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M- Pathology > 1 - Innate Immunity > Flashcards

1 - Innate Immunity Flashcards

1
Q

Aetiology

A

Causes of disease

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2
Q

Pathogenesis

A

How diseases develop

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3
Q

Necrosis

A

Uncontrolled cell death - hypoxia

Cells swell, organelles rupture and release enzymes into cytosil

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4
Q

Apoptosis

A

Controlled cell death
Cell shrinks, blebbing
Pyknosis and karyorrhexis

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5
Q

Pyknosis

A

Compaction of nucleus

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6
Q

Karyorrhexis

A

Loss of mitochondrial membrane potential, leading to nuclear fragmentation

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7
Q

Commensals

A

Microorganisms that are always with us

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8
Q

Pathogens

A

Infectious organisms that cause disease

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9
Q

Afferent arm of immune system

A

Discrimination of ‘self’ from ‘non self’

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10
Q

Effector limb of immune system

A

Recognition by receptors triggers inflammation and effector mechanisms to destroy pathogens

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11
Q

Innate immunity

A

In place before infection occurs

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12
Q

Cells of innate immunity

A

Phagocytes
Eosinophils
Mast cells
Natural killer cells

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13
Q

Soluble proteins of innate immunity

A

Cytokines
Acute phase proteins
Complement
Inflammatory mediators

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14
Q

An ulcer is caused by a…

A

Break in the epithelium

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15
Q

Function of inflammation

A

Eliminate pathogen
Repair damage
Return to state of homeostasis

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16
Q

Chronic inflammatory response occurs when…

A

Infections are not cleared rapidly

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17
Q

Features of localised acute inflammation:

A

Calor
Dolor
Rubor
Tubor

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18
Q

Inflammation

A

The coordinated response to infection or tissue injury

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19
Q

Results of inflammation:

A

Vasodilation
Increased vascular permeability
Emigration of leukocytes
Accumulation of cellular, protein rich exudate

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20
Q

Transudate

A

Fluid leakage

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21
Q

Exudate

A

Fluid and protein leakage into inter endothelial spaces

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22
Q

5 stages of innate inflammatory immune response

A 
Recognition
Vascular response
Elimination
Resolution
Induction of adaptive immunity
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23
Q

PRR

A

Pattern recognition receptors

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24
Q

Cells with PRRs

A

Innate immune cells

Complement

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25
Q

Acute inflammatory exudate

A

Recruitment of cells and soluble factors from blood to site of damage

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26
Q

Fibrinogen is converted to

A

Fibrin

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27
Q

Induction of adaptive immunity

DC

A

Dendritic cells take up pathogen fragments (antigens) and migrate to regional lymph node where adaptive immune response is generated

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28
Q

DC

A

Dendritic cell

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29
Q

Haematopoiesis

A

Generation of leukocytes in bone marrow

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30
Q

Lymphoid lineage gives rise to…

A

B cells
T cells
Natural killer cells

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31
Q

NK cells

A

Natural killer cells

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32
Q

Myeloid lineage gives rise to…

A 
-GRANULOCYTIC
Neutrophils
Eosinophils
Basophils
-MYELOMONOCYTIC
Monocytes
Mast cells
Dendritic cells
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33
Q

Macrophages are formed from…

A

Monocytes- migrate into tissue and mature

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34
Q

Mast cells - when activated …

A

Degranulate very quickly

Release histamine

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35
Q

Sentinel cells

A

Sense tissue damage

Macrophages and mast cells

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36
Q

Resident cells

A

Beneath epithelial surfaces

Macrophages and mast cells

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37
Q

Complement

A

Soluble protein system

Proteins activate each other sequentially by a cascade of proteolytic cleavage

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38
Q

Functions of complement

A

Activation of inflammation
Opsonisation of microbes
Lysis of target cells

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39
Q

C3 has an unusual…

A

Internal thioester bond

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40
Q

C3a

A

Small fragment
Stimulates vascular permeability
Recruits effector cells to site of damage

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41
Q

Anaphylatoxin

A

Recruits effector cells to site of damage

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42
Q

C3b

A 
Large fragment
Binds covalently to bacteria surface
Tags bacteria for phagocytosis
Cleaves C5
C5b => cell lysis
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43
Q

Complement fixation

A

C3b binds covalently to bacterial surface

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44
Q

Activation of complement

A

Alternative pathway
Classical pathway
Lectin pathway

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45
Q

Alternative pathway

A 
Slow and continuous C3->C3a+C3b
Spontaneous hydrolysis (tick over)
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46
Q

