Chapter 21 Nonspecific Body Defenses and Immunity

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Chapter 21Nonspecific Body Defenses and
Immunity
G.R. Pitts, J.R. Schiller, and James F. Thompson,
Ph.D.
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Defense Systems

• Innate (nonspecific) defenses
• External body membranes
• Inflammation
• Antimicrobial proteins, phagocytes and other
  cells
• Adaptive (specific) defenses
• T cells and B cells

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Innate Defense System

• Surface Barriers
• First line of defense mechanical and chemical
  protection
• Skin
• Mucosal Membranes
• Internal Nonspecific Defenses
• Second line of defenses
• Phagocytes
• Natural Killer cells (NK lymphocytes)
• Inflammation
• Antimicrobial proteins
• Fever

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Skin and Mucosal Membranes

• Mechanical Protection
• Epidermis
• nose hairs, nails
• Mucous membranes - line certain organ systems
• mucus prevents drying, traps foreign things
• respiratory tract cilia sweep mucus out
• Lacrimal apparatus -- tear glands and ducts
• wash the eye to dilute microbial growth
• Saliva - dilute microbes on the oral cavity
• Urine - flow dilutes, and acid pH helps kill,
  microorganisms
• Defecation and vomiting - expel toxins and
  microbes

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Skin and Mucosal Membranes

• Chemical Protection reduce bacterial growth
• Skin
• sebum (unsaturated FAs) forms oily layer
• perspiration has fatty acids, salts (NaCl), and
  mildly acid pH
• Lysozyme
• in perspiration, tears, saliva, nasal secretions,
  other tissue fluids
• enzyme breaks down bacterial cell walls
• Hyaluronic acid
• gel-like matrix in most connective tissues
• slows the spread of many infectious agents
• Gastric juice - stomach nearly sterile due to
  acid pH, 2
• Vaginal secretions mildly acid pH

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Innate Defense Phagocytes

• Macrophages (derived from monocytes) are the
  chief tissue phagocytic cells
• Free macrophages wander through tissues in search
  of microbes and cellular debris
• Fixed macrophages Kupffer cells (liver),
  microglia (brain), dust cells (lungs)
• Neutrophils become phagocytic when encountering
  infectious material
• Eosinophils are weakly phagocytic, deploy
  destructive granules against parasitic worms

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Mechanism of Phagocytosis

• Chemotaxis
• Adherence recognition of external carbohydrates
  and proteins
• Aided by opsonins
• Ingestion
• Killing and digestion

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Innate Defense Natural Killer Cells

• Distinct group of large granular lymphocytes (NK
  lymphocytes Null Killer lymphocytes)
• Nonspecific killers respond to the lack of
  self-antigens and to the presence of certain
  surface oligosaccharides
• Kill virus-infected body cells and some tumor
  cells by releasing various defensive molecules
  not by phagocytosis
• Act before the antigen-specific immune system is
  activated
• Secrete potent chemical signals that enhance the
  inflammatory response

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Innate Defense Inflammation

• Inflammation
• Signs
• Redness
• Heat
• Swelling
• Pain
• Loss of Function
• Function
• Prevent spread of damage
• Dispose of pathogens and debris
• Set stage for tissue repair

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Inflammation

• Stage 1 Vasodilation and increased vessel
  permeability
• Macrophages and cells lining the gastrointestinal
  and respiratory tracts carry Toll-Like Receptors
  (TLRs) that recognize specific classes of
  microbes
• TLReceptor activation causes cytokine release
• promotes inflammation chemotaxis
• Mast cells secrete histamine
• Other cells secrete various regulatory factors
• Histamine, kinins, prostaglandins, leukotrienes,
  complement
• Cause local vasodilation
• Increase capillary permeability resulting in edema

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Inflammation Stage 1

• Edema increased plasma filtrate seeps into
  tissue spaces bringing some immune proteins
• Helps to dilute harmful substances
• Increases supply of oxygen and nutrients needed
  for metabolism, inflammation and repair
• Allows entry of clotting proteins, which reduces
  the spread of mibrobes

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Inflammation

• Stage 2. Phagocyte moblization
• Leukocytosis-inducing factors increase
  neutrophil production
• Margination (pavementing)
• Diapedesis (amoeboid movement)
• Chemotaxis of WBCs
• neutrophils rapid arrival
• monocytes slower arrival

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Inflammation

• Stage 3. Tissue repair
• Tissue regrowth and repair of damage or scar
  formation
• Pus
• dead phagocytes and other WBCs, damaged tissue,
  and perhaps microbes
• if too numerous for effective removal by
  phagocytes, an abscess may develop

