annoying immu3102 stuff Flashcards
1
Q
what are 3 ways we group cytokines
A
receptor structure
cellular activity
biological activity
2
Q
pleiotropic definition
A
acts on different target cells
3
Q
redundant
A
multiple cytokines have the same effect
4
Q
synergistic
A
cooperative effect of multiple cytokines
5
Q
antagonistic
A
inhibition of one cytokines
6
Q
are cytokines stored?
A
No, they are not stored. They are synthesised on demand
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
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
9
Q
What is the structure of an IL2 receptor
A
it is composed of alpha beta and gamma chains
10
Q
What is the function of the beta and gamma chains on IL2
A
they mediated IL2 signalling.
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
12
Q
Interferons
A
A family of pleiotropic cytokines that play essential role in controlling the replication of viral, intracellular bacterial and parasitic pathogens
13
Q
Type 1 and 3 interferons
A
produced by tissue cells and innate immune cells-essential for anti-viral immunity
14
Q
type 2 interferon
A
produced predominately by activated lymphocytes, important for the control of intracellular bacterial and parasitic infection.
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.
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
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.
18
Q
IL-1Ra
A
naturally occuring cytokine that functions as a receptor antagonist.
19
Q
IL-1Ra deficiency causes
A
excessive inflammation. Has to be treated with recombinant human IL-1Ra
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
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
22
Q
What do NKT cells recognise
A
Lipid antigens presented on CD1d (an MHC class1 like molecule)
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
24
Q
What are the functions of MAIT cells
A
MR1 with vitamin B metabolites-
25
gamma delta T cells recognise?
empty non presenting MHC like molecules
surface associated and soluble structures
butyrophilins and phosphonantigens
26
ILC3
like Th17
phagocytosis, Il22, IL17, GM-CSF
27
ILC2
sorta like Th2
alternative macrophage activation
IL4, Il5, AREG
28
ILC1
macrophage activation, IFN_gamma, granzymes, perforin
29
ILC2 homeostasis
IL13 drives epithelial cells towards secretory lineages
AREG- controls epithelial cell proliferation and differentiation needed for repair after pathogen expulsion
30
ILC3
IL22, protects epithelial barrier: promote proliferation and protect from apoptosis. Instructs epithelial cells to make anti-bacterial peptides
31
Difference between regional immunity and immune cells in blood and lymphoid organs
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
32
What makes up the gastrointestinal barrier?
A single layer of epithelial cells
lamina propria beneath the epithelial layer
peyer's patches and mesenteric lymph node
33
What are the functions of enterocytes?
absorb nutrients
34
What are the functions of enteroendocrine cells
produce hormones
35
what are the functions of microfold cells
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
36
What are the functions of paneth cells
```
produce antimicrobial molecules
Secrete antimicrobial peptides like
a-defensins
lysozyme C
REGIII
```
37
what are the function of tuft cells
sense parasites
| produce IL25 to activate ILC2 and Th2
38
What are the important functions of gut epithelial cells
```
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
39
What are the function of Peyer's patches
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
40
What is the function of the lamina propria
diffusely distributed immune cells; the site of the effector phase of a GI immune response
41
What could IgA do
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
TGF beta slide
unknown
43
What are 2 potential functions of dendritic cells in the gut
they could stimulate either a protective T cell response or induce Treg responses to suppress immunity to ingested antigen and commensal organisms
44
What is the role of vitamin A in intestinal immunity (check)
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
What do ILC3 do in the gut
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
What do ILC2s do in the gut
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
What is the function of Th17 in the gut
elimination of extracellular bacteria and fungi
protection of mucosal barrier function
48
What is the function of Th 2 cells in the gut
elimination of helminths
| enhance mucus secretion and muscle contraction
49
What is the function of intraepithelial lymphocytes
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
How does SFB help commensals
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
Immune cell sensing of commensals
IgA switching molecules APRIL, BAFF, TGF beta causes secretory IgA to be produced
52
How does dietary fibre affect commensals (check)
SCFA
| increase tolerogenic DC and Treg
53
The skin
multiple layers of epithelial cells
| Dermis beneath epithelial layer
54
keratinocytes function
they produce antimicrobial peptides
cytokines to direct inflammation and immune cell differentiation
chemokines to recruit immune cells
And help express innate immune receptors
55
What are the functions of dendritic cells on the epidermis
