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annoying immu3102 stuff Flashcards

1
Q

what are 3 ways we group cytokines

A

receptor structure
cellular activity
biological activity

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2
Q

pleiotropic definition

A

acts on different target cells

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3
Q

redundant

A

multiple cytokines have the same effect

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4
Q

synergistic

A

cooperative effect of multiple cytokines

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5
Q

antagonistic

A

inhibition of one cytokines

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6
Q

are cytokines stored?

A

No, they are not stored. They are synthesised on demand

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7
Q

What are cytokine receptors like?

A

Some consist of an extracellular domain for cytokine binding and they also have a cytoplasmic tail for initiating signaling pathway

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8
Q

Some miscellaneous cytokine facts

A

soluble cytokine receptors can act as decoys to inhibit cytokine functions

a receptor sub unit can be utilised by different cytokine receptors

the receptors and their corresponding cytokines are divided into several families based on their structure and activities

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9
Q

What is the structure of an IL2 receptor

A

it is composed of alpha beta and gamma chains

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10
Q

What is the function of the beta and gamma chains on IL2

A

they mediated IL2 signalling.

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11
Q

What happens if IL2R gamma has a mutation?

A

The mice have X-linked severe combined immunodeficiency: the mice have profoundly diminished T and NK cells, normal numbers but non-functional B cells

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12
Q

Interferons

A

A family of pleiotropic cytokines that play essential role in controlling the replication of viral, intracellular bacterial and parasitic pathogens

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13
Q

Type 1 and 3 interferons

A

produced by tissue cells and innate immune cells-essential for anti-viral immunity

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14
Q

type 2 interferon

A

produced predominately by activated lymphocytes, important for the control of intracellular bacterial and parasitic infection.

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15
Q

How does the Jak-STAT signaling pathway work?

A

cytokine mediated receptor dimerization. Jak mediated phosphorylation of receptor chains. This causes the recruitment of STATS to cytokine receptor. This causes JAK-mediated phosphorylation and dimerization of STATs and causes the translocation of STATs to the nucleus causing transcription.

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16
Q

Pro-inflammatory cytokine IL-1

A

2 forms of IL1,

it can be produced by activated monocytes, macrophages, neutrophils and endothelial cells. This causes the production of pro IL1 beta and activates inflammasomes

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17
Q

IL1 receptors

A

IL1R1 is active. IL1RII is inactivie. the soluble ILR1II receptor competes with IL1 R acting as a decoy to prevent signalling.

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18
Q

IL-1Ra

A

naturally occuring cytokine that functions as a receptor antagonist.

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19
Q

IL-1Ra deficiency causes

A

excessive inflammation. Has to be treated with recombinant human IL-1Ra

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20
Q

IL10 where is it produced

A

can be produced by Th1 cells, CD8+ T cells, T regulatory cells and antigen-driven regulatory CD4+ T cells.

Also produced by innate cell types including macrophages, DC, mast cells and eosinophils

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21
Q

The functions of IL10

A 
inactivation of macrophages and dendritic cells
inhibition of pro-inflammatory cytokine secretion. Inhibition of expression of MHC class II and costimulatory molecules

Inhibits the maturation of dendritic cells from monocyte precursors

limits the ability of macrophages to kill intracellular organisms

supresses Th1 by inhibiting the production of Th1 polarizing cytokine IL12 by DCs and macrophages

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22
Q

What do NKT cells recognise

A

Lipid antigens presented on CD1d (an MHC class1 like molecule)

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23
Q

What are some homeostatic roles of NKT cells

A

they have a potential role in protection and gut homeostasis: pro-inflammatory and part of shaping microbiota in the small intestine

Adipose tissue: potential role in homeostasis of adipose tissue: protective or pathogenic, depending on interaction with M1 or M2 macrophages

presentation of self-lipids

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24
Q

What are the functions of MAIT cells

A

MR1 with vitamin B metabolites-

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25
Q

gamma delta T cells recognise?