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Effects of Inflammation

• Increased blood flow results in increased local
  temperature and local cellular metabolism
• Increased capillary permeability and phagocytic
  migration to the injured tissue

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Innate Defense Antimicrobial Proteins

• Attack microorganisms directly
• Interfere with microbial reproduction
• The most important are
• Interferons
• The Complement System
• Transferrins which bind Fe2 in plasma,
  inhibiting bacterial growth

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Interferons (IFNs)

• Produced by most tissue cells when infected by a
  virus
• Diffuses to uninfected cells and binds to surface
  receptors
• stimulates macrophages and natural killer
  lymphocytes
• stimulates production of antiviral proteins which
  block viral replication
• inhibits growth of virally infected cells
• suppresses growth of tumor cells
• Alpha IFN is used against
• hepatitis C virus
• herpes virus (genital warts)

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The Complement System

• 20 plasma and cell membrane proteins that exist
  as inactive precursors
• When activated, the complement system functions
  to complement or enhance certain immune,
  inflammatory, and allergic responses
• Kills bacteria and certain other microbial cell
  types (our cells normally are protected from
  complement attack)
• Stimulates chemotaxis in leuckocytes
• Enhances the effectiveness of both nonspecific
  and specific defenses

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Complement Pathways

• Classical Pathway is triggered by the specific
  immune system
• Requires binding of antibodies to antigens of
  invading organisms
• Complement C1 then binds to the antigen-antibody
  complexes (complement fixation)
• Alternative Pathway is triggered by non-specific
  interaction among factors B, D, and P, and
  microbial cell wall polysaccharides (complement
  fixation)
• Both pathways involve an enzyme cascade

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Complement Pathways

• Both pathways converge on C3, which cleaves into
  C3a and C3b
• C3b initiates formation of a membrane attack
  complex (MAC)
• MAC causes cell lysis by creating many hundreds
  of microscopic holes in the cells plasmalemma
• C3b is also an opsonin

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Innate Defense Fever

• Pyrogens reset the temperature set-point in the
  hypothalamus
• Inhibits some microbes from growing
• Increases bodys metabolic rate, which speeds up
  immune defenses and tissue repair
• Increases effects of antimicrobial substances
  produced by the immune system
• Stimulates liver and spleen to sequester iron and
  zinc (needed by microorganisms)
• High fevers are dangerous

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Innate Defense System Review

• Surface Barriers
• Skin
• Mucosal membranes
• Internal Nonspecific Defenses
• Phagocytes
• Natural Killer cells (NK lymphocytes)
• Inflammation
• Antimicrobial proteins
• Fever

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Adaptive Defense

• The adaptive immune system
• Acts to immobilize, neutralize, or destroy
  foreign substances and cells
• Amplifies the inflammatory response and activates
  complement
• Is antigen-specific, systemic, and has memory
• Recognizes specific foreign molecules
• Has two interdependent arms
• Humoral, or antibody-mediated immunity (AMI)
• Cellular, or cell-mediated immunity (CMI)

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Adaptive Defense

• Definitions
• Immunity the ability of the body to defend
  itself against specific foreign invaders
  (molecules or cells)
• Immunogenicity the ability to stimulate
  proliferation of specific lymphocytes and
  specific antibody production
• Reactivity the ability of activated lymphocytes
  and their products, antibodies, etc., to interact
  with specific antigens

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Adaptive Defense

• Definitions
• Specificity the antigen triggers focused immune
  defenses (from particular lymphocytes lineages)
  that respond only to the antigens of this foreign
  substance/cell
• Memory the immune system produces clones of
  specific memory lymphocytes (T B) which react
  rapidly when the particular foreign
  substance/cell is encountered again
• Specificity and memory differentiate this system
  from the nonspecific (innate) defenses

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Adaptive Defense

• Antigen any substance which provokes specific
  immune responses
• Antigenic determinants
• Parts of antigens that trigger the specific
  immune response
• An antigen may be an entire microorganism or only
  small structures or subregions of large molecules

Most antigens are complex and express multiple
types of antigenic determinants.
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Chemical Nature of Antigens

• Complete Ag complex macromolecules - usually
  proteins (nucleo-, lipo-, glyco-) -- sometimes
  carbohydrates or lipids
• Are immunogenic reactive
• Incomplete Ag smaller molecules (haptens)
• react with antibodies but cannot cause an immune
  response without aid (protein carrier)
• e.g., poison ivy, drug allergies

