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WEEK 9 SEM 4 > Innate immunity- in Health and in Disease > Flashcards

Innate immunity- in Health and in Disease Flashcards

1
Q

What is the innate immune response?

A

first line of defence
very fast
PREVENTS, CONTROLS AND SOMETIMES ELIMINATES INFECTIONS

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2
Q

Why is innate immune response important?

A

keeps tissue damage/infection in check before the adaptive immune response

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3
Q

What does the innate immune system consist of?

A

barrier- skin, mucosa
cells- phagocyte, basophile, mast cells, natural killer cells, innate lymphoid cells
soluble molecules- effector proteins, inflammation mediators

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4
Q

Where are phagocytes made?

A

phagocytes such as polymorphonuclear cells, monocytes/macrophages, and dendriticcells-these are made in the bone marrow from the myeloid lineage

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5
Q

Where are basophils, mast cells and eosinophils made?

A

made in the bone marrow from the myeloid lineage

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6
Q

Where are natural killer cells made?

A

made in the bone marrow from the lymphoid lineage

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7
Q

Where are the innate lymphoid cells made?

A

bone marrow from the lymphoid lineage

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8
Q

What are the barriers of the human body?

A

skin
mucosa
chemical barriers= Antibacterial enzymes eg lysozyme in tears and saliva// Antimicrobial peptides are produced by epithelial cells, PMN, NK cells and cytotoxic T lymphocytes, examples include defensins and cathelicidins. These kill the bacteria by damaging their cell membrane.

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9
Q

What does mucus do?

A

covers the microorganism
prevents it sticking to epithelium
cilia wafts it away (to stomach)

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10
Q

What can CF lead to and why?

A

lung infections
bc there is defective mucus production (too thick)
cilia cant clear the mucus

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11
Q

What is the nucleus of a natural killer normally shaped as?

A

kidney bean

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12
Q

What is main function of natural killer cell?

A

eliminate virus infected cells

eliminate tumour cells

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13
Q

How do natural killer cells function?

A

have cytotoxic enzymes- lyse toxic cells

produce inflammatory cytokines such as interferon gamma

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14
Q

What is the difference between a natural killer cells and a CD 8 T cell?

A

natural killer needs no activation to kill cells
CD8 T cell (PART OF THE ADAPTIVE IMMUNE SYSTEM) needs to be activated and differentiated into cytotoxic T lymphocytes to kill cells infected by virus

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15
Q

What do natural killer cells contain?

A

granules in their cytoplasm which have cytotoxic enzymes:

  1. perforin
  2. cytolytic enzymes (granzymes A and B)
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16
Q

What does perforin do?

A

create pores in target cells

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17
Q

What does natural killer cell work with?

A

macrophage

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18
Q

Where is interferon gamma released from?

A

CD4 T helper 1 lymphocytes

NKC can produce them themselves too

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19
Q

How does a natural killer cell release interferon gamma?

A
  1. macrophage gets infected by virus or bacteria
  2. it produces IL-12
  3. this activates NK cells
  4. They produce interferon gamma
  5. interferon gamma acts back on macrophage
  6. higher ability to kill the phagocytosed microbe
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20
Q

How do natural killer cells recognise virus infected/ malignant cells?

A

NK cells have ACTIVATING AND INHIBITOR receptors on THEIR cell surface.

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21
Q

What are the inhibitory receptors natural killer cells express?

A

killer inhibitory

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22
Q

What are examples of killer inhibitory receptors?

A

NKG2A receptors belong to the C type lectin pathway leucocyte Ig like receptors

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23
Q

What are the activating receptors natural killer cells express?

A

KG2D receptor,
killer inhibitory receptors (same as inhibitory receptor), CD16 receptor which is a receptor for the Fc portion of an antibody (antibody tail)

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24
Q

How do the activating receptors work of a natural killer cell?

A

the activating receptors have a small tail
it goes into cytoplasm of NK cell
they work together by coupling with adaptor proteins

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25
Q

What do inhibitory receptor cells recognise?

A

recognize ligands on healthy cells

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26
Q

What do activating receptor cells recognise?

A

recognize ligands that are upregulated on infected/injured/stressed cells

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27
Q

Where are inhibitory and activating receptors found?

A

in all cells

28
Q

What does the interaction of NK and other cells depend on?

A

the balance of signals from inhibitory and activating receptors

29
Q

What do all healthy cells express?

A

MHC1 on their surface

30
Q

Which receptor recognises MHC1?

A

inhibitory receptor on NK cell recognise MHC1 and then block signal from activating receptors so NK cells dont kill good cells

31
Q

What do viral cells do to MHC1?

A

downregulate the expression of MHC1
bc virus and malignant cells dont want to be recognised by the CD8+ cells (THEY SCANE Mhc1 CELLS for self peptides)
so abnormal cell can survive

32
Q

What is MHC1 made of?

A

MHC I is made up of HLA-A, HLA-B, HLA-C-MHC II is made up of HLA molecules other than A B C

33
Q

What is the difference between inhibitory and activating receptors?

A

activating has:
short intracellular domain
intracellular domain in inhibitory has specific motif (ITIM motif)

34
Q

Why can’t activating receptors work on their own?

A

they have short intracellular domain
can’t signal on their own
have to work with adaptor protein DAP

35
Q

What is the motif made of on the activating receptors?

A

called ITIM motif (immunoreceptor tyrosine based inhibitory motif)
contains tyrosines which can be phosphorylated as a consequence of receptor activation

36
Q

What is the motif on the DAP protein?

A

called ITAM (immunoreceptor tyrosine based activation motif)

37
Q

How does the inhibitory receptor work?

