Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FTIB > immunology > Flashcards

immunology Flashcards

1
Q

what are the key things that the immune system need to be able to discriminate between

A

self and non self

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how do we develop allergies

A

when the immune system acts on thing that it shouldn’t - it is oversensitive to something that isn’t actually harmful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

give a very brief overview of the initial response to infection

A
  1. activation of local innate immune cells
  2. increased permeability of local blood vessels
  3. migration into tissues of more immune cells and plasma proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are macrophages, dendritic cells and mast cell

A
  • they are all derived from haematopoietic cells
  • they are all leukocytes and cause the blood vessels to become sticky and dilate, each has a different effect
  • they are all part of the innate immune system and generate an inflammatory response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

where in the body and macrophages, dendritic cells and mast cells found

A

in all parts of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the first cells that get recruited in the innate immune response

A

neutrophils followed by monocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what do neutrophils and monocytes do in the innate immune response

A

they stick to the blood vessel wall and migrate through the gaps to the infection site causing an acute inflammatory response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what did Charles janeway predict

A

the presence of host receptors that recognise conserved patterns on pathogenic molecules - the immune system must do more than differentiate between self and non self
he thought these receptors would probably be germline encoded

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are PAMPs

A

they are pathogen associated molecular patterns and are what make microbes look different to host cells and this is how the immune system recognises them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are viral PAMPs

A

viral surface nucleic acid glycoproteins which are sensed by pattern recognition receptor proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are bacterial PAMPs

A

bacterial cell wall components are sensed by pattern recognition receptor proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what are fungal PAMPs

A

polysaccharides in the fungal cell wall are recognised by pattern recognition receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are protozoa PAMPs

A

glycolipids are sensed by pattern recognition receptor proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what did polly matzinger propose

A

the immune system senses damage or danger rather than just non self because some microbes are dangerous and some are not so there would need to be a way to discriminate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are DAMPs

A

danger associated molecular patterns

trigger the immune system to respond too danger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the differences between host and microbial DNA

A

there are differences in structure and location
host - located in the nucleus and is ds
microbe - often have nucleic acids that are found in other parts of the cell and some have ss DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how can sense cell death from protein abundance

A

nuclear and cytoplasmic proteins are released from cells when they undergo trauma or death so usually these are present in very low abundance in the extracellular environment so they can be used as a way of sensing death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how can metabolites be used for sensing cell death

A

extracellular ATP is usually in extremely low abundance and rises due to cell death or damaged tissue which again acts as a signal that the immune system might have to respond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

the adaptive immune system attempts to prevent …………………………

A

re-infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are the steps in information transfer from pathogen to adaptive immunity

A

pathogen - causes some sort of damage or disturbance to host tissue
innate response - activation of dendritic cells, mast cells and macrophages which induce a local inflammatory response which attracts other cells
adaptive immunity - appropriate specific response to pathogen antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what gives rise to leukocytes

A

haematopoietic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

describe the transfer of information from the innate to the adaptive immune response

A
  • some cells will migrate out of the infection sit and drain into the surrounding lymph nodes
  • dendritic cells can carry the pathogenic antigens to the local immune system in adaptive immunity
  • adaptive immunity is driven by B cell and T cell activation and is highly specific to defined antigens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what do CD4+ T cells do

A

they produce soluble mediators called cytokines which direct activation of different parts of the immune system

  • they can activate B cells to make antibodies to clear the pathogen
  • they can increase the proliferation of killer CD8+ T cells which can kill infected cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how does adaptive immunity provide protection to reinfection

A

by providing immunological memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

are wbc and leukocytes the same thing

A

yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are the different types of innate immune cells and what are their functions

A
  • dendritic cells - they engulf pathogens and activate the adaptive immune cells
  • mast cells - respond to trauma and infection by releasing toxic molecules and vaso active peptides which drive inflammatory responses and kill pathogens
  • macrophages and monocytes - engulf and destroy pathogens - macrophages are tissue resident cells and monocytes are recruited from the blood
  • neutrophils - the most common wbc and are attracted very quickly - they are not found in the tissue in the absence of infection but they migrate quickly from the blood when there is an infection and start to phagocytose the pathogens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what do epithelial cells act as

A

tissue barriers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

where are the places that we tend to get infections and give some examples

A

the places where we have an environmental interface

e.g. GI tract, respiratory tract, genital/urinary tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what are the cells at the outermost part of our interfaces

A

epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what do epithelial cells express a lot of that is part of the immune system

A

pattern recognition receptors - they sense invasion by pathogens and help start the immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what are fibroblasts

A

cells that usually form the network right under the tissue barrier and also have receptors which participate in the immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

which pathogens are better at causing disease

A

those that can evade aspects of the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

how does complement act to control pathogens

A

when you scratch your arm it does red and raised because the blood vessels become leaky allowing cells and fluid to leak into the site where the tissue trauma has occurred
complement is a series of plasma proteins which act in an enzymatic cascade
it is mainly used in the innate response but can be activated by antibodies in the adaptive response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what are the 3 main effects of complement