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Adaptive Defense

• Antigen receptor diversity
• gt1 billion different antigenic determinants are
  recognized by the body
• Genetic recombination shuffles and reorganizes
  different Ab genes
• Major histocompatibility complex antigens (MHC)
• unique to each individuals cells help in
  identifying what is self versus foreign
• 2 classes of MHC antigens (markers)
• class I MHC found on all body cells except
  RBC's
• class II MHC - only on antigen presenting cells
  (APCs), thymus cells, and activated T cells

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Antigen-Presenting Cells (APCs)

• APCs phagocytize, process, and present antigens
  to lymphocytes
• APCs do not respond to specific antigens
• APCs contribute to coordinating specific immunity
• Macrophages
• Dendritic (Langerhans) cells
• B lymphocytes
• The major initiators of adaptive immunity are
  APCs, which actively migrate to the lymph nodes
  and secondary lymphoid organs and present
  antigens to T and B cells

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Class I MHC Proteins

• Found on all cells, except RBCs
• Recognized by T lymphocytes and APCs
• Display peptides from endogenous antigens
• Endogenous antigens are
• Associated with body cells
• Degraded by proteases and enter the endoplasmic
  reticulum
• Transported through special membrane channels
• Bound with MHC class I molecules on the ER
  membrane
• Migrate to the cell membrane as a complex Ag --
  MHC class I molecule

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MHC Class I Proteins
This is a form of Antigen Presentation
Cancer cells often do something quite similar to
the virus-infected cells. (Foreign MHC Class I
Ags are the source of tissue transplant
rejections.)
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MHC Class II Proteins

• Immune cell identity markers found only on mature
  B cells, some T cell classes, and
  antigen-presenting cells
• MHC Class II proteins are synthesized in the ER
• A phagosome containing a pathogen (with exogenous
  antigens) merges with a lysosome
• MHC Class II proteins migrate into the phagosome
  where the antigen macromolecules are degraded and
  particular antigen peptides are bound to the MHC
  Class II markers
• Ag-- MHC class II complex then migrates to the
  cell membrane and displays antigenic peptide for
  recognition by CD4 TH cells

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MHC Class II Proteins
This is a key function of our APCs in most
Ag-specific defenses.
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Lymphocytes Provide Ag Specificity

• B and T lymphocytes develop in bone marrow
• Lymphocytes mature and develop immunocompetence
  (ability to recognize specific antigen) in
  different locations
• B cells mature in the bone marrow and provide
  Ab-mediated immunity
• T cells mature in the thymus and provide
  cell-mediated immunity

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Immunocompetent B or T cells

• Naive cells display a unique surface receptor for
  a specific antigen once mature
• Receptor expression occurs before a cell
  encounters the foreign antigen it may later
  attack
• It is genes, not antigens, that determine which
  foreign substances our immune system will
  recognize and resist
• Naive cells circulate to secondary lymphoid
  tissue where they may encounter antigens later
• B and T cells become fully functional only after
  binding with their recognized antigen

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Immunocompetent T Cells

• T cells mature in the thymus under positive and
  negative selection pressures
• Positive selection outer thymic cortex
• Selects functional T cells which become both
  immunocompetent and potentially self-tolerant
• Non-selected cells die via apoptosis
• Negative selection inner thymic cortex
• Kill or regulate off T cells that react with
  self-antigens

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Immunocompetent B Cells

• B cells become immunocompetent and self-tolerant
  in bone marrow
• Some self-reactive B cells are killed by
  apoptosis (clonal deletion)
• Some self-reactive B cells can modify their
  anti-self properties (receptor editing)
• Some self-reactive B cells are released from the
  bone and are inactivated by negative regulation
  (anergy)

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Cell-Mediated Immunity

• CMI is involved in most aspects of specific
  immune defense
• Three populations of T lymphocytes regulate
  specific immunity
• Helper TH cells which carry CD4 markers
• Suppressor TS cells
• Memory T cells
• cytotoxic TC cells which carry CD8 markers
  destroy tumor cells and virus-infected cells
  they also attack transplanted cells and tissues

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Cell -Mediated Immunity

• Basic steps
• Recognition by T lymphocytes of antigen presented
  by an antigen-presenting cell with matching MHC
  Class II markers
• Proliferation and differentiation of T cells once
  activated
• Production of clones of identical effector T
  cells capable of recognizing a specific antigen
• Appropriate action (help, attack, memory,
  suppression) from T cell subclones

