2. Natural immunity Flashcards

1
Q

What is natural immune response?

A

It is innate immune response which provides immediate defense

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2
Q

What is acquired immune response?

A

It is adaptive immune response which develops with time

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3
Q

What is the functional relationship of innate and adaptive immune response?

A
  1. Pathogen recognition and initial attack
  2. Transmission of Pathogen Information to Adaptive Immune System
  3. Specific Attack on Pathogens
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4
Q

What are the mechanical barriers for first line defense?

A

skin, mucous membranes, cough, sneeze

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5
Q

What are the chemical barriers for first line defense?

A

skin pH: ~5,5
stomach pH: 1,2-3

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6
Q

What are the biological barriers for first line defense?

A

in the mouth saliva contains antibacterial agents
- defensin (also in toothpaste)
- lysozyme (also in toothpaste)
- lactoperoxidase (also in toothpaste)
- lactoferrin (also in toothpaste)
- antibody – natural IgM ; IgA

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7
Q

What are the molecules for first line defense?

A

Complement system
IgA

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8
Q

What are the cells for first line defense?

A

Innate lymphoid cells

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9
Q

First line barrier:
-> What does the The SKIN / MUCOUS MEMBRANES contain?

A

Mucus contains antimicrobial secretions

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10
Q

First line barrier:
In general defensins are expressed along the first line barriers which are ___ (3)

A
  • In salivary gland
  • In Paneth cells of the small intestine
  • In many leukocytes (e.g. neutrophils)
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11
Q

What are defensins? What do they form?

A

Most defensins are amphipathic molecules (positively charged and hydrophobic parts), and form holes in the membrane.

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12
Q

2 examples of defensins of the saliva

A

Alpha-defensins HNP 1- 4
Beta-defensins hBD1 hBD2 hBD3

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13
Q

What is the origin of Alpha-defensins HNP 1- 4?

A
  • Neutrophils
  • Gingival sulcus
  • Sites of inflammation
  • Salivary duct cells
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14
Q

What is the origin of Beta-defensins hBD1 hBD2 hBD3?

A

Epithelia, salivary ducts

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15
Q

What is lysozyme?

A

peptidoglycan N-acetylmuramoyl hydrolase that destroys bacterial cell wall by breaking glycosidil bonds between peptidoglycan components

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16
Q

What are 2 types of phagocytes?

A
  1. Neutrophils
  2. Macrophages
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17
Q

Which phagocytes are the most abundant leukocytes in the circulation appear first at site of infection?

A

Neutrophils

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18
Q

Macrophages mature from ___ in tissue

A

circulating momocytes

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19
Q

Characteristics of MPS (mononuclear phagocyte system)

A

Contain tissue-resident macrophages and recruited macrophages

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20
Q

Overview of phagocytosis and intracellular killing

A

I. Recognition and attachment - microbes bind to phagocyte receptors
II. Engulfment
- Phagocyte membrane zips up around microbe
- Fusion of phagosome with lysosome
III. Killing and degradation
- Killing of microbes by by ROS
- Degradation of microbes by lysosomal enzymes in phagolysosome

(ROS: highly reactive oxidizing agents
NO combines with superoxide to produce highly reactive peroxynitrite radicals(

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21
Q

What is the cause of CGD (Chronic granulomatous disease)?

A

Failure of phagocyte oxidase: Defective production of reactive oxygen species results in a failure to kill phagocytosed microbes.

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22
Q

What is granular formation?

A

Composed of activated macrophages, which try to eliminate the microbes

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23
Q

2 activation types of recruited macrophages

A
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24
Q

Elimination of apoptotic cells by macrophages

A
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25
Q

What are the 3 important granulocytes?

A
  1. Neutrophil
  2. Eosinophil
  3. Basophil
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26
Q

What is the function of neutrophil?

A

Phagocytosis

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27
Q

What is the function of eosinophil?

A

Degranulation against parasites

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28
Q

What is the function of basophil?

A

Degranulation against extracellular bacteria

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29
Q

What are the 3 Neutrophil effector functions (killing mechanism)

A
  1. Intravesical killing as in macrophages
  2. Frustrated phagocytosis
  3. Extracellular DNA trap
30
Q

What is the role of immature Dendritic cells?

A

Antigen uptake
Antigen processing

31
Q

What is the role of mature Dendritic cells?

A

Antigen presentation
Constimulation
T cell activation

32
Q
  • Lymphocytes and lymph return to blood via ____
A

thoracic duct

33
Q

Naive lymphocytes enter ___ from blood

A

lymph nodes

34
Q

How antigens reach lymph node? (dendritic cells)

A
35
Q

What are Innate lymphoid cells (ILCs)?

A

Subsets of bone marrow–derived cells with lymphoid morphology and effector functions similar to those of T cells:
- early first line defense against pathogens – mostly in mucosal tissue
no T cell receptors

36
Q

3 types of Innate lymphoid cells (ILCs)

A
37
Q

NK CELLS has dual receptor system
-> What does it mean?

A

Killer-activating receptor
Killer-inhibitory receptor - MCHI inhibits killing activity

38
Q

Innate immune response has limited specificity
-> What are 3 strategies in recognition?