A

empty non presenting MHC like molecules

surface associated and soluble structures

butyrophilins and phosphonantigens

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26
Q

ILC3

A

like Th17

phagocytosis, Il22, IL17, GM-CSF

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27
Q

ILC2

A

sorta like Th2
alternative macrophage activation

IL4, Il5, AREG

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28
Q

ILC1

A

macrophage activation, IFN_gamma, granzymes, perforin

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29
Q

ILC2 homeostasis

A

IL13 drives epithelial cells towards secretory lineages

AREG- controls epithelial cell proliferation and differentiation needed for repair after pathogen expulsion

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30
Q

ILC3

A

IL22, protects epithelial barrier: promote proliferation and protect from apoptosis. Instructs epithelial cells to make anti-bacterial peptides

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31
Q

Difference between regional immunity and immune cells in blood and lymphoid organs

A

normally, blood and lymphoid are sterile

In regional sites, they are non-sterile-so there is an additional need to react between pathogenic and commensal organisms and discern innocuous from harmful antigens

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32
Q

What makes up the gastrointestinal barrier?

A

A single layer of epithelial cells
lamina propria beneath the epithelial layer
peyer’s patches and mesenteric lymph node

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33
Q

What are the functions of enterocytes?

A

absorb nutrients

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34
Q

What are the functions of enteroendocrine cells

A

produce hormones

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35
Q

what are the functions of microfold cells

A

sample antigen from lumen
transport antigens across epithelium to underlying lymphoid structures

Do not process antigen, but deliver cells in vesicles to be captured and processed by DC

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36
Q

What are the functions of paneth cells

A 
produce antimicrobial molecules
Secrete antimicrobial peptides like
a-defensins
lysozyme C
REGIII
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37
Q

what are the function of tuft cells

A

sense parasites

produce IL25 to activate ILC2 and Th2

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38
Q

What are the important functions of gut epithelial cells

A 
express TLRs and NLRs which can recognise PAMPs and produce cytokines that trigger immune cell migration and differentiation
T independent IgA class switching and IgA release

They are tightly regulated
so high expression levels

can depend on cell polarization

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39
Q

What are the function of Peyer’s patches

A

structure like the LN in GALT,
it is different to LN as it is not encapsulated (antigen is delivered directly through M cells independent of lymphatics)

Heaps of B cells: ratio of B:T cells is 5x greater than LN

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40
Q

What is the function of the lamina propria

A

diffusely distributed immune cells; the site of the effector phase of a GI immune response

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41
Q

What could IgA do

A

binds to bacteria in the lumen and shapes colonisation
it neutralises fast-growing and invasive pathogens

stabilise slow growing commensals

prevent microbes from crossing the epithelial barrier

42
Q

TGF beta slide

A

unknown

43
Q

What are 2 potential functions of dendritic cells in the gut

A

they could stimulate either a protective T cell response or induce Treg responses to suppress immunity to ingested antigen and commensal organisms

44
Q

What is the role of vitamin A in intestinal immunity (check)

A

Vitamin A is transformed to all-trans retinoic acid by retinaldehyde dehydrogenase in CD103+DC found only in the gut and in intestinal epithelial cells.

Along with TGF-beta, vitamin A induces generation of peripheral TRegs and promotes the switching to IgA

It also induces the expression of gut-homing molecules on T and B cells:
integrin binds to MADCAM1 on endothelial cells in lamina propria

and CCR( binds to CCL25 on intestinal epithelial cells

45
Q

What do ILC3 do in the gut

A

They release IL 17 to create an inflammatory response to microbes

They release IL22 and Il17 to protect barrier by stimulating defensin production and enhancing tight junctions

46
Q

What do ILC2s do in the gut

A

IL13 drives tuft cell and goblet cell expansion and mucus production

IL5 activates eosinophils to degrade outer integument of helminths

AREG- causes epithelial cell differentiation and proliferation

47
Q

What is the function of Th17 in the gut

A

elimination of extracellular bacteria and fungi

protection of mucosal barrier function

48
Q

What is the function of Th 2 cells in the gut

A

elimination of helminths

enhance mucus secretion and muscle contraction

49
Q

What is the function of intraepithelial lymphocytes

A

reside within the epithelium monolayer
alpha beta or gamma delta T cells..
don’t require priming by DC-they are antigen experienced.

