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Humoral Immune Response

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can handle different types of microbes ... Ab response to different Ag depends on the ... Receptor IgM and IgD highly variable with short cytoplasmic domains ... – PowerPoint PPT presentation

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Title: Humoral Immune Response


1
Chapter 7
  • Humoral Immune Response
  • Activation of B Lymphocytes and Production of
    Antibodies

2
Antibodies
  • Part of the adaptive immune response functions to
    neutralize and eliminate extracellular microbes
    and microbial toxins
  • More useful against polysaccharide and lipids and
    these types of toxins B cells respond to many
    Ag types
  • Naïve B cells recognize Ag but cant make Ab
    until activation allows differentiation to Ab
    secreting

3
Phases and Types of HIR
  • Naïve B-cells have 2 classes of membrane bound Ab
    IgM and IgD
  • act as receptor for Ag
  • Activation of Ag specific cells leads to clonal
    expansion
  • Go from 1 to 4000 Ab secreting cells
  • Differentiation into effector cells secreting Ab
  • secreted Ab is same specificity of as naïve
    membrane bound receptor but during
    differentiation can cause Ab with different heavy
    chain and effector function heavy chain class
    (isotype) switching
  • can handle different types of microbes
  • Repeated exposure to causes Ab with increasing
    affinity to Ag affinity maturation
  • improved Ab

4
Recognition and Activation
5
T-Cell Dependence??
  • Ab response to different Ag depends on the
    requirement of T-cell help
  • B-cells recognize many Ags protein,
    polysaccharide, lipid and small chemicals
  • T-cells that recognized Ag play role in
    activation and powerful inducer of isotype
    switching
  • no T-cell protein Ag makes poor or no Ab
    response T-dependent to get good Ab
  • Polysaccharidde, lipid and non-protein Ag
    stimulate Ab production without T helper cells
    T independent
  • little heavy chain switching or affinity
    maturation

6
Responses
  • Ab responses differ qualitatively and
    quantitatively
  • 1? response is the first time exposed
  • small amounts of Ab produced
  • 2? response is the subsequent exposure
  • more Ab produced
  • if to a protein, see isotype switching and
    affinity maturation
  • increase in TH cells with repeated stimulation
  • Ag recognition ACTIVATES B-lymphocytes

7
  • Must be able to tell the difference between 1?
    and 2? responses

8
Stimulation of B-Cells by Ag
  • Initiated when Ag-specific B-cells in lymphoid
    follicles of the spleen, LN and mucosal lymphoid
    tissues recognize Ab
  • Ag of microbes in tissues or blood are
    transported and concentrated in B-cell rich
    follicles how is not well defined
  • Ag without processing NATIVE CONFORMATION
  • triggers signaling pathways
  • requires 2nd signals produced during innate
    immune response

9
Ag-Induced Signaling in B-Cells
  • Membrane Ig receptors cluster (bind and move
    together) and trigger biochemical signals that
    are transduced by receptor-associated signal
    molecules
  • similar to T-cells activation
  • must cross-link 2 or more receptors for signal
    transduction 2 or more Ag in an aggregate or
    repeating epitopes of one Ag molecule binds
    adjacent Ig molecules
  • Polysaccharide, lipid and other non-protein Ag
    have multiple identical epitopes in each molecule
    (bind numerous Ig receptors on B-cell)
  • transduced by receptor-associated proteins

10
Signals
  • Receptor IgM and IgD highly variable with short
    cytoplasmic domains
  • recognize Ag but do not transduce signals
  • IgM and IgD are non-covalently linked to Ig? and
    Ig? to make the B-cell receptor (BCR) complex
  • Ig? and Ig? contain conserved immunoreceptor
    tyrosine-based activation motifs (ITAM) seen in
    other activation receptors
  • 2 or more Ag receptors cluster, Tyr in ITAM of
    Ig? and Ig? are phosphorylated by kinase
    associated with BCR complex
  • Tyr-PO4 is the docking sites for adaptor protein
    which gets phosphorylated and recruits a number
    of signal molecules
  • Signal cascade not as well understood as T-cells
    but essentially similar activates trnscription
    factor that turn on genes whose proteins involved
    in B-cell proliferation and differentiation

11
B-Cell Activation
  • Syk is similar to ZAP-70

12
Complement and B-Cell Activation
  • B-cells express receptor for a complement protein
    which provides signals to activate B-cells when
    bound to ligand
  • Complement is activated by microbes and Ab
    attached to microbes functions as effector
    mechanism of host defense (Chapter 8)

13
Complement Activation of B-Cells
  • Microbe has C3d (cleavage product of C3) coating
    the surface
  • B-cells has type 2 complement receptor (CR2 or
    CD21) and it binds to C3d
  • B-cells recognize microbe Ag by the Ig receptor
    and also recognizes C3d on CR2 receptors
  • C3d acts as the 2nd signal for B-cell activation
  • CR2 enhances Ag-dependent activation of B-cells
  • Ag recognition is 1st step

14
Activation
  • Microbes themselves or innate immune response to
    microbes provide signals in addition to Ag
    recognition to activate lymphocytes
  • C3d is similar to co-stimulators in T-cell
    activation

15
Consequences of Ag-Mediated B-Cell Activation
  • Initiate B-cell proliferated and differentiation
  • Prepare B cells to interact with TH cells if
    protein Ag
  • B-cell enters cell cycle and proliferates
    clonal expansion
  • Produces more IgM and secrete IgM early phase
    immune response induced

16
Early Phase is Greatest
  • Response is greatest for polysaccharide and
    T-independent Ag
  • multivalent
  • cross-links many Ag-receptors
  • activates C strongly
  • Proteins cant do the 1st 2 so make weak response
    without TH response
  • lack multiple, identical epitopes

17
Additional Steps
  • At least 3 other changes to the B-cell to enhance
    ability to interact with TH cells acting as APC
  • increase the expression of B7 costimulator
    molecule (2nd signal for T-cells)
  • expression of cytokine receptors cytokine
    mediators of TH cells
  • decrease the expression of chemokine receptors
    chemokines keep B-cell in follicles, without
    chemokines they can migrate out of follicle to
    where TH cells are

18
Function of T-Helper Cells
  • Required for strong response to protein Ag
  • B-cell and T-cell must recognize protein Ag and
    come together to stimulate B-cell proliferation
    and differentiation in the lymphoid tissue
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