Adaptive (Acquired) Immunity (3rd line of defense)

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Adaptive (Acquired)Immunity (3rd line of defense)

• Chapter 7

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Adaptive/Acquired Immunity

• Antigens Anything that cases a biological
  immune response by this system of cells
• Specificity Some antibodies are quite specific
  to an antigen others are general to a type or
  form
• Memory b-memory cells are formed and remain to
  combat future exposures quickly (Active vs
  Passive immunity
• Antibodies the proteins formed by b-cells that
  combat antigens whether chemical or biological
• Lymphocytes cells involved in this response

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Adaptive Immunity

• Clonal diversity
• Production of T (Killer cell mediated response)
  and B lymphocytes (humoral/antibody response)
• Antigen recognition zone of attachment
• Lymphocyte specificity Classes of
  Immunoglobulins
• Clonal selection CD cluster recognition table
  7-2
• Antigen processing Recognition and binding
  depend on size of molecule/cell/tissue/organism
  and class
• Cellular interaction

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Active vs. Passive Immunity

• Active immunity
• Antibodies or T cells produced after either a
  natural exposure to an antigen or after
  immunization
• Passive immunity
• Preformed antibodies or T lymphocytes are
  transferred from a donor to a recipient

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Recognition and Response

• Required for a successful immune response
• Clusters of differentiation (CD)
• Originally used to describe proteins found on the
  surface of lymphocytes
• Now it is a labeling system used to identify a
  family of proteins on many cells

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Antigens

• Immunogens vs. antigens
• Antigenic determinant (epitope)
• Self-antigen
• Tolerance
• Central and peripheral tolerance
• Molecular size
• Haptens
• Allergens

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Antigen Presentation

• Antigen-presenting cells (APCs)
• Major histocompatibility complex (MHC)
• Glycoproteins on the surface of all human cells
  (except RBCs)
• Also referred to as human leukocyte antigens
  (HLAs)
• MHC class I molecules
• A, B, and C
• MHC class II molecules
• DR, DP, and DQ
• MHC class III molecules

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Antigen Presentation
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Transplantation

• Cells in transplanted tissue from one individual
  will have a different set of MHC surface antigens
  than those of the recipient
• Therefore, a recipient can mount an immune
  response against the foreign MHC molecules
• Haplotype
• Combination of A, B, C, DR, DQ, and DP alleles

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Transplantation
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CD1

• Antigen-presenting molecules
• Found on antigen-presenting and thymus cells
• Present lipid antigens

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Antigen Recognition

• Antigen is directly recognized by circulating
  antibody, antigen receptors on B cells (BCR), and
  T lymphocytes (TCR)

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Antibodies

• Also called immunoglobulins
• Produced by plasma cells
• Classes of antibody
• IgG, IgA, IgM, IgE, and IgD
• Characterized by antigenic, structural, and
  functional differences

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Antibodies
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Antibodies
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Immunoglobulin G (IgG)

• Most abundant class (80-85)
• Transported across the placenta
• Four classes
• IgG1, IgG2, IgG3, and IgG4

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Immunoglobulin A (IgA)

• Two classes
• IgA1 molecules are found predominantly in the
  blood
• IgA2 molecules are found predominantly in normal
  body secretions
• IgAs found in body secretions are dimers anchored
  by a J chain and a secretory piece
• Secretory piece may function to protect IgAs
  against enzyme degradation

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Immunoglobulin M (IgM)

• Largest of the immunoglobulins
• Pentamer stabilized by a J chain
• First antibody produced during the primary
  response to an antigen
• Synthesized during fetal life

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Immunoglobulin D (IgD)

• Limited information on IgD function
• Low concentration in the blood
• Located primarily on the surface of developing B
  lymphocytes
• Function as one type of B cell antigen receptor

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Immunoglobulin E (IgE)

• Least concentrated of the immunoglobulin classes
  in the circulation
• Mediator of many common allergic responses
• Defender against parasites

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Antibody Structure

• Antigen-binding fragment (Fab)
• Recognition sites (receptors) for antigenic
  determinants
• Crystalline fragment (Fc)
• Responsible for biological function
• Polypeptide chains (4)
• Light chains (2) and heavy chains (2)

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Antibody Structure

• Hinge region
• Constant and variable regions
• Complementary determining regions (CDRs)
• Framework regions (FRs)

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Antigen Binding

• Amino acid sequences of the variable regions of
  the heavy and light chains
• Framework regions control antibody folding
• Lock and key
• Noncovalent chemical interactions
• Antibody valence
• IgG, IgD, and IgE2
• IgA4
• IgMtheoretically 10, likely 5

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B Cell Receptor Complex

• Located on surface of B cells
• Consists of
• Antigen-recognition molecules
• Monomer IgM and IgD
• Accessory intracellular-signaling molecules
• Ig-alpha and Ig-beta heterodimers

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T Cell Receptor Complex

• Antibody-like transmembrane protein (TCR)
• Accessory proteins for intracellular signaling
• Referred to as CD3

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Generation of Clonal Diversity

• All necessary receptor specificities are produced
• Takes place in the primary (central) lymphoid
  organs
• Results in immature but immunocompetent T and B
  cells
• Primarily occurs in the fetus