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T Cell Activation- Step 1Antigen Bindingand
AntigenPresentation
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T Cell Activation- Step 2 Co-Stimulation

• T cells must bind to MHC Class II surface
  receptors on an APC
• After co-stimulation with cytokines, T cells
  enlarge, proliferate, and form clones
• Activated T cells differentiate and perform
  functions according to their T cell class

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T Lymphocyte Activity

• Primary T cell response usually peaks within a
  week
• T cells then undergo apoptosis within a month
• Reduced activity parallels elimination of antigen
• This is a negative feedback control
• A few Memory T cells remain to respond to any
  future exposure to the same antigen

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Helper TH Lymphocytes

• Regulatory cells that play a central management
  role in the immune response
• Once primed by APC antigen presentation, TH
  cells
• Stimulate proliferation of other T cell classes
• Stimulate B cells that have already become bound
  to antigen
• There is NO coordinated immune response without
  TH cell function

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Helper TH Lymphocytes

• TH cells interact directly with B cells that have
  antigen fragments on their surfaces bound to MHC
  Class II receptors
• TH cells express CD4 cell identity markers
• TH cells stimulate B cells to divide more rapidly
  and begin antibody formation
• B cells may be activated without TH cell help by
  binding to T cellindependent antigens (certain
  microbial polysaccharides)
• Most antigens, however, require TH co-stimulation
  to activate B cells
• Cytokines released by TH amplify nonspecific
  defenses

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Cytotoxic Tc Lymphocytes

• TC cells express CD8 cell identity markers
• TC cells, or killer T cells, are the only T cells
  that can directly attack and kill other cells
• They circulate throughout the body in search of
  body cells that display the antigen to which they
  have been sensitized
• Their targets include
• Virus-infected cells
• Cells with intracellular bacteria or parasites
• Cancer cells
• Foreign cells from blood transfusions (WBCs and
  platelets) or tissue and organ transplants

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Cytotoxic Tc Lymphocytes

• Bind to self/anti-self complexes on any body cell
• Infected or abnormal cells can be destroyed as
  long as appropriate antigen and co-stimulatory
  regulators (e.g., IL-2) are present
• In contrast, Natural Killer cells activate their
  killing machinery when they bind to a different
  MHC-related cell surface marker on cancer cells,
  virus-infected cells, and transplanted cells

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Cytotoxic Tc Lymphocyte Actions

• Secrete perforins which cause cell lysis by
  creating transmembrane pores
• Secrete lymphotoxin which fragments the target
  cells DNA
• Secrete gamma interferon which stimulates
  macrophage attack

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Suppressor Ts Lymphocytes

• TS cells immune regulatory cells which release
  cytokines that suppress the activity of both T
  cells and B cells
• Generated when other specific T cell clones are
  generated
• Negative feedback control to bring the body back
  to normal after the battle has been won

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Antibody-Mediated Immunity

• Antigen challenge the first encounter between
  an antigen and a naive B lymphocyte
• Antigen presentation usually occurs in the spleen
  or a lymph node, but can occur in any lymphoid
  tissue
• Antigen presentation usually made by a
  macrophage, but some B cells can react directly
  against certain bacterial antigens
• Binding of the antigen to the B cells specific
  Ag receptor activates the B cell

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Primary Response
Activated B cells grow and divide, forming clones
bearing the same antigen-specific receptors and
secreting the same antigen-specific Ab

• Most clone cells become plasma cells that secrete
  specific antibodies
• Clones that do not become plasma cells become B
  memory cells that can respond to subsequent
  exposures to the same antigen

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Primary Response

• Initial B cell differentiation, proliferation,
  and Ab synthesis requires time after the first Ag
  exposure
• Lag period 3 to 6 days after antigen challenge
• Peak plasma levels of antibody are achieved in
  10 days
• Antibody molecules also reach the interstitial
  fluids, especially where inflammation exists
• Antibody levels then decline gradually if there
  is no additional Ag exposure

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Secondary Response

• Any subsequent exposure to the same antigen
• Sensitized memory cells (B and T) respond within
  hours
• Antibody levels peak in 2 to 3 days at higher
  plasma levels than in the primary response
• Activated B subclones generate antibodies that
  bind with greater affinity
• Plasma antibody levels can remain high for weeks
  to months

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Primary and Secondary Antibody Responses
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Immunological Memory

• Immunization is possible because memory B cells
  and memory T cells persist after the initial Ag
  exposure