Immediate immune protection to initial entry of pathogens and can kill infected epithelial cells

50
Q

How does SFB help commensals

A

Adhesion of SFB to epithelium
this causes the release of serum amyloid A
DC secrete IL-1beta and IL 23
support Th17 and ILC3s
this causes pathogen defense and barrier integrity

51
Q

Immune cell sensing of commensals

A

IgA switching molecules APRIL, BAFF, TGF beta causes secretory IgA to be produced

52
Q

How does dietary fibre affect commensals (check)

A

SCFA

increase tolerogenic DC and Treg

53
Q

The skin

A

multiple layers of epithelial cells

Dermis beneath epithelial layer

54
Q

keratinocytes function

A

they produce antimicrobial peptides
cytokines to direct inflammation and immune cell differentiation
chemokines to recruit immune cells

And help express innate immune receptors

55
Q

What are the functions of dendritic cells on the epidermis

A

The ones on the skin are called langerhans cells (they are a specialised DC expressing langerin)

They take up protein antigen process them to peptides and migrate to ln

56
Q

What is the role of vitamin D in cutaneous immunity (check)

A

They imprint expression of skin homing molecules on T cells activated in skin draining LN

57
Q

What is the specialised functions of immune cells in T cells

A

most T cells are memory T cells,
epidermal CD8 are poised to rapidly respond to pathogen re-encounter

Dermal T cells are CD8 and CD4, causes central memory, effector memory and resident memory

58
Q

immune privilege hall marks

A

blood tissue barrier
absence of lymphatics
local immunosuppressive strategies

59
Q

What is the revolutionary idea after the JC virus disease experiment

A

T cell or monocyte trafficking into the brain must be keeping this latent virus in check

60
Q

What pregnancy

A

pregnancy has taught us a lot about the immune system at privileged sites

Tregs are expanded
tolerogenic molecules and cytokines produced

HLA expression modified

apoptotic molecules expressed

61
Q

atopic

A

people who have allergies to environmental antigens

62
Q

allergens

A

antigens that elicit immediate hypersensitivity

63
Q

allergy

A

a disorder caused by immediate hypersensitivity

64
Q

Anaphylaxis

A

mast cell-derived mediators can restrict airways to the point of asphyxiation and produce cardiovascular collapse

anaphylaxis was coined to indicate that IgE could confer the opposite of prophylaxis(protection)

65
Q

What is an allergic response caused by

A

an antigen induced Th2 generation and IgE production and mast cell or basophil activation

66
Q

What do Th2 and type 2 ILCs do to cause allergies

A

Th2 cells secrete cytokines including IL4, IL5 and IL13 that work in combination with mast cells, eosinophils and ILCs to promote inflammatory responses to antigens with tissues

Type 2 ILCs do basically the same thing as Th2- they release IL5 and IL13

67
Q

How does the mast cell get activated

A

mast cells and basophils have a FceRI which binds IgE.
IgE functions as an antigen receptor on the surface of mast cells and basophils

This function is accomplished by IgE binding to FceRI on these cells

68
Q

Where are FceR1 found

A

mast cells, basophils, macrophages , epidermal langerhans cells, eosinophils, and activated monocytes

69
Q

What are FCeR1 molecules composed of

A

an alpha chain that binds the Fc region of IgE, and a beta chain

and finally 2 gamma chains responsible for signalling.

70
Q

Activation of mast cells results in 3 types of biological responses. What are they?

A

secretion of the preformed granule contents by exocytosis
synthesis and secretion of lipid mediators

synthesis and secretion of cytokines

71
Q

biogenic amines

A 
major mediator of this class is histamine
They cause contaction of the endothelial cells leading to increased vascular permeability and leakage of plasma into the tissues

stimulates endothelial cells to synthesize vascular smooth muscle cell relaxants which cause vasodilation

These actions of histamine produce the wheal and flare response of immediate hypersensitivity

72
Q

Granule enzymes and proteoglycans released by mast cells

A

neutral serine proteases, tryptase, chymase, contribute to tissue damage in immediate hypersensitivity reactions

73
Q

What cytokines are released by mast cells

A

TNF, IL1, IL4, IL5, Il6, IL13, CCL3, CCL4, IL3 and GM-CSF

74
Q

What do the lipid mediators of mast cells do

A

They are synthesized and release rapidly, acting on blood vessels, bronchial smooth muscle and leukocytes.

