Download Immune system II

The Generation of Specific Immunity
Antibody structure
! Antibodies classified by
specificity (antigen,
binding site) and class
(general structure,
function)
! Differences in variable
regions produce
different specificities;
differences in constant
regions produce
different classes of
antibodies
!
Survey of effective
antigens suggests that
thousands of
antibodies are possible
Antibody formation
Multiple exposures to antigen induce a “memory response”
IgG
IgM
IgM
(blue)
(red)
Questions...
! Why is there a memory response?
! With so many antibodies, why are there none
that react with one’s own proteins?
! Where do all the specific binding sites come
from?
! How is the genetic information for that many
proteins stored?
! How and why does the type of immunoglobulin
change after reinnoculation?
! How are antibodies induced by the presence of
antigen?
There are several types of lymphocytes
involved in the immune response
(B for bone)
(T for thymus)
Clonal selection
Why is there a memory response?
! Lymphocyte stem cells (B cells and others)
differentiate to become potential antibody
producing cells, each capable of producing one
antibody (of random specificity).
! Presence of antigen stimulates cell division of
the cell(s) that make antibodies that react with
that antigen to produce a clone of antibody
producing cells.
! Once stimulated, there are more of the clone
ready to be re-stimulated—thus the memory
response.
With so many antibodies, why are there none
that react with one’s own proteins?
! Early in the beginning of stem cell
differentiation, clones that produce anti-self
antibodies are removed.
Stimulation of a
B cell clone involves
a membrane-localized
binding site
How do the large number of specific binding sites arise?
How is the genetic information for that many proteins stored?
! Antibody genes come from diverse combinations of
gene parts
! B-cell maturation joins V (variable), D (diversity)
and J (joining) segments to form variable region of
gene, connected to C (constant) region
! Thus, each clone has a different variable (VDJ)
region and produces a protein with a different
specificity
! B-cell maturation joins V (variable), D (diversity)
and J (segments) to form variable region of gene,
connected to C (constant) region
! After transcription in a plasma cell, RNA splicing
joins the VDJ region to the constant region
How and why does the type of immunoglobulin
change after reinnoculation?
Class switching changes
the constant region
How are antibodies induced by the presence
of antigen?
Antigen-presenting cells and T Cells
MHC and antigen presentation
! Class II MHC (major histocompatibility
complex): antibody-like membrane protein
! MHCs in different clones: different specificities
! Alpha and ß chains with binding sites
! Constant region anchors molecule to plasma
membrane
! Macrophages with Class II MHC take up antigen
and break it into pieces; display pieces on MHC
on surface.
MHC and antigen presentation
! Alpha and ß chains with binding sites
! Constant region anchors molecule to plasma
membrane
(Looks the same on a
macrophage)
MHC and antigen presentation
! Macrophages with Class II MHC take up antigen
and break it into pieces
! Display pieces on MHC on surface.
! Present antigen pieces to TH cells
Macrophage
activates TH cell
TH cells stimulate
B cells to become
plasma cells
Cellular immunity: all cells display internal antigens on their
surface through Class I MHC proteins
TC (cytotoxic) cells recognize foreign antigens
•Foreign (non-self: skin grafts, virus-infected cells,
some cancerous cells)
•Self: T cells removed during embryogenesis
TC cells kill the cells with foreign antigens
Summary
! T and B lymphocytes, and the MHC and
immunoglobulin gene systems, work together to
protect the vertebrate body from a) bacterial,
fungal, and protist infections, b) viral infections, and
c) cancerous changes in cells.
! Development of the immune system involves
changes in gene activity (and even gene structure)
in clones of cells
! Development of the immune system also involves
responses to exogenous influences (antigens) and
signal cascades
! Major new principle: cells change their genetic
information (in random fashion) as a part of
development; use selection to choose the useful
information (Darwinian development!)
! Does this occur in any other organ system? No
evidence, but maybe in the brain?