• with any subsequent exposure, the immune system
  responds more quickly, forcefully
• secondary response - antibodies produced during
  subsequent exposures are produced in greater
  quantities and have a greater attraction for
  antigen

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Antibodies

• Are unique soluble proteins secreted by activated
  B cells and plasma cells in response to an
  antigen
• Are capable of binding specifically with that
  antigen
• Constitute much of the gamma globulin fraction of
  plasma proteins
• Also called immunoglobulins

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Basic Antibody Structure

• Four polypeptide chains linked together with
  disulfide bonds
• The four chains bound together form an antibody
  monomer
• Each chain has a variable (V) region at one end
  and a constant (C) region at the other
• Variable regions of the heavy and light chains
  combine to form the antigen-binding site

Ag
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Antibody Structure

• Antibodies responding to different antigens have
  different V regions but the C region is the same
  for all antibodies in a given antibody class
• C regions form the stem of the Y-shaped antibody
  monomer and determine
• the class of the antibody
• the cells and chemicals to which the antibody can
  bind
• how an antibody class functions in eliminating
  antigens

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Classes of Antibodies

• IgD monomer attached to the surface of B cells,
  important in B cell activation
• IgM pentamer released by plasma cells during the
  primary immune response
• IgG monomer that is the most abundant and
  diverse antibody in primary and secondary
  responses crosses the placenta and confers
  passive immunity
• IgA dimer that helps prevent attachment of
  pathogens to mucosal surfaces
• IgE monomer that binds to mast cells and
  basophils, causing histamine release when
  activated

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Antibody Functions

• All antibodies form an antigen-antibody (immune)
  complex
• Antibodies do not directly destroy antigen,
  though they may immobilize or inactivate Ag
• Antibodies act as opsonins and tag Ag for immune
  attack and destruction
• Defensive mechanisms triggered by antibodies
  include neutralization, agglutination,
  precipitation, opsonization, and complement
  fixation

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Antibody Mechanisms of Action

• Neutralization Antibodies bind to and block
  specific sites on viruses or exotoxins, thus
  preventing these antigens from binding to
  receptors on tissue cells
• Antibodies bind to the same determinant on more
  than one antigen forming antigen-antibody
  complexes that are cross-linked into large
  lattices
• Agglutination Cellular antigens are
  cross-linked, causing cell clumping
• Precipitation Soluble molecules are
  cross-linked into large insoluble complexes

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Antibody Mechanisms of Action

• Opsonization Bound Abs facilitate phagocyte
  adherence
• Complement Fixation IgM and IgG antibodies bound
  to cellular Ags bind complement via the Classical
  Pathway
• The complement cascade causes chemotaxis,
  opsonization, phagocytosis and cell lysis
• Complement activation enhances the inflammatory
  response

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Summary of Antibody Actions
Figure 21.13
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Monoclonal Antibodies

• Monoclonal antibodies are purified tissue culture
  preparations of a specific antibody for a single
  antigenic determinant which are produced from
  descendents of a single B cell
• Commercially prepared monoclonal antibodies are
  used
• To provide passive immunity
• In research applications
• In clinical laboratory testing
• In the treatment of certain cancers

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Adaptive Immunity Summary

• A defensive system with two interdependent arms
  (CMI AMI) that uses lymphocytes, APCs, and
  specific molecules to recognize and destroy
  foreign substances
• Adaptive immune responses depend on the ability
  of its cells to
• Distinguish foreign from self molecules
• React with foreign substances (antigens) by
  binding to them
• Communicate with one another to effect a
  coordinated protective response specific to those
  antigens

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Adaptive Immunity Summary

• To start an immune response, APCs, B and T
  lymphocytes must recognize foreign antigen
• Antigen-Presenting Cells and some B cells
  recognize and immediately bind to certain
  antigens in the blood, the extracellular fluid
  (ECF), or other tissue spaces
• More often, B and T cells only recognize antigen
  (protein fragments) when Ag is presented by the
  macrophages in combination with MHC Class II
  surface markers and stimulation is provided by Th
  lymphocytes

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Summary of the Immune Response
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Clinical Classification of Immunity

• Active Immunity the bodys own B and T
  lymphocytes encounter antigens and produce
  specific responses against them immunological
  memory does occur
• Naturally Acquired response to a microbial or
  parasitic infection
• Artificially Acquired response to a vaccine of
  dead or attenuated (weakened) pathogens
• Passive Immunity An outside source of immune
  cells or molecules is provided to a recipient
  immunological memory does not occur protection
  ends when the donated materials are naturally
  eliminated from the body
• Naturally Acquired the mother to her baby via
  the placenta (IgG) or via lactation
  (colostrum/milk) (IgM IgA)
• Artificially Acquired the injection of serum,
  gamma globulin, or leukocyte transfusion

