INNATE IMMUNITY VS. ADAPTIVE IMMUNITY PART 2 (VIDEO 6)
Now, I will tell you about lymphocyte clones.
We have within our body many clones of lymphocytes that are specific for different antigens.
What I mean by clone here is a population of lymphocytes expressing identical antigen receptors
and hence identical specificities; here I show you three different clones for example.
These clones are derived from a single precursor cell.
They have the ability to respond to a specific antigen and proliferate subsequently.
For instance, when a B cell clone specific for antigen X encounters this the antigen X, it gets
activated and differentiates into the cells that can produce a specific antibody against X, that is,
anti-X antibody.
Similarly, when a B cell clone specific for antigen Y encounters the antigen Y, it gets activated
and differentiates into the cells that can produce specific antibody against Y, that is, anti-Y
antibody.
However, B cell clones with irrelevant specificities do not get activated and produce no antibody.
Basically, T cells also respond to antigen in an identical manner, except that they require antigen
presentation by dendritic cells, as I will describe later.
So, lymphocytes respond to antigens at the clonal level.
A particular antigen selects the clone to be activated.
So, this concept is called the clonal selection theory, which was initially put forward in the 1950s
and eventually yielded several Nobel Prize winners.
In the case of B cells, after some rounds of cell division, the antigen-responding cells, which
are called plasma cells, produce antibodies and antibodies produce membrane-bound antigen
receptors they are secreted as antibody molecules from plasma cells.
And this concept: a specific clone is selected for proliferation by antigen, is called clonal
selection theory.
Here I show you the way how the adaptive immune system responds to antigens.
The lymphocytes that are seeing antigens for the first time are called naïve cells.
They are immunologically inexperienced, but upon encounter with a specific antigen, for
instance, antigen X, they mount a so-called primary response in which activated B cells secrete
antibodies specifically reactive against antigen X.
This response declines with time, but when the same antigen X comes in for the second time,
memory B cells are now activated, developing a much stronger and much more long-lasting
response, which is called the secondary response, or secondary immune response.
When a different antigen comes in, it evokes only the primary response, showing the specificity
of the adaptive immune response.
The way T cells respond to antigens is very similar to this, but T cells produce cytokines but not
antibodies.
Now, let us look at the issue of where lymphocytes are produced, where they mature, and where
they respond in the body.
All lymphocytes are derived from stem cells.
These stem cells reside in the bone marrow.
Subsequently, B cells are produced and mature in the bone marrow, whereas T cells are
produced and mature in the thymus.
The bone marrow and the thymus are thus the places where these cells are produced, and
hence, they are called primary lymphoid organs.
From these organs, only mature cells leave and enter the circulation, and continue to circulate
throughout the body.
These are naïve T and B cells you find in the blood and lymphoid organs.
They may encounter specific antigens in the secondary lymphoid tissues, such as the lymph
nodes, spleen, and other peripheral lymphoid tissues, and they respond there.
If lymphocytes see antigens in the secondary lymphoid tissues, one may wonder how antigens
get into these tissues.
Microbes enter the body usually by crossing the epithelial barriers, such as those in the skin, the
gastrointestinal tract, or the respiratory tract.
Dendritic cells are abundant in these areas and capture the invading microbes and their
products.
They sense the pathogen-associated molecular patterns or PAMPs of the microbes and become
activated to produce proinflammatory cytokines.
They then lose adhesiveness to the tissue and move into the lymphatic vessels or blood
vessels.
Antigens that evaded uptake by dendritic cells also move into the lymphatic vessels and blood
vessels.
Thus, the microbes and their products are transported into the peripheral lymphoid tissues and
are subsequently recognized by T cells and B cells.
So, in the case of lymphoid antigens, antigens are delivered into lymphatics, finally a lymph
node captures these antigens and T cells respond there.
In the case of blood-borne antigens, the spleen captures antigen and immune response takes
place there.
So, antigen that enter the lymphatic vessels, are transported into lymph nodes.
Whereas those that enter the blood vessels, are transported to the spleen.
So, microbial antigens are displayed in peripheral lymphoid tissues for T cell recognition.
Upon encounters with antigens, naïve lymphocytes differentiate into effector cells and memory
cells.
Here, you see naïve cells, effector cells and memory cells.
B cells can recognize native antigens in the absence of dendritic cells and differentiate into
plasma cells to secrete antibodies or into memory cells that can respond to the same antigen
more rapidly and more vigorously upon a second encounter.
In contrast, T cells recognize antigens only with the aid of dendritic cells; and this step is called
antigen presentation, because dendritic cells process the internalized antigen and present it as
antigenic peptides to T cells.
T cells then proliferate and differentiate into cytokine-secreting effector cells or memory cells.
Naïve cells, effector cells, and memory cells have the following properties.
Naïve cells are quiescent, meaning not cycling or dividing, and live for weeks to months.
They have no effector function and migrate mainly to lymph nodes.
In contrast, effector cells are usually cycling and live only for days.
Activated B cells secrete antibodies, whereas helper T cells secrete cytokines, and cytotoxic T
cells can kill microbe-infected cells.
On the other hand, memory cells are quiescent, live long, but have no effector function,
migrating through the lymph nodes and bone marrow
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