TOPIC 6 Immune System Resistance to Disease

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TOPIC 6 Immune SystemResistance to Disease
Biology 221 Anatomy Physiology II
Chapter 21 pp. 778-787
E. Lathrop-Davis / E. Gorski / S. Kabrhel
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Overview Functions

• Resistance is the result of a functional system
  rather than anatomical system. It includes parts
  of several systems.
• The functions of resistance include
• protecting the body against pathogens, such as
• microbes, which are prokaryotic and
• parasites, which are eukaryotic
• eliminating tissues and cells that have been
  damaged, infected by viruses or killed
• distinguishing between self and non-self antigens
  (mainly proteins) and removing the things that
  dont belong.

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Overview

• Two types of resistance work together against
  disease
• Innate resistance is also called nonspecific
  resistance.
• Inate resistance represents a general defense
  against wide range of pathogens.
• A rapid response occurs because these mechanisms
  are in place at birth.
• The mechanisms of inate resistance include
  intact membranes, phagocytes, antimicrobial
  chemicals, and inflammation.

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Overview

• Two types of resistance work together against
  disease
• Adaptive resistance is also called specific
  resistance.
• Adaptive resistance offers specific responses to
  specific pathogens.
• The response is slower than innate system because
  it must be acquired as person is exposed.
• Mechanisms of adaptive resistance include T cell
  lymphocytes and antibodies, which are produced by
  plasma cells (derived from B cell lymphocytes).

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Nonspecific Resistance - Overview

• The three main mechanisms of nonspecific
  resistance are
• physical barriers
• cellular barriers and
• fever.

See Table 22.2, p. 801
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Physical Barriers - Overview

• Physical barriers to pathogens include
• intact skin
• intact mucous membranes and
• mucus.

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Physical Barriers Intact Skin

• Skin consists of keratinized stratified squamous
  epithelium. Multiple layers of closely packed
  cells prevent entry of most pathogens.
• The skin is relatively dry, which inhibits growth
  of some pathogens.
• Sebaceous gland secrete antibacterial chemicals,
  such as lysozyme and certain fatty acids.
• The normal bacterial flora compete with
  pathogens, thus inhibiting growth of the
  pathogens.
• The skin is slightly acidic and slightly salty
  (from sweat), both of which inhibit certain types
  of bacteria.

Fig. 5.3, p. 152
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Physical Barriers Mucous Membranes

• Mucous membranes line body cavities open to
  outside, including the digestive, urinary,
  reproductive, and respiratory tracts.
• Like the skin, the closely packed cells of the
  nonkeratinized stratified squamous epithelium
  that lines openings where abrasion is most likely
  to occur (mouth, pharynx, esophagus, vagina,
  parts of rectum and urethra) provide an intact
  barrier to entrance of pathogens.

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Physical Barriers Mucous Membranes

• The pH in some areas is low varying from slightly
  acidic (mouth, vagina, urethra) to highly acidic
  (stomach). This prevents the growth of many types
  of pathogens.
• Antimicrobial proteins, such as lysozyme in
  saliva and lacrimal fluid, also inhibits growth.
• Normal bacterial flora compete with pathogens.

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Physical Barriers Mucus

• Mucus is produce by glands (such as goblet
  cells). Hairs help trap particles caught in the
  mucus.
• Cilia move particle-laden mucus. The ciliary
  escalator present in the trachea and bronchi
  moves mucus and particles up to throat where the
  particle-laden mucus can be swallowed or spit out.

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Cellular Responses Inflammation

• The functions of inflammation include
• preventing the spread of pathogens or damaging
  chemicals to other tissues
• removing dead cells and pathogens from tissues
  and
• preparing tissues for repair by increasing blood
  supply and removing debris.
• The four cardinal signs of inflammation are
• redness, heat, swelling, and pain.

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Main Inflammatory Chemicals

• Important inflammatory chemicals include
  histamine, kinins, prostaglandins, complement and
  cytokines.
• Histamine is secreted by basophils and mast
  cells.
• Histamine causes vasodilation and increased
  capillary permeability. This increases blood flow
  and contributes to the redness, heat and swelling
  associated with inflammation.
• Antihistamines are used to reduce the effects of
  histamines.