A

amplification of the immune response
opsonisation of pathogens
formation of membrane attack complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

how does complement amplify the immune response

A
  • soluble C3a and C5a are released at infection site and the increased influx of immune cells controls pathogens
  • complement proteins in plasma become activated and start to cleave each other into a and b fragments. they act as chemoattractant molecules, diffusing form the infection site towards the local blood vessels
  • neutrophils and monocytes sense the chemoattractants and migrate towards the site of infection - hence the response is amplified
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

how does complement lead to opsonisation of pathogens

A
  • complement fragments bind to the surface of pathogens and some of the tissue cells or neutrophils have receptors for these fragments and recognise the pathogens coded with the complement
  • this causes improved phagocytosis, leading to faster clearance and killing of pathogens
  • it makes the microbes tastier to the phagocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

how does complement activate the formation of the membrane attack complex (MAC)

A

terminal parts of the complement cascade C5-C9 proteins form hydrophobic rings structures which can insert itself into bacterial membranes causing pores to form which leads to death through osmotic lysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

how are our own cells not affected by complement

A

they are resistant
CD46 protein inactivates C3b
CD59 protein stops the MAC from forming
C1 inhibitor cleaves early complement components to stop amplification of the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what strategies have pathogens evolved to evade the complement cascade

A
  • smallpox virus protein - has protein complex called SPICE which inactivates C3b
  • influenza and HIV pick up host complement inhibitors
  • e.coli recruits the C1 inhibitor blocking the early activation stages of complement
  • Schistosoma and Trypanosoma - gave excess CRIT which blocks early stages in complement activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

bacteria cell wall components are PAMPs, why don’t they change their cell wall components to evade the immune system

A

their structure is essential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

which part of gram +ve cell walls is detected by PRRs

A

they have very thick cell walls composed of peptidoglycan - the peptidoglycan is detected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what is peptidoglycan

A

small peptides cross linked into long glycan chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what other substance is also present in the peptidoglycan of gram +ve bacteria that is recognised by PRRS

A

teichoic acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

what part of gram -ve bacteria is recognised by PRRs

A

they have a thin peptidoglycan layer but have an extra membrane called the outer membrane
the peptidoglycan is not so accessible
the outer membrane contains LPS which is recognised by PRRs (TLR4) and is also important for structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what are TLRs

A

plasma membrane molecules that mostly recognise PAMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what are NLRs

A

nucleotide binding oligomerization domain like receptors which recognise a range of PAMPs and DAMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what are CLRs

A

C type lectin like receptors that mostly recognise pathogen carbohydrates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what are ALRs

A

absent melanoma 2 like receptors which recognise bacterial or viral cytoplasmic DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

what are RLRs

A

retinoic acid inducible gene 1 like receptors which recognise pathogen ss or ds RNA which is important for sensing viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

where are bacterial and fungal PRRs (TLR and CLR) found

A

on the cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

where are viral and bacterial PRRs found (TLRs)

A

the endosomes - pH change allows viral replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

where are DAMP and PAMP sensing PRR (NLR) found

A

in the cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

where are DNA and RNA sensing PRRs (ALR and RLR) found

A

in the cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

how can pathogens hide from PRR recognition

A
  • the flagellin of helicobacter pylori has evolved to reduce recognition by TLRs - the bacteria have mutated the recognised sequence in flagellin so that it isn’t recognised by PRR
  • polio steals RNA host 5’ caps from host mRNA to make it look like host mRNA to hide it form NLRs
  • listeria bacteria mutates some of its cell wall components so that is evades NLRs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

what is meant by redundancy

A

we have so many receptors that we have a very good chance of detecting pathogens even if they mutate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

are PRR only found on immune cells

A

no they are found on non immune cells too

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

what are the consequences of PRR activation

A
  • tells neighbouring cells about the threat - makes inflammatory cytokines
  • tells the adaptive immune system - phagocytose the microbe and take it to the draining lymph node
  • limits microbe replication - control pathogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

what links PRR activation to altered immune responses

A
  1. bacteria activating PRRs results in a kinase cascade which results in NF-kB TF activation as it degrades it inhibitor
  2. NF-kB translocates into the nucleus and drives altered gene transcription e.g. chemoattractants produced, inflammatory response initiated
  3. this allows the cell to warn the immune system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

how can bacteria reduce NF-kB activation and inhibit the immune system

A
  • e.coli produces virulence factor that injects into cells and degrades NF-kB
  • shigella enzyme of gram -ve bacteria causes degradation of an activator of NF-kB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

what part of the body does influenza infect

A

epithelial cells in the respiratory tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

what are the steps in influenza infection

A
  1. influenza activates the MyD88/NF-kB pathway
  2. influenza replicates in the nucleus but puts its nucleic acids back out again to form new virous particles
  3. during this RNA can be recognised by RIG-1 receptors which can induce apoptosis of infected cells or induces production of type 1 interferons which are recognised by receptors on the surrounding cells which activate an antiviral pathway
  4. influenza inhibits PRR activation and reduces the immune response by producing NS1 which inhibits NF-kB and blocks RIG-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

is the innate immune system fixed in how it can respond

A

yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

what are the time scales for innate and adaptive immunity

A

innate - takes hours to com into effect

adaptive - takes days to come into effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

