Download LectureGuideAdaptiveImmune(CH15) 7e

Lecture Guide for Chapter 15
Adaptive Immune Response
This is a lecture guide summarizing the events that occur to activate both B cells
and T cells and generate an immune response. Let’s get started!
When talking about the immune system it is important to identify the key players
in the process. First there are the specialized immune cells known as the lymphocytes, B
cell and T cells. In order to understand how these cells are activated and communicate
with other cells of the immune system we must discuss the MHC markers, also known as
self markers.
The MHC markers are receptors (or markers) that are found on the cell surface of
our body cells. They are glycoproteins, synthesized at the rough endoplasmic reticulum
and then sent to the Golgi apparatus for final processing and packaging in a vesicle. They
are transported to the surface of the cell membrane in a vesicle where they are finally
integrated into the cell membrane.
There are two kinds of MHC receptors, Class I and Class II. Class I MHC
markers are made by all body cells except red blood cells. When there receptors are made
they also integrate a piece of a protein (specifically short chains of amino acids known as
peptides) found in the in the cytoplasm into the structure of the receptor. Class I MHC
markers are able to “show” what is going on in the inside of a cell and represent
endogenous antigen. For example, if a cell is infected with a viral infection, there will be
viral proteins present in the cytoplasm. These viral proteins will become integrated into
the structure of the MHC receptor, “showing” the presence of the virus inside this cell.
MHC Class II markers are made in a similar fashion to MHC Class I, synthesized in the
rough endoplasmic reticulum, transported to the Golgi apparatus, and also to the
phagolysosome. At the phagolysosome a peptide fragment is picked up and integrated
into the final structure of the receptor. In other words, MHC Class II markers are able to
display fragments of what has been ingested via phagocytosis (exogenous antigen) to the
rest of the immune system cells. Summary: MHC class I helps to alert the immune
system to intracellular pathogens (viruses and intracellular bacteria) by sampling
endogenous antigens, and MHC class II helps to alert the immune system to extracellular
pathogens (bacteria that grow outside of cells) by sampling exogenous antigens.
How are B cells activated?
Remember that B cells mature in the bone marrow from stem cells. When they are
mature, they are actually regarded as naïve B cells and are found in the lymph nodes.
Naïve B cells have B cell receptors on their cell surface that are similar in structure to
antibodies. These receptors have a unique binding region (on the tips) to a particular
antigen. When the correct antigen finds the correct naïve B cell, the antigen will bind to
the B cell receptor. The binding promotes the Naïve B cell to ingest the antigen:B cell
receptor complex and process it just like a regular phagocytic cell. (Remember when a
phagocytic cell “eats” something, they want to display the evidence on a MHC Class II
marker).The result is the production of a MHC Class II marker (with a fragment of the
processed antigen in the cleft of the marker) by the B cell which bound the antigen. The
B cell will “call” (by the release of cytokines) a Helper T cell to confirm that the material
found in the MHC Class II marker is foreign. If the Helper T cell recognizes the material
as foreign, the T cell will release cytokines which activate the B cell to further
differentiate into an “activated B cell”. Some of the activated B cells become plasma cells
that make antibodies at a rate of 2000 antibodies/second! Some of the activated B cells
become memory B cells. The end result is the activation of naïve B cells to plasma cells
and the production of antibodies.
All B cells are programmed to first make IgM antibodies upon activation and after
a few days are able to switch on genes to make another class of antibody, such as IgG.
The significance behind this is that a patient who has just recently responded to a
pathogen will have IgM antibodies present in their blood. If they have IgG antibodies
present then they have been responding to the pathogen for longer than a week, or have
activated memory B cells.
How are T cells activated?
There are two different types of T cells that are discussed in this chapter, Helper T
cells and Cytotoxic T cells. Cytotoxic T cells are responsible for the cell-mediated
immune response. Helper T cells communicate directly with both B cells and Cytotoxic
T cells and coordinate the immune response. T cells have a unique receptor on the cell
surface called a T cell receptor or TCR. This receptor will target specific MHC markers
on other cells and bind at this site. In other words, the TCR is used by T cells to bind
directly to other cells via the MHC marker or self marker.
Dendritic cells are important in the activation of naïve T cells. When the dendritic
cell collects material (by pinocytosis and phagocytosis) and processes it making MHC
Class I and MHC Class II markers, the cells travel to the lymph nodes. At the lymph
nodes, the dendritic cell will “roll” around in the nodes in hopes of activating a naïve T
cell.