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Main Inflammatory Chemicals

• Kinins are proteins (e.g., bradykinin) that cause
  vasodilation and increased capillary
  permeability.
• Kinins induce chemotaxis, that is, they draw WBCs
  to the affected area.
• Kinins stimulate pain receptors.
• Prostaglandins are fatty acid molecules (in the
  lipid class of macromolecules) that sensitize
  blood vessels to other inflammatory chemicals and
  thus enhance inflammation.
• Like kinins, prostaglandins stimulate pain
  receptors.

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Other Inflammatory Chemicals

• Complement is a complex of proteins that has
  several functions including enhancing
  inflammation. (Covered shortly)
• Cytokines are proteins released by various WBCs
  and tissue cells. Many enhance various aspects of
  inflammation

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Process of Inflammation

• The process of inflammation begins with release
  of inflammatory chemicals.
• These chemical induce the vascular changes
  associated with inflammation, including
  vasodilation and increased capillary
  permeability.
• These changes result in hyperemia, or increased
  blood flow to the area, is a result of
  vasodilation.
• Exudate formation occurs due to increased
  capillary permeability. This fluid lost to the
  tissue contains plasma proteins such as clotting
  proteins and antibodies. It also causes the
  swelling associated with inflammation.

See Fig. 22.2, p. 797
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Process of Inflammation

• Increased blood flow increases the local
  temperature leading to increased cellular
  metabolism. This increases the effectiveness of
  WBCs and tissue repair. It also causes the area
  to become hot.
• Increased blood flow also brings increased oxygen
  and nutrients to tissue and cellular defenders.
• Leakage of clotting proteins walls off pathogens
  to limit spread and forms a network of fibers for
  tissue repair.

See Fig. 22.2, p. 797
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Process of Inflammation (cont)

• Phagocyte mobilization includes several steps
• Chemicals induce leukocytosis, an increase in the
  number of leukocytes (especially neutrophils).
• Chemotaxis due to chemicals released during
  inflammation draws leukocytes to injured area.
• Endothelial cells in the affect area produce
  membrane proteins that promote margination (also
  called pavementing) in which leukocytes adhere
  to capillary wall.

See Fig. 22.3, p. 798
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Process of Inflammation (cont)

• Diapedesis occurs as neutrophils squeeze
  themselves through the capillary wall.
• Neutrophils phagocytize pathogens and debris.
• Monocytes reach the affected area more slowly
  than neutrophils.
• Pus formation occurs with severe infection as
  WBCs, dead and dying tissue cells, and pathogens
  accumulate.

See Fig. 22.3, p. 798
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Phagocytes in Inflammation

• Neutrophils respond most quickly (usually within
  a few hours) and are thus associated with acute,
  local infections.
• Monocytes respond more slowly (usually within
  8-12 hours) and are thus associated with chronic
  infections.
• Monocytes enter affected tissues and become
  macrophages with more lysosomes needed for
  phagocytosis.

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Cellular Responses Major Phagocytes

• Macrophages are derived from monocytes that have
  moved into and reside in tissues. Macrophages can
  be classified as free or fixed.
• Free (also called wandering) macrophages move
  through tissues.
• Fixed macrophages generally stay in particular
  tissues and are associated with certain organs.
  The Kuppfer cells of the liver and microglia of
  the brain are examples.

http//www.usc.edu/hsc/dental/ghisto/gi/c_90.html
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Cellular Responses Major Phagocytes

• Neutrophils are also called microphages.
• Neutrophils respond quickly to localized
  infections where they undergo degranulation. This
  release of chemicals stored in their granules
  destroys pathogens but also kills the neutrophil.

http//www.usc.edu/hsc/dental/ghisto/bld/c_1.html
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Cellular Responses Other Phagocytes

• Eosinophils respond most to parasitic worms and
  release chemicals to destroy the worm.
• Mast cells reside in tissues where they release
  histamine during inflammation.
• Mast cells are the least common and respond to
  variety of bacteria. Their phagocytic role is
  uncertain.

Eosinophil http//www.usc.edu/hsc/dental/ghisto/b
ld/c_3.html
Mast Cell http//image.bloodline.net/stories/stor
yReader1682
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Mechanism of Phagocytosis

• Phagocytosis begins with microbial adherence,
  which requires the recognition of bacterium as
  non-self, that is, that it doesnt belong in
  the body.
• This is more difficult with encapsulated
  bacteria.
• Opsonization is enhanced phagocytosis due to the
  presence of complement proteins and/or antibodies
  attached to the bacterium.
• After adhering, the phagocyte forms pseudopodia
  and engulfs the particle into a phagocytic
  vesicle.
• The phagocytic vesicle is then joined with a
  lysosome.
• The particle is digested. The indigestible
  material is removed from the phagocyte by
  exocytosis.