A
  1. Pathogen - non-self
  2. Missing - self
  3. Altered-self
39
Q

Innate immune response has limited specificity
=> Thus, they have 3 strategies in recognition
-> What is the characteristics of missing-self strategy?

A

Immunreaction is blocked in case of self markers
(missing in microorganisms)

40
Q

Innate immune response has limited specificity
=> Thus, they have 3 strategies in recognition
-> What is the characteristics of altered-self strategy?

A

Non healthy self markers

41
Q

Innate immune response has limited specificity
=> Thus, they have 3 strategies in recognition
-> What is the characteristics of pathogen-nonself strategy?

A

Characteristic markers of pathogens
(missing in the host)

42
Q

Phagocytes have two types of receptors on their surfaces
-> What are they?

A
  1. Opsonic receptors - Fc receptors and complement receptors
  2. pathogen recognition receptors (PRRs)
43
Q

What is Opsonization?

A

Facilitation of phagocytosis

44
Q

What is Opsonization?

A

Facilitation of phagocytosis

45
Q

What is happening here?

A

OPSONIZATION

46
Q

What is happening here?

A

OPSONIZATION

47
Q

The structure of Fc receptors

A
48
Q

The role of Fcγ receptors

A
  1. bind IgG
  2. facilitate phagocytosis (regulate B-cell activation)
49
Q

The role of Fcε receptors

A

1/ Bind IgE
2/ High affinity receptor is expressed on mast cells and basophils – have role in immunity against parasites and allergy (low affinity receptor has regulatory function)

50
Q

What is happening here?

A

Fc receptor mediated phagocytosis

51
Q

Name 4 Secreted pattern recognition receptors

A
52
Q

List 2 Intracellular cytoplasmatic Pathogen recognition receptors (PRRs) with their roles

A
  1. RIG-I-like Helikases (RLHs, RLR) - recognize virus
  2. Nod-like Receptors (NLRs) - recognize intracellular bacteria
53
Q

List 3 membrane Pathogen recognition receptors (PRRs)

A

I. Scavenger receptors
(CD14: LPS receptor)
II. Lectin receptors
(macrophage mannose receptor)
III. Toll like receptors: carbohydrates, lipids, nucleic acid

54
Q

membrane Pathogen recognition receptors (PRRs)
-> What are 2 types of TOLL-LIKE RECEPTORS (TLR)

A
  1. Plasmamembrane receptors
  2. Intravesicular receptors
55
Q

membrane Pathogen recognition receptors (PRRs) - TOLL-LIKE RECEPTORS (TLR)
-> Characteristics of Plasmamembrane receptors

A

Lipid or protein TLR ligands are recognized on the plasma membrane
- e.g. LPS, flagellin

56
Q

membrane Pathogen recognition receptors (PRRs) - TOLL-LIKE RECEPTORS (TLR)
-> Characteristics of Intravesicular receptors

A

Nucleic acids are recognized by TLRs in the endosome

57
Q

Ligand binding to TOLL-LIKE RECEPTORS (TLR) trigger ____

A

the activation of a signal cascade

58
Q

EVEN WITHOUT PHAGOCYTOSIS IL-1, TNF-alfa, IL-6
-> How do pathogen recognition occur?

A
  1. Macrophage expresses receptors for many bacterial constituents
  2. Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
  3. Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
59
Q

What type of inflammation is happening here?

A

Local inflammation

60
Q

How many signal(s) does activation of the natural immune cells require?

A
61
Q

What are DAMPs?

A

molecules released upon necrosis, that trigger the generation of extracellular pro-inflammatory molecules

62
Q

4 examples of DAMPs?

A
  • HMGB1: intracellular nucleosome stabilizing DNA- binding protein
  • Heat-shock proteins
  • uric acid
  • Genomic double-stranded DNA
63
Q

Components of the inflammasome

A

NLRP3
ASC
pro-caspase-I

64
Q

What does the inflammasome activate?

A
65
Q

Common feature of Autoinflammatory disorders (inflammasomopathies)

A

increasing IL-1 beta secretion (due to the defective regulation of the pro- IL-1 beta
-> active IL-1 beta transition)

66
Q

What is Aphthous-like ulceration?

A

manifestation in some of the auto-inflammatory syndromes

67
Q

What do PAMP and DAMP stands for?

A

PAMP: Pathogen associated molecular pattern
DAMP: Damage associated molecular pattern

68
Q

What is happening in Danger model

A

Necrotic cell death releases DAMPs which will bind to DAMP receptor
-> DC maturation
-> CD80 and/or CD86 co-stimulatory molecule
-> Migration to lymph node

69
Q

What is happening in Stranger model

A

Pathogen releases PAMPs which will bind to PPR receptor
-> DC maturation
-> CD80 and/or CD86 co-stimulatory molecule
-> Migration to lymph node

70
Q

Why is COSTIMULATION required in immune response?

A

COSTIMULATION required for initial activation of T cells

71
Q

Natural (innate) immune system
-> Toll-like receptors based CONNECTION between ___ and ___

A

natural and adaptive immunity