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Immunology > Innate Immunity: Cellular Mechanisms > Flashcards

Innate Immunity: Cellular Mechanisms Flashcards

1
Q

What are the granulocytes and where are they

A

Neutrophils, eosinophils and basophils

In blood and can migrate into tissue

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2
Q

__ cells are resident in tissues, particularly at epithelial surfaces and is characterized by the presence of abundant intracellular granules

A

Mast

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3
Q

NK cell

A

Circulating

Viral infections and tumor cells

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4
Q

Neutrophils

A

Killing and removal of bacteria and fungi

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5
Q

Eosinophils

A

Control infection with multicellular parasites

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6
Q

Basophils and mast cells

A

Allergy (common debilitating immune disorder)

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7
Q

Sequence of events for granulocyte

A

Resting. Signalling. Activation. Migration from blood and effector function

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8
Q

Appearance of neutrophils

A

Polymorphic(multilobed) nucleus and neutral staining granules
Abundant in circulation
6 hour half life in blood and 1-2 days in tissue
Replaced from bone marrow

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9
Q

In good health, _ neutrophils will be seen in tissue

A

Few

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10
Q

What are the two main types of granules in neutrophils

A

Primary or azurophilic granules

Secondary of specific granules

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11
Q

Primary/azurophilic granules

A

First appear during their development in bone marrow

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12
Q

Secondary or specific granules

A

Appears later

3 times more common in the cytoplasm

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13
Q

What stimuli mobilize the granules in neutrophils

A

Products of bacterial cell walls, complement proteins, the leukotreine group of lipid mediators and small bioactive peptides called cytokines

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14
Q

N-formulated peptides (FMLP)

A

Bacterial derived and bind to receptors not he neutrophil surface

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15
Q

The complement product, ___ binds to specific surface receptors on neutrophils

A

Ic3b

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16
Q

Leukotreines

A

Products of the lipooxygenase pathway or arachidonate metabolism and some, such as LTB4 have potent stimulators effects on neutrophils

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17
Q

Chemokine CXCL8 (IL-8) and TNF-a (a granulocyte-monocyte csf..gym-csf)

A

Potent effects on neutrophils

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18
Q

What is in primary/azurophilic granules of neutrophils

A

Microbicidal things

Myeloperoxidasecathepsin G
Proteinase-3
Elastase
Lysozyme
Defensins
Bactericidal.permeability increasing protein (BPI)
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19
Q

What is in secondary/specific granules

A

Microbicidal things

Cytochrome b558 and other respiratory burst components
Lysozyme
Lactoferin

And migration things
Collagenase
CD1 I b/CD18(CR3)
N formyl methionyl leucylphenylalanine receptor (FMLP-R)

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20
Q

Following activation of what are lipids in the cell membrane concerted de novo into inflammatory mediators that have potent effects on vasculature and on inflammatory cells such as neutrophils

A

Mast cells, macrophages, granulocytes, and lymphocytes

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21
Q

What are the 3 major classes of lipid mediators, converted from membrane phospholipids by phospholipase A2

A

Prostagladin D2
Leukotrines
Platelet activating factor

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22
Q

Prostagladin D2 (PGD2)

A

From cyclooxygenase pathway of arachidonic acid metabolism
Binds receptors on smooth muscle in vascular endothelium leading to vasodilation
-increase blood supple and slows leukocytes passing through tissue allowing them to migrate fromt he blood

PGE2 and PGF2 made my macrophages also inflammatory

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23
Q

Leukotreines

A

Formed when arachdonic acid is converted through the lipooxygenase pathway
Mast cell synthesis-LTB4, C4, D4, E4
Neutrophil synthesizes LTB4

Cause vasodilation and extravasation of fluid into the tissues

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24
Q

PAF

A

Produced by mast cells and also has effect of relaxing vascular smooth muscle

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25
Q

NSAIDS

A

Asprin blocks cyclooxygenase so can control arthritis

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26
Q

Side effect nsaid

A

Increasing stomach inflammation —fatal hemorrhage

Cox-2 selective for pain and inflammation and spares stomach problems

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27
Q

The lipid mediators are released as a result of ___ reactions and have profound effects on smooth muscle in lung, causing bronchial constriction …manifests as ___

A

Inflammation

Asthma (tightness in chest, wheezing,

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28
Q

Leukotreines and prostaglandins are made from ___ ____. PAF is made from _____

A

Arachidonic acid

Lysoglyceryl platelet activating factor

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29
Q

Prostagladin are made through what pathway. Leukotreines are made through what pathway. PAF is made through what pathway

