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Immunology > Lecture 5&6 phagocytosis and complement system > Flashcards

Lecture 5&6 phagocytosis and complement system Flashcards

1
Q

ability of some cells to ingest foreign particles

A

phagocytosis

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2
Q

are a class of cells which are capable of ingestion and killing of microorganisms that incite inflammation response

A

phagocytes

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3
Q

first to accumulate around the invaders and initiate the phagocytic process are ___________.

Later, local and blood borne ________ also migrate to the tissue sit of initiate phagoycytosis

A

neutrophils (suicide bombers)
macrophage(seriel killers)

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4
Q

what are the professional phagocytes

A

neutrophils
macrophage

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5
Q

list the sequence of events involved in phagocytosis/destruction of engulfed

A

1.chemotaxis
2. adherence
3. ingestion
4. destruction
egestion (only in the case of macrophages)

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6
Q

delivery of phagocytic cells to the site of infection

A

chemotaxis

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7
Q

phagocytic adherence to the target

A

adherence

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8
Q

engulfment of the target particle

A

ingestion

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9
Q

intracellular killing and digestion of the target

A

destruction

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10
Q

additional step to remove dead material before macrophages start to kill again

A

egestion

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11
Q

coating of a hydrophilic material with opsonins that include IgG, IgM, C3b

** make bacteria tasty for neutrophil/macrophages

A

opsonization

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12
Q

neutrophil can phagocytose anything more _________ than itself

A

hydrophobic

neutrophils don’t bind hydrophilic material

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13
Q

what are the 2 types of coating possible through opsonization

A

antibody
complement

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14
Q

the 2 neutrophil membrane receptors important in phagocytosis

A

Fc receptors
C3b receptors

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15
Q

bind antibody that is bound to an antigen, especially IgG antibody

A

Fc receptors

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16
Q

bind to C3b when it is coating bacteria

A

C3b receptor

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17
Q

once neutrophil bind to opsonized material, it is readily engulfed forming a _______________

A

phagosome

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18
Q

membrane bound vesicle (compartment) containing the ingested microbe or material

A

phagosome

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19
Q

formation of the phagolysosome

A

phagosome migrates into cytoplasm and collides with lysosomal granules which explosively discharge their contents into the membrane enclosed vesicle (phagosome)

membranes of phagosome and lysosome actually fuse resulting in a digestive vacuole called the phagolysome

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20
Q

what happens in the phagolysosome

A

killing and digestion of engulfed microbe take place

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21
Q

why does destruction of microbe only occur inside the phagolysosome

A

its so that the toxic substances and lethal activities of the phagocytes are turned against themselves

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22
Q

after phagolysosome formation the first detectable effect on bacterial physiology is the loss of ________.

By 10 to 30 min after ingestion many pathogenic/nonpathogenic bacteria are _______ followed by lysis and digestion of bacteria by _____________

A

viability
lysis
lysosomal enzymes

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23
Q

What are the 3 intracellular killing processes

A
  1. lytic enzymes and antimicrobial peptides from granules
  2. oxidative metabolism (respiratory burst)
  3. neutrophil extracellular traps
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24
Q

list the primary granules

A

hydrolases
lysozyme
defensins
myeloperoxidase

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25
Q

list the secondary granules

A

lysozyme
lactoferrin
collagenase

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26
Q

breaks covalent bonds by adding water, important for degrading dead bacteria or dead tissues

A

hydrolases

27
Q

breaks down peptidoglycan in gram-positive bacteria

found in many secretions in the body

A

lysozyme

28
Q

small cationic proteins that kill bacteria, especially gram-positive, that are 29-42 amino acids long and have hydrophobic outside and hydrophilic interior and inserts into a membrane to form a pore

also called antimicrobial peptides

A

defensins

29
Q

an enzyme that has an important role in the oxygen mediated killing mechanism

A

myeloperoxidase

30
Q

chelates iron

A

lactoferrin

31
Q

degrades connective tissue, so it can move through to the site of inflammation

A

collagenase

32
Q

most potent killing mechanism of neutrophil

A

oxygen mediated killing mechanism (myeloperoxidase)

33
Q

where does oxygen mediated killing mechanism occur and what products does it kill

A

occurs in phagolysome
killing products of respiratory burst include:
1. hypochlorite
2.hydrogen peroxide
3. aldehydes
4.oxygen radicals

34
Q

removal of dying of neutrophils by macrophages

A

macrophage and neutrophil interact by CD31

if neutrophil “acknowledges” macrophage= healthy neutrophil and macrophage leaves neutrophil alone

if neutrophil DOES NOT “acknowledge” macrophage= neutrophil is dying and macrophage kills neutrophil

35
Q

M2 cells

A

clean up crew
alternative activation

increases tissue repair, increases MHC class 2 expression, and reduces microbial killing

36
Q

M1 cells

A

phagocytic cells- macrophages

classical activation

increased- size, movement, MHC 2 expression, lysosomal enzymes, NO production

37
Q

what do stimulated neutrophils release extracellularly? ___________ and ____________

what does this extracellular degranulation create?