See Fig. 22.1, p. 795
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Mechanism of Phagocytosis (cont)

• A respiratory burst is used against pathogens
  that resist lysosomal enzymes (e.g., tuberculosis
  bacteria).
• The burst is stimulated by chemicals released
  by specific immune system.
• The burst produces free radicals (e.g., NO,
  H2O2, and bleach-like compounds) that oxidize
  macromolecules in the bacterium.
• Defensins are antimicrobial proteins produced by
  neutrophils.

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Cellular Responses Natural Killer (NK) Cells

• NK cells are large, granular lymphocytes.
• NK cells are responsible for immunological
  surveillance, that is, they respond to abnormal
  antigens in the bodys own cells. These abnormal
  cells include cancer cells and virally-infected
  cells.
• NK cells release perforins that produce channels
  in target cell membrane and cause the nucleus to
  degrade.
• NK cells produce other chemicals that enhance
  inflammation.

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Antimicrobial Proteins Complement

• Complement consists of a group of at least 20
  plasma proteins that circulate in inactive form
  until they activated by one of two pathways.
• The two pathways of activation are the classical
  and alternative pathways.
• The classical pathway is linked to immune system.
  
• In this pathway, activation results from
  interaction of antigen-antibody complexes with
  complement proteins.
• The alternative pathway results from interactions
  of complement proteins with polysaccharides on
  surface of certain microorganisms

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Antimicrobial Proteins Complement

• Both pathways start cascades resulting in
• enhanced actions of nonspecific and specific
  resistance mechanisms, including inflammation and
  opsonization and
• lysis of bacterial cells.

Fig. 22.5, p. 800
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Antimicrobial Proteins IFNs

• Interferons (INFs) are a group of related
  proteins secreted by body cells infected with
  virus. This does nothing to help the infected
  cell, but does help prevent the spread of the
  virus.
• Alpha (?) and beta (?) INFs secreted by
  leukocytes and fibroblast, respectively,
  stimulate synthesis of PKR in nearby uninfected
  cells.
• PKR is a protein that blocks protein synthesis at
  ribosomes thereby preventing viral replication in
  the host cell.
• ? interferon also helps reduce inflammation.

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Antimicrobial Proteins IFNs

• Gamma interferon stimulates activity of
  macrophages and NK cells
• INFs are produced artificially and used
  clinically to treat genital warts (caused by
  herpes virus), also used in treatment of
  hepatitis C, and viral infections in organ
  transplant patients.

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Antimicrobial Proteins Lysozyme

• Lysozyme is produced as part of tears saliva.
• It is useful in killing unencapsulated bacteria.

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Fever

• Fever is increased body temperature in response
  to pathogens.
• It involves resetting of the bodys thermostat
  in the hypothalamus from the normal of 98.2oF
  (36.2oC).
• Leukocytes and macrophages secrete chemicals
  called pyrogens in response to bacteria and other
  foreign particles. These stimulate the
  hypothalamus to reset the bodys temperature
  higher.

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Fever

• A mild fever increases metabolic activity and
  enhances activity of phagocytes and tissue
  repair.
• A mild fever also causes the liver and spleen to
  sequester iron and zinc, two nutrients needed by
  bacteria to multiply.
• A high fever (gt 105 oF or 40.5 oC) damages
  proteins of the sick person. Fevers over 106oF
  are potentially life-threatening.

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Specific (Adaptive) Resistance

• Specific resistance is alsoknown as acquired
  resistance or adaptivce resistance.
• Characteristics of specific resistance include
  that
• it is antigen specific that is, responds only to
  specific pathogens (viruses, bacteria, toxins) to
  which the body has been exposed
• it is systemic that is, it responds to pathogens
  no matter where they are in the body
• it differentiates between normal (self) antigens
  and foreign (non-self) antigens
• it has memory so that the response is faster
  after the first exposure.

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Specific (Adaptive) Resistance

• There are two types of adaptive resistance based
  on what type of lymphocytes are involved and how
  they are involved.
• Humoral immunity, also called antibody-mediated
  immunity, is the result of specific antibodies
  (immunoglobulin proteins) present in the blood.
• Cellular immunity, also called cell-mediated
  immunity, is the result of a specific group of
  cells called T cell lymphocytes.