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
What is the role of vitamin D in cutaneous immunity (check)
They imprint expression of skin homing molecules on T cells activated in skin draining LN
57
What is the specialised functions of immune cells in T cells
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
immune privilege hall marks
blood tissue barrier
absence of lymphatics
local immunosuppressive strategies
59
What is the revolutionary idea after the JC virus disease experiment
T cell or monocyte trafficking into the brain must be keeping this latent virus in check
60
What pregnancy
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
atopic
people who have allergies to environmental antigens
62
allergens
antigens that elicit immediate hypersensitivity
63
allergy
a disorder caused by immediate hypersensitivity
64
Anaphylaxis
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
What is an allergic response caused by
an antigen induced Th2 generation and IgE production and mast cell or basophil activation
66
What do Th2 and type 2 ILCs do to cause allergies
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
How does the mast cell get activated
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
Where are FceR1 found
mast cells, basophils, macrophages , epidermal langerhans cells, eosinophils, and activated monocytes
69
What are FCeR1 molecules composed of
an alpha chain that binds the Fc region of IgE, and a beta chain
and finally 2 gamma chains responsible for signalling.
70
Activation of mast cells results in 3 types of biological responses. What are they?
secretion of the preformed granule contents by exocytosis
synthesis and secretion of lipid mediators
synthesis and secretion of cytokines
71
biogenic amines
```
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
Granule enzymes and proteoglycans released by mast cells
neutral serine proteases, tryptase, chymase, contribute to tissue damage in immediate hypersensitivity reactions
73
What cytokines are released by mast cells
TNF, IL1, IL4, IL5, Il6, IL13, CCL3, CCL4, IL3 and GM-CSF
74
What do the lipid mediators of mast cells do
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
What are products of the cyclooxygenase pathway
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
What are the products of the lipoxygenase pathway
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
What happens in an immediate hypersensitivity reaction
There is a wheal and flare reaction
78
What happens in the late phase reaction
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
When does a Wheal and flare reaction happen
when an individual who has previous encountered an allergen and produced IgE antibody is challenged by intradermal injection
80
What is the wheal caused by
swelling, due to leakage of plasma from the venules
81
what is the flare caused by
blood vessels at the margins become engorged with red blood cells producing a characteristic red rim
82
What happens in the late phase reaction
accumulation of inflammatory leukocytes; neutrophils, eosinophils, basophils and T cells
83
what is the definition of an epigenetic trait
It is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence
84
What are the 3 common epigenetic modifications
DNA methylation and histone modifications
| non coding RNA
85
What is DNA methylation
addition of a methyl group onto the 5' carbon position of cytosine of a cytosine-phosphate guanine dinucleotide to produce 5 methylcytosine
86
What enzyme adds methyl groups to DNA
DNA methyltransferase
87
Where does DNA methylation happen
it occurs at gene promoters and enhancers
88
What is the effect of DNA methylation
repression of gene expression through reduced transcription factor accessibility
89
What is DNA hydroxymethlation
unknown...it is like an intermediate between methylated DNA and transcriptionally active chromatin
90
What are histone modifications
They are histones modified at their amino terminal tails. It causes changes in their charge and the packing of chromatin and therefore accessibility
91
What are the kinds of modifications on histones
acetylation, methylation, phosphorylation, citrullination
92
What is the effect of histone modifications
can either activate or repress gene expression
93
lineage commitment (recheck)
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
How is pax5 an example of a transcription factor for lineage commitment
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
What are examples of epigenetics in the immune system
```
lineage commitment
VDJ recombination
T cell differentiation
Memory generation and maintenance
Innate trained immunity
```
96
how are Tregs showing epigenetics
They have a tissue specific specialisation
97
trained immunity
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
What epigenetic mechanisms underly trained immunity
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
Chronic non-bacterial osteomyelitis
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
Psoriasis
systemic autoimmune/inflammatory condition that manifests with skin involvement
increases in microRNAs in keratinocytes
increase in inflammation
reduces Foxp3
101
systemic lupus erythematosus
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
