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RUSVM Immunology > Innate immunity, NKcells, Inflammation > Flashcards

Innate immunity, NKcells, Inflammation Flashcards

1
Q

What are the physical barriers of the innate immune system?

A

Mechanical
Chemical
Microbiological

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2
Q

Mechanical barriers of the innate immune system

A 
Skin
Ciliary movement 
Peristaltic movement 
Washing by tears and saliva 
Mucous layers
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3
Q

Chemical barriers of the innate immune system

A

Sweat- fatty acids inhibit bacterial growth
Tears and saliva- lysozyme and phospholipidae inhibits growth of infectious agents
Low pH of sweat and gastric juices
Surfactants - opsonins

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4
Q

What are the humoral barriers of the innate immune system?

A 
Complement system 
Coagulative system 
Latoferin and transferin 
Lysozyme 
Interferons 
Interleukin 1
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5
Q

Some molecules of the coagulateive system may act as _________________ factors, attracting other cells to the site of damage

A

Chemotatic

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6
Q

Beta -lysine is produced by __________ and has what effect against G+ bacteria during coagulation?

A

Platelets

Bactericidal effects

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7
Q

Lactoferin and transferring _______ __________ to inhibit bacteria growth

A

Bind iron

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8
Q

What role do interferons play in innate immunity

A

Inhibit infection and replication of viruses

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9
Q

Interleukin 1 plays what role in the innate immune response?

A

Increase temp during inflammation and induce acute phase proteins which are bactericidal

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10
Q

Neutrofiels are identified by expression of ______ on their cell surface

A

CD66

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11
Q

What two types of granules do neutrophils contain?

A

Azurophilic -defensins, proteolytic enzymes (elastase, cathespin G), lysozyme, and myeloperoxidase

Secondary granules - lysozyme, lactoferin, and NADPH oxidase components

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12
Q

Macrophages are identified by expression of what three surface proteins?

A

CD4, CD11b, or F4/80

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13
Q

Macrophages react to danger signals such as?

A

N-formal-methionine- secreted by bacteria
Peptides of coagulative system
Complement protein
Cytokines - secreted by tissue macrophages

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14
Q

What receptors are used for the initiation of phagocytosis?

A
  1. Fc receptors on macrophages: bind to antibody Fc region
  2. Complement receptors : Bind C3b complement component (which is bound to antigen)
  3. Scavenger receptors (SRA, CD68, Lox-1, or CD36) bind polyamines on bacterial surface
  4. Toll like receptors - recognize PAMP
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15
Q

What is the process of phagocytosis

A
  1. Chemotaxis
  2. Detect and bind to target object through receptors
  3. Endocytosis
  4. Enclosed in phagosome
  5. Fuses with lysosome to become phagolysosome
  6. Digestion
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16
Q

What are the two killing pathways of neutrophils, monocytes, and macrophages?

A

Oxidative - reactive oxygen species and reactive nitrogen species

Non oxidative - lysosomal toxic substances

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17
Q

What is referred to as the respiratory burst during phagocytosis?

A

Increased use of oxygen and glucose

Leads to the formation of ROS which are toxic to microorganisms

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18
Q

What is the process of ROS generation?

A
  1. Glucose metabolized to NADPH and Pentose
  2. NADPH activated by cytochrome oxidase
  3. NADPH uses O2 to produce superoxide anion (O2-)
  4. O2- reduced to H2O2 and 1O2 by superoxide dismustase
  5. O2- and H202 reduced to OH- and hydroxyl radical OH
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19
Q

What is the antimicrobial action of NO?

A

Bacteria bound by phagocyte through TLR
Secrete TNFa -> induce expression of inducible nitric oxide synthetase (iNOS)
L-Arginine to make L-citrulline and NO

NO is toxic to microorganisms

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20
Q

What are the mechanisms of non-oxidative intracellular killing?

A

Cationic proteins= damage cell wall
Lysozyme =damage mucopeptide in cell wall
Lactoferrin =sequester iron
Proteolytic and hydrolytic enzyme =kill bacteria

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21
Q

What are PAMPS and on what cells are they found?

