Podcast
Questions and Answers
Which of the following is a result of the activation of the complement system?
Which of the following is a result of the activation of the complement system?
What is the primary function of C3b in the complement system?
What is the primary function of C3b in the complement system?
Where do progenitor T cells further develop and undergo T-cell receptor rearrangement?
Where do progenitor T cells further develop and undergo T-cell receptor rearrangement?
Which of the following is a cardinal sign of inflammation?
Which of the following is a cardinal sign of inflammation?
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What is the primary role of bradykinin in inflammation?
What is the primary role of bradykinin in inflammation?
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Which type of T cell recognizes antigen presented on MHC class II molecules?
Which type of T cell recognizes antigen presented on MHC class II molecules?
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What is required for the activation of T cells?
What is required for the activation of T cells?
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Which pathway directly activates complement?
Which pathway directly activates complement?
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What is the function of TH1 subset of CD4+ helper T cells?
What is the function of TH1 subset of CD4+ helper T cells?
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What is the result of histamine-mediated vasodilation?
What is the result of histamine-mediated vasodilation?
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What is the mechanism of killing by cytotoxic T cells?
What is the mechanism of killing by cytotoxic T cells?
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What is the role of C5a in the complement system?
What is the role of C5a in the complement system?
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What is the result of the activation of the Hageman factor (Factor XII)?
What is the result of the activation of the Hageman factor (Factor XII)?
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Which cytokine is involved in the activation of macrophage?
Which cytokine is involved in the activation of macrophage?
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What is the function of B7 on antigen-presenting cells (APCs)?
What is the function of B7 on antigen-presenting cells (APCs)?
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What is the function of IL-2 in the activation of cytotoxic T cells?
What is the function of IL-2 in the activation of cytotoxic T cells?
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What is the primary function of selectins in the process of neutrophil arrival and function?
What is the primary function of selectins in the process of neutrophil arrival and function?
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Which cytokines increase cyclooxygenase activity in perivascular cells of the hypothalamus, leading to fever?
Which cytokines increase cyclooxygenase activity in perivascular cells of the hypothalamus, leading to fever?
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What is the primary function of integrins in the process of neutrophil arrival and function?
What is the primary function of integrins in the process of neutrophil arrival and function?
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What is the result of the interaction between selectins on endothelial cells and sialyl Lewis X on leukocytes?
What is the result of the interaction between selectins on endothelial cells and sialyl Lewis X on leukocytes?
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What is the primary function of cellular adhesion molecules (ICAM and VCAM) in the process of neutrophil arrival and function?
What is the primary function of cellular adhesion molecules (ICAM and VCAM) in the process of neutrophil arrival and function?
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What is the primary function of PGE2 in the inflammatory response?
What is the primary function of PGE2 in the inflammatory response?
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What is the primary function of histamine in the inflammatory response?
What is the primary function of histamine in the inflammatory response?
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What is the result of a defect in the integrin CD18 subunit?
What is the result of a defect in the integrin CD18 subunit?
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Study Notes
Inflammation and Wound Healing
Fever
- Pyrogens (e.g., LPS from bacteria) stimulate macrophages to release IL-1 and TNF, which increase cyclooxygenase activity in perivascular cells of the hypothalamus.
- Increased PGE2 raises the temperature set point.
Neutrophil Arrival and Function
Step 1 - Margination
- Vasodilation slows blood flow in postcapillary venules.
- Neutrophils marginate from the center of flow to the periphery.
Step 2 - Rolling
- Selectin "speed bumps" are upregulated on endothelial cells.
- P-selectin is released from Weibel-Palade bodies mediated by histamine.
- E-selectin is induced by TNF and IL-1.
- Selectins bind sialyl Lewis X on leukocytes, resulting in rolling of leukocytes along the vessel wall.
Step 3 - Adhesion
- Cellular adhesion molecules (ICAM and VCAM) are upregulated on endothelium by TNF and IL-1.
- Integrins are upregulated on leukocytes by C5a and LTB4.
- Interaction between CAMs and integrins results in firm adhesion of leukocytes to the vessel wall.
- Leukocyte adhesion deficiency is commonly due to an autosomal recessive defect of integrins (CD18 subunit).
Step 4 - Transmigration and Chemotaxis
- Leukocytes transmigrate across the endothelium of postcapillary venules and move toward chemical attractants (chemotaxis).
- Neutrophils are attracted by bacterial products, IL-8, C5a, and LTB4.
Step 5 - Phagocytosis
- Consumption of pathogens or necrotic tissue; phagocytosis is enhanced by opsonins (IgG and C3b).
T Cells
- T cells use the TCR complex (TCR and CD3) for antigen surveillance.
- TCR complex recognizes antigen presented on MHC molecules:
- CD4+ T cells: MHC class II
- CD8+ T cells: MHC class I
- Activation of T cells requires (1) binding of antigen/MHC complex and (2) an additional 2nd signal.
CD4+ Helper T-Cell Activation
- Extracellular antigen is phagocytosed, processed, and presented on MHC class II, which is expressed by antigen-presenting cells (APCs).
- B7 on APCs binds CD28 on CD4+ helper T cells, providing the 2nd activation signal.
- Activated CD4+ helper T cells secrete cytokines that "help" inflammation and are divided into two subsets:
- TH1 subset: secretes IFN-γ, activates macrophages, promotes B-cell class switching from IgM to IgG, and promotes TH1 phenotype.
- TH2 subset: secretes IL-4, facilitates B-cell class switching to IgE, IL-5 (eosinophil chemotaxis and activation, and class switching to IgA), and IL-13 (function similar to IL-4).
CD8+ Cytotoxic T-Cell Activation
- Intracellular antigen is processed and presented on MHC class I, which is expressed by all nucleated cells and platelets.
- IL-2 from CD4+ TH1 cell provides the 2nd activation signal.
- Activated cytotoxic T cells are activated for killing, which occurs via:
- Secretion of perforin and granzyme; perforin creates pores that allow granzyme to enter the target cell, activating apoptosis.
- Expression of FasL, which binds Fas on target cells, activating apoptosis.
Alternative Pathway
- Microbial products directly activate complement.
- Mannose-binding lectin (MBL) pathway: MBL binds to mannose on microorganisms and activates complement.
- All pathways result in the production of C3 convertase (mediates C3 → C3a and C3b), which, in turn, produces C5 convertase (mediates C5 → C5a and C5b).
- C5b complexes with C6-C9 to form the membrane attack complex (MAC).
Cardinal Signs of Inflammation
- Redness (rubor) and warmth (calor): due to vasodilation, resulting in increased blood flow.
- Swelling (tumor): due to leakage of fluid from postcapillary venules into the interstitial space (exudate).
- Pain (dolor): bradykinin and PGE2 sensitize sensory nerve endings.
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Description
This quiz covers the process of inflammation, including fever response and neutrophil arrival and function in wound healing.
