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Immunology Handouts Friday

Immunology Handouts Friday

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Published by Aya Sobhi

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Published by: Aya Sobhi on Apr 20, 2012
Copyright:Attribution Non-commercial


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Innate Immune System:
Anatomical Barriers:
Mechanical- skin, mucous membranes, mucociliary escalator
Chemical- sweat, skin, saliva, tears, HCl (stomach acid), defensins, surfactant
Biological-normal flora competing with pathogens
Humoral Components
 Cellular Components:
Monocytes-become macrophages in the tissue
NK cells-killing virus infected and malignant cells
Eosinophils- killing parasites and helmiths (worms)
Phagocytosis and Intracellular Killing:
Phagocytes: Neutrophils
Characteristic, multilobular nucleus
Granules in cytoplasm- PRIMARY (contain lysozyme, cationic proteins, lysozyme, defensins,elastase and MPO). SECONDARY contain lysozyme, NADPH oxidase, lactoferrin.Phagocytes: Macrophages
Kidney shaped nucleus
Lysosomes contain lysozyme
Not many granulesPhagocyte Response to Infection:1.
THE “SOS” Signals
 These molecules send an SOS signal to the phagocyte to alert them of an infection. These are:
N-formyl methionine containing peptides
Clotting system peptides
Complement products
Phagocyte ResponseOnce the phagocyte has been alerted, the phagocyte responds by:
Vascular adherence: it sticks to the endothelial cells via adhesion molecules such as P selectinand E-selectin.
Diapedesis: phagocyte moves in between the endothelial cells
Chemotaxis: substances sent from the infected tissue (chemoattractants) attract the phagocyteinto the tissue.
Activation: the phagocyte becomes activated
Phagocytosis and killing
Initiation of phagocytosis:Attachment of the phagocyte to the pathogen happens via receptors:
Complement receptors
Scavenger receptors
Receptor for IgG FcR (if antibodies against the pathogen have been produced). This is a goodexample of how the innate and acquired immune systems are linked.
Toll-like receptors- which recognise broad patterns on bacterial cell walls.4.
Phagosome formation (pathogen contained in the phagosome)
Granule/lysosome fusion
Phagolysosome formation
How is the bacteria killed in the phagolysosome?
Via chemical reactions which use up oxygen (hence they are given the name RESPIRATORY BURST) thatproduce free radicals such as superoxide anions which are toxic using the enzyme myeloperoxidase.Other substances can also kill the pathogen such as lactoferrin which is found in the phagocyte granulesand defensins and cationic proteins. These are oxygen independent mechanisms.In addition, macrophages have another mechanism of killing which involves Nitric oxide which can betoxic to pathogens.
 Several different cells including NK and LAK cells, K cells, activated macrophages and eosinophils arecapable of killing foreign and altered self target cells in a non-specific manner. These cells play animportant role in the innate immune system.
1. NK and LAK cells
 Natural killer (NK) cells are also known as large granular lymphocytes (LGL) because they resemblelymphocytes in their morphology, except that they are slightly larger and have numerous granules. NKcells can be identified by the presence of CD56 and CD16 and a lack of CD3 cellsurface markers. NK cells are capable of killing virus-infected and malignant targetcells but they are relatively inefficient indoing so. However, upon exposure to IL-2and IFN-gamma, NK cells become
lymphokine-activated killer (LAK) cells, which are capable of killing malignant cells. Continued exposureto IL-2 and IFN-gamma enables the LAK cells to kill transformed as well as malignant cells. LAK celltherapy is one approach for the treatment of malignancies.How do NK and LAK cells distinguish a normal cell from a virus-infected or malignant cell? NK and LAKcells have two kinds of receptors on their surface
a killer activating receptor (KAR) and a killerinhibiting receptor (KIR). When the KAR encounters its ligand, a killer activating ligand (KAL) on thetarget cell the NK or LAK cells are capable of killing the target. However, if the KIR also binds to its ligandthen killing is inhibited even if KAR binds to KAL. The ligands for KIR are MHC-class I molecules. Thus, if atarget cell expresses class I MHC molecules it will not be killed by NK or LAK cells even if the target alsohas a KAL which could bind to KAR. Normal cells constitutively express MHC class I molecules on theirsurface, however, virus infected and malignant cells down regulate expression of class I MHC. Thus, NKand LAK cells selectively kill virus-infected and malignant cells while sparing normal cells.
2. K cells
 Killer (K) cells are not a morphologically distinct type of cell. Rather a K cell is any cell that mediatesantibody-dependent cellular cytotoxicity (ADCC). In ADCC antibody acts as a link to bring the K cell andthe target cell together to allow killing to occur. K cells have on their surface an Fc receptor for antibodyand thus they can recognize, bind and kill target cells coated with antibody. Killer cells which have Fcreceptors include NK, LAK, and macrophages which have an Fc receptor for IgG antibodies andeosinophils which have an Fc receptor for IgE antibodies.

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