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Clonal Selection

• Immunocompetent T and B cells migrate from the
  primary lymphoid organs to the secondary lymphoid
  organs to await antigen
• Primarily after birth
• Clonal selection is initiated by antigen
• Final products
• Plasma cells that produce antibody, effector
  cells that help Th, Tc, or Treg, and memory B and
  T cells

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T Cell Maturation

• The thymus is the central lymphoid organ of T
  cell development
• T cells move from the thymic cortex to the
  medulla
• Changes
• Development of the T cell receptors and
  expression of surface molecules
• T cells are released into the blood and take up
  residence in the secondary lymph organs

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Antigen Processing and Presentation

• Antigens require processing and presentation by
  antigen-presenting cells (APCs)
• Dendritic cells, macrophages, and B lymphocytes
• For processing and presentation to occur, the
  antigen must be of the appropriate type, the
  lymphocytes must be prepared to recognize the
  presented antigen, and the antigen must be
  presented appropriately

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Antigen Processing and Presentation
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Antigen Processing and Presentation
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Helper T Lymphocytes

• Help the antigen-driven maturation of B and T
  cells
• Facilitate and magnify the interaction between
  APCs and immunocompetent lymphocytes
• Steps
• Th interacts through antigen-specific and
  antigen-independent mechanisms
• Undergoes differentiation
• Mature Th interacts with plasma or T-effector
  cells

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Antigen Processing and Presentation
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Helper T Lymphocytes

• Subsets
• Th1 cells provide help in developing
  cell-mediated immunity
• Th2 cells provide help in developing humoral
  immunity
• Differences based on cytokine production

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B Cell Activation

• When an immunocompetent B cell encounters an
  antigen for the first time, B cells with specific
  BCRs are stimulated to differentiate and
  proliferate
• A differentiated B cell becomes a plasma cell
• A plasma cell is a factory for antibody
  production
• Single class or subclass of antibody

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Primary and Secondary Responses

• Primary response
• Initial exposure
• Latent period or lag phase
• B cell differentiation is occurring
• After 5 to 7 days, an IgM antibody for a specific
  antigen is detected
• An IgG response equal or slightly less follows
  the IgM response

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Primary and Secondary Responses

• Secondary response
• More rapid
• Larger amounts of antibody are produced
• Rapidity is due to the presence of memory cells
  that do not have to differentiate
• IgM is produced in similar quantities to the
  primary response, but IgG is produced in
  considerably greater numbers

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Class Switch

• Immunocompetent B cells use IgM and IgD as
  receptors
• During clonal selection, B cells have the option
  of changing the class of the antibody
• One of four IgGs, one of two IgAs, IgE, or an IgM
  in a pentamer form
• DNA rearrangement

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B Cell Clonal Selection
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T Cell Activation

• Binding antigen to specific T cell receptors
• Allows
• Direct killing of foreign or abnormal cells
• Assistance or activation of other cells
• T regulatory cells (Treg)
• Regulate the immune response to avoid attacking
  self
• Memory T cells

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T Cell Activation
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Superantigens (SAGs)

• Bind the variable portion of the TCR and the MHC
  class II molecules outside of their
  antigen-presentation sites
• Activates a large population of T lymphocytes
  regardless of antigen specificity
• SAGs induce an excessive production of cytokines
• Causes fever, low blood pressure, fever, and
  potentially shock

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Antibody Function

• Direct
• Neutralization
• Agglutination
• Precipitation
• Indirect
• Opsonization
• Degree of antibody protection is assessed by an
  antibody titer

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Secretory (Mucosal) Immune System

• Lymphoid tissues that protect the external
  surfaces of the body
• Antibodies present in tears, sweat, saliva,
  mucus, and breast milk
• IgA is the dominant immunoglobulin
• Small numbers of IgG and IgM are present

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Secretory (Mucosal) Immune System
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IgE Function

• Provides protection from large parasites
• Initiates an inflammatory reaction to attract
  eosinophils
• When produced against innocuous environmental
  antigens, they are a common cause of allergies
• Fc portions of IgEs are bound to mast cells

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IgE Function
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Cell-Killing Mechanisms

• Cytotoxic T lymphocytes
• Destroy cancer cells or cells infected with virus
• Perforin, granzymes, or direct receptor
  interactions

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Cell-Killing Mechanisms
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Other Cells

• Natural killer (NK) cells
• Complement Tc cell mechanisms
• Regulatory T cells (Treg)
• Provide peripheral tolerance
• Affect recognition of antigen and suppress
  proliferative steps of antigen recognition

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Fetal and Neonatal Immunity

• Antibody function is deficient
• Capable of primary IgM response unable to
  produce an IgG challenge
• Immunity provided by maternal antibody
• Trophoblastic cells transport maternal IgG across
  the placenta
• Newborn IgG levels are near adult levels

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Fetal and Neonatal Immunity
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Aging and Immune Function

• Decreased T cell activity
• Thymic size is 15 of its maximum size
• Decreased production of specific antibodies
• Increase in circulating antigen-antibody
  complexes
• Increase in circulating autoantibodies
• Decrease in circulating memory B cells