what do B lymphocytes produce in adaptive immunity

A

antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

what to T lymphocytes produce in adaptive immunity

A

T effector cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

what are the 2 main types of adaptive immunity

A

humoral and cell mediated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

what happens in humoral immunity

A
  1. antibody mediated extracellular attack

2. B lymphocyte secretes antibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

what happened in cell mediated immunity

A
  1. intracellular attack

2. T cells activate response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

where do B cells mature

A

the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

where do T cells mature

A

the thymus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

what are the 2 types of T cell response in cell mediated immunity

A

phagocytosed microbes –> helper T lymphocyte - activation of macrophages
microbes replicating in infected cells –> cytotoxic T lymphocyte - kills infected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

describe T cell receptors

A

different on each T cell - unique specificity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

describe B cell receptors

A

they are antibodies - surface immunoglobulins

they are different on each B cell - unique specificity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

what is the clonal selection theory

A

the process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific to the antigen. The lymphocytes proliferate into a clone of effector cells and memory cells for that antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

what are the steps in clonal selection

A
  1. a single progenitor cell gives rise to a number of lymphocytes each with different specificity
  2. removal of self reactive immature lymphocytes by clonal deletion
  3. left with a pool of mature naiive lymphocytes
  4. recirculation to peripheral secondary lymphoid organs
  5. proliferation and differentiation of activated specific lymphocytes to form a clone of effector cells
  6. effector cells (helper T, cytotoxic T, B cell) eliminate antigen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

what are our secondary lymphoid organs

A

spleen and lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

what causes lymphocyte activation

A

when a foreign molecule and a lymphocyte receptor bind with high affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

what are the receptors on the effector cells the same as

A

the parent cells receptor that was activated and proliferated by clonal selection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

what causes autoimmunity

A

because lymphocyte receptors are generated randomly some might recognise self

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

what are the basic phases of the adaptive immune response

A
  1. antigen presenting cell (naiive T/B lymphocyte)
  2. clonal expansion
  3. differentiation
  4. lymphocyte activation (antibody producing cell, effector T lymphocyte)
  5. humoral and cell mediated immunity (elimination of antigens)
  6. apoptosis
    7 surviving memory cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

what does the need for proliferation and differentiation in adaptive immunity result in time wise

A

a 4-7 day delay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

what do helper T cells do in cell mediated immunity

A

they help B cells
they help cytotoxic T cells
they direct innate immune responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

describe the T cell receptor complex

A

it is on the surface of the cell

CD3 allows recognition and identification of these cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

how are T cells subdivided into 2 groups

A

they either have CD4 surface molecule or CD8 surface molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

which type of T cells have CD4 and CD3 surface molecules

A

T helper

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

which type of T cells have CD8 and CD3 surface molecules

A

cytotoxic T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

what do helper T cells recognise antigens presented as

A

they recognise antigens presented in MHC II on the surface of antigen presenting cells and help them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

what do cytotoxic T cells recognise antigens presented as

A

they recognise antigens presented in MHC I on many cells types and can be induced to kill

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

what is the key link between innate and adaptive immunity

A

antigen presenting cells (APCs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

give 2 examples of antigen presenting cells

A

macrophages

dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

what is the link between humoral and cell mediated immunity

A

antigen presenting B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

what are antigens presented in the context of and what is this known as in humans

A

MHC which is HLA in humans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

what signals do T cells require to activate

A
  1. antigen presentation in the context of MHC
  2. surface molecule Costimulation
  3. soluble molecules - cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

what are the 3 kinds of signal that APCs deliver to naïve T cells

A
  1. activation - APC in MHC context
  2. survival - Costimulation
  3. differentiation - cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

what are the difference between MHC I and MHC II

A

MHC I - presented on all nucleated cells apart from rbc and present to CD8 T cells (cytotoxic)
MHC II - restricted to professional APCs (e.g. dendritic cell) and present to CD4 T cells (helper)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

what do helper T cells do

A

they help antigen driven maturation of B and T cells

  1. Th interacts though antigen specific and antigen independent mechanisms
  2. undergoes differentiation
  3. mature Th interacts with plasma or T effector cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

why do we need different subsets of Th cells

A

to be able to deal with different types of pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

how are we protected form mycobacterium tuberculosis

A

IFN gamma and activated macrophages - macrophages kill things better if they are activated by IFN gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

how are we protected form leishmania

A

IFN gamma and activated macrophages - macrophages kill things better if they are activated by IFN gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

how are we protected form schistosome

A

mast cells activate the innate immune response

IgE mediates mast cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

what are the two Th subsets

A

Th1 and Th2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

in initial T cell activation are T cells divided into subsets

A

no they appear uncommitted and make transcripts associated with both subsets
differentiation requires continued activation and sustained differentiation signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

what happens to immature dendritic cells in the periphery when they encounter a microbe

A
  1. immature DC express PRRs which respond to PAMPs
  2. ligation of the PRR causes DC activation and migration to draining lymph nodes
  3. activated DC express high levels of pMHC and costimulatory molecules to engage with specific T cells
  4. activated DC make soluble mediators that influence Th cell differentiation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

how are Th 1 cells made

A

activated DCs produce Il-12 (cytokine) which drives NK cells to produce IFN gamma (cytokine). the presence of both of these drives commitment of a Th cell to a Th 1 cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

how do Th1 cells protect against extracellular and intracellular pathogens

A

by producing IFN gamma, TNF alpha (cytokine) and IL-2 (cytokine)

106
Q

what are the effects of Th1 cells

A
  • induction of ROI in macrophages which are toxic to pathogens (TB, leishmania)
  • help doe long lived protective CD8 T cells
  • induce chemokine release to attract immune cells to infection site and increase vascular permeability to aid access
  • help to B cells
  • enhance APC activity and MHC II expression
  • cause apoptosis in infected cells
  • coordinate granuloma formation to wall of pathogen
107
Q

production of IFN gamma and IL-12 push those cells to become cells that make ……………….