ALTERNATIVE PATHWAY

A 
Hydrolysis of thioester bond
C3(H2O)
Plasma protein Factor B binds
Cleaved by Factor D into Ba and Bb
--> C3(H2O)Bb = C3 convertase
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47
Q

Properdin (P)

A

Serum protein

Stabilises alternative pathway C3 convertase

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48
Q

PAMPs

A

Pathogen associated molecular patterns

Structures shared by classes of microbes

49
Q

Classical and lectin pathways rely on …

A

Recognition of PAMPs

50
Q

TLR

A

Toll like receptor

51
Q

CRP

A

C-reactive protein

52
Q

MBL

A

Mannose binding lectin

53
Q

What inhibits C3 convertase?

A

Factor H

54
Q

Lectin pathway

A

MBL - soluble PRR forms oligomers with MANNOSE and FUCOSE residues on pathogens
MBL associates with MASPs (proteases) activated after binding to pathogen surface
-activate C4 and C2
C4b2a = C3 convertase

55
Q

MASP

A

MBL associated serine protease

56
Q

Classical pathway

A

Functions in innate AND adaptive immunity

Pathogen sensed by C1 binding to pathogens or antibodies

57
Q

C1q is a…

How?

A

Pathogen sensor

  • binds directly to bacteria
  • via CRP that binds phosphocholine of lipopolysaccharides on pathogen cell wall
  • via Fc of immunoglobulin
58
Q

C1r and C1s

A

Proteases

Activated when C1q is bound

59
Q

C1 complex

A

C1q to C1s or C1r

60
Q

Cells with Fc receptors

A

Neutrophil
Macrophage
Eosinophil
NK cell

61
Q

Eukaryotic cells escape complement activation by making regulatory proteins…

A

Decay accelerating factor
Membrane cofactor protein
(Degrade C3 convertase or prevent formation)

62
Q

DAF

A

Decay accelerating factor

63
Q

MPC

A

Membrane cofactor protein

64
Q

Anaphylatoxins C3a and C5a

A

Increase blood vessel permeability
Upregulate endothelial cell adhesion molecules
Increase smooth muscle contraction
Degranulate mast cells

65
Q

Anaphylactic shock

A

Excessive histamine release

66
Q

Recognition of microbes by phagocytes

A
  • Complement receptors and Fc receptors
  • Binding triggers actin assembly allowing plasma membrane to engulf particle
  • Enclosed in phagosome, fuses with lysosome forming phagolysosome
  • Pathogen killed, oxidative burst, ROS
67
Q

Complementary function of phagocytosis cells

A

Neutrophils-increase rapidly in number with infection, short lives
Phagocytosed by macrophages

68
Q

Pus contains

A

Dead/dying neutrophils
Fibrin
Debris

69
Q

MAC

A

Membrane attack complex

70
Q

Membrane attack complex

A

C3b activates C5, initiates assembly
Hydrophobic regions of C6 C7 C8 become exposed and bind to membrane
C9 polymerises on C5b678 complex to form a channel that disrupts integrity of microbe

71
Q

Regulation of MAC in human cell

A

CD59 binds to assembling MAC

Prevents C9 binding and forming pore

72
Q

Paracrine

A

Act on other cell types

73
Q

Autocrine

A

Act on the same cell type

74
Q

Endocrine

A

Act systemically

75
Q

Redundancy

A

Functions of cytokines can be performed by other, different cytokines

76
Q

Pleiotropism

A

A single cytokine has many different functional effects

77
Q

Examples of cytokines

A

Interleukins IL - cell activation and behaviour
Interferons IFN - antiviral, cell activation
Tumour necrosis factor TNF - inflammatory functions

78
Q

Soluble protein systems

A
  • Kinin-bradykinin (inflammatory mediator)
  • Clotting system-thrombin-fibrin
  • Fibrinolytic system-breaks down clot in controlled way
79
Q

Examples of

Lipid inflammatory mediators

A

Macrophages
Neutrophils
Mast cells

80
Q

Lipid inflammatory mediators produce

A
  • Arachidonic acid -> prostaglandins and leukotrienes

- Platelet activating factor -> recruit and activate neutrophils and eosinophils

81
Q

TLR activation

A 
Recruit adaptor molecules (MyD88)
Release of cytokines
--> acute inflammatory exudate
Dendritic cell maturation
--> adaptive immunity
82
Q

