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Immunology and Haematology > Innate Immune System > Flashcards

Innate Immune System Flashcards

1
Q

What kind of response does innate immune system provice?

(speed, specificity)

A

Fast, non-specific initial response

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2
Q

What are some cells of the innate immune system?

A
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3
Q

What are some functions of the innate immune system?

A
  • Antigen recognition
  • Recruitment of immune cells
  • Natural killer cell cytotoxicity
  • Phagocytosis
  • Opsonisation of pathogens
  • Activation of complement cascade
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4
Q

What receptors are used within the innate immune system?

A

Innate immune system uses a range of pattern recognition receptors (PRRs):

  • Detect distinct molecular ‘motifs’ that are common amongst groups of certain pathogens, but absent from host cells
    • Example of motif is pathogen-associated molecular patterns (PAMPs), different microorganisms display different PAMPs
      • An example of this is bacterial lipopolysaccharide (LPS) which is found on cell membrane of all gram negative bacteria
    • Another example is damage-associated molecular patterns (DAMPs)
      • When host cell dies due to tissue injury, contents of cell are released into extracellular environment
      • Some of these components alerts immune system that unscheduled cell damage has occurred
      • Not only due to infection, release induced inflammatory response
      • Some DAMPs are DNA, histones, ATP
  • Found on cell membrane, in cytosol and on endosomal membrane
  • Examples of PRRs
    • Toll-like receptors (TLRs)
      • Found on macrophages, monocytes and dendritic cells
    • C-type lectin receptors (CLRs)
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5
Q

What does PRRs stand for?

A

Pattern recognition receptors

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6
Q

What are examples of PRRs

A
  • Examples of PRRs
    • Toll-like receptors (TLRs)
      • Found on macrophages, monocytes and dendritic cells
    • C-type lectin receptors (CLRs)
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7
Q

What does TLRs stand for?

A
  • Toll-like receptors (TLRs)
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8
Q

What does CLRs stand for?

A
  • C-type lectin receptors (CLRs)
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9
Q

On what cells are TLRs found?

A
  • Found on macrophages, monocytes and dendritic cells
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10
Q

What are examples of molecular ‘motifs’?

A
  • Example of motif is pathogen-associated molecular patterns (PAMPs), different microorganisms display different PAMPs
    • An example of this is bacterial lipopolysaccharide (LPS) which is found on cell membrane of all gram negative bacteria
  • Another example is damage-associated molecular patterns (DAMPs)
    • When host cell dies due to tissue injury, contents of cell are released into extracellular environment
    • Some of these components alerts immune system that unscheduled cell damage has occurred
    • Not only due to infection, release induced inflammatory response
    • Some DAMPs are DNA, histones, ATP
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11
Q

What does PAMPs stand for?

A

Pathogen-associated molecular patterns

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12
Q

What is an example of a PAMPs?

A
  • An example of this is bacterial lipopolysaccharide (LPS) which is found on cell membrane of all gram negative bacteria
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13
Q

What does LPS stand for?

A

Bacterial lipopolysaccharide

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14
Q

Where is LPS found?

A
  • An example of this is bacterial lipopolysaccharide (LPS) which is found on cell membrane of all gram negative bacteria
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15
Q

What does DAMPs stand for?

A

Damage-associated molecular pattern

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16
Q

What are DAMPs?

A
  • When host cell dies due to tissue injury, contents of cell are released into extracellular environment
  • Some of these components alerts immune system that unscheduled cell damage has occurred
  • Not only due to infection, release induced inflammatory response
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17
Q

What are examples of DAMPs?

A
  • Some DAMPs are DNA, histones, ATP
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18
Q

What does recognition of PAMPs and DAMPs do?

A

Recognition of PAMPs and DAMPs induces inflammatory response, which is first response to foreign invasion:

  • Prevents pathogen from spreading or causing additional damage
  • Eliminates threat and promotes healing
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19
Q

Describe the initial process of inflammation?

A
  1. Pathogen recognition by resident macrophages within affected tissue
  2. Pro-inflammatory cytokines released
    1. Such as IL-1 and TNF-a
  3. This increases vascular permeability and causes endothelial cells of neighbouring blood vessels to express cellular adhesion molecules (CAMs)
    1. Such as selectins and ICAM-1
  4. Enables leukocytes to adhere to and migrate through the endothelium to reach affected tissues
  5. Chemokines also released which act as chemical attractors to recruit immune cells
    1. Example of chemokine is CXCL-8 which is released by macrophages and endothelial cells to attract neutrophils and other granulocytes
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20
Q

What are examples of the initial pro-inflammatory cytokines released in the beginning of inflammatory process?

A
  1. Such as IL-1 and TNF-a
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21
Q

What does CAMs stand for?

A

Cellular adhesion molecules

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22
Q

What are examples of CAMs?

A
  1. Such as selectins and ICAM-1
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23
Q

What does expression of CAMs allow?

A
  1. Enables leukocytes to adhere to and migrate through the endothelium to reach affected tissues
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24
Q

What do chemokines do?