A

IFN gamma

108
Q

Th1 increase …… activity making them more likely to present to them so they get even more ……

A

APC

IFN gamma

109
Q

give examples of autoimmune diseases that Th1 are involved in

A
  • coeliac disease - autoimmune response to gluten - T cells activate macrophage in the gut causing inflammation
  • rheumatoid arthritis - T cells activate macrophages in joint causing sustained inflammation
  • multiple sclerosis - immune response against the CNS
  • Inflammatory bowel disease - immune system attacks the gut
110
Q

autoimmune diseases occur due to differentiation of Th cells in the wrong ………….

A

context

111
Q

how are Th2 cells made

A
  1. DC are exposed to Th2 stimuli e.g. damage at epithelial surfaces
  2. DC produce lower levels of activation molecules (pMHC, costimulatory) than those exposed to Th1 stimuli
  3. Basophils PRR are activated by PAMPs and basophils produce IL-4 which drives commitment of Th cell too Th2
112
Q

how do Th2 cells control helminth infections

A

Th2 cells produce IL- 4, 13, 5, 9, 25 and parasite specific IgE to control helminth infections

113
Q

what are the effects of Th2 cells in parasite proteciton

A
  • mast cell degranulation causing release of mediators to enhance parasite expulsion
  • IL-13 promotes mucous production to enhance expulsion of eggs/worms in response to injury
  • IL–4 and 13 act on macrophages involved in tissue repair and angiogenesis
  • Il-5 induced eosinophilia releases cytotoxic cationic proteins that damage parasites
  • collagen production for wound repair and encapsulation of parasite egg (IL-13)
114
Q

give examples of how Th2 cells cause allergy and asthma

A
  • collagen/fibrosis driven by Il-13 in airways of asthmatics
  • mast cell degranulation releases many inhibitors that causes smooth muscle constriction, vascular permeability e.g. in asthma and allergic dermatitis
  • IL-13 promotes mucous production in allergy/asthma response
  • IL-5 induced eosinophilia release cytotoxic cationic protein that cause tissue damage
  • IL-4 and 13 act on macrophages
115
Q

what do the 2 types of Th cells differentiate from

A

naïve CD4 T cell in response to environmental cues

116
Q

Th1 are characterised by the production of …..

A

IFN gamma

117
Q

Th2 are characterised by the production of ……..

A

Il-4

118
Q

why don’t we have Th1 and Th2 cells of every specificity

A

because that would be too costly - we have the ability to switch T cells into one form or another instead

119
Q

the immune system must adapt to compete in the ………… ……..….. with pathogens

A

arms race

120
Q

what is humoral immunity dependent o

A

B cells and antibodies

121
Q

what are antibodies

A

immunoglobulins

122
Q

how many classes of antibodies are there

A

5: IgA, D, E, G, M

123
Q

what is indicated by antibodies being found at very high levels in serum and give an example of on that is

A

indicates they are important - IgG1

124
Q

what are B cells helped by

A

T cells

125
Q

how do T cells help B cells

A
  1. antigen recognition induces expression of effector molecules (memb bound molecules (Costimulation) and cytokines) by the T cell which activates the B cell
  2. B cells proliferate
  3. differentiation of B cells to resting memory cells and antibody secreting plasma cells
126
Q

how do T cells and B cells get together

A
  • activated T and B cells move towards opposite areas and they meet at the edge of the follicle
127
Q

activated T cells migrate towards the ………………….

A

follicles of the lymph node

128
Q

activated B cells migrate towards the ……………..

A

paracortex of the lymph node

129
Q

what happens when T and B cells meet

A

they meet at the edge off the follicle and interact

  1. B cells returning to the follicle undergo rapid proliferation and form a GC
  2. the T cells influence GC output to produce
    - affinity matured memory B cells - increasing affinity
    - long lived high affinity plasma B cells - provide protection
130
Q

what is the other Th subset other than 1 and 2

A

T follicular helper cells

131
Q

Thf cells are close/distant form other CD4 T cell lineages

A

distant

132
Q

Thf cells have a unique collection of effector molecules with high levels of what

A

SURFACE MOLECULE SIGNALS THAT ARE COSTIMULATORY
ICOS
CD4DL
STABILISE INTERACTION BETWEEN T AND B CELLS
SLAM family e.g. DC84
SAP - slam associated protein

133
Q

what are important molecules in T-B cell interactions (cell-cell contact)

