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
What do inhibitory receptor cells recognise?
recognize ligands on healthy cells
26
What do activating receptor cells recognise?
recognize ligands that are upregulated on infected/injured/stressed cells
27
Where are inhibitory and activating receptors found?
in all cells
28
What does the interaction of NK and other cells depend on?
the balance of signals from inhibitory and activating receptors
29
What do all healthy cells express?
MHC1 on their surface
30
Which receptor recognises MHC1?
inhibitory receptor on NK cell recognise MHC1 and then block signal from activating receptors so NK cells dont kill good cells
31
What do viral cells do to MHC1?
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
What is MHC1 made of?
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
What is the difference between inhibitory and activating receptors?
activating has: short intracellular domain intracellular domain in inhibitory has specific motif (ITIM motif)
34
Why can't activating receptors work on their own?
they have short intracellular domain can't signal on their own have to work with adaptor protein DAP
35
What is the motif made of on the activating receptors?
called ITIM motif (immunoreceptor tyrosine based inhibitory motif) contains tyrosines which can be phosphorylated as a consequence of receptor activation
36
What is the motif on the DAP protein?
called ITAM (immunoreceptor tyrosine based activation motif)
37
How does the inhibitory receptor work?
ITIM motifs are activated recruit phosphates remove phosphate group in activating receptor so inhibits it
38
How do ITAM motifs work?
ITAM motifs activate through activating activating receptor on NK cell recruit protein tyrosine kinase phosphorylates pathway promotes signalling
39
What are the cytolytic and cytotoxic ways of natural killer cells?
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
What is chediak highashi syndrome ?
natural killer cell defect | cells have problem moving vesicles in cytoplasm in a controlled manner
41
What kind of defects can be seen in Natural Killer cells?
absence of circulating NK cells NK number is normal but dont function NK defects- cant save themselves from viruses
42
What is an innate lymphoid cell?
- look like lymphocytes - similar function to lymphocytes - produce cytokines - there are many different kinds of innate lymphoid cells (ILC) - generated in bone marrow
43
What does ILC 1 do?
- secrete interferon gamma | - defense against viruses
44
What does ILC 2 do?
- secrete IL5 and IL13 - expresses transcription factor GATA 3 - defense against helminths, and allergic inflammation
45
What does ILC3 do?
- secrete IL17 - ILC 3 secrete IL17 (also secreted by T helper 17 cells) - help with infections in the gut
46
What are lymphoids with limited diversity?
- have features of T and B lymphocytes and innate cells - have limited diversity - recognise limited antigens
47
How do ILCs differ from lymphoids with limited diversity?
- In contrast to ILCs, these cells do express T cell receptors or B cellreceptors
48
What are the different types of lymphoids with limited diversity?
- gamma delta T cells - natural killer T cells - mucosa associated invariant T cells (MAIT) - B-1 B cells - marginal zone B cells
49
What are gamma delta T cells?
- 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
What are natural killer T cells?
- 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
What are mucosa associated invariant T cells (MAIT) cells?
- 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
What are B1-B cells?
- 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
What are marginal zone B cells?
- present in the secondary lymphoid organs such as the spleen and lymph nodes - produce IgM - protect against bacteria in blood borne infections
54
What defects can be seen in phagocytes?
- low in number | - less function
55
Give examples of phagocytic defects?
- chronic granulomatous disease - chediak higashi syndrome - leucocyte adhesion defects
56
What is chronic granulomatous disease?
- 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
What normally happens with phagocytes encountering a pathogen?
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
What is chediak higashi syndrome?
- 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
What does LYST gene do?
- helps vesicles in cytoplasm go to the right place
60
What do leucocyte adhesion defects do?
- integrin defects - selectins defect - the phagocyte cannot exit the blood cell into tissue to clear up pathogens
61
What are complements?
- plasma proteins | - activated by microbes
62
What do complements do?
- directly kill microbes | - coat microbes- make phagocytosis easier
63
What does a C2, C4, C1q defect cause?
SLE like syndrome
64
What does C3 deficiency cause?
infection with pyogenic bacteria
65
What does C5-C9 (MAC) deficiency cause?
infections with Neisseria (N. meningitidis, N. gonorrhoeae)
66
What does C1 INH deficiency cause?
- hereditary angioedema:−increased cleavage C4, - oedema in skin/mucosa - abdominal pain, vomiting, diarrhoea, airway obstruction
67
What does DAF, CD59 deficiency cause?
- recurrent intravascular haemolysis (RBC lysis)