A

P-cyclooxygenase
L-lipooxygenase
PAF_acetyl transferase

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30
Q

What is a cytokine

A

Polypeptide released by a cell in order to change the function of the same or another cell. Important chemical messengers

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31
Q

Pleitropy

A

Cytokine with many different effects

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32
Q

Autocrine

A

Act on cell that releases it

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33
Q

Paracrine

A

Act on cells immediately around

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34
Q

Endocrine

A

Cytokines act like hormones

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35
Q

Chemokine

A

Natural chemical mediators
Act as chemotactic molecules
Trafficking of cells

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36
Q

CXCr5 and CCR4

A

Coreceptors used by HIV to get into target cell

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37
Q

CXC

A

Two cysteine residues separated by any aa

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38
Q

CC

A

Two cysteine next to each other

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39
Q

CX3C

A

Two cysteines separated by any 3 aa residue

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40
Q

C

A

One cysteine

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41
Q

Chemokine receptors

A

G protein receptors with 7 transmembrane spanning domains

More chemokine than receptors-they are shared

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42
Q

CXCL12

A

Development of secondary lymphoid organs

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43
Q

MPO

A

Major microbicidal system

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44
Q

Cathepsin G and related serprocidins, proteinase-3 and elastase

A

Deadly to a range of gram positive and negative organisms and some candida

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45
Q

Cathespins B D E

A

Bactericidal

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46
Q

Defensins

A

Cysteine rich antibacterial and antifungal polypeptides

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47
Q

Three defensins make up 5% of all protein in a neutrophil and act by insertion into pathogen membranes to disrupt ion fluxes. Name them.

A

HNP1-3

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48
Q

BPI

A

Toxic ot gram negative bacteria

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49
Q

What’s in secondary granules

A

Preformed receptors and an assortment of proteins

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50
Q

Cytochrome b558 and its associated proteins

A

Major bactericidal mechanism

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51
Q

Presynthesized receptors for some molecules capable of activating them (FMLP, complement)

A

Ok

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52
Q

Collagenase and elastase

A

Break down fibrous structures int he extracellular matrix , facilitating progress of the neutrophil through the tissues

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53
Q

What activates neutrophils and when are they released

A

C5a, LTB4, FMLP, CXCL8 (IL8)

At site of inflammation

54
Q

How does a neutrophil get to tissue

A

Signal, bind, adhere, cross into tissue

55
Q

What are the 3 basic steps of neutrophil crossing into tissue

A

Rolling, adhesion and transmigration (specialized adhesion molecules)

56
Q

The interface between tissue and blood is formed by ___ cells

A

Endothelial

57
Q

Tissue signals are given out by endothelial cells lining the post capillary venues. Why

A

Flow is at its slowest here

58
Q

Tissue damage, results in release of mediators from _____

A

Mast cells, such as histamine

59
Q

What does histamine do

A

Dilation of vessels to increase leafiness and reduce rate of blood flow facilitate neutrophil access to site

60
Q

Rolling /marination

A

Neutrophils adhere very lightly to endothelium and let go…slowing down.

61
Q

What molecules are responsible for rolling

A

Selectins, on endothelium

62
Q

What effect does CXL8, FMLP, TNFa have on endothelium

A

Express stronger adhesion molecules…

ICAMS on endothelium

63
Q

What effect does CXCL1-3,5,6,8 and C5a and FMLP have on neutrophils

A

Express LFA1

64
Q

What are the three main families of surface proteins for adhesion

A

Selectin, integrity, ICAM (intracellular adhesion molecules)

65
Q

Selectins

A

P-selectin platelet
E-selectin-endothelium
L-selectin leukocyte

66
Q

Where is P selectin also found

A

On activated endothelium

67
Q

What do P and E selectin bind to

A

Sialylated carbohydrate residue which is constituitively expressed on circulating immune cells -
for rolling

68
Q

What do L selectins bind to

A

Glycoproteins cell adhesion molecule (GlyCAM-1) found on the high endothelial venues of lymph nodes
For homing to lymph nodes
Or a glycoproteins cell adhesion molecule on mucosal endothelium, called MAdCAM-1

69
Q

GlyCAM-1 and MAdCAM-1 guide leukocytes to particular tissues and have been termed ___

