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24 Cards in this Set

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  • Back
What are the steps for leukocyte migration during innate immunity?
1. Rolling/ Adhesion
2. Tight Binding
3. Diapedesis
What occurs in the first step of leukocyte migration during an innate immune reaction?
There is a weak interaction between carbohydrate residues on PMN surface and selectins on the endothelium. Seen as rolling on microscope. Functions as immune surveillance system.
What occurs in the second step of leukocyte migration during an innate immune reaction?
Tight binding. Local queues cause an increase in leukocyte intregrin affinity for ICAMs on endothelial surface. This causes rolling to stop and firm adhesion to the endothelium
What occurs in the third step of leukocyte migration during an innate immune reaction?
Diapedesis. Leukocytes send signals to the local endothelial cells to contract and separate. PECAM-PECAM zippering mediates leukocyte-endothelium interaction. Leukocyte enters between endothelial cell
Are leukocytes the only cell that undergoes diapedesis?
Lymphocytes also perform diapedesis, however the receptors for adhesion and migration are different. VLA4 (integrin) adn VCAM (epethilium)
What is a possible therapy that utilizes VLA4 interupption?
Since VLA4-VCAM interaction is important for immune response during sepsis and allergic diseases, VLA4 targeting drugs could be used in asthma treatment
What are the basic characteristics of the innate immune system?
Germline encoded with no DNA recombination. Fast acting with no clonal expansion and distribution of effectors is non-clonal. The effectors recognize molecular patterns as non-self. All cells have some capacity to respond
What are the basic characteristics of the adaptive immune system?
Somatically engineered Ig, created via DNA recombination, is the primary mediator. The response is slower (~6days) and is a clonal expansion of lymphocytes based on recognized epitopes. Effectors (lymphocytes, DCs, Macrophages) recognize altered self. Primary structure(TCR), Tertiary (BCR, Ig)
What are the types of receptors that are important for innate immunity?
2. TLRs
3. Lectins
Describe the features of a GPCR
G-protein coupled receptor has 7-transmembrane spanning structure which activates heterotrimeric G-proteins. Activation occurs via binding by chemokines, N-formyl-met bacterial peptides, and complement proteins.
Describe the features of a TLR
Toll-like receptors are low affinity receptors that interact with pathogenic ligand. They recognize repetitive subunits on pathogens and they sometimes work with co-receptors to facilitate stronger binding. Example (TLR4 recognizes LPS)
Describe the features of Lectins
Lectins (selectins, collectins, etc.) are receptors that bind carbohydrate residues and mediate adhesion to repetitive sugar units on bacterial surface
What size particles can be endocytosed? phagocytosed?
Particles smaller than 1 micrometer are typically endocytosed. Particles larger than 1 micrometer are phagocytosed.
What cytoskeletal component is important in phagocytosis?
Actin. Actin polymerization pushes pseudopodia toward and around phagocytic target forming a phagocytic cup.
What is non-opsonic phagocytosis?
Occurs when repeating carbohydrate patterns on microbes are recognized by cell surface receptors such as integrins, scavenger receptors, and lectins
Scavenger receptors recognize what types of molecules?
Scavenger receptors have broad specificity for bacterial surfaces epitopes, oxidized proteins, and lipoproteins
What mediates opsonic phagocytosis?
Opsonic phagocytosis is mediated by deposition of antibodies or compliment on microbes that target them for recognition by receptors on leukocytes
Once a pathogen is phagocytosed what happens?
Following engulfment, the pathogen resides in a phagosome which will fuse with a lysosome to form a phagolysosome. Hydrolytic enzymes from the lysosome will kill the pathogen
What are the major players in the process of oxidative burst used to kill pathogens?
NADPH Oxidase produces superoxide via electron donation by NADPH. Superoxide dismutase forms hydrogen peroxide. Myeloperoxidase (MPO) uses chlorine to produce hypochlorite ion. Peroxynitrite is another highly reactive and corrosive oxidative species.
What disease is caused by a defect in the oxidative burst machinery?
Chronic Gramulomatis Disease (CGD). Rare disorder where a component of the NADPH oxidase system is missing. It is characterized by recurring infections, abscesses, and granulomas, and early death.
What are some non-oxidative means used by cell to kill pathogens?
Release of stored proteins such as lysozime, lactoferrin, proteases, defensins, other cationic proteins. Defensins are small cationic proteins, made by leukocytes and epitheial cells, form pores in bacterial membrane
Lysozime made by leukocytes disrupts peptidoglycans
What are the main functions of compliment?
Elaboration of chemoattractants for inflammatory cells, opsonization of pathogens, making membrane attack complex for killing of pathogens
Name the pathways for compliment activation?
classical: antibody-antigen complex activates compliment
alternate: pathogen surface activates compliment
MB-Lectin: lectins bound to pathogen activates compliment
The pathways for compliment activation have this common point of convergence.
All pathways converge on C3/C5 convertase which cleaves C3 and C5