789942
Description
Flashcards by sophietevans, updated more than 1 year ago
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Created by sophietevans
almost 10 years ago
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| Question | Answer |
| What are the cardinal signs? | Rubor (redness/erythema), dolor (pain), calor (heat), tumor (swelling), and functio laesa (loss of function). |
| What is the purpose of the mechanisms leading to the cardinal signs? What are the by proxy effects? | Within minutes after tissue injury, there is an increase in vascular diameter resulting in a rise of blood volume in the area. Higher blood volume heats the tissue and causes it to redden. Vascular permeability also increases, leading to leakage of fluid from the blood vessels, particularly at postcapillary venules, which results in accumulation of fluid (oedema) that swells the tissue (tumor). |
| What is the balance that leukocytes must strike when migrating along vessel walls towards a site of tissue damage? | They must adhere to the inflamed endothelium strongly enough so that they are not swept away by the flowing blood but they must also be bound reversibly so that they may roll towards the inflamed region, and must penetrate the endothelial layer and gain access to the underlying tissue. |
| What is diapedesis? | 'Pushing a foot through' - the process by which a leukocyte extends a podocyte, a process of cytoplasm and cell membrane, between the endothelial cells of the blood vessel in order to extravasate. |
| What is required of the blood vessel in order for extravasation to occur? | Vasodilation |
| In the resting, inactivated state, neutrophils 'roll' along the vessel walls. What is happened when they are doing this? | Glycoproteins on their cell membranes (E- and P-selectins) bind loosely with mucin-like cell adhesion molecules (CAMs) and sialylated lactosaminoglycan on the endothelial cells of the vessel wall. |
| What induces the formation of stronger interactions between neutrophils and the endothelial cells of a vessel wall in the first step of extravasation? | Binding of chemokines or other chemoattractants to receptors on the membrane of neutrophil cells triggers an activating signal that induces a conformational change and clustering in a molecule of the neutrophil membrane called integrin. This increases the affinity of integrin for intercellular adhesion molecules (ICAMs) on the endothelium, and these interactions stabilise adhesion of the neutrophil to the endothelial cell. As well as increased affinity of the neutrophil integrins for ICAMs, the endothelium has an increased expression of these ICAMs: cytokines and other mediators act on the local endothelium, causing vesicles of receptors to fuse with the endothelial membrane and the receptors to be expressed. |
| What holds the tissues of our bodies together? | Molecular interactions between the cells - a homotypic interaction between platelet-endothelial call adhesion molecule-1 (PECAM) molecules on adjacent cells. |
| The immune system is unique in that the cells can traverse from one part of the body to another. The same cell adhesion molecules can be used by leukocytes to interact with tissue cells. What are the families of cell adhesion molecules? Which do endothelial express? | Mucin-like adhesion molecules, selectins, integrins, and immunoglobulins. Endothelial cells express all of these for their homotypic interactions, and leukocyte-specific forms for their interactions with leukocytes. Some of these are expressed constitutively, while others are expressed only in response to local rises in the concentrations of cytokines produced in an inflammatory response. |
| How is junctional integrity of the vessel wall maintained when leukocytes extravasate? | The leukocyte can squeeze in between two neighbouring endothelial cells without disrupting the integrity of the endothelial barrier. It accomplishes this by homotypic binding of platelet-endothelial cell molecule-1 (PECAM-1) on the leukocyte with PECAM-1 on the endothelium. PECAM-1 is normally found within the endothelial junction in a homotypic interaction. Thus, when the leukocyte PECAM-1 binds to endothelial PECAM-1, the junctional integrity is maintained. |
| Which type of leukocyte is generally the first type to adhere to an inflamed endothelium and extravasate to the site of tissue damage/infection? | Neutrophils |
| Why do neutrophils not bind to non-inflamed endothelium and extravasate? | Due to lack of E- and P-selectins on the endothelium. |
| Which selectin cell-adhesion molecule do neutrophils express in order to adhere to the E- and P-selectins on inflamed endothelium? | L-selectins, as well as mucin-like PSGL-1. |
| Name two chemokines involved in the activation of neutrophils, which results in greater adhesion to Ig-superfamily cell adhesion molecules (due to a G-protein activated conformational change)? | IL-8 and macrophage inflammatory protein -1β (MIP-1β). |
| Gradients of additional chemoattractants then guide the neutrophils to the site of infection. Name three chemoattractants which contribute to directed migration and activation of neutrophils by binding to cell membrane receptors. | Complement split product C5a, leukotrienes, and bacterial peptides containing N-formyl peptides (e.g. N-acetylmuramic acid). |
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