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Antigens (Ags)

• Substances that activate immune system and elicit
  response are called antigens. Two characteristics
  of antigens are
• immunogenicity, which means they cause production
  of antibody by plasma cells and
• reactivity, meaning that they react with
  antibodies, if present.
• Antigenic determinants, or epitopes, are the
  parts of the antigen that are recognized by T
  cells and antibodies.
• Epitopes are usually protein based or sugar
  (carbohydrate) based.

Fig. 22.6, p. 803
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Antigens (cont)

• A complete antigen has both immunogenicity and
  reactivity.
• Complete anitgens are usually large molecules,
  typically with more than one antigenic
  determinant.
• Most are foreign proteins or nucleic acids some
  are lipids or large polysaccharides.
• Haptens, also called incomplete antigens, are
  reactive but not immunogenic.
• Haptens are generally small molecules but can
  combine with other molecules to become complete
  antigens, i.e., become immunogenic.

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Antigens (cont)

• Self-antigens are major histocompatibility
  complex (MHC) proteins, which are glycoproteins
  found on individuals own cells.
• Self-antigens are used by the body to determine
  what does and what does not belong.
• There are two major types of self-antigens
• Class I MHC proteins that are found on all cells
  of body and
• Class II MHC proteins that are found only on
  cells involved in immune response.

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Antigens (Ags) Terms

• Agglutination occurs when antibodies bind to
  antigenic determinants of cells and cross-links
  several together resulting in clumping.
• Cross-reactions between blood types is an
  example.
• Precipitation occurs when antibodies bind to
  antigenic determinants of soluble antigens such
  as toxins and cause clumping.
• Neutralization occus when antibodies cover active
  site(s) on the antigen.

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Cells of the Immune System

• Lymphocytes become immunocompetent, or capable of
  responding to antigens, in primary lymphoid
  organs (bone marrow or thymus), where they also
  learn self-tolerance (recognition of bodys own
  protein antigens).
• After becoming immunocompetent, lymphocytes move
  to secondary lymphoid tissue to become exposed to
  antigens, then they return to blood and lymph
  circulation.
• There are 2 major types of lymphcytes involved in
  immunity
• B cells also called B lymphocytes and
• T cells also called T lymphocytes.

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Cells of the Immune System

• B cells, also called B lymphocytes, become
  immunocompetent in bone marrow.
• B cells develop into plasma cells after exposure
  to antigen. Plasma cells produce antibodies to
  the specific antigen to which the cell has been
  exposed.
• B cells are involved in humoral immunity.
• T cells, also called T lymphocytes, become
  immunocompetent in the thymus.
• T cells are active in cellular immunity.

Fig. 22.8, p. 805
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Cells of the Immune System APCs

• Antigen-presenting cells (APCs) engulf foreign
  particles and present fragments of the foreign
  proteins on their own surface to T cells so that
  the latter can recognize and respond to them.
• Several types of cells serve as APCs
• dendritic cells, including the Langerhans cells
  of epidermis,
• macrophages, and
• activated B cell lymphocytes.

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Humoral Immunity

• Humoral immunity relies on B cells.
• The primary response is the response to the first
  exposure to an antigen.
• The antigen binds to a B cell with the
  appropriate receptors and is engulfed by the B
  cell.
• The B cells then divides into clonal daughter
  cells (all alike) that become plasma cells, which
  secrete antibodies, or become memory cells, which
  lie are ready for subsequent exposures.
• Primary response usually takes 3-6 days.
• Secondary responses are much faster and stronger
  due to presence of memory B cells.

Fig. 22.9, p. 807
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Passive Versus ActiveHumoral Immunity
Active - the body has been exposed
Passive - antibodies are given to a recipient
Naturally Acquired
Infection (may or may not have symptoms)
Antibodies passed from mother to fetus or infant
Artificially Acquired
Vaccine (dead or attenuated live but weakened
pathogens)
Injection of gamma globulin (e.g., rabies
antitoxin, snake antivenoms)
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Antibodies

• Antibodies are immunoglobulins (Igs) and make up
  the gamma globulin part of plasma proteins.
• Their general structure is that they
• consist of 4 polypeptide chains held together by
  disulfide bonds, known as an antibody monomer
  and
• each chain has a variable and a constant region.
• See Table 22.3, p. 811 for the various types of
  antibodies.

