Chapter
15 - Specific Defenses
When
general attack responses are not enough to stop the spread of an invader & illness
follows, three types of white blood cells (macrophages, T cells, & B cells) will
counterattack. Their interactions are the
basis of the immune system. Two important
characteristics of the immune system are its specificity & its memory.
Summary
Table: White Blood Cells Involved in Specific
Defense Responses:
1. Macrophages
-
phagocytic; involved in inflammatory, antibody-mediated, & cell-mediated responses
(nonspecific responses); important not only for phagocytosis, but also for antigen presentation.
2. Lymphocytes (these are not all of the lymphocytes, but some of
the important ones)
a.
B
cells
- produce antibodies (Ab) [Y-shaped protein molecules
which bind to specific targets (antigens) & tag them for destruction by phagocytes or
the complement system].
b. Cytotoxic
T cells -
involved in the cell-mediated response; directly destroy body cells already infected by
certain viruses or parasitic fungi.
c.
Helper
T cells
- involved in the antibody-mediated & cell-mediated responses; they stimulate the
rapid division of B cells & cytotoxic T cells by producing compounds called
interleukins.
d. Memory
cells
- certain B cell & T cells, which are produced during a first encounter with a
specific invader (primary immune response), but are not directly involved in this first
attack; they circulate freely & respond rapidly to any subsequent attacks (secondary
immune response) by the same type of invader.
Recognition
of Self & Nonself
Among
the surface proteins on your own body cells are MHC
markers ("self" markers), which are normally ignored by your own white blood
cells; MHC markers are unique to each individual (no one has the same kinds, except in the
case of identical twins); microbes, etc. also have markers [called antigens (Ag) because they are foreign to your
cells] on their surfaces which are not ignored by white blood cells; antigens are usually surface proteins with
distinct configurations that trigger immune responses.
I. PRIMARY IMMUNE RESPONSE:
A
first-time encounter with an antigen elicits a primary immune response from the
lymphocytes & their products. We will
consider an antibody-mediated immune response & a cell-mediated immune response to
such an encounter:
A. Antibody-Mediated
(Humoral) Immune Response -
The main targets of this type of response are extracellular organisms: bacteria,
extracellular phases of viruses, some fungal parasites, & some protozoans. Antibodies can't bind to antigen if the invader
has already entered the cytoplasm of a host cell!! The
following events involve a bacterial infection:
1. Macrophages -
When bacteria enter the body, their invasion triggers a general inflammatory response,
& macrophages engulf some of the bacterial cells by phagocytosis. The engulfed bacteria move into the cytoplasm of
the macrophages inside vesicles. These
vesicles fuse with lysosomes (vesicles containing digestive enzymes) & enzymes digest
the bacterial cells, but do not destroy their surface antigens. At the same, the cell synthesizes MHC markers
& is packaging them into vesicles in its golgi apparatus. The vesicles containing the antigen & the
vesicles containing the MHC markers fuse. Inside
the vesicle, the antigen binds to the MHC markers (now called antigen-MHC marker
complexes). The vesicle containing the
complexes undergoes exocytosis & the complexes are inserted in the cell membrane of
the macrophage. Macrophages can now present
the antigen to other white blood cells (ex. helper T cells).
2. Helper
T cells -
When the appropriate helper T cells make contact with the macrophages, some of their
membrane-bound antigen-receptors bind to the
macrophage antigen-MHC complexes (these receptors are specific for these particular
complexes - they won't bind to any other type!). This
binding causes macrophages to secrete a compound called interleukin that stimulates the helper T cells to
secrete their own interleukins. The helper T
cell interleukins will cause activated B cells to start dividing (see below).
3. B cells
a.
B
cells "mature" in bone marrow. While
each B cell is maturing, it makes many copies of just one kind of antibody (each B cell is
unique in that it will only make one kind of antibody that no other B cell makes - each
kind of antibody will only react to one antigen). While
the B cell is maturing, some of the antibodies it is producing become positioned at the
cell's surface, where they will later bind to a specific antigen. The "tail" of each antibody is embedded
in the cell membrane, & the "arms" stick out above the cell membrane's
surface. From the bone marrow, B cells
migrate to the lymph nodes, the spleen, or lymphatic tissue in the g.i. tract.
b. When
a B cell is released from the bone marrow into circulation, it is known as a "virgin" B cell because its antibodies
have not yet made contact with antigen.
c.
A
virgin B cell with the right antibodies binds to a specific antigen. Some of the antigen is then taken into the B cell,
combined with MHC markers, & moved to the B cell surface (see how macrophages do this
above). The B cell is now said to be activated; it's no longer virgin - it's come into
contact with a specific antigen.
d. If
an activated B cell interacts with the appropriate interleukin-producing helper T cell
(see above under helper T cell), the B cell will start dividing quickly, giving rise to a clonal population of identical B cells.
e.
Part
of the B cell clonal population differentiates into plasma cells, which secrete thousands of copies
of the particular antibody that had been produced by the virgin B cell (the antibody
actually leaves the plasma cells!). Antibodies
have different effects on antigen:
1.) Neutralizing
- the binding of Ab with AG blocks or neutralizes the damaging effect of some bacterial
toxins and prevents attachment of some viruses to body cells.
2.) Immobilization
- If Ab forms against cilia or flagella of motile bacteria, the Ab-Ag complex may cause
the bacteria to lose their motility, limiting their spread into nearby tissues.
3.) Agglutination
- Because antibodies have tow or more sites for binding to Ag, the Ab-Ag reaction may
cross-link pathogens to one another, causing agglutination (clumping together); this
enhances phagocytosis.
4.) Activation
of complement system-
complement proteins cause lysis of microbe; complement also cause opsinization, which
enhances phagocytosis.
