Download The Lymphatic System

The Lymphatic System
Specific Immunity
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The Immune Response
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AntigenAntigen-specific
Systemic
Has memory
Specific immunity differs from innate immunity in three main ways. Specific
immunity is antigen-specific, meaning that cells or antibodies target specific
antigens rather than having generalized responses that apply to all pathogens. It is
systemic, meaning that it occurs throughout the body and is generally not localized
to just one area of infection. It has memory which means that after our bodies have
been exposed to an antigen the first time, our lymphatic system produces memory
cells for that antigen – the next time the same antigen is introduced, the memory
cells will stimulate an extremely fast, extremely powerful response that can often
wipe out the pathogen before it has a chance to cause significant tissue damage.
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The Immune Response
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Antigens:
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Nonself & selfself-antigens
Haptens
An antigen is defined as any substances that can stimulate an immune response in
our bodies. There are thousands of possible antigens, and our lymphatic system
manufactures lymphocytes with receptors for every possible antigen. Each
individual lymphocyte, though, can only recognize one antigen. So, really, we have
thousands of different kinds lymphocytes, each one “tuned” to a specific antigen.
Although most antigens come from outside the body (on invading pathogens), some
of our body’s own cells also have antigens. How does our body know not to identify
our own self-antigens? The answer seems to be that we make lymphocytes with
receptors for the self-antigens just like for any other antigens, but that those cells
are killed off before they reach maturity. If those cells did reach maturity and enter
the blood stream, our lymphatic system would attack some of our own cells. It is
believed this is how multiple sclerosis works, for example. Antigens tend to be big,
but sometimes small molecules, called haptens, can be mis-identified as antigens
as well and cause an immune response. This is how allergies happen.
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The Immune Response
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Cells of immunity:
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Lymphocytes: B cells vs. T cells
Macrophages
Types of immunity:
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Humoral vs. cellular
There are two different categories of specific (adaptive) immunity. Antibodymediated immunity (also called humoral immunity) involves lymphocytes (B cells in
particular) releasing antibodies which bind to specific antigens. The binding of these
antibodies to their antigens stimulates an array of immune responses. Cellmediated (also called “cellular”) immunity does not involve antibodies. Instead,
lymphocytes (T cells in particular) attack pathogens directly.
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The life of a lymphocyte. All lymphocytes are born in the red bone marrow. From
there, they mature either in the bone marrow (B cells) or migrate to the thymus
gland (T cells) and become immunocompetent (ready-for-action). The mature B and
T cells then circulate in the blood or concentrate in lymph nodes and the spleen.
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Humoral Immunity
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Primary humoral
response:
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Clone formation from
immature B cell
Plasma cells
 Memory B cells
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Secondary humoral
response
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Memory cells
The difference between the primary and secondary immune responses is that the
primary immune response occurs on the first exposure to any antigen. It is slow, but
effective. The secondary immune response occurs at all subsequent invasions by
the same antigen. It is faster and stronger. Here’s how the primary response for B
lymphocytes works: a single B cell is activated, either because it recognized its
specific antigen or because a helper T cell (more on those later) activated it. This
causes the B cell to rapidly divide into a cluster of hundreds of cells. This cluster of
cells is called a clone and all lymphocytes in a clone are identical – they all
recognize the same antigen. Most of the cells of this clone differentiate into plasma
cells. These are cells that can produce antibodies against the recognized antigen.
We’ll see how antigens take care of invading cells in a moment. The rest of the cells
become memory B cells, which remain in the body for a long time (perhaps
forever) and activate the immune response very quickly if the same antigen is
detected again. Memory cells are responsible for stimulating secondary immune
responses and are formed during the primary immune response.
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Humoral Immunity
This figure just shows visually all of the steps in antibody-mediated immunity.
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Humoral Immunity
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Antibodies
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Structure
Variable region
 Constant region
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Effects
Agglutination
 Neutralization
 Complement fixation
 Precipitation
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Antibodies are polypeptide chains (just proteins – not living things) that can bind to a
specific antigen. Each antibody is uniquely tuned to one particular antigen. Every
antibody is composed of four peptide chains – two identical “heavy chains” which
don’t vary much from antibody to antibody and two identical “light chains” which
vary a lot. Antibodies tend to be Y-shaped. The arms of the Y are called the
variable region of the antibody. This is where the antibody binds to antigens. Since
there are two arms, each antibody can bind to two antigens (of the same type),
basically clumping the antigens together (agglutination). The base of Y is called the
constant region. The structure of the constant region determines what happens
once an antibody binds to its antigen. There are several possible defensive
reactions.
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An antibody’s constant region defines what class the antibody belongs to and what
its defensive reaction is once the antibody binds to an antigen.
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Cell-Mediated Immunity
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T cells (No antibodies)
Macrophage Antigen presentation
Cell-mediated immunity differs from antibody-mediated immunity in that it utilizes
different types of lymphocytes and antibodies are not used to stimulate defensive
actions. Cell-mediated immunity involves T cells (not B cells, like antibody-mediated
immunity). Instead of producing antibodies, T lymphocytes attack or respond to
pathogens directly. Unlike most B cells, T cells cannot directly recognize an antigen.
Instead, they can only recognize an antigen once it has been engulfed and
phagocytized by a macrophage. The macrophage then presents the antigen parts to
the T cell for recognition. If the T cell recognizes the one antigen it is tuned to
respond to, it becomes activated and begins to divide rapidly (just like B cells did)
and forms a clone. Like with B cells, the T lymphocyte clone cells will differentiate,
but they will not form plasma cells of course – plasma cells make antibodies, and T
cells do not make antibodies.
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Cell-Mediated Immunity
The usual pathway of the immune response begins with phagocytosis of an antigen
by a macrophage. The macrophage then “presents” the antigen parts to a helper T
cell, which becomes active and secretes lymphokines, which stimulate division in B
cells (leading to antibody-mediated immune responses) and cytotoxic T cells
(leading to cell-mediated immune responses).
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Cell-Mediated Immunity
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Types of T cells
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Cytotoxic (killer) T cells
Helper T cells
Suppressor T cells
Memory T cells
There are four major types of T lymphocytes that can be formed from T lymphocyte
clone cells. The most active is the cytotoxic T cell, sometimes called a “killer T
cell.” These cells are similar to natural killer (NK) cells because they are good at
targeting virus-infected and tumor cells, but unlike NK cells, cytotoxic t cells are
specific – they have receptors for just one type of antigen and they only act against
that one antigen. Their activity can be described as a “kiss of death.” They bind very
briefly with their target antigen (the kiss) and secrete an enzyme called perforin
through exocytosis. The perforin integrates itself into the target cell’s membrane,
eventually ripping a hole in (perforating it) and causing the cell to lyse (the death).
Cytotoxic T cells do not hang around to watch their target cells die, though, they
move from target cell to target cell, “kissing” each one.
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Both antibody-mediated immune responses and cell-mediated immune responses
occur in tandem. They work together to deal with any infection. This figure
summarizes the effects of both B and T cells.
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HIV
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Retrovirus
Tropism
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1˚: Helper T cells
2˚ : Macrophages,
dendritic cells
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HIV
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Replication cycle
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CD4 receptor binding
Incorporation
Reverse transcriptase
 Integrase
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Latency
Activation: NFNF-κB
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HIV
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Transmission
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Modes of transmission
Epidemiology
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HIV
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Course of infection
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Incubation
Acute infection
Latency
AIDS
Causes of helper
T cell loss
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HIV
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Treatments
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RTIs and HAARTs
Entry inhibitors
Bone marrow transplant?
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