Transcript Slide 1

Specific Immunity—3rd line of defense
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Who are the players?
Antigens
Antibodies and B-cells
Antibody editing and clonal selection
Cytotoxic T-cells
Helper T-cells
MHC and antigen processing
Who are the players?
• Antigens: foreign proteins, usually part of virus or bacteria
• Antibodies: Proteins made by immune cells that “recognize”
or bind with particular antigens. Original diversity of antibodyproducing cells depends on recombination of genetic
sequences during cell development
• Macrophages: phagocytic cells in blood)
• Cytotoxic T-cells: “killer” white blood cells
• Helper T-cells: present antigens so that good “match” can be
found among antibody-making cells
• B-cells: recognize antigens and make antibodies
• MHC: Major Histocompatiblity Complex—allows body to
recognize own cells so that their proteins don’t trigger immune
response, also important in clonal selection
• Clonal selection: process by which B and T-cells that make
antibodies that recognize body’s own antigens (“autoantigen”)
are eliminated during development.
Antigens
• Proteins (or sometimes carbs) that are
recognized (glom onto) specific
antibody
• Exogenous antigens: On outside or
free of pathogen
• Endogenous antigens: From
pathogens that live and reproduce
inside host cell. Immune cells can
only see these antigens when they are
“presented” on surface of host cell
surface, incorporated into cell
membrane
• Auto-antigens: Body’s own antigens.
Immune cells that recognize these
antigens are eliminated during immune
system development (by antibody
editing or clonal selection/deletion—
more below)
• Each antibody has
specific antigen binding
site formed by variable
regions of heavy and light
amino acid chains.
Variation among
antibodies in these
binding sites comes from
random recombination
from billions of possible
DNA/gene combinations.
• Rest of heavy and light
chains are constant giving
antibodies their
characteristic shape and
function
Antibodies
a.
b.
c.
d.
Disable pathogens by
glomming (agglutinating)
them together
Neutralize toxins by
glomming onto them on the
surface of pathogens
Stick to surface of pathogen
so it can be recognized by
phagocytic cells
Immunoglobulins are classes
of antibodies—each class
has more specific immune
function
What do antibodies do?
Where do
antibodies
come from?
• Made by B-cell lymphocytes
• 1011 B-cells in body, each with specific antibody, present for life
• Each B-cell has 100,000’s of copies of its antibody embedded
in cell membrane, called B-Cell Receptors (BCR)
• When a BCR reacts or gloms onto an antigen that it recognizes,
that cell is stimulated to produce free antibodies that are
secreted into blood as immunoglobulin (Ig)
How can each cell have its own different
antibody if they all have the same DNA?
• Nobel Price for Susumu Tonegawa
• DNA is processed and can change as new cells are formed
• Recombining regions of DNA that make the antibody recognition site
produces all the billions of different combinations of antibodies (and BCRs,
TCRs) that recognize any possible invader by the proteins it has on its
surface (so we hope!)
Antibody editing
by clonal selection
or deletion
• Variety of B-cells produced
by random recombination of
genes for variable regions of
antibody
• During B-cell development,
certain clonal lines are
eliminated because their
antibodies glom onto the
bodys own antigens
• B-cell production and clonal
selection occurs in bone
marrow during early years of
life
B-cells and antibodies—
end result is macrophage ingestion
• Each B-cell make specific
antibody which is present
on cell surface as BCR (B
cell receptor)
• When that cell “recognizes”
an antigen (the antigen
sticks to the BCR), then it
begins producing free
antibody (immunoglobulins
or Ig’s) to secrete into the
blood
• Those Ig’s work to
eliminate the source and
possible damage caused
by this antigen via
agglutination, neutralization
and opsonization
• End result is generally
macrophage ingestion or
lysis of invading microorganism…
Antibody action…
…Result—
Macrophage
on the attack!!
B-cells and antibodies—
end result is macrophage ingestion
• Each B-cell make specific
antibody which is present
on cell surface as BCR (B
cell receptor)
• When that cell “recognizes”
an antigen (the antigen
sticks to the BCR), then it
begins producing free
antibody (immunoglobulins
or Ig’s) to secrete into the
blood
• Those Ig’s work to
eliminate the source and
possible damage caused
by this antigen via
agglutination, neutralization
and opsonization
• End result is generally
macrophage ingestion or BUT…usually B-cells cannot recognize antigens on
lysis of invading microtheir own…and the simple antibody response is
organism…
usually not sufficient to fight an infection.
THUS…T-cells (oh, no)….
T-cell lymphocytes
• Also made in bone marrow, but
mature in thymus (thus “T”)
• Have TCR (T-cell receptor),
much like BCR), but don’t
produce Ig’s
• Also about 1011 T-cells, each
with its own specific antigen
recognition site, produced by
random recombination of
genetic sequence and edited
via clonal selection in thymus
• 90% of lymphocytes in blood
are T-cells. Also in lymph
nodes, spleen, Peyer’s patches
of intestines
• Three types of T-cells:
Cytotoxic T-cells (CD8)
• Recognize and kill other
cells of the body—why?
• Those cells are infected by
virus or other intra-cellular
pathogen
• Cells “process” antigen from
virus and “present” it on cell
surface embedded in cell
membrane so that TCR’s or
antibodies can “recognize”
that non-self antigen
Helper T-cells (CD4)—two types
• Type 1—stimulate cytotoxic Tcells
• Type 2—stimulate B-cells
• Helper T-cells recognize
antigens, but can do nothing
about it on their own. They
secrete cytokines (such as
interleukin) to direct what kind of
immune response should be
activated.
• For most infections, Helper T’s
are crucial for a robust response.
• Thus, in AIDS, these cells are
killed, as they themselves
present HIV viral antigens and
invite cytotoxic T-cells or
macrophages to ingest them.
• Without the helper T-cells, good
response to most infections
cannot be mounted.
Antigen processing and MHC
• Phagocytes that have ingested pathogens, as
well as cells infected with virus can “process”
and “present” antigens on their cell
membrane
• MHC molecules aid in this process
• By presenting antigens, the immune
response is greatly accelerated
• Especially important in stimulating early
response to previous pathogens
(immunological memory—coming next!)
Antigen processing and MHC
• Nice one-page summary
review of specific immune
response
• From the molecules of
HIV text
• http://www.mcld.co.uk/hiv/
?q=helper%20T%20cells
This animation has everything you need to know
about the specific immune response…
http://www.apchute.com/lymphatic/inflam.swf