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Clinical Classification of Immunity
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Organ and Tissue Transplants

• The four major types of grafts are
• Autograft graft transplanted from one site on
  the body to another in the same person
• Isograft graft between identical twins (or
  clones) individuals with the same genotype
• Allograft graft between individuals that are
  not identical twins, but belong to same species
• Xenograft grafts taken from another animal
  species

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Prevention of Graft Rejection

• Donors are selected to minimize differences in
  MHC Class I antigens HLA (human leukocyte
  antigens)
• Unnecessary for routine blood transfusions since
  RBCs lack HLAs
• Prevention of rejection is accomplished by using
  various immunosuppressive drugs
• Survival and longevity of grafts have varying
  success
• Immunosuppressive drugs depress the patients
  immune system so it is less effective in
  defending against pathogens and cancer

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Pathologies Immunodeficiencies

• Human Immunodeficiency Virus
• HIV enters certain cell types by receptor
  mediated endocytosis
• infects primarily helper T cells
• attaches to the CD4 protein on cell surface
• A retrovirus
• carries its genetic material as RNA
• inserts its genetic material into host cell DNA
  with the enzyme reverse transcriptase
• cell makes copies of the virus, releases them for
  further infection
• May be carried silently in cells for years, being
  passed on during ordinary mitosis
• Activation of HIV life cycle destroys THelper
  cells
• Weakened immune response to all foreign invaders,
  benign or aggressive

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Pathologies Autoimmune Diseases

• Multiple Sclerosis (MS) myelin sheath (white
  matter) attacked and destroyed
• Myasthenia Gravis ACh receptors at
  neuro-muscular junction of skeletal muscle
  attacked and destroyed
• Graves Disease thyroid cells TSH receptor
  attacked and stimulated causing excess thyroid
  hormone (T3 T4) production
• Type I Diabetes - destruction of pancreatic islet
  cells eliminates insulin secrection

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Pathologies Autoimmune Diseases

• Systemic Lupus Erythematosus (SLE) generalized
  attack on connective tissues and nuclear antigens
• Glomerulonephritis - destruction of the
  glomerular capillaries causes impaired renal
  function
• Rheumatoid Arthritis - destruction of the
  synovial membranes in joints

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Pathologies Cancer

• The immune system probably evolved first to
  respond to cancer cells
• when a new cancer cell develops, new surface
  marker proteins (tumor antigens) often appear
• if the immune system recognizes these new surface
  markers as non-self, it will destroy the cell
  expressing them
• this immune surveillance is most effective in
  eliminating virus-induced tumor cells because
  they tend to express viral antigens which are not
  self
• Leukemias and Lymphomas cancers of leukocytes

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Pathologies Hypersensitivities

• Immediate hypersensitivities (allergies)
• First exposure merely sensitizes one to an
  allergen (penicillin, venoms, dust, mold, pollen,
  etc.)
• APCs digest and inappropriately present the
  allergen
• Subclones of B cells secreting IgE predominate in
  response
• Anti-allergen IgE attaches to mast cells and
  basophils
• Later exposures produce dramatic responses
• Antigen binds to IgE on mast cells and basophils
• Ag-IgE binding triggers these cells to release
  much histamine and other inflammatory molecules
• Local reactions swelling, rashes, erythema,
  itching
• Systemic reactions asthma, anaphylactic shock,
  death

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Pathologies Subacute Hypersensitivities

• Caused by IgG and IgM
• Occurs 1-3 hr after exposure and lasts 10-15 hr
• Cytotoxic reactions
• Ab bind to Ag on specific cells causing
  phagocytosis and complement-activated lysis
• May occur after transfusion of mismatched blood
• Immune-complex hypersensitivities
• Ags are widely distributed or insoluble Ag-Ab
  complexes cant be removed
• Intense inflammation
• Severe damage to local tissue
• Also involved in autoimmune diseases

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Pathologies Delayed Hypersensitivities

• Occurs 1-3 days after exposure
• Cell-mediated immune response
• Causes mild swelling to serious cytotoxic tissue
  damage (contact dermatitis, e.g., TB skin test,
  poison ivy, latex gloves, etc.)
• Note Sometimes allergies may be temporarily
  transferred by blood or plasma transfusions.

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End Chapter 21