CLR

A

C-type lectin receptor

PRR - fungal infection

83
Q

NLR

A

NOD like receptor

Sense stress and form inflammasomes

84
Q

Recruitment of leukocytes to site of infection

A

Neutrophils and monocytes recruited by
Binding adhesion molecules on endothelial cells
Chemo-attractants produced in response to infection

85
Q

Rolling

A

Thrombin and histamine induce p-selectin on endothelial cells
E-selectin appears induced by IL1 and TNFa
Selections bind glycoprotein ligands on neutrophil
Low affinity - leads to rolling of cells

86
Q

Tight adhesion

A

Adhesion molecules of integrin family LFA1 on endothelial cells
Bind to neutrophils
Integrins activated to high affinity state due to chemokines from infection site

87
Q

Chemokines

A

Small proteins

Chemo-attractants to regulate leukocyte traffic

88
Q

Diapedesis

A

Emigration of leukocytes through endothelium into surrounding tissue

89
Q

CXCL8

A

(IL8) recruits neutrophils from blood

90
Q

Neutrophils guided along chemokine concentration gradient…

A

Chemokine receptors bind chemokine

Guided by altering adhesive property

91
Q

Monocytes bind endothelium adhesion molecules

A

Monocytes integrins VLA-4
Bind
Adhesion molecules VCAM-1

92
Q

Pyrogens

A

Cytokines - increase body temperature, cause fever

93
Q

Acute phase proteins secreted:
From
By

A

Liver

Cytokines (IL6)

94
Q

Acute phase proteins - enhance fixation of complement

A

MBL (mannose binding lectin)

CRP (C-Reactive Protein)

95
Q

MBL

A

Mannose binding lectin

96
Q

CRP

A

C-Reactive protein

Indication of inflammation

97
Q

Sepsis

A

When pathogens enter the bloodstream

98
Q

What prevents pathogens entering the blood and disseminating?

A

Blood clotting

Local expression of TNFa

99
Q

Septic shock

A

TNFa =>
Vasodilation
Loss of blood pressure
Heart failure

100
Q

Switch from damage to repair…

A

Shift towards anti-inflammatory mediators

Triggered by engulfment of apoptotic neutrophils by macrophages

101
Q

Macrophages function by:

A

Phagocytosis
Secreted products
Increased MHC molecules

102
Q

Secreted products of macrophages

A

ROS and NO
Cytokines
FGF and VEGF
Metalloproteinases

103
Q

FGF

A

Fibroblast growth factor

104
Q

VEGF

A

Angiogenic growth factor

105
Q

Metalloproteinases

A

Enzymes involved in wound healing, angiogenesis, tumour metastasis

106
Q

Eosinophils in granulation tissue

A

Release granules containing toxic proteins

Death of parasites, but also damages host tiasue

107
Q

Inflammatory mediators:

A

Prostaglandins

Leukotrienes

108
Q

Fibroblasts:
Recruited by
Induce

A

FGF

Collagen synthesis

109
Q

Angiogenesis:
Induced by
Induces

A

Cytokines VEGF

Pre existing vessels send out capillary sprouts

110
Q

Steps in angiogenesis

A 
Endothelial cells break off basement membrane
Migrate to site of injury and repair
Proliferate
Differentiate to form lumen
Acquire supporting pericytes
111
Q

Type 1 interferons

A 
IFNa and IFNb
Made when cell infected with virus
Interferes with viral replication
Alerts neighbouring cells
Activates NK cells
112
Q

Type 2 interferons

A

IFN gamma
Made by activated NK cells
Activates macrophages

113
Q

NKR

A

Natural killer cell rexeptors

114
Q

MHC class 1
Where?
What?

A

Surface of all nucleated cells
NK cell ligand
Presents antigen to T cells

115
Q

Missing self

A 
Virally infected cells, MHC class 1 is down regulated 
NK cell can become activated if activating receptor is engaged
116
Q

Induced self

A 
Stress (DNA damage or infection) ligands for activating NKR are up regulated 
NK activation by overriding MHC class dependent inhibition
117
Q

KIR

A

Killer immunoglobulin like receptors

118
Q

NK effector functions

A
  • Release granule contents (perforin) form pores in cell membrane and allow granites to enter
  • enhance adaptive immune response, binding Fc antibodies
  • source of cytokines that activate macrophages
119
Q

What do dendritic cells do?

A

Carry antigens to secondary lymphatic organs

M- Pathology (7 decks)

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