Brainscape's Knowledge GenomeTM

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


See full index

BoD > Miscellaneous > Flashcards

Miscellaneous Flashcards

1
Q

What are the two top causes of death globally

A

Ischaemic heart disease and stroke

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

What did Virchow propose was the basis of disease

A

Cell injury

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

What cancel injury be inflicted bye

A

Extremes of oxygen tension or pH

Lack of ATP

Exposure to toxins, drugs and chemicals (xenobiotics)

Cold and heat

Prolonged deprivation of vital nutrients

Trauma and ageing

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

Name some adaptations to stress

A

Hyper Trophy

Hyperplasia

Atrophy

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

What happens in cell atrophy?

How is this achieved

A

Cell volume diminishes over several hours or days through reduction in the complexity of the cytoplasm
Organelles are encapsulated by intracytoplasmic membranes and digestion by fusion with lysosomes

My digestion of cellular proteins by that proteasome system, backed up by autophagy

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

True or false

If cells are unable to adapt, they will suffer cell damage that may be reversible or irreversible

A

True

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

How is reversible injury to cells seen

A

As cell swelling or fatty deposits

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

What is cell swelling commonly caused by?

A

Sodium/potassium pump shutdown leading to an influx of sodium and hence water into the cell and mitochondria

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

Describe apoptosis briefly as a death process

A

A death process that requires the cell to retain control over its own energy metabolism

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

What happens in necrosis

A

There is a loss of cell volume homoeostasis and cellular swelling and rupture of internal and plasma membranes occurs

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

How can necrosis cause an inflammatory reaction

A

Intra cellular contents leak into extracellular space and can reach the bloodstream

Some components are chemotactic for neutrophils and elicit in acute inflammatory response

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

Necrosis is poorly controlled and tends to spread

True or false

A

Trim

It involves sheets or groups of adjacent cells

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

Name six cellular targets of cell injury

A

Mitochondria

Decreased ATP

Membrane damage

Cytoskeletal damage

Increased reactive oxygen species

DNA damage, unfolded protein accumulation

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

What are free radicals

How can they be created

A

Molecules that have unpaid electrons and nitric oxide

Ionising radiation and xenobiotics
When tissue is re-oxygenated after hyperoxia, free radicals are generated resulting in reperfusion injury

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

Do free radicals have a long half life

What can they do

A

No but they are highly reactive, causing strand scission in nucleic acid and disruption of protein structure

They also damage lipid membrane is creating additional free radicals

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

Can free radicals be useful

A

ROS and NO Can be utilised by neutrophils and a macrophages to good effect to kill invading microorganisms

However this may damage host cells

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

What is reperfusion injury

What happens next

A

A dramatic destruction of the endothelium of small but vessels carrying renewed bloodflow to a previously hypoxic area

The recruitment of neutrophils is encouraged and this may cause further damage.
Platelets are also recruited with thrombin to seal off the blood supply. This is thrombosis

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

What does decreased ATP need to

A

Reduce activity of the membrane sodium potassium pump

Increased glycolysis

Influx of calcium

Ribosomal detachment and loss of protein synthesis

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

Why is reduced activity of the sodium/ potassium pump bad

A

Sodium accumulates in the sale and calcium is lost

Water accumulates causing ER dilation and cell swelling

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

Why is increased glycolysis due to reduced oxygen supply to mitochondria bad

A

Lactic acid is produced and pH is reduced resulting in decreased cellular enzyme activity

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

Why is an influx of calcium after decreased ATP supply bad?( 3)

A

Increased activity of intracellular proteases, phospholipases, endonucleases and ATPases

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

Name a response pathway to stress that is common to all living cells

A

The heat shock response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the heat shock response

A

Cytoplasmic HSFs dissociate from HSPs

HSFs trimerise and translocate to the nucleus and suppress transcription of many genes and activate transcription of HSPs

HSPs are responsible for preconditioning (where cells exposed to minor injury become resistant to more major stresses)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the unfolded protein response to stress

A

This response and shows the rate of protein synthesis does not exceed the sales capacity to complete the folding process

The UPR activates signalling cascades that increase synthesis of folding chaperones, enhances presume of protein degradation and slows down protein translation

The UPR is usually reversible and is part of host cell shutdown

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

Is cell shutdown reversible or irreversible

What happens

A

It is a primitive reversible response to injury and is initiated within minutes

RNA and DNA synthesis is suppressed and many enzyme catalysed reactions are inhibited

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

What can the ER protein concentration reach

What happens at this concentration

A

100mg/ml

Unwonted precipitation and aggregation of proteins can occur unless proteins are correctly folded and chaperoned

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Give two important examples of stress kinase pathways

A

Jun N-terminal Kinase (JNK) / SAPK

P53

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

What is the SAPK pathway

A

The stress activated protein kinase pathway

This is the same as Jun N-terminal Kinase pathway

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

What does the blood that leaks into the stomach from a peptic ulcer look like

What will emesis look like

A

Green brown as has been broken down by acid

Coffee granules

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

What makes up Pus

A

Fibrin and neutrophils

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

What makes collagen

A

Fibroblasts

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

If NSAIDs are mentioned in the question, what should you be thinking

A

PEPTIC ULCERS

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

How can you test for helicobacter infection

A

Urease test

Helicobacter parasites produce urease not seen in humans normally
Therefore if you add urea it will be broken down into NH3 and CO2

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

If the stomach surface looks microscopically like cobblestones, what should you be thinking

A

Stomach inflammation

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

What does Zollinger Ellison syndrome cause

A

Gastric tumours (gastrinomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What must we be tolerant to?