A
  • TcR - recognition of cognate pMHCII on B cell
  • BcR - acquisition of Ag and B cell activation
  • MHC II - presentation to Thf - critically important
  • CD28/86 - maintenance of Thf phenotype
  • CD4OL/CD40 - promotes B cell survival and proliferation
  • ICOS/ICOSL - T cell entry to follicle, promotes Tfh cytokine production
  • SLAMF and SAP - critical in stabilising T-B cell contact
134
Q

what are important molecules in T-B cell interactions (soluble) - cytokines

A
  • preventing death - IL-4
  • aiding maturation and differentiation - IL-5,6,21 TGF beta
  • promoting proliferation - IL-2,4
  • enhancing processing and presentationIL-4 increases MHC II expression
  • promoting isotype switching - IL-4, IgG1, IgE. IFN gamma, Ig62c, TGF beta, IgA
135
Q

what is the germinal centre

A

sites of lymphocytes undergoing division in follicles of secondary lymphoid tissue
the main site where high affinity antibody secreting plasma and memory B cells are generated

136
Q

the germinal centre is associated with .. cell dependent antibody responses

A

T

137
Q

describe the structure of the germinal centre

A

can be split into 3 sections
1 - mantle zone
2 - light zone
3 - dark zone

138
Q

describe the mantle zone of the GC

A

contains non specific B cells

139
Q

describe the light zone of the GC

A

contains follicular DCs and T cells

140
Q

describe the dark zone of the GC

A

contains proliferating B cells

141
Q

how do B cells combat rapid bacterial growth

A

they proliferate very quickly and randomly mutate the antibody variable region

142
Q

what id affinity maturation

A

when the average affinity of serum antibodies to its target antigen increases over time
it occurs due to somatic hypermutation (SHM) of the antibody variable region

143
Q

B cells in an individual GC are usually ………… related but the GC is a specialised site that supports events required for ………… …………..

A

clonally

affinity maturation

144
Q

describe the Darwinian selection pressure in the GC

A

we get random generation of new receptors which could have better or worse affinity for the antigen it is trying to recognise
we want optimal recognition and get rid of any intermediate, low or self recognition
Darwinian selection makes this happen

145
Q

after somatic hypermutation we have antibodies with different affinities - describe the 3 possible fates

A

high affinity - adequate BCR signal - adequate T cell help - survival
intermediate affinity - adequate BCR signal - inadequate T cell help - apoptosis
low affinity - Inadequate BCR signal - apoptosis

146
Q

the GC supports affinity maturation through which 3 processes

A

clonal proliferation
somatic hypermutation
affinity maturation

147
Q

newly mutated receptors are selected against the antigen held by the ……… …….. ………. and require continued help to survive the selection process

A

follicular DC

148
Q

proliferating GC B cells accumulate in the ……… ……….. and SHM preferentially occurs here

A

dark zone (centroblasts)

149
Q

proliferating B cells migrate from the dark zone to the ……..……. ……….

A

light zone (centrocytes)

150
Q

what happens to B cells in the light zone

A
  1. they moves along FDC network
  2. higher affinity B cell receptors able to bid Ag on FDC
  3. now process and present Ag on MHC II
  4. presentation of pMHC II to cognate GC Tfh elicits help
  5. higher affinity BCR - better Ag capture - more Ag presentation
151
Q

what does dysregulation of T-B cell interaction result in

A

immune diseases and disorders

152
Q

what are some immune diseases and disorders caused by impaired T-B cell interaction

A
  • HIGM - CD4O/L cannot isotype switch - cannot make IgG so get lots of infections
  • overabundance of Thf in murine models and patients with autoimmune disorders (too much T cell help –> too many antibodies)
  • CD4OL, ICOS mutations producing reduced Tfh results in severe defects in protective humoral immunity (B cells secreting antibodies impaired without T cell help)
153
Q

how can we use T cell help for vaccines

A

we can take an antigen and put it onto a protein to make a conjugate vaccine
e.g. haemophilus influenza type b vaccine - polysaccharide and tetanus toxoid - vaccine elicits T cell help and we get a much better antibody response

154
Q

what parts of the adaptive immune response do we get memory from

A

all of them

  • CD4 T cell responses
  • CD8 T cell responses
  • B cell and antibody responses
155
Q

how is the secondary response different to the primary response

A

it is faster and bigger due to immunological memory

156
Q

what is the basis of vaccination

A

protection form reinfection

157
Q

what are therapeutics for infection, allergy, autoimmunity, cancer and transplantation

A

vaccine and immunomodulatory drugs

158
Q

approximately how many microbes are in the body and where are most of them found

A

10^14 and most of them are found in the colon

159
Q

what % of microbes found in the body are non culturable

A

80%

160
Q

what do we use to identify bacteria since many of them are non-culturable

A

16S sequencing and whole genome sequencing

161
Q

what is 16S sequencing

A

it uses the 16S region of rRNA which is conserved between all bacteria so primers can be made to sequence that section and amplify it using PCR
the sequence shows minor differences between bacteria and this is what is used to identify them

162
Q

what is whole genome sequencing

A

when we sequence the entire genome and compare it to sequences of other bacteria

163
Q

compare the advantages and disadvantages of 16S sequencing and whole genome sequencing

A

16S sequencing only uses a small region of DNA so it is relatively cheap and quick
whole genome sequencing is more expensive, slower and computation intensive
whole genome sequencing provides a more detailed description of the bacteria and can identify their functions but a bacteria can only be identified is it has already been sequenced

