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Immunology (a) > inflamation and phagocytosis > Flashcards

inflamation and phagocytosis Flashcards

0
Q

the __ and ____ events that highlight ____ inflammation serve to deliver mediators of host defense (_____ and _______) to sites of microbial invasion and or tissue injury

A 
vascular 
cellular
acute
leukocytes
plasma proteins
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1
Q

inflamation

A

the reaction o vascularized living tissues to local injury

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2
Q

inflammation is

A
  • an evoke response set in motion by some kind of stimulus; occurs only in living things
  • fairly stereotypical regardless of the inducing stimulus
  • an overlapping series of events that form a continuum
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3
Q

the inflammation response may have three out comes:

A
  1. elimination of the causative agent
  2. walling off of the inflammation from the rest of the body with subsequent healing of the lesion
  3. persistence of the causative agent, leading to chronic inflammation or spread throughout the body
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4
Q

although inflammation is characteized by the controlled passage of cells, ____ and _________ into the injured tissue, sometimes it can be ___ _____ than the initiating stimulus

A

plasma
plasma components
more harmful

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5
Q

rubor

A

caused by increased blood flow, dilation of arterioles and vascular perfusion of the area

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6
Q

tumor

A

caused by diapedesis of blood cells and plasma from the post capillary venules into the damaged tissue

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7
Q

calor

A

local increase in tissue temperature

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8
Q

dolor

A

caused by stimulation of neuronal pathways by bradykinin, histamine, serotonin, and prostaglandin

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9
Q

functio laesa

A

loss of function

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10
Q

the local inflammatory response is ____ accompanied by ____ changes collectively called the ____ phase response or _____ ____ response syndrome.

A

always
systemic
acute
systemic inflammatory

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11
Q

these systemic responses to infection are due to the actions of _____ ____ such as ___________, ________, and _______ secreted by activated macrophages, mast cells, etc.

A

proinflamatory cytokines
tumor necrosis factor
interleukin-1
interleukin-6

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12
Q

other cytokines that also participate in the acute phase response include ____ ____ ___ that stimulat the bone marrow to produce more white blood cells

A

colony stimulating factor

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13
Q

the acute phase response includes the following:

A
  • fever
  • leukocytosis
  • increased synthesis of acute phase proteins
  • decrease in the plasma concentration of iron.
  • decrease in appetite
  • increased secretion of many hormones, notably ACTH and cortisol
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14
Q

T or F

low concentration of free iron enhances bacterial replication

A

F

-High

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15
Q

acute phase proteins

A

are plasma proteins whose concentrations change by at least 25% during inflamation

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16
Q

what is a negative acute phase protein?

A

albumin

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17
Q

acute phase proteins are synthesized mostly by the

A

liver

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18
Q

acute phase proteins play various rolls in the innate immune system, they include:

A
  • complement proteins
  • C-reactive protein
  • mannose-binding protein
  • iron binding proteins
  • lipopolysaccharide-binding protein
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19
Q

C-reactive protein

A

has the ability to bind to the C-protein of pneumococci.

-binds to bacteria and promotes their uptake by phagocytic cells a process referred to as opsonization.

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20
Q

opsonization

A

the uptake of bacteria by a phagocytic cell

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21
Q

mannose-binding protein

A

binds to mannose residues on the surface of a bacterial cell, resulting in its opsonization

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22
Q

what is an example of an iron binding protein

A

haptoglobin

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23
Q

lipopolysaccharide- binding protein

A

enhances the ability of macrophages and other cells to detect and respond to Gram-negative bacteria

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24
Q

microvasculature consist of:

A

afferent arterioles, the capillary networks, and the efferent venules

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25
Q

following tissue injury, initation of the inflammatory response occurs at the level of the ____ and _____ ____ venules

A

capillary

postcapillary

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26
Q

arterioles

A

the initial response is transient vasoconstriction, mediated by neurogenic and chemical stimuli. then vasodilation occurs with increased blood flow to the inflamed area

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27
Q

capillaries

A

the reaction of endothelial cells in the capillaries to vasoactive mediators leads to EC retraction, gap formation, and increased permeability

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28
Q

post capillary venules

A

primary anatomic site for inflammation- related leakage

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29
Q

T or F

endothelial cells are less sensitive to vasoactive mediators

A

F

more sensative

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30
Q

chemical mediators

A

are chemical messengers that
enhance blood flow,
increase vascular permeability, or
induce the emigration of leukocytes from the blood stream to the
site of tissue injury.

