Lecture 10 Immunoglobulins aka Antibodies

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Lecture 10Immunoglobulins aka Antibodies

• Chris Chase
• September 27, 2004

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Recirculating B cells are trapped by foreign
antigens in lymphoid organs
B cells enter lymph node and leave blood via high
endothelial venules
B cells proliferate rapidly
Antigen enters node in afferent lymphatic
Germinal centre releases B cells that
differentiate into plasma cells
GERMINAL CENTRE Transient structure of Intense
proliferation
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Mucosal Immune Surfaces
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Complementary determining regions (CDRs)
Variable
Constant
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Changes in the CDR of variable regions map to
three hypervariable regions CDR1, CDR2 and CDR3
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Hinge region allows flexibility-IgA, IgD, IgG
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Ab Binding Sites, Polyclonal and Monoclonal
Antibodies

• Chris Chase
• September 29, 2004

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Humoral effector mechanisms NEUTRALIZATION
NEUTRALIZING ANTIBODIES
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Passive Antibody Immunity

• Maternal Passive Antibody
• Humans and mice- Moms antibody is transferred to
  the fetus in last 3 months of pregnancy
• Cattle, horses, pigs and sheep- Maternal antibody
  is concentrated in the milk called colostrum.
  Transfer occurs in the 1st 12-24 hrs of life.

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Allotypic Idiotype
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Lecture 12 October 1, 2004 Antibody Gene
Rearrangement
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Genetic Organization of light and heavy chains
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B cell Rearrangements- Studs or Duds??

• Studs (Productive)
• Rearrangements are imprecise -to be expressed
  must be in frame
• Duds
• Out of frame
• Pseudogenes
• Less that 1 of 3 in both VL-JL and VH-DHJH are
  productive lt1/9 (11) of pre-B-cells mature
• Second chance-two alleles if one strikes out,
  the second may productively rearrange

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Generation of Antibody Diversity

• Seven Mechanisms Total possible gt1010 different
  antibody combining sites
• Multiple germ-line segments-human 51 VH ,
  27 D, 6 JH, 40 Vk, 5 Jk, 31 Vl, 4 Jl
• Combinational V-J and V-D-J
• Humans Heavy chain (51 X 27 X 68262)
• Light chain k (40 X 5200)
• Light chain l (31 X 4124)

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Generation of Antibody Diversity

• Seven Mechanisms Total possible gt1010 different
  antibody combining sites
• Junctional Flexibility
• P-region nucleotide addition (P-addition)
• N-region nucleotide addition (N-addition)

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Lecture 13 October 4, 2004 Antibody Gene
Rearrangement/ Antigen-Antibody Interactions
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Class Switching
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Antigen-Antibody Interactions

• Affinity
• Avidity

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Scatchard Plots
Monoclonal
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Antigen-Antibody Interactions

• Avidity- interactions between a multivalent
  antibody and antigen

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Antigen-Antibody InteractionsLecture 14 October
6, 2004
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Precipitation reactions- Bivalent and Polyclonal
or Multiple Epitopes
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Precipitation reactions
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Enzyme-Linked Immunosorbent Assay
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Immunofluorescence
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Lecture 15 October 8, 2004 Major
Histocompatibility Complex
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Major Histocompatibility Complex

• Two functions-
• Self- identify the cells belong to that
  individual vs non-self- graft rejection
• Present antigen to T-lymphocytes
• Polymorphic
• Many alternative forms or alleles at each locus

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Lecture 16 October 13, 2004 Major
Histocompatibility Complex
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Peptide Binding with MHC I
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Peptide Binding for MHC II
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Cellular Distribution of MHC
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Activation of Antigen Presentation System

• Signal 0- Danger signal
• Signal 1- Antigen presentation
• Signal 2- Co-stimulatory- receptor and cytokines

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Signal 2
Signal 1
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Figure 8-21
T Helper Cells need both antigen and
costimulatory signals