A

nuclear material
granular proteins (DNA, histone, granular material)

mesh that traps the bacteria and the antimicrobial proteins kill the bacteria (NETosis)

38
Q

a group of serum and cell surface proteins activated by factors such as the combination of antigen and antibody resulting in the generation of enzyme cascades that have a variety of biological consequences including cell lysis and opsonization

A

complement

39
Q

what are the 3 pathways that activate complement

A
  1. classical pathway
  2. alternative pathway
  3. MB-Lectin pathway
40
Q

what activates classical pathway

A

when a complement fixing antibody (IgM, IgG) binds antigen

binding site for complement on Fc portion of the antibody “opens up” when the antibody is bound to antigen

41
Q

what activates lectin pathway

A

initiated by soluble pattern recognition molecules (PRR) that bind to carbohydrates on the microbial surface

this activates enzymes that activate complement

(MBL binds to mannose on pathogen)

42
Q

what activates alternative pathway

A

initiated by C3b binding on the cell wall of pathogens

C3 spontaneously breaks down to C3a and C3b

43
Q

classical pathway is involved in what kind of immunity

A

innate and adaptive

44
Q

alternative pathway is involved in what kind of immunity

A

part of the innate immunity

**adaptive immunity is not required for this pathway to be initiated

45
Q

MB-Lectin pathway is involved in what kind of immunity

A

part of the innate immunity; adaptive is not required to initiate this pathway

46
Q

Mammalian cells do not have ____________ on their cell surface, so MBL pathway is initiated on microbes but not self-cells

A

mannose

47
Q

how do the three complement pathways differ

when are they the same

A

differ in the initiation of the cascade

pathways are the same from C3 through terminal pathway and formation of membrane attack complex

48
Q

describe the process:

initiation of the classical pathway

A
  1. antigen-antibody binding initiates the classical pathway
  2. when antigen binds with antibody, theres is a conformational change in the Fc portion of the antibody that allows C1 (first protein of complement cascade to bind to antigen-antibody complex

must be 2 Fc binding sites for C1 to bind, so one IgM or 2 IgG needed for initiation*

  1. activated C1 cleaves C4 into C4a and C4b
  2. C4b binds to a membrane and C2 binds to membrane bound C4b
  3. activated C1 cleaves C2 when its bound to C4b leading to formation of C4b2b (classical pathway C3 convertase)
  4. C3 convertase cleaves into a and b; C3b is an opsonin
  5. C3b binds C5 and then C4bC2b cleaves C5 leading to initiation of terminal pathway
49
Q

describe the process:

activation of alternative pathway

A
  1. C3 spontaneously breaks into C3a and C3b
  2. C3b’s reactive carbonyl group will covalently bind to cell surface
  3. Factor B can bind to C3b
    4.Factor D can cleave factor B bound to C3b
    5.C3bBb is the alternative pathway C3 convertase
50
Q

describe the process:

activation of MBL pathway

A

** mannose binding lectin (MBL) is a soluble PRR**
1. MBL binds to mannose (a PAMP) on microbes
2. bound MBL activates MASP-2, MBL- associated serine protease which has similar activity to C1
3. MASP-2 cleaves C4 and the cascade is initiated

51
Q

why is 1 IgM more efficient than 2 IgG molecules

A

it has a pentameric (5 sided) shape which provides the same conformation as 2 IgG molecules

52
Q

this part of the complement cascade is the same for all three pathways

A

terminal complement pathway

53
Q

what initiates the terminal pathway

A

cleavage of C5

54
Q

Biological consequences of complement activation:

C1 to C2a

A

increased vascular permiability

55
Q

Biological consequences of complement activation:

C1 to C3a

A

anaphylatoxin
microbial killing

56
Q

Biological consequences of complement activation:

C1 to C3b

A

immune regulation
opsonization

57
Q

Biological consequences of complement activation:

C1 to C5b67

A

leukocyte chemotaxin

58
Q

Biological consequences of complement activation:

C1 to C5a

A

neutrophil chemotaxis
anaphylatoxin
lysosomal enzyme secretion
neutrophil activation
increased vascular permeability
smooth muscle contraction

59
Q

Biological consequences of complement activation:

C1

A

cell membrane lysis

60
Q

3 functions of complement that eliminate microbes

A
  1. opsonization and phagocytosis
    2.complement-mediated cytolysis
    3.stimulation of inflammatory reactions
61
Q

describe: opsonization and phagocytosis

A
  1. binding of C3b to microbe (opsonization)
  2. recognition of bound C3b by phagocyte C3b receptor
  3. phagocytosis and killing of microbe
62
Q

describe: complement-mediated cytolysis

A
  1. binding of C3b to microbe, activation of late components of complement
  2. formation of membrane attack complex (MAC)
  3. osmotic lysis
63
Q

describe: stimulation of inflammatory reactions

A
  1. proteolysis of C3 and C5 to release C3a and C5a
  2. recruitment and activation of leukocytes by C5a and C3a
  3. destruction of microbes by leukocytes

Immunology (12 decks)

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