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31
Q

exogenous sources of chemical mediators:

A

bacterial LPS

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32
Q

endogenous chemical mediators originate from both ___ and ____

A

plasma

host cells

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33
Q

cellular sources of chemical mediators include

A
  • platelets
  • connective tissue mast cells
  • basophils
  • neutrophils
  • endothelial cells
  • fibroblast
  • monocyte/ tissue macrophages
  • injured tissue
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34
Q

vasoactive mediators include:

A
  • histamine
  • serotonin
  • bradykinin
  • nitric oxide
  • leukotriene
  • prostaglandins
  • platelet -activating factor
  • anaphylatoxins
  • LPS
  • cytokines
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35
Q

chemotactic factors

A
  • C5a
  • leukotriene
  • formylated peptides
  • chemokines
  • PAF
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36
Q

vasoactive mediators cause

A

vasodilation
increased vascular permeability
endothelial expression of adhesion molecules

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37
Q

chemotactic factors cause

A

recruitment and stimulation of inflammatory cells

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38
Q

T or F

most functions can be elicited by multiple mediators and most mediators serve multiple functions.

A

T

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39
Q

Many mediators exert their effects ____ and do not circulate systemically in ___ concentration.

A

locally

high concentrations

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40
Q

LPS

A

released from the cell wall of Gram-negative bacteria is recognized and bound to LPS binding protein present in plasma

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41
Q

macrophage activation happens when:

A

LBP enhances the transfer and presentation of LPS to the CD14 receptor on macrophage cell membrane

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42
Q

the activated macrophage synthesizes and secretes vasoactive mediators of inflammation including:

A 
IL-1
IL-6
CXCL-8
TNF- alpha
PAF
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43
Q

nitric oxide

A
  • important mediator of inflammation
  • causes vasodilation by relaxing vascular smooth muscle
  • reduces platelet aggregation and adhesion
  • is a potent microbicidal agent
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44
Q

nitric oxide is produced by

A

activated endothelial cells and

activated macrophages

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45
Q

leukocyte recruitment begins with

A

dilation of post capillary venules

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46
Q

what are the steps that follow dilation of postcapillary venules

A
  1. leukocyte rolling
  2. activation
  3. margination/pavementing
  4. transendothelial migration
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47
Q

subsequent movement through the extracellular matrix to the site of inflammation or tissue injury occurs under the influence of

A

chemotactic factors

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48
Q

the 4 major families of adhesion molecules are:

A

selectins
addressins
integrins
immunoglobulin superfamily

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49
Q

selectins

A

adhesion molecules expressed on platelets, leukocytes, and endothelial cells that promote the initial localization and rolling of leukocytes along endothelium at sites of tissue injury

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50
Q

each selectin molecule is a _____ chain transmembrane_____ with an extracellular lectin domain

A

single

glycoprotein

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51
Q

P-selectin

A

is preformed and is stored within Weibel-palade bodies of ECs and the alpha-granules of platelets.

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52
Q

Pselectin binds to an _____ on ___, ______, and ______ cell surfaces call P-selectin glycoprotein ligand-1

A

addressin
neutrophil,
monocyte
T-lymphocyte

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53
Q

E selectin

A

is synthesized and expressed by endothelial cells within 1-2 hours after proinflamatory cytokine activation

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54
Q

e selcting binds to e-selectin ligand-1 on the surface of

A

granuloytes, monocytes, and t lymphocytes

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55
Q

L-selectin

A

is expressed on lymphocytes, granulocytes, monocytes, and macrophages

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56
Q

L-selectin binds to

A

CD34
glycan-bearing cell adhesion molecule-1
mucosal addressin cell adhesion molecule-1

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57
Q

Vascular addressins

A

mucin-like molecules that possess carbohydrate regions that bind the lectin domain of selectins

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58
Q

addressins are expressed on the surfaces of

A

leukocytes and endothelial cells

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59
Q

T or F

selectin-addressin binding is a strong bond

A

F- they are not a strong bond

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60
Q

integrins

A
  • are transmembrane adhesive proteins expressed on leukocytes
  • composed on alpha and beta subunits, arranged as heterodimers
  • several subfamilies that express a conserved beta chain
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61
Q

major functions of integrins are to

A

mediated adhesion of leukocytes to endothelial cells, extracellular matrix proteins, and adhesion of T cells to antigen presenting cells or target cells

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62
Q

T or F

some integrins bind to proteins that participate in the inflamatory response.

A

T

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63
Q

integrins are always present on the surface of leukocytes but are quicly up-regulated in numbers and adhesiveness following activation of leukocytes by

A

chemoattractants

64
Q

the up-regulated sticky integrins on activated leukocytes then bind to their counterreceptors on ECs, resulting in the stable adhesion of leukocytes to the endothelium, this is also know as:

A

pavementing

65
Q

the significance of integrin proteins in leukocyte extravasation is demonstrated by ______ ______ _______ disease, which is characterized by recurrent bacterial infections.

