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Phagocytosis A. Recognition & attachment of particle to be ingested B. Engulfment - formation of phagocytic vacuole C. Killing or degradation 1. Recognition & attachments: Leucocytes recognize microbes and dead cells by receptors a. Mannose receptor -bind mannose and fucose residues of glycoprotein in microbial cell wall b. Scavenger receptors - originally defined as molecules that bind modified LDL particles. Also bind microbes c. Mac 1 integrins Efficiency of phagocytosis increased by opsonization. Opsonins – Bind to specific receptors on leukocytes Receptors - Fe fragment of IgG Fc gamma R1 - C & C CR 1, 2, 3 - Plasma proteins: 1. Mannose binding lectins C1q 2. Fibrinogen 3. Fibronectin Integrins 4. C-Reactive proteins Neutrophils & macrophages: can recognize engulf bacteria & extraneous matter (in absence of opsonins) 2. Engulfment: a. Pseudopods of phagocyte flow around the microbe to be engulfed Microbe enclosed in a phagosome Q Q Q Q 3b 3bi Q

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  • Phagocytosis

    A. Recognition & attachment of particle to be ingested

    B. Engulfment - formation of phagocytic vacuole

    C. Killing or degradation

    1. Recognition & attachments:

    Leucocytes recognize microbes and dead cells by receptors

    a. Mannose receptor -bind mannose and fucose residues of

    glycoprotein in microbial cell wall

    b. Scavenger receptors - originally defined as molecules that bind

    modified LDL particles. Also bind microbes

    c. Mac 1 integrins

    Efficiency of phagocytosis increased by opsonization.

    Opsonins

    Bind to specific receptors on leukocytesReceptors

    - Fe fragment of IgG Fc gamma R1

    - C & C CR 1, 2, 3

    - Plasma proteins:

    1. Mannose binding lectins C1q

    2. Fibrinogen

    3. Fibronectin Integrins

    4. C-Reactive proteins

    Neutrophils & macrophages: can recognize engulf bacteria & extraneous

    matter (in absence of opsonins)

    2. Engulfment:

    a. Pseudopods of phagocyte flow around the microbe to be

    engulfed Microbe enclosed in a phagosome

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  • b. Phagosome fuses with lysosome phagolysosome

    c. Degranulation into phagolysosome and bacterial killing.

    d. Biochemical events of engulfment same as chemotaxis Killing

    3. Degradation

    a. Mainly: O dependent Mechanisms

    i. Activation of NADPH oxidase

    ii. HOCl: - Halogenation

    iii. Peroxidation

    b. Lesser known mechanism is H O - MPO - halide: - but its the most.

    efficient bactericidal system -effective. against fungi, viruses, protozoa,

    helminths

    Example

    Which of the following is most important in the bactericidal activity?

    AIPG 2011

    A. Hydrolase

    B. Peroxidase

    C. Transferase

    D. Dismutase

    Solution

    B. Peroxidase

    c. Dead organism

    Study(Http://Gradestack.Com/Dr-Bhatia-Medical-Coaching-Institute/Pathology/3168/Subject-Study)

    1. Cell Injury(http://gradestack.com/Dr-Bhatia-Medical-Coaching-Institute/Causes-Of-Cellular-Injury/16081-3168-9159-study-wtw)

    2. Inflammation(http://gradestack.com/Dr-Bhatia-Medical-Coaching-Institute/Response-Of-Vascularized-Connective-Tissue-To/16082-3168-9317-study-wtw)

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    PhagocytosisQ

    http://gradestack.com/Dr-Bhatia-Medical-Coaching-Institute/Pathology/3168/subject-studyhttp://gradestack.com/Dr-Bhatia-Medical-Coaching-Institute/Causes-Of-Cellular-Injury/16081-3168-9159-study-wtwhttp://gradestack.com/Dr-Bhatia-Medical-Coaching-Institute/Response-Of-Vascularized-Connective-Tissue-To/16082-3168-9317-study-wtw

  • Comment

    a. lysosomal hydrolases

    b. MPO deficient leukocytes: superoxide, hydroxy singlet oxygen

    c. O - independent Mechanism: through action of substances in

    leukocyte granules

    i. Bactericidal permeability increasing protein (BPI) -

    phospholipase activation, permeability

    ii. Lysozyme- hydrolyses the glycopeptide coat of bacteria

    iii. Lactoferrin

    iv. Major basic protein: Eosinophils

    v. Cytotoxic to many parasites

    vi. Defensins:

    pH of phagolysosome: 4 5

    d. Release of leukocyte products

    Mechanism of release:

    a. Regurgitation during feeding: If Phagocytic vacuole remains

    transiently open to outside

    b. Frustrated phagocytosis: on flat surface (e.g. GBM ~ immune

    complexes)

    c. Surface phagocytosis: Mech. by which phagocytes facilitate

    ingestion of bacteria & other foreign material by trapping it

    against resistant surface

    d. Cytotoxic release: After phagocytosis of potentially

    membranolytic substances (e.g crystals)

    e. Exocytosis: Secondary granules of neutrophils After

    phagocytosis - apoptotic cell death and engulfment of Neutrophil

    by monocyte

    3. Neoplasia(http://gradestack.com/Dr-Bhatia-Medical-Coaching-

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    Acute Inflammation

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