A

self

innocuous substances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What was an antigen be injected with to elicit a strong adaptive response?

A

adjuvant

38
Q

What do adjuvant’s often contain

A

bacterial products, which stimulate macrophages

or dendritic cells through Pattern Recognition Receptors.

39
Q

What does complete freund’s adjuvant contain

A

ground up mycobacteria

40
Q

What do adjuvants do (2)

A

cue the immune system that an infection is taking place.

convert soluble protein into particulate material, which is ingested by antigen presenting cells
such as macrophages

41
Q

What are the 2 types of tolerance?

A

central - occurs during lymphocyte development

peripheral- occurs after the lymphocytes leaves the primary organ

42
Q

Describe clonal selection of T cells

A

1 - generate TCRs irrespective of specificity
2 - select small number of TCRs that work with self MHC molecules to see foreign antigens

positively select clones with some affinity for MHC
negatively select clones that bind too strongly to MHC+ peptide

43
Q

What does negative selection in the thymus result in

A

deletion of thymocytes whose T cell receptors

have ‘high affinity’ for self.

44
Q

Why should B cells not need to be tolerised

A

they should need T cell help

45
Q

How do self reactive B cells avoid apoptosis

A

by replacing the light chain via receptor editing

46
Q

What happens to a b cell when it binds to high doses of soluble self antigen

A

anergy rather than apoptosis

47
Q

Describe an experiment which demonstrates negative selection of self reactive B cells during maturation in the bone marrow

A

Mice expressed a transgene encoding IgM
against the H-2Kk MHC molecule. In Kd mice, and not Kk, the immature B cells did not bind self antigen and a large number of mature B cells in the spleen expressed antiKk as membrane Ig. Conversely, when the mice expressed Kk (as well as Kd), the
immature B cells recognised the molecule
and were deleted. More detailed analysis of
these mice showed that a small number of
mature cells expressed the µ chain encoded
by the transgene. They had undergone light
chain editing and no longer bound to Kk.

48
Q

Name one problem with central tolerance

How can this be circumvented

A

Many antigens are not expressed in the thymus or the bone marrow

expression of AIRE which activates peripheral genes in the thymus

49
Q

What is AIRE

A

A transcription factor
which turns on many ‘peripheral’ genes in the thymus, so that
the developing T cells may be exposed to their products.

50
Q

What happens if you lack AIRE

A

APECED,

autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

51
Q

Describe the four proposed mechanisms for peripheral tolerance

A

Ignorance
Split Tolerance
Anergy
Suppression

52
Q

Describe the ignorance mechanism of peripheral tolerance

A

when potentially self-reactive T cells are not activated. This
could be because antigens are hidden from the immune system in locations that are not freely
exposed to surveillance (eg brain and testes)

53
Q

Name 3 immunologically privileged sites

why are they considered to be this

A

brain
eye
testes

not freely exposed to surveillance from the immune system`

54
Q

What does split tolerance reflect

A

the notion that, as many pathways in the immune

system are interdependent, they do not all need to be tolerised.

55
Q

What is the most frequent situation of split tolerance

A

where T cell tolerance has been established but autoreactive B cells are still present. Without T cell help the B cells are ‘helpless’. The explanation of this is that it takes 100-1000- times more antigen to tolerise B cells than it does T cells

56
Q

Why is the b cell / t cell split tolerance common for self serum proteins

A

it takes 100-1000- times more antigen to tolerise B cells than it does T cells

57
Q

What is anergy

A

a state of non responsiveness

58
Q

How can anergy be induced in a T cell

A

if the receptor is engaged by the MHC molecule but the second signal is absent

59
Q

What happens to anergised cells

A

they do not die but biochemical changes take place so it no longer responds

60
Q

How are immature B cells anergised

A

exposure to soluble antigen in large amounts without cross linking occurring on the surface

61
Q

What is suppression

A

autoreactive T cells are prevented from reacting by the presence of other T
cells,

AKA Regulation

62
Q

What T cells are involved in suppression?

what do they express?

What is the transcription factor?

A

Treg cells (CD4)

high levels of IL2 receptor CD25

FOXP3

63
Q

Where do natural Tregs develop

A

thymus

64
Q

What is the affinity of Tregs for self antigens in MHC molecules?

How is it therefore affected by selection

A

intermediate

not deleted by negative selection.