When Helper T cells are activated they orchestrate the immune response between
the B cells, macrophages and other T cells. Remember that helper T cells will ONLY
recognize antigen that is presented on a MHC Class II marker. These cells will monitor
the presence of exogenous antigen that is presented on these MHC markers. If a B cell
has bound a particular antigen and presented it via MHC Class II marker, it will produce
cytokines to draw a Helper T cell to confirm whether or not the material the B cell has
found is foreign. If the Helper T cell recognizes the antigen fragment in the MHC marker
as foreign, the Helper T cell will release cytokines to activate the B cell to divide and
become plasma cell. Remember that plasma cells are the only form of B cell capable of
producing antibodies. The activated Helper T cell will also activate Cytotoxic T cells at
the same time. If a Helper T cells binds with a macrophage displaying an MHC Class II
marker with foreign antigen, it will release cytokines to further activate the macrophage
to become a “more efficient” macrophage. (see Fig 15.22)
The Cytotoxic T cells are able to recognize foreign antigen when it is presented to
MHC Class I markers. In this case, Cytotoxic T cells are responsible for monitoring the
“health” of all of our body cells. A Cytotoxic T cell will bind to a body cell using its
TCR to “dock” or bind to the body cell at the MHC Class I marker. If the antigen
presented in the MHC marker is foreign, the Cytotoxic T cell will release pre-formed
cytotoxins that kill the targeted host cell. In this way the Cytotoxic T cell is able to get rid
of abnormal body cells or cells infected with viruses. (see figure 15.21)
Natural Killer cells are a type of lymphocyte but not a T cell. They do not bind to
cells at the MHC marker, instead they target cells that LACK MHC Class I markers or
cells that are coated in antibodies. Once they identify a cell that is abnormal (due to one
of the above features) they will release chemicals similar to the Cytotoxic T cells that
promote cell death. Think of why a body cell may not produce a MHC Class I marker….
In reviewing the function of the B cells and the T cells in the immune response,
begin to think about what happens when you have a bacterial infection. For instance, if
you got a bacterial infection as a result of cutting your finger, what aspects of the innate
and adaptive immune response will be working to help protect you and to initiate the
immune response? What if you got a stomach virus (hopefully not!), what aspects of the
immune response would be working to help fight the viral infection. What components of
the immune response are only activated when you have a bacterial infection?
Also important in this chapter is a closer look at antibodies. These are proteins
synthesized by plasma cells (also considered effector B cells). They consist of two heavy
chains and two light chains, and are held together by disulfide bonds. There are five
different classes of antibodies that can be made by B cells. The first class made by all
activated B cells are IgM. These antibodies have a pentamer structure, consisting of 5 Y’s
linked together by a joining chain. The large size of these antibodies make them unable to
cross the placenta barrier, however they do activate complement. These IgM are good at
clumping lots of antigen, remember they can bind up to 10 antigens at a given time.
IgG antibodies are the second class of antibody made by an activated B cell.
These are single monomers, able to cross the placenta barrier, and also can activate
complement. This class is the most abundant in the blood and has the longest half life of
all the antibodies of about 25 days.
IgA antibodies exist as dimers, two Y’s linked together with a joining chain and
also have an additional secretory component added. This added secretory component
keeps the antibodies from degradation by enzymes such as proteases. These antibodies
are found on the mucous membranes and in body secretions such as saliva and breast
milk.
IgE antibodies are not very common, exist as single monomers in the blood.
These antibodies are known to bind by the “tail” portion of the antibody to basophils and
mast cells. This class of antibody is made in response to allergens, generating antibodies
of the class IgE which can bind to cells and cause them to “degranulate” or relaease
granules containing such things as histamine.
IgD antibodies are the most rare antibody found in the blood. Most often it is
found bound to cells and while the function of these antibodies is still unknown it is
thought they play a role in the development or activation of the B cells. Perhaps these
antibodies are the “B cell receptors” that are found on the surface of naïve B cells.
In reviewing the different classes of antibodies, it is important to understand the
role that these proteins play in the body. Figure 15.8 identifies some key functions of
antibodies, especially how they can enhance the immune response. Review the figure and
see if you can include some of these functions of antibodies in your discussion of how the
body responds to either a viral or bacterial infection.
I hope that this lecture guide helped to clarify the function of the immune system!