Transcript Evolutionary Genetics

Immunogenetics
Genetic Changes that Provide for
Homology and Diversity Among
Immune System Proteins
T cell receptor
Stimulate an
immune response
Antibody
Immune System Cells and Receptors
Communication
Among Immune
System Cells
1. Macrophage
engulfs
7. Division gives invader
rise to memory B
cells and plasma
cells
2. Macrophage
displays
“processed”
antigen on
MHC molecule
6. Activated Helper
T cell stimulates
division of selected
B lymphocyte
4. Helper T Cell
binds to
Macrophage
3. Invader binds to B
lymphocyte that
carries antibody
matching the antigen
5. Macrophage
releases cytokines to
activate Helper T cell
Clonal Selection of B cells
B lymphocyte with
antibody matching
the antigen is
stimulated to divide
Each B lymphocyte
has a unique antibody
on its surface
B cell-bound antibodies
recognize antigens on a
bacterial or viral invader.
Circulating antibodies
mark the invader for
destruction.
Applying Your Knowledge
1.
2.
3.
4.
5.
T cell receptor
MHC Protein
Antibody
All of these are correct.
None of these is correct.
A. Which one is used to display antigen
on the surface of a macrophage?
B. Which one is secreted by plasma cells?
C. Which one recognizes displayed
antigen on the surface of a
macrophage?
Antibody Structure
Antibody has 2 heavy chains and 2 light chains.
Each chain has variable (V) and constant (C) region
joined by a J region.
Variable regions bind to antigen.
Constant regions bind to cells or other antibodies.
Structure and Expression of Light Chain Genes
30-50
Somatic
recombination
brings one V and
one J segment
together
RNA Processing
leads to one VJC
combination
5
Structure and Expression of Heavy Chain Genes
51 V
27 D
Somatic
recombination brings
one V, D and J
segment together
near a C segment
RNA Processing
leads to one VDJC
combination
6J
Somatic Recombination
Generating Antibody Diversity
Germ Line
Diversity
Combinatorial
Joining
Junctional
Diversity
Multiple V, D, J Segments
Large number of V, D, J combinations
by somatic recombination
Mutations produced at the junctions
between gene segments by
exonuclease and terminal transferase
activities
V genes undergo an increased mutation
Somatic
Hypermutation rate as immune cells divide throughout
the response period
Joining Light & Combining different light and heavy
Heavy Chains chains increases the number of unique
antibodies formed
Applying Your Knowledge
1.
2.
3.
4.
Junctional Diversity
Germ Line Diversity
Somatic Recombination
Somatic Hypermutation
Which choice best explains or causes
• The presence of multiple V, D and J
segments in DNA of precursors to B
cells?
• The increase in variability of V regions as
the immune response progresses?
• The formation of unique VJC
combinations for heavy and light chains?
How did the arrangement of
antibody genes arise?
• Changes in gene number and
organization are due to
–Duplication
–Diversification
–Selection
Levels of Duplication
Individual Genes
Multigene Families
Gene Superfamily
Action of Natural Selection
Natural selection acts on the genetic
variability caused by mutation
If the Mutation is
The gene will be
Neutral
Unselected
(Remain or Disappear as a
result of genetic drift)
Deleterious
Eliminated
Advantageous
Fixed
Three Multigene Families Encode Antibodies
Immune System Receptors Belong to the
Immunoglobulin Gene Superfamily
• A Gene Superfamily is a large set of related
genes that is divisible into smaller sets or
families
• Genes in each family are more closely related
to each other than to genes in other families
• Multigene families within this Superfamily
– Antibody Genes
– T cell receptor genes
– MHC protein genes
Immunoglobulin Superfamily Genes
Share a Common Homology Unit
Applying Your Knowledge
1. Duplication
2. Diversification
3. Selection
A.
B.
C.
Which process would lead to different
sequences for V regions of IgM and TcR?
Which process causes an increase in the
number of homology units?
Which process would establish a new variant of
the homology unit as part of the gene family?