A

Pathogen-associated molecular patter
-found on pathogen
Eg lipoplysaccharide, peptidogylan, lipoteichoic acids, mannan

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22
Q

What are DAMPs and on what cells are they found?

A

Damage-associated molecular patterns

From damaged host cells

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23
Q

What host molecules can recognized PAMPS

A

PRR (pattern recognition receptors)

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24
Q

What are the 5 classes of PRR?

A
  1. Toll-like
  2. NOD-like
  3. Rig-like
  4. C-type lectin
  5. Peptidoglycan-recognition protein
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25
Q

Binding of PAMP through TLR causes ?

A

Signals transcription and translation of proinflammatory cytokines

(MyD88 is central to signaling)

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26
Q

NOD-like receptors detect what kind of pathogens and cause what response?

A

Pathogens in cytoplasm (PAMP and DAMP)
NOD1- bacterial peptidoglycans
NOD2- muramyl dipeptides

Activates NF-kB transcription -> transcription of pro inflammatory cytokines

Activates IRF3/7 to -> Type 1 interferons

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27
Q

RIG like receptors detect ________ in the cytoplasm and induce production of?

A

Detect viral RNA

Induce IFN and inflammatory cytokines production

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28
Q

C type lectin receptors bind to ____________ to recognize fungal infections

A

Carbohydrates

Expressed on macrophages and dendritic cells

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29
Q

Peptidogylcan recognition receptors bond to ________ and induce production of _________

A 
Peptidogycan 
Defensins (antimicrobial peptides)
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30
Q

What is the acute phase response?

A

Change in serum proteins during and infection

The proteins that change in level are called acute phase response proteins

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31
Q

Where are acute phase response proteins produced? And how is production induced?

A

Liver

Pro-inflammatory cytokines produced by phagocytes (tNFa, IL-1, IL-6)

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32
Q

C-reactive proteins bind to __________ to promote uptake by _________ and activate complement mediated attack

A

Polysaccharides/phosphorylcholine

Phagocytes

Eg. Mannose-binding lectin

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33
Q

Natural Killer cells are also known as?

A

Large granular lymphocytes

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34
Q

What is the role of NK cells in the innate immune response?

A
  1. Kill cells which are stressed, infected with virus or tumor cells (following cytokines activation Il2 and IFNy, they become lymphokine activated killer cell)
  2. Cytokines and chemokine production - IFNy, TNFa, IL7, and IL22, MIP1a, MIP1B
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35
Q

How do NK cells recognize abnormal cells?

A

Infected cells- suppressed expression of MHCI

High expression of MHC I chain related A(MICA), MICB, Rae-1, and H60

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36
Q

What two types of receptors are on NK cells?

A

Activating and inhibitory receptors

Activation of NK cells is regulated by a balance between signals from activating and inhibitory receptors

Eg high level of activating cells- > killing of target
High level of Inhibitory signals ->no killing

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37
Q

If MHCis is expressed on a cell and binds to an inhibitory receptor on the NKcell, will the cell live or be killed?

A

Live

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38
Q

A cell has an MHCI bound to and inhibitory receptor and an activating receptor is bound to a stress protein, does the cell live or is it killed?

A

Killed

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39
Q

A non-self MHC I molecule signals and NK cell to ?

A

Kills

Allogenic cells
Express and MHC molecule that doesnt agree with the inhibitory cell on the NK cell

40
Q

What are the two types of NKcell inhibitory and activating signals?

A

Immunoglobulin like receptors (KIR)

Lectin like receptors (KLR)

41
Q

What are the features of Killer immunoglobulin-like receptors

A

Transmembrne
Polymorphic
Expressed on NK cells and lymphocytes

Include:
Leukocyte immunoglobulin-like receptor (LILRs) - NK cell and leukocytes

NK46k - NKcells

42
Q

What type of NK cell recognizes stress proteins such as MICA, MICB, ILBP, Rae1, MULT1 and H60?