Arachidonic acid is metabolized by either the cyclooxygenase or lipoxygenase pathways

75
Q

What are products of the cyclooxygenase pathway

A

so mast cells release lipid mediators. One of these lipids can be metabolised by pathways to produce stuff. One of these metabolic pathways is called the cyclooxygenase pathway, The main mediator released here is prostaglandin D2. PGD2 signals smooth muscle cells and acts as a vasodilator and a brochoconstrictor

Promotes neutrophil chemotaxis and accumulation at inflammatory sites

76
Q

What are the products of the lipoxygenase pathway

A

so mast cells release lipid mediators. One of these lipids can be metabolised by pathways to produce stuff.
leukotriens-especially LTC4. LTC4 is made by mucosal but not connective tissue mast cells and basophils. They bind to specific receptors on smooth muscle cells, different from the receptors for PGD2 and cause prolonged brochoconstriction

77
Q

What happens in an immediate hypersensitivity reaction

A

There is a wheal and flare reaction

78
Q

What happens in the late phase reaction

A

The immediate wheal and flare reaction is followed 2 to 4 hours later by a late phase reaction consisting of the accumulation of inflammatory leukocytes including neutrophils, eosinophils and Th2 cells

79
Q

When does a Wheal and flare reaction happen

A

when an individual who has previous encountered an allergen and produced IgE antibody is challenged by intradermal injection

80
Q

What is the wheal caused by

A

swelling, due to leakage of plasma from the venules

81
Q

what is the flare caused by

A

blood vessels at the margins become engorged with red blood cells producing a characteristic red rim

82
Q

What happens in the late phase reaction

A

accumulation of inflammatory leukocytes; neutrophils, eosinophils, basophils and T cells

83
Q

what is the definition of an epigenetic trait

A

It is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence

84
Q

What are the 3 common epigenetic modifications

A

DNA methylation and histone modifications

non coding RNA

85
Q

What is DNA methylation

A

addition of a methyl group onto the 5’ carbon position of cytosine of a cytosine-phosphate guanine dinucleotide to produce 5 methylcytosine

86
Q

What enzyme adds methyl groups to DNA

A

DNA methyltransferase

87
Q

Where does DNA methylation happen

A

it occurs at gene promoters and enhancers

88
Q

What is the effect of DNA methylation

A

repression of gene expression through reduced transcription factor accessibility

89
Q

What is DNA hydroxymethlation

A

unknown…it is like an intermediate between methylated DNA and transcriptionally active chromatin

90
Q

What are histone modifications

A

They are histones modified at their amino terminal tails. It causes changes in their charge and the packing of chromatin and therefore accessibility

91
Q

What are the kinds of modifications on histones

A

acetylation, methylation, phosphorylation, citrullination

92
Q

What is the effect of histone modifications

A

can either activate or repress gene expression

93
Q

lineage commitment (recheck)

A

team effort between lineage specific transcription factors and epigenetic modifications.

Chromatin remodelers interact with lymphoid specific transcription factors to prime lymphoid gene expression and downregulate self-renewal genes of stem cells.
Polycomb repressor complexes antagonise lymphoid gene expression by establishing repressive histone marks at their promoters

94
Q

How is pax5 an example of a transcription factor for lineage commitment

A

pax5 recruits chromatin-remodeling, histone-modifying and transcription factor complexes to control gene expression
=> represses 230 lineage inappropriate genes

=> activates around 120 B cell specific genes

95
Q

What are examples of epigenetics in the immune system

A 
lineage commitment
VDJ recombination
T cell differentiation
Memory generation and maintenance
Innate trained immunity
96
Q

how are Tregs showing epigenetics

A

They have a tissue specific specialisation

97
Q

trained immunity

A

long-term functional reprogramming of innate immune cells after a primary challenge that leads to an altered response to a secondary challenge
1) can be induced after prr or cytokine stimulation

98
Q

What epigenetic mechanisms underly trained immunity

A

So after some innate cell has been stimulated, when it goes back to rest, it has mildly condensed chromatin. This is an intermediate between highly condensed chromatin and open chromatin.

basically, it has mild DNA methylation whereas unstimulated state has high DNA methylation

99
Q

Chronic non-bacterial osteomyelitis

A

inflammasome associated autoinflammatory bone condition
reduced regulatory cytokine IL 10 and decreased CpG methylation of inflammasome components

This caused increased proinflammatory cytokine IL20 and inflammasome activation

100
Q

Psoriasis

A

systemic autoimmune/inflammatory condition that manifests with skin involvement

increases in microRNAs in keratinocytes
increase in inflammation
reduces Foxp3

101
Q

systemic lupus erythematosus

A

systemic autoimmune disease with the presence of autoantibodies and autoreactive lymphocytes against nuclear antigens.

Changes in gene expression in CD4 T cells support autoantibody producing B cells (DNA methylation and histone acetylation) this 5 mC increases type 1 IFN from neutrophils

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