65
Q 
What happens to Tregs on contacting self antigen presented by
MHC class II molecules
A

suppress the proliferation of naive T cells responding to autoantigens
presented on the same antigen presenting cell

66
Q

Name 2 cytokines that aid the downmodulation action of Tregs

What are other methods of downregulating T cells

A

IL-10
TGF-beta

induced activation of an enzyme (IDO) by DCs which inhibits T cell
growth by depleting tryptophan,

inhibition of proinflammatory cytokines,

signalling to the APC to decrease
B7 co-receptor expression which is recognized by CTLA-4 which is highly expressed by Treg (and activated
conventional T cells).

67
Q

Name proposed mechanisms of peripheral induction of Tregs

A

the cytokine profile upon antigenic
stimulation;

chronic low-dose antigen exposure; lack
of co-stimulation;

presentation of antigen by immature
DCs

68
Q

Where might presentation of antigen by immune DCs to induce Tregs occur

A

in the GALT

69
Q

Describe GALT

A

gut associated lymphatic tissue

a microenvironment rich in
TGF-β where cells may be exposed to the
microbiome and food antigens

70
Q

Why might you not have Tregs

What happens to boys this age

A

IPEX - congenital mutations in FOXP3

die by age 2 due to autoimmunity and lymphoproliferation

71
Q

What is IPEX

A

Immunodysregulation polyendocrinopathy enteropathy X-linked

mutation in FOXP3 and congenital lack of Treg

72
Q

What do scurfy mice lack

A

FOXP3

Die after 4-6 weeks

73
Q

What happens in both IPEX and Scurfy mice

A

In both cases, effector T cells undergo

massive proliferation and cause lethal autoimmunity

74
Q

What are the factors that affect tolerance

A

timing,

dose of antigen,

amount of co-stimulation

location

75
Q

Describe Medawar’s neonatal tolerance experiment

A

Mouse A injected at birth with bone marrow from B
6 months later: A grafted with B’s skin and C’s skin
B graft accepted
C graft rejected

If repeated but B’s marrow injected a week after birth, tolerance is not achieved and both grafts rejected

76
Q

Interpret the experiments of Medawar involving mice B and C

A

bone marrow stem
cells from mouse B establish chimerism in the host. Some of these cells differentiate into antigen presenting
cells and migrate to the thymus where they tolerise developing thymocytes by deletion (central tolerance).
Lifelong chimerism is needed to maintain tolerance but even a low level of chimerism is sufficient. If the
transfer is done later the number and maturity of the peripheral T cell pool of the host is sufficient to destroy
the donor stem cells before they can engraft.

77
Q

What are the tolerance mechanisms involved in pregnancy

A
  1. physical barrier
  2. lack of MHC class I on trophoblast
  3. Immunosuppression
78
Q

Describe how the trophoblast is developed to be tolerated by mum

A

Trophoblast cells that form the outer layer of
the placenta in contact with maternal tissues
do not express classical class I molecules
and so are not targets for cytotoxic T cells.

79
Q

What immunosuppressive factors are produced to increase tolerance in pregnancy

A

-fetal protein and IDO
(indoleamine 2,3-dioxygenase, a tryptophan
catabolising enzyme)

80
Q

What are 2 examples of knowledge of tolerance being used clinically?

A

cancer

co-receptor blockade

81
Q

Describe co-receptor blockade in tolerance

A

Block CD28 (which is essential for T cell activation)

82
Q

What drug can be used to increase tolerance via co-receptor blockade

What is it

Why does this work

A

abetacept

soluble CTLA4 fusion protein

CTLA4
binds B7.1 and B7.1 to with greater affinity than does CD28, Injection of Abetacept prevents T cells from receiving
their costimulatory signal.

83
Q

When would you use abetacept

A

to treat rheumatoid arthritis and to prevent graft rejection.

84
Q

The immune system is important in dealing with which cancers

eg?

A

tumours associated with viruses

e.g.
Kaposi’s in immunosuppressed AIDS patients

85
Q

Why can cancers be targeted by the immune system?

A 
tumours make altered protein antigens that could be
presented by MHC class I.
86
Q

Why can tumours that have altered proteins that could be presented by MHC CI molecules continue to grow

A 
lost MHC class I
expression by mutation or loss of fragments of chromosome.
87
Q

What are 2 new cancer therapies targeting tolerance

A

Ipilimumab - Ab against CTLA4

Anti-PD1 antibody

88
Q

Describe how ipilimumab works

A

Ipilimumab=antibody against CTLA4

prevents CTLA4 from binding to CD80 or CD86.

This breaks mechanism of immune tolerance and enhances signaling via CD28.

It works by activating a strong immune response against neoantigens
expressed by the cancerous melanocytes

89
Q

What is ipilimumab approved for treatment of

A

Ipilimumab is approved for

the treatment of metastatic melanoma

90
Q

What are neoantigens

A

Typically, UV light (from too much exporue to the sun) causes
mutations that alter self peptides. These proteins now look “foreign” to the immune system and are hence
referred to a neoantigens.

91
Q

What is PD1

A

expressed by activated T cells, and like CTLA4, delivers a negative signal to the T cells.

92
Q

How does CTLA4 normally work

A

CTLA4 competes with CD28 and prevents costimulatory signals from being transmitted to the naïve T cells.

BoD (11 decks)

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