BI 112 Davison
lecture notes, for Wednesday, March 17, 2003
II.
Specific Defenses
Involves white blood cells more appropriately called lymphocytes
because they are concentrated in the lymphatic system but also occur in
blood stream and interstitial fluid.
There are two major types of lymphocytes:
B cells – mature in bone marrow; produce
antibodies that attack the intruder
T cells – mature in thymus; attack your
cells infected by an intruder; also promote B cell activity
Both B and T cells possess antigen receptors.
Definitions:
Antigen – a chemical (often a protein) that
invokes an immune response. Typically,
antigens are found on the surface of invading organisms.
Pathogens hopefully have antigens.
If they did not, we would not have an immune response to defend
ourselves against them.
Antigen receptor – a protein molecule on the
surface of B or T cells. The
shape of the antigen receptor molecule is complementary to the shape of
the antigen it recognizes. Each
B or T cell has only one type of antigen receptor but it is repeated for a
hundred thousand times across the surface of the cell.
Thus a given B or T cell can only recognize one type of antigen.
See figs. 43.6 & 43.9 for highly diagrammatic illustrations of
B and T cell antigen receptors.
Specific Defenses require the ability to
Distinguish Self from Nonself
Your body is able
to recognize a foreign intruder or a cell infected with a foreign intruder
not because of a physical sensation of its presence, but because of a
chemical recognition system.
The immune system develops a population of B and T
cells that collectively possess a million different antigen
receptors. Since antigen
receptors are the product of genetic instructions, it was long a mystery
as to how there could be more antigen receptor types than there are types
of genes in our entire genome. The
enormous variety of antigen receptor types is produced by independent
genetic recombination that occurs in maturing B and T cells.
Essentially new alleles are produced within the maturing B and T
cells giving them the ability to synthesize new types of proteins (antigen
receptors), thus giving them the collective ability to recognize many
types of antigens. These
novel alleles where not inherited from your parents, they are created anew
in your bone marrow tissue (see p. 905 for additional info.).
Of further interest on a theoretical note, some the
antigen recognition sites that develop may, by chance, be complementary in
shape to normal self proteins. Should
these B and T cells mature one would expect an autoimmune disorder
in which the body’s immune system attacks normal body tissue. It is thought that such B and T cells self-destruct before
they have a chance to harm other cells.
The exact cause of autoimmune disorders is not fully
understood. Autoimmune
diseases to be aware of include: 1)
Type I diabetes (“insulin dependent diabetes” or “juvenile
onset diabetes”) which is caused by the immune system destroying the
pancreatic cells that produce insulin; and 2) multiple sclerosis, a
neurological disease in which T cells destroy the myelin surrounding nerve
cells of the central nervous system.
Before considering the major types of immune
responses triggered by antigen recognition, be aware of the following
comforting fact: many
invaders have more than one antigen, thus several “types” of B and T
cells can recognize a given invader.
Immune Responses of Specific Defenses
Once an antigen receptor binds to an antigen, a
response is triggered within the lymphocyte.
The responses are complex. Some
of the responses are explained below.
A key concept involved in the two major types of responses we will
cover (Antibody-Mediated Immunity [a.k.a humoral immunity] and Cell-Mediated
Immunity) is clonal expansion.
Clonal
Selection.
A Key Concept!
This process allows for the cloning of those specific
types of B or T cells whose antigen receptors have contacted complementary
antigens belonging to intruders that have entered your body. Thus, the antigen itself “selects” which B or T cells
proliferate and take an active role.
“The concept of clonal selection is so fundamental to
understanding immunity that it is worth restating: Each antigen, by
binding to specific receptors, selectively activates a tiny fraction of
cells from the body’s diverse pool of lymphocytes; this relatively small
number of selected cells gives rise to clones of thousands of cells, all
specific for and dedicated to eliminating that antigen.”
(p. 906 in Campbell and Reece 2002)
1st
- Contact between antigen receptor sites and antigens activates the B or T
cell.
2nd
- The activation thus triggered includes the proliferation of memory
cells (long lived B or T cells that mount a quick response in any
future invasion by same pathogen) and other cells that actually lead to
the destruction of the intruder, namely plasma cells and cytotoxic
T cells.