164
Q

what are maternal factors that determine the human microbiome

A

gut microbiota
vaginal infection
periodontitis

165
Q

what is periodontitis

A

information in the genes

166
Q

what are birth factor that determine the human microbiome

A

vaginal or caesarean delivery

167
Q

what are postnatal factors that determine the human microbiome

A

antibiotics
breast feeding
host genetics and environment
(these influences all occur before 3 yo - after that the bacterial community is stable for 60-70years)

168
Q

bacteria live on cells that have a layer of ………. on them. this requirement is seen in …………, ……………. and ……………… as these organisms have co-evolved with bacteria for thousands of years

A

mucous

humans, corals and plants

169
Q

what is a normal population of bacteria

A

the regular distribution of bacteria that most healthy people have in their body
those who have inflammatory bowel disease or obesity have a different population of bacteria

170
Q

what is the most common genus in the colon

A

Bacteroides

171
Q

bacterial communities are complex, stable and …………….. and are affected by many factors, especially …………..

A

interdependent

diet

172
Q

bacteria metabolise complex carbohydrates from plants and produce what

A

short chain FA

173
Q

what vitamins do bacteria produce

A

B3, 5, 6, 12
biotin
tetrahydrofolate
Vit K

174
Q

how do bacteria limit pathogen colonisation

A

they outcompete them and may protect against epithelial injury if you have ingested something scratchy and damaging

175
Q

what are the functions of the short chain FA

A

they are the main energy source for epithelial cells and they directly affect the immune system
there presence results in the production of Treg cells and inhibits DCs
they have an anti inflammatory effect on intestinal epithelial cells which reduces the risk of autoimmunity

176
Q

why is there little evidence of efficiency when it comes to probiotics

A

host bacteria are already stable so outcompete the probiotics but there is no harm in taking them

177
Q

give 6 examples of diseases associated with changes in microbiota

A 
acne
rheumatoid arthritis
obesity 
IBS
inflammatory bowel disease 
multiple sclerosis
178
Q

are diseases associated with changes in microbiota caused by changes in microbiota or are the diseases what causes the change in the microbiota

A

it is unclear

179
Q

what are the 2 branches of inflammatory bowel disease

A

colitis and crohn’s disease

180
Q

what are the 3 factors that cause inflammatory bowel disease

A

host genetics
microbiota
innate and adaptive immune response

181
Q

what are the steps in development of inflammatory bowel disease

A
  1. lesions generated by the immune response against microbes cause inflammation
  2. bacteria that thrive in inflammation then grow driving further inflammation creating a cycle
182
Q

what bacteria is often found in hospitals and id generally resistant to antibiotics

A

Clostridium difficile

183
Q

what does clostridium difficile cause

A

it enter the body and multiplies in the GI tract causing inflammation over the normal intestinal bacteria
they release toxins that damage the colon and may lead to pseudomembrane formation

184
Q

what is a treatment for c difficile

A

faecal transplants which replaces c difficile with a normal bacterial community from a donor

185
Q

what are the risks of a faecal transplant and how do we minimise this

A

exposure to unknown pathogens and transfer of illness so donors and samples must be carefully matched

186
Q

what does a break in the immune system’s tolerance to self result in

A

autoimmunity

187
Q

there are multiple chechpoints in the education of lymphocytes to remove those that react to ………..
some autoreactive lymphocytes are kept but regulated by ……………. mechanisms so that they can’t drive disease
if these mechanisms fail it can lead to ……………..

A

self
tolerogenic
autoimmune disease

188
Q

regulation of lymphocytes in the thymus involves …………… and ……………. selection

A

positive and negative

189
Q

what is positive selection

A

it destroys lymphocytes that cannot recognise MHC II

190
Q

what is negative selection

A

it destroys lymphocytes that recognise self peptides in MHC II

191
Q

what does peripheral regulation include

A
  • regulatory T and B cells
  • DCs sensing danger
  • Costimulation
  • ignorance
  • privilege
192
Q

what does a lack of regulation of lymphocytes result in

A

broken tolerance and pathological events from autoimmunity

193
Q

can innate and adaptive immune cells both be involved in autoimmunity

A

yes

194
Q

how do Treg cells regulate the immune system

A

they reduce the response one the infection has cleared

195
Q

how are treg cells important in the autoimmune response

A

if they are deficient this helps drive the autoimmune response

196
Q

what are autoantibodies

A

antibodies produced by B cells in the autoimmune response

197
Q

……. …….. specific for autoantigens may help generate the anti host response by helping to produce antibodies

A

T cells

198
Q

T cells in graves disease are ……. …………. …….. …….

