examples, explain the difference between active and passive immunity.
•Active immunity develops naturally in response to an infection
•It can also develop following immunization, also called vaccination
•In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an
immune response to an immunological memory
•Passive immunity provides immediate, short-term protection
•It is conferred naturally when IgG crosses the placenta from mother to fetus or when
IgA passes from mother to infant in breast milk
•It can be conferred artificially by injecting antibodies into a nonimmune person


43. Describe how immunizations can serve as an example of active immunity.
•Active immunity develops naturally in response to an infection
•It can also develop following immunization, also called vaccination
•In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an
immune response to an immunological memory


44. Why is immune rejection an example of a healthy immune system?

•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


45. Briefly describe the following features of immune

    rejection.

a. Explain how antibodies against blood types are

    present. •Antibodies to nonself blood types exist in

    the body

b. What is the role of MHC in tissue and organ

    transplants?

•MHC molecules are different among genetically

    nonidentical individuals

•Differences in MHC molecules stimulate rejection of

    tissue grafts and organ transplants

•Chances of successful transplantation increase if donor

    and recipient MHC tissue types are well matched
c. Why are bone marrow transplants medically unique?

•Transfusion with incompatible blood leads to

    destruction of the transfused cells

•Immunosuppressive drugs facilitate transplantation

•Lymphocytes in bone marrow transplants may cause the

    donor tissue to reject the recipient

Concept 43.4 Disruptions in immune system function can elicit or exacerbate disease

46. What are allergies?

•Allergies are exaggerated (hypersensitive) responses to antigens called allergens

 47. Label Figure 43.23 and then use it to explain (•In localized allergies such as hay
fever, IgE antibodies produced after first exposure to an allergen attach to receptors
on mast cells) a typical allergic response.

•The next time the allergen enters the body, it binds to mast cell–associated IgE
molecules
•Mast cells release histamine and other mediators that cause vascular changes leading to
typical allergy symptoms
 48. Explain what happens if a person experiences anaphylactic shock.

 An acute allergic response can lead to anaphylactic shock, a life-threatening reaction
 that can occur within seconds of allergen

 49. Autoimmune diseases occur when the immune system turns against particular
     molecules of the body. Describe the cause and symptoms of the following
     autoimmune diseases.

 •In individuals with autoimmune diseases, the immune system loses tolerance for self
      and turns against certain molecules of the body
 •Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis,
      insulin-dependent diabetes mellitus, and multiple sclerosis:
 •Inborn immunodeficiency results from hereditary or developmental defects that
      prevent proper functioning of innate, humoral, and/or cell-mediated defenses
 •Acquired immunodeficiency results from exposure to chemical and biological agents
 (See online for the following)

 Lupus: A painful, complex autoimmune disease, Lupus affects millions of
 people across the country and world, but 9 out of 10 are women. Lupus
 is a disease that can affect many parts of the body. One person with
 lupus may have swollen knees or other joints and unexplained fever.
 Another person may be tired all the time or have kidney trouble.
 Someone else may have skin rashes or lose the hair on their scalp.
 Lupus can also involve the lungs, heart and/or the brain. Usually, one
 person doesn't have all the possible symptoms.


Rheumatoid arthritis: A chronic, systemic inflammatory disorder that may affect many
tissues and organs, but principally attacks flexible (synovial) joints. The process
produces an inflammatory response of the capsule around the joints (synovium)
secondary to swelling (hyperplasia) of synovial cells, excess synovial fluid, and the
development of fibrous tissue (pannus) in the synovium. The pathology of the disease
process often leads to the destruction of articular cartilage and ankylosis of the joints.
Rheumatoid arthritis can also produce diffuse inflammation in the lungs, membrane
around the heart (pericardium), the membranes of the lung (pleura), and white of the
eye (sclera), and also nodular lesions, most common in subcutaneous tissue. Although
the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in both
its chronicity and progression, and RA is considered a systemic autoimmune disease.


Type 1 diabetes mellitus: (Type 1 diabetes, T1DM, IDDM, or, formerly, juvenile
diabetes) is a form of diabetes mellitus that results from autoimmune destruction of
insulin-producing beta cells of the pancreas.[2] The subsequent lack of insulin leads to
increased blood and urine glucose. The classical symptoms are polyuria (frequent
urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight
loss.[3]
Multiple sclerosis: (abbreviated to MS, known as disseminated sclerosis or
encephalomyelitis disseminata) is an inflammatory disease in which the fatty myelin
sheaths around the axons of the brain and spinal cord are damaged, leading to
demyelination and scarring as well as a broad spectrum of signs and symptoms.[1]
Disease onset usually occurs in young adults, and it is more common in women.[1] It has
a prevalence that ranges between 2 and 150 per 100,000.[2] MS was first described in
1868 by Jean-Martin Charcot.[3]


 50. Explain how immunodeficiency diseases are different from autoimmune diseases.
       Immunodeficiency diseases
      •Inborn immunodeficiency results from hereditary or developmental defects that
      prevent proper functioning of innate, humoral, and/or cell-mediated defenses
      •Acquired immunodeficiency results from exposure to chemical and biological agents
      •Acquired immunodeficiency syndrome (AIDS) is caused by a virus
      Autoimmune diseases
      Our bodies have an immune system, which is a complex network of special
      cells and organs that defends the body from germs and other foreign
      invaders. At the core of the immune system is the ability to tell the difference
      between self and nonself: what's you and what's foreign. A flaw can make the
      body unable to tell the difference between self and nonself. When this
      happens, the body makes autoantibodies (AW-toh-AN-teye-bah-deez) that
      attack normal cells by mistake. At the same time special cells called
      regulatory T cells fail to do their job of keeping the immune system in line.
    The result is a misguided attack on your own body. This causes the damage
    we know as autoimmune disease. The body parts that are affected depend on
    the type of autoimmune disease. There are more than 80 known types.

51. Just as our immune system has evolved to thwart pathogens, pathogens have
    evolved to thwart our immune system. Describe the following pathogen
    strategies.
      Antigenic variation:
     •Through antigenic variation, some pathogens are able to change epitope expression
     and prevent recognition

     •The human influenza virus mutates rapidly, and new flu vaccines must be made
     each year

     •Human viruses occasionally exchange genes with the viruses of domesticated
     animals

     •This poses a danger as human immune
      Latency:

     •Some viruses may remain in a host in an inactive state called latency

     •Herpes simplex viruses can be present in a human host without causing symptoms

      Attack on the immune system: HIV:

     •Human immunodeficiency virus (HIV) infects helper T cells

     •The loss of helper T cells impairs both the humoral and cell-mediated immune
     responses and leads to AIDS

     •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 cancers
     that take advantage of an immune system in collapse

     •The spread of HIV is a worldwide problem

     •The best approach for slowing this spread is education about practices that
     transmit the virus


52. Explain how the high mutation rate in surface antigen genes in HIV has hampered
    development of a vaccine for AIDS. (You might take note that HIV—human
    immunodeficiency virus—is the virus that causes the disease AIDS—acquired
    immunodeficiency syndrome. These acronyms are often used incorrectly.)
Regular surface change creates pharmaceutical difficulty to create the appropriate
    suppressant before change has, once again, occurred
•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 cancers that
take advantage of an immune system in collapse

Testing Your Knowledge: Self-Quiz Answers
Now you should be ready to test your knowledge. Place your answers here:

1.         2.        3.         4.          5.         6.

				
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