5.) Opsinization
- Antibodies enhance phagocytosis by coating the microbe (remember that complement protein
can also be opsonins).
f. Some
of the B cell clones differentiate into memory B
cells, which are involved in a secondary response (will be discussed later).
How
do B cells produce the millions of different antibodies required to detect all of the
millions of possible antigens? Part of each arm of an antibody is a polypeptide
chain made up of amino acids, folded into a groove or cavity, which "fits" with
the antigen (there are poor fits & better fits - the better the fit the better the
immune response). All B cells have the same
genes for coding the amino acids in the chain, but each maturing B cell shuffles the
genetic code into one of millions of possible combinations, so that the sequence of amino
acids then gets shuffled (this changes the shape of the protein, thus changing the shape
of the antibody). So B cells can give rise to
virtually unlimited chain configurations. Therefore,
when an antibody comes into contact with an antigen for the very first time, the right
antibody just happened to be there! Your
immune system did not produce the virgin B cell antibodies in response to a particular
antigen! It is our genes that determine what
specific foreign substances our immune system will be able to recognize & resist! (The same rule applies to T cell Ag receptors.)
The 5 Classes of Antibodies (Ab):
(Ab's
are part of the immunoglobulin (Ig) family of proteins)
1.) IgG
- largest class, activates the complement system; effective opsonin (enhances
phagocytosis); only Ab that can cross the placenta (protects the newborn for several
months after birth); predominates in secondary immune responses; all antitoxins belong to
this class (remember antitoxins are antibodies made against exotoxins made by G(+) &
G(-) bacteria); found in blood & extracellular fluids.
2.) IgA
- second largest class; found in blood and body secretions (saliva, milk, mucus, tears);
protects mucosal surfaces, especially preventing attachment of viruses; its presence in
colostrum defends the g.i. tract of newborn humans against infection.
3.) IgM
- extremely effecting in fixing complement; sometimes called early Ab, because it is the first Ab to form
during a primary immune response; its structure allows it to build complex Ag-Ab lattices
that clump, forming a visible precipitate; it’s found in blood & extracellular
fluids.
4.) IgD
- main type of Ab displayed on the surface of B cells.
5.) IgE
-
fixed to the surface of basophils; stimulates the microbe to release histamine when the
basophil binds to Ag; basophils then releases histamine; this can contribute to allergies
B. Cell-Mediated
Immune Response (Cellular Immunity) -
This type of response deals with viruses & other pathogens that have already
penetrated host cells (they are intracellular!), where they remain hidden from antibodies. In the cell-mediated immune response, the host
cells are killed by cytotoxic T cells (killer T cells) before the pathogens can replicate
& spread to other cells. The following
events involve a viral infection:
1. Cytotoxic
T cells
or Killer T cells - Cells in the bone marrow
give rise to forerunners of killer T cells, which travel to the thymus gland, where they
mature into killer T cells. Each T cell
produces antigen receptors that become positioned at its surface (these receptors are not
antibodies, but are similar!!!). Ag receptors
recognize specific Ag-MHC marker complexes. When
an Ag enters the body, only a few T cells have receptors that can recognize & bind to
the Ag.
2. Killer
T cells are released into circulation by the thymus gland.
When a virus infects a cell, viral proteins become associated with MHC markers on
the host cell's surface.
3. The
antigen receptors of killer T cells, bind to the antigen-MHC complexes of macrophages,
infected cells, etc.
4. Cytotoxic
T cells secrete perforins (proteins that punch
holes in the infected cell's cell membrane).
5. This
kills the infected cell, but prevents the virus from replicating & spreading to other
cells.
Note: As
in antibody-mediated immune responses, macrophage-stimulated helper T cells stimulate
killer T cells to divide by secreting interleukins. This
creates a clonal population of killer T cells, all with the same antigen receptor as the
original killer T cell (these cells are not called plasma cells!!!!!). As with B cells, some of the clones become memory
T cells & will be involved in a secondary immune response. (When the body rejects a tissue graft or an organ
transplant, cytotoxic T cells are one of the reasons why.
They recognize MHC markers on the grafted cells as being foreign. Organ recipients take drugs to destroy cytotoxic T
cells, but this compromises their ability to mount immune responses against pathogens.)
1.
Active
- a product of a person's own immune system.
a.
naturally
acquired
- comes from infections encountered in daily life.
b.
artificially
acquired
- stimulated by vaccines.
2.
Passive
- Ab's produced elsewhere are given to a person.
a.
naturally
acquired
- refers to Ab's transferred from mother to fetus across the placenta & to the newborn
in colostrum & breast milk.
b. artificially
acquired
- consists of Ab's formed by an animal or a human & administered to an individual to
prevent or treat infection; ex. hepatitis A, diphtheria.
III. SECONDARY IMMUNE RESPONSES:
A
secondary immune response to a previously encountered antigen can occur in 2 or 3 days. It is greater in magnitude than the primary
response & of longer duration. This is
because some of the B & T cells of the clonal populations do not get involved in the
primary response attack. They circulate for
years as memory cells. When a memory cell encounters the same type of
antigen that initiated the primary response, it divides at once (no helper T cells are
needed to stimulate cell division!). A large
clonal population of active B or T cells can then be produced in just a matter of days.
IV.
IMMUNIZATIONS:
Defined: Immunization
means deliberately introducing an antigen into the body that can provoke an immune
response & the production of memory cells. The
first injection elicits a primary immune response. A
second injection (the "booster shot") elicits a secondary response, which
provokes the production of even more antibodies and memory cells to provide long-lasting
protection against the disease. We will
discuss the types of vaccines in chapter 15.