A

anti-thryroid follicular epithelial cells

199
Q

how are innate cells like macrophages and neutrophils implicated

A
  • through cytokine release
  • through destructive enzymes
  • effector pathways e.g. ROIs
  • netosis leading to autoantigen presentation
200
Q

most autoimmune diseases are monogenic/polygenic

A

polygenic

201
Q

why is GWAS a key area of study for autoimmune diseases

A

because there are lots of risk alleles to be found

202
Q

which genes are important in the immune system and what do mutations in these gens result in

A 
AIRE
FOXP3
LRBA
STAT1
STAT3
mutations in these genes result in increased risk of autoimmune disease
203
Q

a mutation in one gene can lead to many different phenotypes - give an example of this

A

mutation in STAT1 can lead to hyperthyroidism, eczema or chronic mucocutaneous candidiasis

204
Q

why does autoimmunity lead to increased infections

A

because the immune system is impaired

205
Q

how does the environment influence autoimmunity

A

environmentally induced changes in the microbiome induce changes in the immune system

206
Q

how can smoking lead to autoimmunity

A

it can trigger a pulmonary mucosa response

207
Q

is there a cure for autoimmune diseases

A

no, treatment can only lower symptoms

208
Q

describe rheumatoid arthritis

A

predominantly affects joints and gets worse over time
the adaptive and innate immune system and tissues cause an inflammation response which damages cartilage and bone
angiogenesis and lymphangiogenesis leads to increased infiltration of inflammatory molecules

209
Q

what leads to the transition event and break in tolerance in rheumatoid arthritis

A

genetic risk
environmental risk
epigenetic modifications
post translational modifications

210
Q

……..………. may have a positive effect against autoimmunity

A

antioxidants

211
Q

what is a vaccination and what is its purpose

A

it is a means of producing immunity against pathogens by the introduction of live, killed or altered antigens that stimulate the body to produce antibodies against more dangerous forms

212
Q

what did Edward jenner do

A

he routinely practiced variolation

found the potential for the cowpox vaccinia to protect against smallpox and performed the first protection trial

213
Q

what are the only 2 diseases to have been eliminated by vaccination

A

smallpox

rinderpest - cow disease

214
Q

what do vaccines induce in the immune system that is important for protection

A

memory - memory cells make the secondary response much stronger an efficient

215
Q

what are the advantages of memory cells over naïve B lymphocytes

A 
they are long lived 
increased frequency 
rapid proliferation 
produce more antibody 
produce higher affinity antibody 
IgA and IgG have better effector functions - class switching
216
Q

how is the secondary antibody response different the primary one

A

faster stronger response
isotype/class switched
higher affinity

217
Q

IgG has a higher/lower affinity than IgM in the secondary immune response

A

higher

218
Q

why are the secondary responses better than the primary responses

A
  • the GC reaction drives affinity maturation and class switching of memory B cells and long lived plasma cells
  • B cell expresses antigen on MHC II and the T cell recognises this complex. B and T cells communicate - cognate interaction
219
Q

how do most vaccines work

A

by inducing long lived plasma cells and plasma antibody responses

220
Q

what happens to serum antibody levels after vaccination

A

they increase and remain relatively constant throughout life

221
Q

what are the live attenuated UK immunisations

A

MMR
rotavirus
Influenza (LAIV)
shingles (herpes zoster)

222
Q

what are the killed UK immunisations

A 
inactivated polio (salk)
influenza (split virion)
223
Q

what are the subunit UK vaccinations

A

DTP
Influenza surface antigen
Men C
Men quadrivalent (ACWY)

224
Q

what are the recombinant subunit vaccinations

A

HPV

Men B

225
Q

give an example of how an attenuated virus is made

A
  1. pathogenic virus is isolate and cultured on host (human)
  2. virus is incubated on cells of another host (monkey)
  3. virus spontaneously mutates and grows on other host (monkey) dues to them providing a selective environment - doing this repeatedly causes further mutation
  4. virus can now be used as a vaccine as it can no longer grow on human cells
226
Q

why did polio patients have to be put in an iron lung

A

due to paralysis of the diaphragm

intubation hadn’t been invented yet

227
Q

which of the polio vaccines was produced first

A

salk (killed)

sabin (live attenuated)

228
Q

only 40 cases of poliomyelitis occurred in the UK between 1985 and 2002 - what were their causes

A
  • caused by live sabin vaccination
  • wild virus infection acquired overseas
  • unknown but wild virus wasn’t detected
229
Q

why shouldn’t children swim after having the polio sabin vaccination

A

because they can poop out live virus

230
Q

why wasn’t the salk vaccine produced earlier

A

because the sabin vaccine was easy to give and more effective

231
Q

how are killed vaccines made

A
  1. usually use chemicals or heat to kill them
  2. this kills the organism rendering it completely uninfective
  3. killed organism can induce immunity
    e. g. whole cell pertussis vaccine
232
Q

how are subunit vaccines made

A

toxins are the pathogenic fragments of bacteria that make us feel ill
antibodies to toxins can prevent infection
subunit vaccines are purified down to just the antigen
e.g. acellular pertussis vaccine

233
Q

what are chemically inactivated toxins called

A

toxoids

234
Q

describe the carrier protein and hapten use in immunisation

A

carrier proteins - e.g. toxoid recognised by B and T cell
hapten - e.g. polysaccharide (no peptides - only recognised by B cells)
1 - use same carrier protein and hapten for both immunisations then we get a secondary Ab response to hapten
2. different carrier protein but same hapten - no secondary Ab response to hapten
3. carrier protein on its own then same protein with hapten - we get a very strong secondary Ab response to hapten
4. same carrier protein and hapten but deplete T cells between immunisations - no secondary Ab response to hapten

235
Q

we want to direct AB against the carbohydrates on the surface of the bacteria but why is this a problem

A

the immune system cannot mount secondary immune responses to carbohydrates because there is no T cell B cell help because T cells don’t recognise carbohydrates, only proteins
we need a protein for the T cell to recognise B cell presentation