Fig. 22.12, p. 810
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Antibodies

• The variable region of the antibody gives
  specificity to the antibody.
• The variable region includes antigen-binding
  sites that actually attach to the antigen.
• The constant region includes the stem region of
  the heavy chains and the proximal parts of both
  heavy and light chains.
• The stem region determines the actions of the
  antibody and determines the classes to which the
  antibody belongs.

Fig. 22.12, p. 810
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Most Common Antibody Classes

• IgG antibodies are the most abundant and diverse
  plasma antibodies in both primary and secondary
  responses. IgG
• protects against circulating bacteria, viruses,
  toxins
• activates complement and
• crosses placenta to protect fetus.
• IgM antibodies act as antigen receptors on B cell
  membranes. IgM antibodies
• are important to primary response and
• cause agglutination and
• activate complement.

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Less Common Antibody Classes

• IgA antibodies are found primarily in mucus and
  other secretions (e.g, saliva, sweat, intestinal
  juice, milk).
• IgA prevents attachment of antigens to mucosae.
• IgD antibodies act as antigen receptors.
• IgE antibodies are present in skin,
  gastrointestinal and respiratory tract mucosae,
  and tonsils.
• IgE antibodies bind to mast cells and basophils
  and stimulate release of histamine.
• The titre (measured amount) of IgE increases
  during allergy and chronic parasitic infection of
  the GI tract.

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Mechanisms of Antibody Action

• Antibodies are important to phagocytosis and
  activation of the complement system.
• Antibodies enhance phagocytosis by
• neutralization of toxins (covering their
  surfaces)
• causing agglutination of cellular invaders and
• causing precipitation of toxins.
• Antibodies activate complement,which
• enhances inflammation
• causes cell lysis and
• enhances phagocytosis through opsonization.

Fig. 22.13, p. 812
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Cell-Mediated Immunity

• Cell-mediated involves T cells.
• Several types of T cells exist and are shown in
  the following slides and in Table 22.4, p. 818.
  The T cells covered in this presentation are
• Cytotoxic T cells (TC)
• Helper T cells (TH)
• Suppressor T cells (TS) and
• Delayed hypersensitivity T cells (TDH)

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Cytotoxic T Cells (TC)

• Cytotoxic T cells (also called killer T cells)
  destroy body cells that are infected by antigen
  (viruses, bacteria, internal parasites) or have
  non-self antigens (e.g., cancer cells).
• The direct mechanism of action seems to involve
  release of perforin onto membrane of affected
  cell. Other cytotoxic T cells use slightly
  different mechanisms.

Fig. 22.17, p. 820
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Cytotoxic T Cells (TC)

• Other mechanisms include
• lymphotoxin, which causes fragmentation of target
  cell DNA)
• tumor necrosis factor (TNF), which triggers cell
  death, or apoptosis and
• gamma interferon, which stimulates macrophages.

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Helper T Cells (TH)

• Helper T cells stimulate production of B cells
  and cytotoxic T cells that are involved in the
  immune response.
• Without helper T cells, the immune system does
  not respond.
• Cytokines released by helper T cells also
  stimulate macrophages to greater activity.

Fig. 22.16, p. 817
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Other Types of T Cells

• Suppressor T cells (TS) limit activity of T and B
  cells after infection has been beaten.
• Delayed hypersensitivity T cells (TDH) are
  involved in delayed allergic reactions.
• TDH cell secrete interferon and other cytokines
  that enhance nonspecific phagocytosis by
  macrophages.

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T Cell Activation

• Two major steps are involved in activation of T
  cells
• Step 1 is antigen binding.
• The T cell antigen receptor (TCR) binds to the
  antigen-MHC protein complex on the body cell.
• Step 2 is costimulation by signals from APCs.
• recognition of costimulatory signals stimulates
  clonal division of T cells into various types.
• Cytokines are chemicals released by macrophages
  and T cells some act as costimulators.

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Tissue/Organ Transplants

• Four types of transplants are based on the source
  of the tissue.
• An autograft is taken from one site and
  transplanted into another site in same person.
  Skin graft are common examples.
• An isograft occurs between identical twins (or
  members of same clone).
• An allograft occurs between nonidentical
  individuals of same species. Heart and kidney
  transplants are examples.
• Xenografts are transplants between different
  species, such as transplanting pig valves in a
  human heart or a baboon heart into and infant.