A

Addressins

70
Q

P selectin

A

CD62
On endothelium and platelet
Bind sialyl lewis(CD15) on neutrophils

71
Q

E selectin

A

CD62E
On endothelium
Bind sialyl Lewis (CD15s) on neutrophils

72
Q

L selectin

A

CD62L
On neutrophils
Binds GlyCAM-1 on peripheral lymph node endothelium and MAdCAM-1 on mucosal endothelium

73
Q

Integrins

A

Heterodimer ( a and b chain) on leukocytes

Interact with ICAM

74
Q

B2 integrins

A

Adhesion in all leukocytes including lymphocytes

75
Q

B1 integrins

A

T and B cell function

76
Q

Leukocyte function associated antigen-1 (LFA-1)

A

CD11a/CD18
On neutrophils, lymphocytes and monocytes
Binds ICAM-1 and ICAM-2 on endothelium

77
Q

Macrophage-1 (Mac-1) and complement receptor-3 (CR3)

A

CD11b/CD18
On neutrophils, monocytes, and some lymphocytes

Bind ICAM1 on endothelium and iC3b following complement activation

78
Q

P 150/95, and complement receptor 4 (CR-4)

A 
CD11c/CD18
Tissue macrophages (to a lesser extend neutrophils and monocytes)

Bind to iC3b and C4b

79
Q

ICAM1 is also the receptor for ___

A

Rhinovirus

80
Q

ICAMS are expressed one esting endothelium but are up regulated by inflammatory mediators such as __

A

TNFa

81
Q

Note. What else are cd11/CD18 used for

A

Adhesion that are used during other forms of cell to cell contract such as when antigen presenting cells interact with T cells

82
Q

Chemotaxis

A

Direct movement of a cell along a gradient of increasing concentration of the attracting molecule (termed chemoattractant) used by neutrophils

83
Q

What are the most potent chemotactic agents for neutrophils

A

C5a, FMLP, CXCL8 and LTB4

84
Q

Brownian movement

A

Neutrophils have a constant process of random movement akin to gaseous molecules

85
Q

What happens a chemotactic factos binds at one pole of the cell, two processes take place. What are they

A

Granule release, to upregulate receptors for the chemotactic factors at that pole
Neutrophil extends its membrane and cytoplasm into thin, footlike processes known as pseudopodia

86
Q

Pseudopodia

A

Rich in microtubles, actin, myosin and actin binding protein

After extending it anchors itself and the remainder of the cytoplasm is drawn up. A new pseudopodia achors itself and the process is repeated
Like a caterpillar

87
Q

Can neutrophils only phagocytosis one thing at a time

A

No can ingest more than one bacterium or fungus at a time

88
Q

What do you get when large numbers of phagocytes are involved in an infective process

A

Abscess filled with pus (dying neutrophils)

89
Q

Phagocytosis is ineffective in the absence of __

A

Opsonins

90
Q

Common opsonins used by neutrophils

A

C3b and CRP and antibody (specific immune system giving direction to innnate)

91
Q

Reverse phagocytosis

A

Granule contents discharged into external milieu…granule proteins and chromatin combine ot form extracellular fibers that bind gram neg and pos bacteria NET

92
Q

Neutrophils Extracellular traps (NET

A

Form of innate response that binds microorganisms, prevents them from spreading and ensures a high local concentration of antimicrobila agents to degrade virulence factors and kill bacteria

93
Q

What are the two routes that neutrophils use to kill

A

Oxygen dependent and oxygen independent

94
Q

Oxygen independent mechanism of neutrophil killing

A

Lysozyme and cathespins

95
Q

Oxygen dependent mechanisms of neutrophil killing

A

Respiratory burst

H202-myeloperoxidase-halide system

96
Q

What is generated in respiratory burst

A

Superoxide anion 02-
Hydrogen peroxide h202
Singlet oxygen 102
Hydroxyl radical OH

97
Q

Genetic abnormality in which neutrophil working is impaired

A

Recurrent bacterial, fungal infections
Failure to thrive
Organ damage and premature death

98
Q

Some conditions have no secondary granules…

A

Lung and skin nfecitons with staph a and candida

99
Q

Sometimes can’t do respiratory burst

A

Plus forming organisms and fungi cause prolonged infections of bone skin and lungs

100
Q

Sometimes common B chain of integrins is not synthesized
LAD
Leukocyte adhesion defiency