A

Killer-lectin like receptor

NKG2D expressed on NK cells - binds to stress proteins

43
Q

After activation of NK cells, how do they function to overcome infections

A

Lysis of infected cells (cytotoxicity mechanisms)

Activate machrophages by secretion of cytokines

44
Q

What are the cytotoxicity mechanisms of NKcells?

A

Perforin-dependent

CD95/CD95L mechanism

CD16 killing pathway

45
Q

What is the process of perforin-dependent mechanism of NKcells?

A

NK cell releases perforin in granules
Creates a lesion in target cell membrane AKA perforin channel

Granzymes and proteases enter cell and induce apoptosis

46
Q

What is the CD95/ CD95L (Fas/FasL) mechanism of NKcells?

A

NKcells normally express CD95L (FasL)
Target cells increase expression of CD95

Binding induce apoptosis of target cell

47
Q

What is the CD16 killing pathway of NKcells?

A

Recognize target cell through antibody dependent pathway with CD16

CD16 is a Fc receptor

Antibody binds to antigen, NK cell binds to antibody through Fc receptor -> cytotoxicity

48
Q

How is NKcell activity regulated?

A

Cytokines (interleukins and interferons)

Cytokines induce NKcells to lymphocyte activated killer cells (LAK) which have increased cytotoxic activity

49
Q

What are NK Tcells?

A

Cells with properties similar to NK and T ymphocytes
Specificity against few pathogens
Thymic origin

50
Q

NKT cells express a _________that recognize glycolipid antigens on bacteria

A

TCR

NK1.1 (KLR family receptor)

51
Q

How are NKTcells activated

A

IL-5

52
Q

What are NK DCs? What do they express? And what is their main function?

A

Natural killer dendritic cells

Express NK1.1 an CD11c

Spontaneously lyse tumor cells
Present antigen to native Tcells
produce large amounts of IFNy

Link innate and adaptive immunity

53
Q

What are the two types of inflammation?

A

Acute or chronic

54
Q

____________ inflammation fights the early stages of infection and prepares the process that leas to tissue repair

A

Acute

55
Q

_____________ inflammation is characterized by the dominating presence of macrophages in the injured tissue

A

Chronic

56
Q

What are the causes of inflammation

A

Physical agents

  • mechanical
  • thermal

Chemical agents
-toxic gases, acids, bases

Biological agents
-bacteria, virus, parasites, fungi

Endogenous

  • circulation disorder
  • Metabolic products
57
Q

What are the 5 signs of inflammation?

A 
Calor (heat)
Rubor (redness) 
Tumor (swelling)
Dolor (pain)
Functio laesa (loss of function)
58
Q

What leads to the development of heat, redness, and swelling during inflammation

A

Vasodilation increasing blood in the area

Large volume of blood is responsible for redness and heat

Vascular permeability =leaking of fluids =swelling

59
Q

What is responsible pain during inflammation?

A

Leukocyte phagocytose invading pathogens and release mediators

60
Q

What are the pro-inflammatory cytokines?

A

TNFa, IL-1, IL-2, IL-6, and IL-8

61
Q

TNFa and IL-1 induce _______ , ___________, and ___________ production

A

Fever; stress hormone; and synthesis of IL-6, IL-8, and interferon gamma

62
Q

IL-6 stimulates the release of ________________ proteins

A

Acute phase (eg. C-reactive protein)

63
Q

What is the function of pro-inflammatory cytokines?

A

Coagulation cascade, release of NO, platelet-activating factor, prostaglandins, and leukotrienes

64
Q

What promotes chemotaxis, induces extravasation of granulocytes, and degranualtion of neutrophils?

A

IL-1, IL-6, and Il-8

65
Q

What role do the complement proteins C3a and C5a play in inflammation?

A

Increase vascular permeability

Stimulate chemotaxis of neutrophils, eosinophils, and monocytes

66
Q

What are the functions of prostaglandins?

A

Vasodilation, capillary permeability, pain, and fever

Low BP

Enhance effects of histamine

Promote platelet aggregation and vasoconstriction

67
Q

What are leukotrienes and what are they produced by?