A

leukocyte adhesion deficiency

66
Q

immunoglobulin superfamily

A

a family of proteins that share partial amino acid sequence homology and tertiary structural features that were originally identified in immunoglobulin heavy and light chains

67
Q

some members of the family are expressed on the cell surface of cytokine- stimulated ______ cells and _____ and help localize leukocytes to areas of tissue damage.

A

endothelial cells

leukocytes

68
Q

ICAM-1 (CD54)

A

expressed by proinflam. cytokine activated ECs. it is also expressed by a variety of cells including B lymphocytes and monocytes/macrophages

69
Q

ICAM-1 counter receptor is

A

CD11aCD18

70
Q

I CAM-2 (CD102)

A

constitutively expressed at low levels on some ECs. also expressed by monocytes/macrophages and some Tcells.

71
Q

VCAM-1(CD 106)

A

expressed by activated ECs. also expressed by macrophages and other cells

72
Q

VCAM-1 counter receptor is

A

VLA-4

73
Q

Platelet endothelial cell adhesion molecule (PECAM-1)

A

present on neutrophils, platlets, monocytes, B cells;

74
Q

PECAM-1 is also found where

A

junctional complex of activated ECs

75
Q

Homotypic binding

A

PECAM-1 molecule on one cell binds to PECAM-1 molecule on another cell

76
Q

Diapedesis

A

enhanced by binding of PECAM-1 on neutrophils to its twin PECAM-1, expressed on ECs close to the inter-endothelial cell junction

this is an exit sign for neutrophils

77
Q

in most bacterial infections, ______ predominate during the first ________ hours of the inflammatory reaction.

A

neutrophils

6-24

78
Q

in most species, other than ___and ___, neutrophils are the most numerous WBCs in circulation

A

pigs and cattle

79
Q

T or F

Neutrophils respond more slowly to chemotactic agents.

A

False

more rapidly

80
Q

In the later stage( 24-48 hours) of the inflammatory reaction, ____ and ____ predominate.

A

monocytes

lymphocytes

81
Q

in immediate hypersensativity reactions and parasitic infestations _____ predominate

A

eosinophils

82
Q

chemotaxis

A

the energy-dependent, unidirectional migration of cells toward increasing concentrations of a soluble chemotactic agent

a receptor mediated event

83
Q

chemokinesis

A

random, excited movement of cells

84
Q

haptotaxis

A

chemotactic agents bind to extracellular matrix protein, thereby creating a fixed chemotactic gradient

85
Q

leukocyte chemoattractants can be divided into two basic types

A

classical leukocyte attractants

chemokines

86
Q

classical leukocyte attractants

A

act broadly on several cell types, including monocytes, macrophages, and neutrophils

87
Q

classical leukocyte attractants include:

A 
bacterial chemotaxins
dead cells
plasma derived: C5a/C3a/C5b67
platelet activating factor
Leukotriene B4
88
Q

chemokines

A

they are the most important group of chemotactic agents
include:
CXC chemokines
CC chemokines

89
Q

CXC chemokines

A

potent attractants and activators of NEUTROPHILS

most significant is CXCL8 (IL-8)

90
Q

CC chemokines

A

they attract various leukocytes but not neutrophils

91
Q

phagocytosis

A

process by which certain cells of the innate immune system, including macrophages and neutrophils engulf large particles, such as bacteria, fungi, protozoa

92
Q

Elie Metchnikoff

A

credited for discovering phagocytosis
he also concluded that inflammation served as an important defense reaction of the body and played a major part in bringing about recovery from bacterial infections

93
Q

polymorphonuclear neutrophils (PNMs)

A

make up 40-70% of the total blood leukocyte population in most animal species except in pigs in cattle

94
Q

what are the predominate peripheral blood cells in pigs and cattle

A

lymphocytes

95
Q

Majority of PMNs are stored in the _____ and are released when ________ mediators reach the bone marrow via the blood stream, and there, act on the marrow capillaries and on stored PMNs to mobilize them into the circulating blood.

A

bonemarrow

proinflammatory

96
Q

once released from bone marrow _____ do not have the ability to divide and give rise to new cells.

A

neutrophils

97
Q

T or F

an adult human produces over 1X10^11 neutrophils ever week.

