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Life protection > Innate immunity > Flashcards

Innate immunity Flashcards

1
Q

What are examples of effector cells, in specific phagocytes, that stem from the myeloid lineage?

A
  1. Polymorphonuclear cells
  2. Monocytes
  3. Dendritic cells
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2
Q

What are examples of effector cells that are part of the myeloid lineage and are not phagocytes?

A
  1. Basophils
  2. Eosinophils
  3. Mast cells
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3
Q

What are examples of effector cells that stem form the lymphoid lineage?

A
  1. Natural killer cells
  2. Innate lymphoid cells
  3. Lymphoids
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4
Q

What do natural killer cells recognise and do and example cells?

A

Recognise infected & stressed cells and kill them
-Kill virus-infected cells
-Kill malignantly transformed cells(tumour cells)

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5
Q

What do enzymes do natural killer cells produce and what do they do to target cells?

A

express cytotoxic enzymes (lyse target cells)

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6
Q

What protein do natural killer cells produce?

A

produce interferon-γ (IFN-γ)

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7
Q

How are malignant tumour cells killed by natural killer cells?

A

Kill malignant tumour cells without prior activation

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8
Q

In comparison to malignant tumour cells, how are target cells killed by natural killer cells?

A

CD8+ T cells need to be activated and differentiate into CTL (cytotoxic T lymphocytes) to kill target cells

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9
Q

What are there many of in the cytosol of natural killer cells?

A

Many granules in the cytosol

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10
Q

What proteins are present in the cytosol of natural killer cells

A
  1. Perforin
  2. Cytolytic enzymes
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11
Q

What are the specific cytolytic enzymes in the cytosol of natural killer cells?

A

Granzymes A and B

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12
Q

How does macrophage cooperation work in natural killer cells?

A
  1. NK cells collaborate with macrophages in killing microbes
  2. Macrophages produce IL-12 which activates natural killer cells
  3. Natural killer cells produce IFN-γ which activates macrophages, allowing enhanced macrophage killing of phagocytosed microbes
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13
Q

What are inhibitory receptors on natural killer cells?

A
  1. KIRs (killer inhibitory receptors)
  2. NKG2A (C type lectin receptors)
  3. Leucocyte Ig-like receptors
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14
Q

What do inhibitory receptors on natural killer cells recognize?

A

Inhibitory receptors recognise ligands on healthy cells

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15
Q

What are the activating receptors on natural killer cells?

A
  1. NKG2D, KIRs, CD16
  2. Adaptor proteins: DAP10, DAP12
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16
Q

What do activating receptors on natural killer cells recognise?

A
  1. Activating receptors recognise infected/stressed cells
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17
Q

What do all autologous nucleated cells have?

A

All healthy autologous nucleated cells have MHC I

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18
Q

What happens in the interaction between inhibitory receptors on natural killer cells and MHC class I

A
  1. Inhibitory receptors recognise self MHC class I
  2. This results in a blockafe of signals from activating receptors
  3. Ultimately leading to NK cells not attacking healthy autologous cells
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19
Q

What do virus infected cells and malignant(cancer) cells do to MHC I?

A

Downregulate MHC I

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20
Q

What are the steps involved in the recognition of target cells by natural killer cells?

A
  • Activating receptors (NKG2D) recognise ligands that
    are induced on unhealthy cells (stressed, infected by
    microbes, malignantly transformed cells)
  • Signals from activating receptors overwhelm the signals from inhibitory receptors, especially if MHC I is also reduced or lost in unhealthy cells
    –Virus inhibits MHC I expression
    -NK cells attack and kill virus infected / cancer cells
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21
Q

What is the structure of an inhibitory receptor on natural killer cells?

A

-Extracellular:
–KIR3DL
–KIR2DL
-Intracellular:
–ITIM(Immunoreceptor tyrosine-based inhibitory motif

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22
Q

What is the structure of an activatory receptor on natural killer cells?

A

-Extracellular:
-KIR3DS
-KIR2DS
-Intracellular:
–ITAM(Immunoreceptor tyrosine-based activation motif)
–DAP12

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23
Q

What do ITIMs engage in?

A

ITIMs engage phosphatases that block the signalling
pathways triggered by activating receptors

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24
Q

What do ITAMs engage in and what does this promote?