A

Eicosanoid inflammatory mediators produced in leukocytes

LTB4, LTC4, LTD4, LTE4

68
Q

What leukotrienes are smooth muscle contraction

A

LTC4, LTD4, LTD4

69
Q

What leukotriene is a chemoattractant of neutrophils

A

LTB4

70
Q

What factor is generated from lipid in cell membranes and induces platelet aggregation?

A

Platelet-activating factor (PAF)

Also activates neutrophils and is a chemoattractant to eosinophils

71
Q

What plasma protease increases capillary permeability

A

Kinin (particularly bradykinin)

72
Q

What plasma protease produces fibrin peptides during the clotting process?

A

Clotting factors

73
Q

What are the two stages of inflammation ?

A

Vascular response and cellular response

74
Q

The vascular response has three phases, what are they?

A

Phase I- vasoconstriction : momentary with few vessels

Phase II- active vasodilation: dilation of arterioles and capillaries, increased blood flow, and increased cellular metabolism

Phase III- passive vasodilation : blood vessels stop reacting to nervous and humoral stimuli, increase vascular permeability

75
Q

Cellular response is the movement of ________ into the area of injury?

A

Leukocytes

Mainly granulocytes and monocytes

76
Q

What is the sequence by which leukocytes move from the blood to an area of injury during the cellular response?

A

Chemotaxis - leukocytes migrate to chemical signal

Rolling - leukocytes slow down and increase expression of adhesion molecules

Migration - migrate into tissue spaces

Phagocytosis -neutrophils and macrophages engulf and degrade the bacteria and cellular debris

77
Q

For immune system cells to migrate into tissues they must express ________, allowing them to roll and migrate into the tissues.

A

CAM (cell adhesion molecules) -> adhesion to the endothelium

78
Q

What are the 4 families of cell adhesion molecules?

A

Selectins,
Mucins
Integrins
Ig-superfamily CAM

79
Q

A CAM that is a membrane glycoproteins containing lectin binding domains that bind to carbohydrates of mucins

A

Selectins

Most important selectins are selectin E and L

80
Q

What selectin is expressed on leukocytes?

A

Selectin L

81
Q

What selectins are expressed on eduothelium during inflammation?

A

Selectin P and Selectin E

82
Q

What CAM is heavily glycosylated, has Ernie and threonine-rich proteins that bind to selectins?

A

Mucins

83
Q

What CAM is a heterdimeric protein consisting of a and B chains that are covalently joined at the cell surface

A

Integrins

84
Q

What cells express integrins with a B2 chain (Cd18)

A

Leukocytes

85
Q

Integrins bind to ?

A

Ig-superfamily (CAM)

86
Q

What CAM has an immunoglobulin domain and a fibronectin domain

A

Ig-superfamily

87
Q

Ig-superfamily CAMS are expressed on __________cells

A

Endothelial

88
Q

What are the 4 phases of leukocytes extravasation?

A

Rolling

Activation

Adhesion (strict adhesion)

Diapedesis (transendothelial migration)

89
Q

What occurs in the rolling phase of leukocyte extravasation ?

A

Loose binding of leukocytes (CAM mucin) to the endothelial cells (selectin E and P)

Slows down movement

90
Q

What occurs in the activation phase of leukocyte extravasion?

A

Increased cytokines -> increased receptor expression on leukocytes

91
Q

What occurs in the adhesion phase of leukocyte extravasation?

A

Strict adhesion
Activation produces conformational changes in cells

Integrins on leukocytes bind firmly to the endothelium

92
Q

What occurs in the diapedesis phase of leukocyte extravasation?

A

Leukocyte slides between two neighboring endothelial cells

Leukocytes use Homotypic binding of platelet-endothelial-cell adhesion molecule 1

93
Q

What are systemic manifestations of inflammation

A

Acute phase response
Alterations of WBC
High fever
Sepsis and septic shock-

94
Q

How is inflammation terminated

A

Upregulation of anti-inflammatory molecules such as IL-1 receptor antigen and soluble TNF

Apoptosis of pro-inflammatory cells

95
Q

Production of which anti-inflammatory lipoxins will initiate the termination sequence for inflammation

A

Arachionic acid-derived lipoxin

RUSVM Immunology (10 decks)

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