A
  1. Chemokines also released which act as chemical attractors to recruit immune cells
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25
Q

What is an example of a chemokine?

A
  1. Example of chemokine is CXCL-8 which is released by macrophages and endothelial cells to attract neutrophils and other granulocytes
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26
Q

What is chemotaxis?

A

Chemotaxis = process of attracting a cell down a chemical gradient

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27
Q

What is diapedesis?

A

Process of leukocyte migrating through the endothelium to site of tissue infected

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28
Q

Describe the process of diapedesis?

A
  1. Receptors on neutrophil cell membrane bind onto selectin receptors on surface of endothelium
  2. Slows down neutrophil in blood stream and causes it to ‘role’ against endothelium
  3. Chemokines in endothelium of inflammamed tissue enable neutrophils that are weakly bound to endothelium to express integrin’s on their cell membrane
  4. The integrins bind to CAMs such as ICAM-1 receptors on endothelial cells to create tighter bond between neutrophil and endothelium
  5. Vasodilators such as histamine and bradykinin loosen the junctions between neighbouring cells allowing neutrophils to crawl along endothelial surface until they get through a gap junction
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29
Q

What happens when integrins bind to CAMs?

A
  1. The integrins bind to CAMs such as ICAM-1 receptors on endothelial cells to create tighter bond between neutrophil and endothelium
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30
Q

What effect do vasodilators have on junctions between cells?

A
  1. Vasodilators such as histamine and bradykinin loosen the junctions between neighbouring cells allowing neutrophils to crawl along endothelial surface until they get through a gap junction
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31
Q

What are examples of vasodilators?

A

Histamine

Bradykinin

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32
Q

What causes the pain involved with inflammation?

A

Release of bradykinin and histamine from mast cells

33
Q

What symptoms does the release of bradykinin and histmaine from mast cells cause?

A
  • Calor (heat)
  • Rubor (redness)
  • Tumor (swelling)
34
Q

What is the medical term for heat?

A

Calor

35
Q

What is the medical term for redness?

A

Rubor

36
Q

What is the medical term for swelling?

A

Tumour

37
Q

What does APCs stand for?

A

Antigen presenting cells

38
Q

What do APCs do?

A

Present antigens to T helper lymphocytes via MHC II molecules

39
Q

What molecule do APCs use to present antigen?

A

MHC II

40
Q

What are examples of professional APCs?

A
  • Dendritic cells
  • Macrophages
  • B lymphocytes
41
Q

What does atypical APCs mean?

A

Atypical antigen presenting cells includes (meaning do not always express MHC II molecule):

  • Mast cells
  • Basophils
42
Q

What are examples of atypical APCs?

A
  • Mast cells
  • Basophils
43
Q

Describe the difference between MHC I and II?

A
  • MHC I
    • All nucleated cells express this
      • Although platelets do not have nucleus they express this
    • Presents endogenous, or intracellular, antigens or self-marker
  • MHC II
    • Found on antigen presenting cells
    • Presents exogenous, or extracellular, antigens
44
Q

Describe the process of endogenous antigen presentation?

A

When damaged DNA or viruses are found within the cell:

  1. They are process by proteasomes into small peptides
  2. Transported into endoplasmic reticulum where they bind to newly produced class I MHC molecules
  3. Migrate to cell surface for antigen presentation
45
Q

What are endogenous antigens processed by before being presented?

A

Proteasomes

46
Q

Describe the process of exogenous antigen presentation?

A
  1. Engulfed via endocytosis into professional antigen presenting cells
  2. Breaks them down into the antigen and peptides
  3. Peptides bound to class II MHC molecules for antigen presentation on surface
47
Q

What do NK cells develop from?

A

Develop from lymphoid progenitors but a part of innate immune system

48
Q

What is the function of NK cells?

A
  • Target viral infected host cells or cells that have become damaged or malignant
  • Targets cells with reduced or absent MHC I signal
49
Q

How do NK cells differ from T cells?

A
  • Produce quick response
  • Do not create immunological memory
  • Do not require priming by an antigen
50
Q

How do NK cells become activated?

A
  • Binding to activating receptor tries to activate the natural killer cell
    • This happens with damaged or viral infected host cells
  • Binding to MHC I molecule with normal expression inhibits activation of NK cell
  • This balance is evaluated, whichever sends strongest signal determines if NK cell is activated or not
51
Q

Do RBCs activated NK cells?

A

Note that RBC do not express MHC I as they are not nucleated, but they express other surface proteins to stop activation of NK cells

52
Q

What happens once NK cells are activated?

A
  • Release cytolytic granules containing perforin and granzyme
    • Perforin creates pole allowing granzymes to enter
    • Granzymes initiate caspase pathway resulting in apoptosis of target cell
  • Also releases interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-a)
    • IFN-gamma important in activating macrophages for phagocytosis and lysis of foreign particles
    • TNF-a enhances cytotoxic effects of NK cells
53
Q

What does perforin and granzymes do?

