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@@ -1058,19 +1058,6 @@ literal "false"
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Diagnosis and treatment of allograft rejection is a major challenge
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\end_layout
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-\begin_layout Standard
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-\begin_inset Flex TODO Note (inline)
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-status open
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-
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-\begin_layout Plain Layout
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-Maybe talk about HLA matching and why it's not an option most of the time.
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-\end_layout
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-
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-\end_inset
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-
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-\end_layout
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-
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\begin_layout Standard
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To prevent rejection, allograft recipients are treated with immune suppressive
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drugs
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@@ -1237,20 +1224,6 @@ literal "false"
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Memory cells are resistant to immune suppression
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\end_layout
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-\begin_layout Standard
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-\begin_inset Flex TODO Note (inline)
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-status open
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-
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-\begin_layout Plain Layout
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-Expand on costimulation required by naive cells and how memory cells differ,
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- and mechanisms of immune suppression drugs
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-\end_layout
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-
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-\end_inset
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-
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-\end_layout
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-
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\begin_layout Standard
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One of the defining features of the adaptive immune system is immune memory:
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the ability of the immune system to recognize a previously encountered
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@@ -1264,13 +1237,61 @@ literal "false"
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\end_inset
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.
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- When the immune system first encounters a new antigen, the lymphocytes
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- that respond are known as naïve cells – T-cells and B-cells that have never
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- detected their target antigens before.
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+ When the immune system first encounters a new antigen, the T-cells that
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+ respond are known as naïve cells – T-cells that have never detected their
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+ target antigens before.
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Once activated by their specific antigen presented by an antigen-presenting
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cell in the proper co-stimulatory context, naïve cells differentiate into
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effector cells that carry out their respective functions in targeting and
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destroying the source of the foreign antigen.
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+ The
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+TCR
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+\end_layout
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+
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+\end_inset
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+
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+ is cell-surface protein complex produced by T-cells that is responsible
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+ for recognizing the T-cell's specific antigen, presented on a
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+MHC
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+\end_layout
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+
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+\end_inset
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+
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+, the cell-surface protein complex used by an
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+APC
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+\end_layout
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+
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+\end_inset
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+
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+ to present antigens to the T-cell.
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+ However, a naïve T-cell that recognizes its antigen also requires a co-stimulat
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+ory signal, delivered through other interactions between
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+APC
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+\end_layout
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+
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+\end_inset
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+
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+ surface proteins and T-cell surface proteins such as CD28.
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+ Without proper co-stimulation, a T-cell that recognizes its antigen either
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+ dies or enters an unresponsive state known as anergy, in which the T-cell
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+ becomes much more resistant to subsequent activation even with proper co-stimul
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+ation.
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The dependency of activation on co-stimulation is an important feature
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of naïve lymphocytes that limits
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\begin_inset Quotes eld
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@@ -1280,17 +1301,82 @@ false positive
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\begin_inset Quotes erd
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\end_inset
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- immune responses, because antigen-presenting cells usually only express
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- the proper co-stimulation after detecting evidence of an infection, such
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- as the presence of common bacterial cell components or inflamed tissue.
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- After the foreign antigen is cleared, most effector cells die since they
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+ immune responses against self antigens, because
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+\begin_inset Flex Glossary Term (pl)
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+status open
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+
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+\begin_layout Plain Layout
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+APC
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+\end_layout
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+
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+\end_inset
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+
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+ usually only express the proper co-stimulation after the innate immune
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+ system detects signs of an active infection, such as the presence of common
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+ bacterial cell components or inflamed tissue.
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+
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+\end_layout
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+
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+\begin_layout Standard
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+After the foreign antigen is cleared, most effector cells die since they
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are no longer needed, but some differentiate into memory cells and remain
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alive indefinitely.
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Like naïve cells, memory cells respond to detection of their specific antigen
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- by differentiating into effector cells, ready to fight an infection.
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- However, unlike naïve cells, memory cells do not require the same degree
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- of co-stimulatory signaling for activation, and once activated, they proliferat
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-e and differentiate into effector cells more quickly than naïve cells do.
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+ by differentiating into effector cells, ready to fight an infection
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "Murphy2012"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ However, the memory response to antigen is qualitatively different: memory
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+ cells are more sensitive to detection of their antigen, and a lower concentrati
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+on of antigen is suffiicient to activate them
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "Rogers2000,London2000,Berard2002"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ In addition, memory cells are much less dependent on co-stimulation for
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+ activation: they can activate without certain co-stimulatory signals that
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+ are required by naïve cells, and the signals they do require are only required
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+ at lower levels in order to cause activation
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "London2000"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ Furthermore, mechanisms that induce tolerance (non-response to antigen)
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+ in naïve cells are much less effective on memory cells
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "London2000"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ Lastly, once activated, memory cells proliferate and differentiate into
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+ effector cells more quickly than naïve cells do
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "Berard2002"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ In combination, these changes in lymphocyte behavior upon differentiation
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+ into memory cells account for the much quicker and stronger response of
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+ the immune system to subsequent exposure to a previously-encountered antigen.
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\end_layout
|
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\begin_layout Standard
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