A

F

its supposed to be per day

98
Q

Neutrophils circulate in the blood for about ___ to ___ hours and then migrate into tissues where they may survive for up to ___ to ___days

A

4 to 8

4 to 5

99
Q

if a PMN is not recruited into a site of inflammation what happens to it

A

undergoes programmed cell death and is usually phagocytosed by resident macrophages in the liver or spleen

100
Q

the neutrophils of ____, ___, and ________ contain large reddish staining cytoplasmic granules, hence they are refereed to as ____.

A

chickens
rabbits
guinea pigs
heterophils

101
Q

attachment between the neutrophil and the microbe is mediated by the interaction between __ ____ _____ and _____ on the microbe

A

cell surface receptors and ligands

102
Q

_____ and ____ recognize conserved microbial structures that are relatively invariant with a pathogen class. these structures are termed______________(____) eg, LPS, lipoteichoic acid, peptidoglycan, mannose-rich ogliosaccharides, etc. the receptors on phagocytes that recognize them are called____________.

A

neutrophils and macrophages
pathogen-associated molecular patterns (PAMPS)
pattern recognition receptors (PRRs)

103
Q

opsonins

A

are naturally occurring(nonspecific) or acquired (specific) substances that coat microbes and render them more susceptible to phagocytosis

104
Q

Opsonons, being ____ charged proteins help to neutralize the ___ charges on foreign particles, enabling them to bind to negatively charged phagocytes

A

positively

negative

105
Q

Specific opsonin

A

IgG
fab portions bind to epitopes on the microbe
Fc portion binds to Fcgamma receptor on phagocyte

106
Q

nonspecific opsonins

A

complement proteins C3b, iC3b, C4b and a number of plasma proteins including fibronectin, manose-binding lectin (MBL) and C-reactive protein

107
Q

Nonspecific opsonization is ___ effective than IgG coating but can enhance _____ early in the course of infection before specific antibodies are produced.

A

less

phagocytosis

108
Q

following attachment, the adherent particle stimulates ____ formation of the cell membrane.

A

pseudopodia

109
Q

phagosome

A

phagocytic vesicle that is free floating now do to breaking away from the cell membrane

110
Q

following engulfment lysosomal granules migrate through the cytoplasm and fuse with phagosome to form____, where microbicidal molecules and the proteolytic enzymes stored in lysosomes come into contact with and destroy the phgocytized microbe

A

phagolysosome

111
Q

microbial killing occurs with in

A

10-30min

112
Q

primary granules

A

defensins
myelo-peroxidase
neutral and acid hydrolases
lysozyme

113
Q

defensins

A

disrupt plasma membrane

114
Q

myelo-peroxidase

A

respiratory burst

115
Q

natural and acid hydrolases

A

degrade bacterial products

116
Q

lysozyme

A

destroys bacterial cells walls

117
Q

secondary granules

A

lysozyme
lactoferrin
collagenase

118
Q

lactoferrin

A

binds iron

119
Q

collagenase

A

degrades connective tissue

120
Q

respiratory -burst is characterized by

A

two-three fold increases in O2 consumption by the cell, (b) increased glucose oxidation via the hexose monophosphate shunt, and (c) generation of microbicidal reactive oxygen intermediates: superoxide anion, hydrogen peroxide, hypochlorous acid, hydroxyl radical, and singlet oxygen

121
Q

_____ is the most potent microbicidal system in neutrophils

A

H2O2-myeloperoxidase-halide system

122
Q

oxygen independent killing

A

lysozyme
defensins
bactericidal permeability increasing protein

123
Q

lysozyme

A

a mucopeptidase found in serum, sweat, tears, saliva, mucus, nasal secretions, phagocytes and tissue fluids

124
Q

what breaks down bacterial cell wall peptidoglycan by hydrolyzing the glycosidic bond between the monosaccharides of the peptidoglycan backbone, there by rendering the bacterium susceptible to osmotic lysis

A

lysozyme

125
Q

lysozymes are effective against whome

A

gram-positive bacteria

126
Q

defensins

A

a group of small peptides found in phagocytes and certain intestinal cells.
form ion-permeable channels in microbial cell membrane, resulting in escape of essential metabolites
can kill or inactivate a wide variety of bacteria, fungi, and some enveloped viruses

127
Q

bactericidal permeability increasing protein

A

binds specifically to the outer membrane of gram negative bacteria

128
Q

BPI induces

A
  • phospholipase activation
  • phospholipid degranulation
  • increased permeability in the outer membrane of the bacterium
129
Q

neutral and acid hydrolases

A

degrade and digest killed bacteria within the phagolysosome

130
Q

Neutrophils lack ____ , thus they possess a limited supply of energy reserves which cannot be replinished

A

mitochondria

131
Q

following phagocytosis, neutrophils rapidly undergo ___ cell death and are ingested by macrophages

A

apoptotic

132
Q

The MMS consists of _____, _________, and ____ or ____ ____ ____

A

monocytes
macrophages
resident or fixed tissue macrophages

133
Q

upon release from bone marrow, monocytes circulate in the blood for __ to ___ hours before migrating into tissues, where they undergo maturation to become tissue macrophages.