A
  • Perforin creates pole allowing granzymes to enter
  • Granzymes initiate caspase pathway resulting in apoptosis of target cell
54
Q

What role does IFN-gamma have?

A
  • IFN-gamma important in activating macrophages for phagocytosis and lysis of foreign particles
55
Q

What role does TNF-a have in relation to NK cells?

A
  • TNF-a enhances cytotoxic effects of NK cells
56
Q

As well as through receptor binding, what else activates NK cells?

A
  • Release of IFN-gamma and IL-2
  • If antibody-opsonised antigen binds to Fc receptors on NK cell membrane
57
Q

What are examples of phagocytes?

A

Phagocytes are immune cells that perform phagocytosis, includes:

  • Mast cell
  • Neutrophil
  • Monocyte
  • Macrophage
  • Dendritic cell
58
Q

Describe the process of phagocytosis?

A
  1. During an infection cytokines like IFN-gamma or bacterial endotoxins like lipopolysaccharide activate and attract phagocytes
  2. Phagocytes move by chemotaxis towards area of infection
  3. When come into contact, receptors on phagocyte bind to that on pathogen allowing it to be engulfed into a vesicle called a phagosome
  4. Phagosome fuses with lysosome containing enzymes to form a phagolysosome
    1. This can generate toxic reactive oxygen and nitrogen species such as nitric oxide
  5. Phagolysosome degrades and destroys the pathogen, and any leftover waste products are expelled out of phagocyte into surrounding tissue
59
Q

What molecule activate and attract phagocytes?

A
  1. During an infection cytokines like IFN-gamma or bacterial endotoxins like lipopolysaccharide activate and attract phagocytes
60
Q

How do phagocytes move towards the site of infection?

A

Chemotaxis

61
Q

What is an antigen called once it has become engulfed into a vesicle by a phagocyte?

A

Phagosome

62
Q

What is a phagosome called once it has fused with a lysosome containing enzymes?

A

Phagolysosome

63
Q

What is opsonisation?

A

Refers to binding of an opsonin (or tag) to invading pathogen

64
Q

What are examples of opsonins?

A
  • Complement proteins
    • Especially C3b
  • Antibodies
  • Some plasma proteins
65
Q

Describe the function of opsonisation?

A
  • Enhances efficiency of phagocytosis by increasing likelihood of binding occurring between phagocyte and pathogen
  • Achieved by increasing number of binding sites available and by reducing the repellent negative charge that exists on surface of all cells
66
Q

What is the complement cascade?

A

Is a biochemical cascade of plasma proteins that become activated in sequential fashion:

  • Activation of one protein enzymically activates the next protein
67
Q

Describe the function of the complement cascade?

A
68
Q

What are the 3 pathways that activate the complement cascade?

A
  • Classical pathway
    • Activated by immune complexes
  • Lectin pathway
    • Activated by binding of microbial polysaccharides, like mannose, to circulating lectins such as mannose binding lectin
  • Alternative pathway
    • Activated by direct binding of complement proteins to pathogen
69
Q

How is the classical pathway activated?

A
  • Activated by immune complexes
70
Q

How is the lectin pathway activated?

A
  • Activated by binding of microbial polysaccharides, like mannose, to circulating lectins such as mannose binding lectin
71
Q

How is the alternative pathway activated?

A
  • Activated by direct binding of complement proteins to pathogen
72
Q

What is the common point of all 3 pathways activating the complement casacade?

A

Activation of all 3 pathways leads to formation of C3 convertase by amalgamation of various complement proteins:

  • Once activated, common pathway of downstream complement effects and functions initiated
  • Via formation of C3a and C3b
73
Q

What does C3 convertase do?

A

Activation of C3 convertase divides complement protein C3 into:

  • Large fragment C3b
    • Acts as opsonin and precursor for C5 convertase
    • Binding of this onto immune complexes facilitates clearance of these complexes via the reticuloendothelial system
  • Small fragment C3a
    • Pro-inflammatory and acts as an anaphylatoxin
74
Q

What is the function of C3b?

A
  • Acts as opsonin and precursor for C5 convertase
  • Binding of this onto immune complexes facilitates clearance of these complexes via the reticuloendothelial system
75
Q

What is the functionon of C3a?

A
  • Pro-inflammatory and acts as an anaphylatoxin
76
Q

What happens in the complement cascade downstream from formation of C3?

A

Downstream from this the membrane attack complex forms:

  • From fusion of C5b, C6, C7, C8 and multiple C9 molecules
  • Forms a cytolytic pore that literally punches a hole within the cell membrane of rarget
    • Allows extracellular fluid to flow into pathogen, causing osmotic rupture of cell membrane and death
77
Q

What does MAC stand for?

A

Membrane attack complex

78
Q

What complement proteins is MAC formed from?

A
  • From fusion of C5b, C6, C7, C8 and multiple C9 molecules
79
Q

What does MAC do?

A
  • Forms a cytolytic pore that literally punches a hole within the cell membrane of rarget
    • Allows extracellular fluid to flow into pathogen, causing osmotic rupture of cell membrane and death

Immunology and Haematology (23 decks)

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