Memory cells – long-lived; serve to
stimulate the speedy reproduction of the specific type of functional cell
required to defeat a previously encountered invader during a future
infection. Memory cells
allow animals to become immune to previously encountered agents of
infection. Memory cells of
both B and T cell types are produced following antigen detection.
Plasma cells – type of B cell that produces
and releases antibodies; plasma cells are short-lived.
Cytotoxic T cells – a special type of T cell
that destroys your cells that are antigen-bearing; also short-lived.
Two Types of Specific Defense Immune Responses
1. Antibody-Mediated
Immunity or Humoral Immunity –
see figure 43.16
Directly involves B cells and the antibodies they produce.
An antibody is a protein released from a B cell type called a
plasma cell. The antibody
molecule is very similar to the antigen receptor molecule on the surface
of the B cell that detects the antigen.
Once secreted by the plasma cell, the antibody binds to the
antigen. Antibodies are
effective only against extracellular pathogens,
1st - Clonal
expansion of B cells upon activation by antigen.
Division of activated B cells produces plasma cells – B
cells that secrete antibodies
(recall,
antibody – protein that binds to an antigen) as well as a memory
cells.
2nd - The antibodies secreted by plasma
cells attack extracellular pathogens (viruses and bacteria) &
toxins produced by invaders. By
binding to the pathogen, the antibodies neutralize the pathogen,
directly destroy the pathogen, or “tag” the pathogen causing them to
clump or otherwise become available for macrophage engulfment (see fig.
43.16).
On a not so trivial note, there are many B cells that
will not enter clonal expansion without stimulation from helper T cells
(these release cytokines that stimulate other immune cells).
The AIDS virus attacks specifically the helper T cells, thus
greatly impairing the immune system.
Once a pathogen enters an animal cell, the pathogen
is safe from antibody attack. Also,
a cell that has become cancerous is essentially a pathogen within the
body. A second type of immune
response is needed.
2.
Cell-mediated Immunity
Directly involves T cells and their direct assault on infected
cells.
Effective against intracellular pathogens and abnormal cells.
T cells attack your body cells infected by pathogens.
T cells can detect body cells infected by pathogens thanks to the
following:
Fig. 43.9
Major Histocompatibility
Complex molecules (MHC molecules).
MHC molecules are found on the surface of a cell’s plasma
membrane. Most cells of the
body’s tissues have MHC molecules.
MHC molecules are molecules that are continuously produced in all
nucleated cells. As they make
their way to the plasma membrane they pick up a fragment of any number of
the proteins found within the cell’s cytoplasm.
If the cell is infected with viral proteins or bacterial proteins
these foreign proteins (i.e. antigens) will be transported and projected
from the infected cell’s surface. This
then presents [=Antigen Presentation] the antigen to T cells.
Among the antigen presenting cells are macrophages, long-lived
leukocytes also involved in nonspecific immunity. After eating an invading bacterium, macrophages present the
antigen from the bacterium to T cells. Those T cells that have antigen
receptor sites complementary to the antigen presented are stimulated to
undergo clonal expansion. The
resulting population of cytotoxic T cells will attack and destroy infected
cells (also displaying the antigen), thus killing the pathogen inside or
freeing the pathogen for destruction by antibodies released by B cells.
MHC molecules are found on
all nucleated cells’ plasma membranes.
Their function was revealed during research on tissue (“histo”)
transplant rejection (“compatibility”).
MHC molecules present
“self” or “nonself” proteins to the immune system (i.e. T cells).
MHC molecules also present
abnormal “self” molecules from cancerous or damaged cells thus
enabling T cells to destroy them.
Vaccination
Vaccinations allow one to acquire immunity (active immunity) by
exposing your immune system to a weakened pathogen or antigens from the
pathogen. B and T lymphocytes
with complementary antigen receptor sites to the antigen will under clonal
selection. The memory B and T
cells formed will live for many years and will enable a quick response
attack upon the actual virulent form of the pathogen if encountered in the
future.
AIDS
The acronym AIDS stands for Acquired Immunodeficiency Syndrome.
AIDS is caused by HIV, or the Human Immunodeficiency Virus.
HIV attacks T cells, specifically helper T cells; helper T cells
signal B cells to become active and release antibodies. |