A

ITAMs engage protein tyrosine kinase-mediated signalling events (promote target cell killing and cytokine secretion by NK cells)

25
Q

Where are ITAMs often located?

A

ITAMs are often located not in activating receptors but in cytosolic portion of adaptor molecules (e.g. DAP12)

26
Q

How do perforins work?

A

-Forms pores
–Delivery of granzymes

27
Q

What type of granzymes are there and what do they initiate?

A

-Granzymes A,B and C
–Initiate apoptosis

28
Q

Where are perforins and granzymes delivered and what is this to prevent?

A

Delivered at the site of contact between NK cell & target
-Prevents killing of neighbouring healthy cells

29
Q

What do granzymes activate and what does this lead to?

A

Granzymes activate caspases which lead to apoptosis

30
Q

What can granzyme B trigger?

A

Can trigger mitochondrial apoptotic pathway

31
Q

What do innate lymphoid cells have a similar function to?

A

-Similar function to lymphocytes

32
Q

What do innate lymphoid cells not express?

A

do not express TCRs (T cell receptors)

33
Q

Do innate lymphoid cells proliferate of differentiate?

A

no clonal expansion (proliferation) & no differentiation

34
Q

What is the main mechanism in innate lymphoid cells?

A

main mechanism: produce cytokines

35
Q

What are the different type of innate lymphoid cells dependent on?

A

different types of ILCs depending on type of cytokines

36
Q

What are the different types of Innate lymphoid cells and what T helper cell are they like?

A

-ILC1 is Th1 like
-ILC2 is TH2 like
-ILC3 is TH17 like

37
Q

What ILC are natural killer cells related to?

A

NK cells are related ILC 1

38
Q

What cytokines is ILC1 linked with?

A

IFN-γ

39
Q

What cytokines is ILC2 linked with?

A

IL-5, IL-13

40
Q

What cytokines is ILC3 linked with?

A

IL-17, IL-22

41
Q

What is IFN-γ involved in the defence against?

A

Defence against viruses

42
Q

What is IL-5 and IL-13 involved in the defence against?

A

Defence against helminths, allergic inflammation

43
Q

What is IL-17 and IL-22 function?

A

Intestinal barrier function and lymphoid organogenesis

44
Q

What do both T/B lymphocytes and innate cells express?

A

Both express Ag receptors (TCR and BCR)

45
Q

What is there a mutation in and a defect in chronic granulomatous disease and what does this mean?

A

-Mutation in NADPH component
-Defect in oxidative burst
-This means phagocytosed microbes can’t be killed

46
Q

What is defective in chediak higashi syndrome and what does this mean?

A

-Defective Phagasome-lysosome fusion
-This means phagocytosed microbes can’t be killed

47
Q

What happens to the neutrophil count in chediak-Higashi syndrome?

A

Decreased number of neutrophils(neutropenia)

48
Q

How does chediak-Higashi syndrome appear on a blood smear?

A

giant granules in the cytosol of neutrophils

49
Q

What do giant granules in a blood smear of neutrophils suggest?

A

Giant granules = Giant lysosomes

50
Q

What gene is defective in chediak-Higashi syndrome?

A

-Lysosomal trafficking regulator(LYST)
-Defect in lysosome fusion

51
Q

How do neutrophil chemotaxis work?

A
  1. Rolling
  2. Integrin activation by chemokines
  3. Stable adhesion
  4. Migration through endothelium
52
Q

What does a deficiency in C2, C4, C1q complement result in?

A

Result in SLE-like syndrome

53
Q

What does a C3 complement protein deficiency result in?

A

frequent serious infections with pyogenic
bacteria (e.g. Staphylococcus aureus, etc.)

54
Q

What does a deficiency in C5-C9(MAC) deficiency result in?

A

disseminated infections with
Neisseria (N. meningitidis, N. gonorrhoeae)

55
Q

What complement protein deficiency causes hereditary angioedema?

A

C1 INH deficiency

56
Q

What is there an incresed clevage of in C1 INH deficiency?

A

Increased cleavage C4, C2

57
Q

What are the clinical presentations of hereditary angioedema?

A

oedema in skin/mucosa → abdominal pain, vomiting, diarrhoea, airway obstruction

58
Q

What deficiency causes paroxysmal nocturnal haemoglobinuria and what recurring event occurs?

A

DAF, CD59 deficiency
-Recurrent intravascular haemolysis (RBC lysis)

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