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Tissue/Organ Transplant Rejection

• Rejection occurs when antigens on donor tissue
  are attacked by recipients immune system.
• Immunosuppressive therapy is used to decrease
  rejection.
• Corticosteroids are used to suppress
  inflammation.
• Cytotoxic drugs, radiation (X ray) therapy,
  antilymphocyte globulins and immunosuppressant
  drugs (e.g., cyclosporine) are used to reduce
  rejection.
• Supression of the immune system make the person
  more vulnerable to bacterial and viral infection.

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Disorders Immunodeficiencies

• Severe combined immunodeficiency syndromes (SCID)
  are genetic deficiencies of immune system.
• One such disorder involves the adenosine
  deaminase (ADA) enzyme that clears T cells of
  lethal metabolites. (See Discover article for
  assignment 2.)

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Disorders Immunodeficiencies

• Acquired immunodeficiencies are the result of
  insults to the immune system. Acquired
  immunodeficiencies may result from cancer,
  anticancer drugs or viral infection.
• Hodgkins disease supresses the immune system by
  damaging lymph nodes.
• Acquired immune deficiency syndrome (AIDS) is
  caused by HIV virus transmitted in blood, semen,
  and vaginal secretions.
• AIDS changes ratio of helper (TH) to suppressor T
  cells by decreasing the number of TH cells.
• This allows opportunistic infections to
  proliferate.

59
Autoimmune Disorders

• Autoimmune disorders occur when the body fails to
  recognize its own antigens.
• In multiple sclerosis antibodies destroy myelin
  sheaths within the CNS resulting in visual
  impairment, difficulty with motor function, and
  other nerve-related problems.
• In myasthenia gravis antibodies destroy ACh
  receptors of skeletal muscle resulting in
  weakness, loss of somatic motor control and
  eventually respiratory failure.
• In type I diabetes mellitus antibodies destroy
  beta cells in pancreas, resulting in a failure to
  produce insulin.

60
Autoimmune Disorders

• In Graves disease abnormal antibodies resembling
  TSH stimulate the thyroid to produce too much
  thyroxine.
• In systemic lupus erythematosis (SLE) antibodies
  against DNA cause a systemic disease affecting
  the heart, kidneys, lungs, and skin.
• Rheumatoid arthritis (RA) destroys joints.

61
Hypersensitivity Disorders Allergies

• The two major kinds of allergies are immediate
  and delayed.
• Immediate allergies are also called acute or type
  I and begin within seconds of subsequent contact
  with antigen.
• Delayed allergies are also called type IV
  allergies and take hours to days to show a
  response.

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Immediate Hypersenstivities

• Occur in a person after initial exposure. The
  response to 1st exposure normally not seen.
• The most common type of acute hypersensitivity is
  anaphylaxis.
• Anaphylaxis is mediated by interleukin 4 (IL-4),
  which stimulates B cells to mature into
  IgE-secreting plasma cells.
• IgE stimulates release of histamine from
  basophils and mast cells leading to inflammation
  (see inflammatory response).
• Anaphyalxis may be local or systemic.

Fig. 22.19, p. 826
63
Anaphylaxis (cont)

• Local anaphylaxis includes hives in the skin,
  asthma in the airways, hay fever in the nasal
  cavity and GI reactions to certain foods.
• Antihistamines are usually effective in
  minimizing symptoms which normally include runny
  nose, watery eyes, itchy skin.

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Anaphylaxis (cont)

• Systemic anaphylaxis is caused by introduction of
  an allergen into the blood (e.g., venom in bee
  sting or penicillin injection).
• Systemic anaphylaxis causes widespread release of
  histamine leading to widespread vasodilation.
• widespread vasodilation leads to widespread loss
  of fluid to tissues
• widespread loss of fluid causes a radical drop in
  BP leading to anaphylactic shock.
• Systemic responses also include
  bronchoconstriction.
• Systemic anaphylaxis is treated with epinephrine.
• Think About ItWhat does epinephrine do?

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Delayed Hypersensitivity (Type IV) Reactions

• Delayed hypersensitivity reacations are
  cell-mediated responseS.
• These reactions involve cytotoxic and delayed
  hypersensitivity T cells.
• Most familiar are contact dermatitis, responses
  to some heavy metals, cosmetics and deodorants.
• Effects appear hours or even days after exposure.