A

10-20 hrs

134
Q

resident of fixed tissue macrophages and macrophage -like cells

A

serve as the first line of phagocytic defense when microorganisms breach the physical barriers

135
Q

alveolar macrophages are found

A

in the lungs

136
Q

pulmonary intravascular macrophages are found in

A

ruminants, cats, and pigs

in the capillaries of the lungs

137
Q

Free macrophages

A

derived from blood monocytes constitute the majority of macrophages at inflammatory sites. a small portion may come from fixed macrophages which can undergo cell division when appropriately stimulated

138
Q

macrophages play a roll in both ____ and ___ immunity and are important effector cells for the elimination of microorganisms.

A

innate and adaptive

139
Q

macrophages can live for ___ to ___ unless they are destroyed by performing functions

A

months to years

140
Q

Unlike neutrophils, macrophage lysosomes also contain large amounts of _____, which digest the thick lipid membranes possessed by some bacteria.

A

lipases

141
Q

Macrophage membrane receptors consist of

A

cytokine receptors
complement receptors
antibody receptors
integrins

142
Q

__________ receptors on cell membrane bind to mannose or fucose residues in the capsule of LPS f invading bacteria, allowing macrophages to bind directly to ________ bacteria

A

Mannose-binding

nonopsonized

143
Q

Macrophages respond to the same chemoattractants that neutrophils do along with:

A

CC chemokines
cationic peptides released by dead and dying neutrophils
lymphokines released by activated T cells( migration inhibition factor and macrophage chemotactic factor)

144
Q

unlike neutrophils, macrophages are

A

sluggishly motile

145
Q

macrophages can engul

A

rbc
neutrophils
necrotic debris

146
Q

compared to neutrophils, a macrophage is capable of phagocytizing as many as ___ bacteria

A

100

147
Q

activated macrophages can synthesize ___, a vey powerful microbicidal agent

A

nitric oxide

148
Q

in chronic inflammation, macrophage accumulation will persist; this is mediated by multiple mechanisms:

A
  • recruitment of monocytes from circulation
  • macrophage proliferation
  • immoblization of macrophages
149
Q

when stimulated, macrophage may increase in size and form clusters of _____ or several may fuse to form_____

A

epithelioid cells

multinucleated giant cells

150
Q

macrophages play a major roll in:

A

tissue reorganization and wound healing

151
Q

Macrophage proteinases

A

degrade connective tissue; the cellular debris is then phagosytized. they also synthesize and secrete many growth factors that promote the proliferation of fibroblasts and the growth of new blood vessels

152
Q

what are the many functions of macrophages

A

-antigen presentation
-tissue reorganization and wound healing
-secretion
cytokines
enzymes
other factors
-tumor cell destruction
-phagocytosis and destruction of bacteria

153
Q

when neutrophils and macrophages engage in phagocytosis, they can injure normal host tissues by release of

A

ROI and lysosomal enzymes

154
Q

antoproteinases

A
  • synthesized by the liver, leukocytes, and connective tissue
  • present in plasam and tissues (alpha-2 maroglobulin and alpha-1antitrypsin), inhibit leukocyte proteinases, there by preventing and/or minimizing tissue damage
155
Q

escape of reactive oxygen metabolites

A

cytocolic and plasma molecular “scavengers” of oxyradicals limit damage to cells and tissues

catalase and glutathione peroxidase, both present in cells, convert escaped H2O2 to H2O and O2

156
Q

cytotoxicity

A

membranolytic substances such as bacterial leukocidin, urate crystals, can damage the membrane o the phagolysosome, spilling out potent hydrolytic enzyme
kills leukocyte and released into tissues

157
Q

regurgitation during feeding

A

large numbers of bacteria= increased feeding and results in the fusion of the lysosome with the developing phagosome, prior to complete closure
lytic enzymes in lysosome have direct access to the extracellular environment

158
Q

frustrated phagocytosis

A

phagocyte encounters phagocytic stimuli that are too large to be internalized (parasites, bacteria, antigen-antbody immune complexes on basement membrane)
undere these conditions release of lysosomal enzymes by the phagocyte into the surrounding environment occur leading to tissue injury- vasculitis

Immunology (a) (6 decks)

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