Questions and Answers
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?
Where do progenitor T cells further develop and undergo T-cell receptor rearrangement?
Which of the following is a cardinal sign of inflammation?
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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?
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What is required for the activation of T cells?
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Which pathway directly activates complement?
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What is the function of TH1 subset of CD4+ helper T cells?
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What is the result of histamine-mediated vasodilation?
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What is the mechanism of killing by cytotoxic T cells?
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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)?
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Which cytokine is involved in the activation of macrophage?
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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?
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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?
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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?
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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?
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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?
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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.