A

ITIM motifs are activated
recruit phosphates
remove phosphate group in activating receptor so inhibits it

38
Q

How do ITAM motifs work?

A

ITAM motifs activate through activating activating receptor on NK cell
recruit protein tyrosine kinase
phosphorylates pathway
promotes signalling

39
Q

What are the cytolytic and cytotoxic ways of natural killer cells?

A

cytolytic: perforin= form pores in membranes of target cells= allows granzymes to enter
cytotoxic: granzyme= triggers apoptosis pathway via the caspase or mitochondrial pathway

40
Q

What is chediak highashi syndrome ?

A

natural killer cell defect

cells have problem moving vesicles in cytoplasm in a controlled manner

41
Q

What kind of defects can be seen in Natural Killer cells?

A

absence of circulating NK cells
NK number is normal but dont function
NK defects- cant save themselves from viruses

42
Q

What is an innate lymphoid cell?

A
  • look like lymphocytes
  • similar function to lymphocytes
  • produce cytokines
  • there are many different kinds of innate lymphoid cells (ILC)
  • generated in bone marrow
43
Q

What does ILC 1 do?

A
  • secrete interferon gamma

- defense against viruses

44
Q

What does ILC 2 do?

A
  • secrete IL5 and IL13
  • expresses transcription factor GATA 3
  • defense against helminths, and allergic inflammation
45
Q

What does ILC3 do?

A
  • secrete IL17
  • ILC 3 secrete IL17 (also secreted by T helper 17 cells)
  • help with infections in the gut
46
Q

What are lymphoids with limited diversity?

A
  • have features of T and B lymphocytes and innate cells
  • have limited diversity
  • recognise limited antigens
47
Q

How do ILCs differ from lymphoids with limited diversity?

A
  • In contrast to ILCs, these cells do express T cell receptors or B cellreceptors
48
Q

What are the different types of lymphoids with limited diversity?

A
  • gamma delta T cells
  • natural killer T cells
  • mucosa associated invariant T cells (MAIT)
  • B-1 B cells
  • marginal zone B cells
49
Q

What are gamma delta T cells?

A
  • normal T cell receptors are alpha and beta chains
  • this has receptors with gamma and beta chains
  • less diverse
  • recognise limited number of antigens
  • located in epithelia
50
Q

What are natural killer T cells?

A
  • share features of natural killer cells and T cells
  • they express T cell receptors
  • express receptors found on NK cells
  • limited antigen recognising ability
  • present in epithelia and lymphoid organs
  • do not recognise peptides but recognise lipids bound to CD1
51
Q

What are mucosa associated invariant T cells (MAIT) cells?

A
  • like T cells
  • present in mucus
  • express T cell receptors (alpha and beta chains)
  • invariant- recognise limited antigen number
  • recognises metabolites from the synthesis of riboflavin which lots of fungi and bacteria use
  • MAIT cells found in liver
  • produce inflammatory cytokines and cytotoxic molecules
  • clear infected cells
  • defense against gut pathogens
52
Q

What are B1-B cells?

A
  • found in the serous cavities (abdomen) and mucosal tissues (gut and airways)
  • produce low affinity IgM (cannot bind very strongly to antigens)
  • recognize polysaccharides and lipid antigens from bacteria in the gut
53
Q

What are marginal zone B cells?

A
  • present in the secondary lymphoid organs such as the spleen and lymph nodes
  • produce IgM
  • protect against bacteria in blood borne infections
54
Q

What defects can be seen in phagocytes?

A
  • low in number

- less function

55
Q

Give examples of phagocytic defects?

A
  • chronic granulomatous disease
  • chediak higashi syndrome
  • leucocyte adhesion defects
56
Q

What is chronic granulomatous disease?

A
  • mutation
  • inactivates oxygen dependent killing in phagocytes
  • affects oxidative complex that includes NADPH
  • so now when lysosome and phagosome fuse, the reactive oxygen species doesnt work
57
Q

What normally happens with phagocytes encountering a pathogen?

A
  1. phagocyte ingests microbe
  2. phagocyte gets activated
  3. NADPH oxidase assemble
  4. this converts oxygen into a superoxide anion
  5. the anion destroys the microbe
58
Q

What is chediak higashi syndrome?

A
  • defective phagosome and lysosome fusing
  • mutation in LYSosomal Traficking receptor (LYST) gene
  • phagocyte cant kill efficiently
  • so patients get recurrent infection
  • they have neutropenia (neutrophils have large granules)
59
Q

What does LYST gene do?

A
  • helps vesicles in cytoplasm go to the right place
60
Q

What do leucocyte adhesion defects do?

A
  • integrin defects
  • selectins defect
  • the phagocyte cannot exit the blood cell into tissue to clear up pathogens
61
Q

What are complements?

A
  • plasma proteins

- activated by microbes

62
Q

What do complements do?

A
  • directly kill microbes

- coat microbes- make phagocytosis easier

63
Q

What does a C2, C4, C1q defect cause?

A

SLE like syndrome

64
Q

What does C3 deficiency cause?

A

infection with pyogenic bacteria

65
Q

What does C5-C9 (MAC) deficiency cause?

A

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

66
Q

What does C1 INH deficiency cause?

A
  • hereditary angioedema:−increased cleavage C4,
  • oedema in skin/mucosa
  • abdominal pain, vomiting, diarrhoea, airway obstruction
67
Q

What does DAF, CD59 deficiency cause?

A
  • recurrent intravascular haemolysis (RBC lysis)

WEEK 9 SEM 4 (9 decks)

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