A

Failure of leukocyte adhesion

Repeated infection

101
Q

Superoxide dismutase

A

HO2+O2-+H—-> O2+ H2O

102
Q

Myeloperoxidase

A

H2O2-+2Cl-+H+——> H2O2+Cl2+OH-

103
Q

Describe the hydrogen peroxide-myeloperoxidase-halide system

A

H2O2 is generated by the respiratory burst, MPO from the primary granules and a halide such as Cl combine to give chlorine and hydroxyl ions, both of which are toxic to microorganisms

104
Q

Eosinophils comprise _% of granulocytes in circulation

A

3-5

105
Q

NOTE: this statistic hides the amount of eosinophils in tissue. How many there

A

Several hundred times more in the tissues, they collect at epithelial surfaces and may survive for several weeks

106
Q

How identify eosinophils

A

Staining is a result of granule contents, mainly cationic proteins with affinity for acid aniline dyes such as eosin

107
Q

Main role of eosinophils

A

Multicellular parasites

Releases toxic, cationic proteins

108
Q

Eosinophils in allergic disease

A

Asthma

109
Q

What are the two types of eosinophils granules

A

Specific (95%)

Primary (5%)

110
Q

Specific granules

A

Cationic proteins
Major Basic protein (MBP_
Eosinophil cationic protein (ECP, also bactercidal)
Eosinophil neurotoxin

Eosinophil peroxidase-similar to MPO generating toxic metabolites

111
Q

Primary granule

A

LTC4, LTD4, LTC4 PAF

Produces changes in airway smooth muscle and vasculature…allergic responses

112
Q

What are there specific receptors for on eosinophils

A

C3b/C4b (CR-1), iC3b (CR3), C5a and LTB4

IL3, IL5-development and differentiation

GM-CSF-acts on other cells

113
Q

What are highly selective in eosinophil recruitment

A

Eotaxin 1(CCL11) and eotaxin-2 (CCL24)

114
Q

Il-_ is a sufficient growth factor and essential for eosinophils and may also be produced by them

A

IL-5

115
Q

What are the most important factors in neutrophil recruitment and activation

A

I’ll-5 and eotaxins

116
Q

What are the two main features of mast cells and basophils

A

Histamine containing granules

Possession of a high affinity receptor for IgE

117
Q

Half life of histamine

A

5 minutes

118
Q

What is the triple response of histamine

A

Erythema of skin , arterioles dilate, post capillary venues contract
Increased vascular permeability
Histmine acts directly on local axons to induce more widespread vascular changes distant to the injection site

119
Q

What does histamine do

A

Vasodilation
Increase vascular permeability
Smooth muscle contraction in airways

120
Q

What do the protease enzymes do

A

Mainly tryptic enzymes (cf. pancreatic trypsin)
Digestion of basement membrane causes increased vascular permeability
Digestion of CT to increase cell migration
Cleavage of C3->C3a

121
Q

What do proteoglycans do

A

Mainly heparin in mast cells
Mainly chondroitin sulphate in basophils
Responsible for distinctive blue stain
Anticoagulant activity

122
Q

What do chemotactic factors do

A

Eosinophil chemotactic factor for anaphylaxis

Neutrophil chemotactic factos

123
Q

PAF-synthesized de novo

A

Vasodilator

124
Q

LTB-D4-synthesized de novo

A 
Eosinophil activators 
Neutrophil chemoattractants
Platelet activators 
Vascular permeability increased 
Bronchoconstrictors
125
Q

Prostagladins (PGD2)-synthesized de novo

A

Increase vascular perm
Bronchoconstrictors
Vasodilator

126
Q

What are the two receptors for histamine

A

H1 and H2

127
Q

H1 receptors

A

Mediate the vascular and bronchial smooth muscle effects and is blocked by drugs such as mepyramine and terfenadine, which form the basis of many proprietary antihistamines used for allergic reactions such as hay fever

128
Q

H2 receptors

A

Mediate gastric acid secretion and is blocked by the now famous drugs cimetidine and ranitidine, which treat gastric and duodenal ulceration

129
Q

Consequence of mast cell and basophils degranulation

A

Histamine-smooth muscle contraction-airway obstruction tear formation, nasal discharge(coryza), conjunctival redness, gritty eyes and itching
Anaphylaxis-syndrome of circulatory shock and collapse with low blood pressure and chest tightness leading to arrrested breathing and death unless treated

130
Q

How are mast cells and basophils activated

A

IgE-both
C3a, C4a and C5a -activate basophils and lung mast cells
FMLP-basophils

Immunology (14 decks)

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