236
Q

carrier protein + hapten = …………. vaccine

A

conjugate

237
Q

what is the secondary response driven by

A

T cells - they drive class switching and affinity maturation of B cell response to the carbohydrate/polysaccharide in the GC reaction

238
Q

Men C was controlled very well by its vaccine but Men B wasn’t - what has been developed to control Men B

A

Men B, C, W, Y bacillus strain is accelerating the demise of Men B

239
Q

what is herd immunity

A

where the unvaccinated proportion of the population can be protected by those who are vaccinated - the ratio of vaccination required for this to be effective depends on the infective organism - all based on probability

240
Q

we need 95% vaccination for measles, why is this

A

because it is a very good virus - it takes a while to die whereas other diseases are much less robust

241
Q

what is the problem with anti vaccine communities

A

they create a niche that is very susceptible to infection

242
Q

how can vaccination be an altruistic measure

A

it can protect vulnerable people who you are closely associated with

243
Q

what are recombinant subunit vaccines

A

some viruses/bacteria are very hard to grow because they grow in cells that are difficult to cultivate

  1. we isolate genes that encode the protective antigen against the virus - for HPV it is a surface antigen called L1
  2. the gene for L1 is cloned into insect or yeast cells which are easy to grow and culture - make lots of the vaccine protein
  3. we get self assembly of VLPs which are then purified and used as a vaccine
244
Q

what is a VLP

A

virus like protein - no live RNA/DNA - surface of virus assembled into a particle

245
Q

how is the live attenuated flu virus made

A
  1. start off with highly attenuated virus which is cold adapted so can’t replicate lower down in the respiratory tract because it is too warm
  2. some of the virulence genes of the virus are removed to make it more acceptable
  3. we have isolated genes for 4 seasonal surface proteins (HA/NA)
  4. new vaccine made every year and it can be administered intra-nasally since it is a live virus
246
Q

what are the known limitations of the LIAV

A

it is ineffective in over 50s
issues with safety in children with asthma
not for the immunocompromised

247
Q

what is meant by vaccinating to control the transmission agent

A

children are big transmitters of infection - by controlling them we can prevent transmission to vulnerable people in the community

248
Q

what dies the T cell recognise an antigen through

A

its T cell receptor recognises MHC with antigen peptide

249
Q

what are the 3 steps in T cell activation

A
  1. MHC with antigen peptide presents to T cell receptor. cognate signal tells T cell that it’s the antigen specific T cell - this alone causes T cell anergy
  2. Costimulation - DC tells the T cell to activate
  3. cytokines - cytokines from the DC tell the T cell what kind of T cell it should become
    all of these signals turn the anergic phenotype into an activated phenotype
250
Q

what is T cell anergy

A

a regulatory state of the T cell - no immune response

251
Q

whole organism vaccines (…………………, ………………) supply the 3 signals of T cell activation - MHC, Costimulation, cytokine and drive really strong T cell response

A

attenuated and killed

252
Q

how are attenuated recombinant vaccines made e.g LAIV, malaria, TB, HIV - mainly viruses

A
  1. inset protective antigen genes into attenuated pathogen to act as a carrier
253
Q

what are adjuvants

A

agents which act non-specifically to increase the specific immune response or responses to an antigen

254
Q

what are the clinical uses of adjuvants

A

aluminium precipitates used as adjuvants and are a component of many vaccines - they induce Th2 responses

255
Q

what is the problem with aluminium precipitates as adjuvants

A

it only drives antibody responses of B cells, no other responses like increased phagocyte activity

256
Q

which vaccines require Th1 immunity

A

bacterial - TB, leprosy
viral - HIV, influenza
parasite - malaria, leishmania

257
Q

give examples of adjuvants

A 
liposomes/virosomes 
VLPs 
monophosphoryl lipid A
QS21 
MF-59
ASO3 
esoteric - household items
258
Q

adjuvants may act directly via …….

A

DCs - we are trying to make adjuvants that activate DCs e.g. flagellin, LPS, dsRNA

259
Q

what are other new approaches to vaccine production

A

DNA viruses

genetically attenuated vaccines

260
Q

what are DNA vaccines

A
  1. inject plasmid DNA encoding protective antigen into host
  2. host takes up DNA and expresses protein
  3. host immune response to protein enhanced by CpGs in prokaryotic DNA
261
Q

what are genetically attenuated vaccines

A
  1. take existing pathogen and delete essential genes
  2. GM pathogen now unable to proliferate effectively in host but does generate immune response (delete genes involved in adverse effects and keep genes you want to conserve)
262
Q

provide a basic statement on how to make each type of vaccine

A
  1. attenuated - find/make attenuated pathogen using culture methods
  2. killed - kill the pathogen using heat/chemicals
  3. subunit - kill the pathogen and isolate its protective antigens (toxoids)
  4. recombinant subunit - clone genes for protective antigen and express in e.g. yeast and isolate antigen
  5. live recombinant - clone genes for protective antigens and express in vaccine vector e.g. LAIV
  6. genetically attenuated - knock out virulence genes with recombinant technology
  7. DNA vaccine - clone genes into expression vector and inject construct –> proteins made

FTIB (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions