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RUSVM Immunology > Innate immunity, NKcells, Inflammation > Flashcards

Innate immunity, NKcells, Inflammation Flashcards

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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
Binding of PAMP through TLR causes ?
Signals transcription and translation of proinflammatory cytokines (MyD88 is central to signaling)
26
NOD-like receptors detect what kind of pathogens and cause what response?
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
27
RIG like receptors detect ________ in the cytoplasm and induce production of?
Detect viral RNA Induce IFN and inflammatory cytokines production
28
C type lectin receptors bind to ____________ to recognize fungal infections
Carbohydrates | Expressed on macrophages and dendritic cells
29
Peptidogylcan recognition receptors bond to ________ and induce production of _________
``` Peptidogycan Defensins (antimicrobial peptides) ```
30
What is the acute phase response?
Change in serum proteins during and infection | The proteins that change in level are called acute phase response proteins
31
Where are acute phase response proteins produced? And how is production induced?
Liver | Pro-inflammatory cytokines produced by phagocytes (tNFa, IL-1, IL-6)
32
C-reactive proteins bind to __________ to promote uptake by _________ and activate complement mediated attack
Polysaccharides/phosphorylcholine Phagocytes Eg. Mannose-binding lectin
33
Natural Killer cells are also known as?
Large granular lymphocytes
34
What is the role of NK cells in the innate immune response?
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
35
How do NK cells recognize abnormal cells?
Infected cells- suppressed expression of MHCI High expression of MHC I chain related A(MICA), MICB, Rae-1, and H60
36
What two types of receptors are on NK cells?
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
37
If MHCis is expressed on a cell and binds to an inhibitory receptor on the NKcell, will the cell live or be killed?
Live
38
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?
Killed
39
A non-self MHC I molecule signals and NK cell to ?
Kills Allogenic cells Express and MHC molecule that doesnt agree with the inhibitory cell on the NK cell
40
What are the two types of NKcell inhibitory and activating signals?
Immunoglobulin like receptors (KIR) | Lectin like receptors (KLR)
41
What are the features of Killer immunoglobulin-like receptors
Transmembrne Polymorphic Expressed on NK cells and lymphocytes Include: Leukocyte immunoglobulin-like receptor (LILRs) - NK cell and leukocytes NK46k - NKcells
42
What type of NK cell recognizes stress proteins such as MICA, MICB, ILBP, Rae1, MULT1 and H60?
Killer-lectin like receptor | NKG2D expressed on NK cells - binds to stress proteins
43
After activation of NK cells, how do they function to overcome infections
Lysis of infected cells (cytotoxicity mechanisms) | Activate machrophages by secretion of cytokines
44
What are the cytotoxicity mechanisms of NKcells?
Perforin-dependent CD95/CD95L mechanism CD16 killing pathway
45
What is the process of perforin-dependent mechanism of NKcells?
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
What is the CD95/ CD95L (Fas/FasL) mechanism of NKcells?
NKcells normally express CD95L (FasL) Target cells increase expression of CD95 Binding induce apoptosis of target cell
47
What is the CD16 killing pathway of NKcells?
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
How is NKcell activity regulated?
Cytokines (interleukins and interferons) Cytokines induce NKcells to lymphocyte activated killer cells (LAK) which have increased cytotoxic activity
49
What are NK Tcells?
Cells with properties similar to NK and T ymphocytes Specificity against few pathogens Thymic origin
50
NKT cells express a _________that recognize glycolipid antigens on bacteria
TCR | NK1.1 (KLR family receptor)
51
How are NKTcells activated
IL-5
52
What are NK DCs? What do they express? And what is their main function?
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
What are the two types of inflammation?
Acute or chronic
54
____________ inflammation fights the early stages of infection and prepares the process that leas to tissue repair
Acute
55
_____________ inflammation is characterized by the dominating presence of macrophages in the injured tissue
Chronic
56
What are the causes of inflammation
Physical agents - mechanical - thermal Chemical agents -toxic gases, acids, bases Biological agents -bacteria, virus, parasites, fungi Endogenous - circulation disorder - Metabolic products
57
What are the 5 signs of inflammation?
``` Calor (heat) Rubor (redness) Tumor (swelling) Dolor (pain) Functio laesa (loss of function) ```
58
What leads to the development of heat, redness, and swelling during inflammation
Vasodilation increasing blood in the area Large volume of blood is responsible for redness and heat Vascular permeability =leaking of fluids =swelling
59
What is responsible pain during inflammation?
Leukocyte phagocytose invading pathogens and release mediators
60
What are the pro-inflammatory cytokines?
TNFa, IL-1, IL-2, IL-6, and IL-8
61
TNFa and IL-1 induce _______ , ___________, and ___________ production
Fever; stress hormone; and synthesis of IL-6, IL-8, and interferon gamma
62
IL-6 stimulates the release of ________________ proteins
Acute phase (eg. C-reactive protein)
63
What is the function of pro-inflammatory cytokines?
Coagulation cascade, release of NO, platelet-activating factor, prostaglandins, and leukotrienes
64
What promotes chemotaxis, induces extravasation of granulocytes, and degranualtion of neutrophils?
IL-1, IL-6, and Il-8
65
What role do the complement proteins C3a and C5a play in inflammation?
Increase vascular permeability | Stimulate chemotaxis of neutrophils, eosinophils, and monocytes
66
What are the functions of prostaglandins?
Vasodilation, capillary permeability, pain, and fever Low BP Enhance effects of histamine Promote platelet aggregation and vasoconstriction
67
What are leukotrienes and what are they produced by?
Eicosanoid inflammatory mediators produced in leukocytes LTB4, LTC4, LTD4, LTE4
68
What leukotrienes are smooth muscle contraction
LTC4, LTD4, LTD4
69
What leukotriene is a chemoattractant of neutrophils
LTB4
70
What factor is generated from lipid in cell membranes and induces platelet aggregation?
Platelet-activating factor (PAF) Also activates neutrophils and is a chemoattractant to eosinophils
71
What plasma protease increases capillary permeability
Kinin (particularly bradykinin)
72
What plasma protease produces fibrin peptides during the clotting process?
Clotting factors
73
What are the two stages of inflammation ?
Vascular response and cellular response
74
The vascular response has three phases, what are they?
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
Cellular response is the movement of ________ into the area of injury?
Leukocytes | Mainly granulocytes and monocytes
76
What is the sequence by which leukocytes move from the blood to an area of injury during the cellular response?
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
For immune system cells to migrate into tissues they must express ________, allowing them to roll and migrate into the tissues.
CAM (cell adhesion molecules) -> adhesion to the endothelium
78
What are the 4 families of cell adhesion molecules?
Selectins, Mucins Integrins Ig-superfamily CAM
79
A CAM that is a membrane glycoproteins containing lectin binding domains that bind to carbohydrates of mucins
Selectins Most important selectins are selectin E and L
80
What selectin is expressed on leukocytes?
Selectin L
81
What selectins are expressed on eduothelium during inflammation?
Selectin P and Selectin E
82
What CAM is heavily glycosylated, has Ernie and threonine-rich proteins that bind to selectins?
Mucins
83
What CAM is a heterdimeric protein consisting of a and B chains that are covalently joined at the cell surface
Integrins
84
What cells express integrins with a B2 chain (Cd18)
Leukocytes
85
Integrins bind to ?
Ig-superfamily (CAM)
86
What CAM has an immunoglobulin domain and a fibronectin domain
Ig-superfamily
87
Ig-superfamily CAMS are expressed on __________cells
Endothelial
88
What are the 4 phases of leukocytes extravasation?
Rolling Activation Adhesion (strict adhesion) Diapedesis (transendothelial migration)
89
What occurs in the rolling phase of leukocyte extravasation ?
Loose binding of leukocytes (CAM mucin) to the endothelial cells (selectin E and P) Slows down movement
90
What occurs in the activation phase of leukocyte extravasion?
Increased cytokines -> increased receptor expression on leukocytes
91
What occurs in the adhesion phase of leukocyte extravasation?
Strict adhesion Activation produces conformational changes in cells Integrins on leukocytes bind firmly to the endothelium
92
What occurs in the diapedesis phase of leukocyte extravasation?
Leukocyte slides between two neighboring endothelial cells Leukocytes use Homotypic binding of platelet-endothelial-cell adhesion molecule 1
93
What are systemic manifestations of inflammation
Acute phase response Alterations of WBC High fever Sepsis and septic shock-
94
How is inflammation terminated
Upregulation of anti-inflammatory molecules such as IL-1 receptor antigen and soluble TNF Apoptosis of pro-inflammatory cells
95
Production of which anti-inflammatory lipoxins will initiate the termination sequence for inflammation
Arachionic acid-derived lipoxin

RUSVM Immunology (10 decks)

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