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Sem 2 Year 1 > Integrity upto immunity > Flashcards

Integrity upto immunity Flashcards

1
Q

Where do you start to acquire your microbiome?

A

Start to acquire it in the uterus, can be altered by mother’s antibiotics use and what she is eating

Mode of delivery gives different microbiome- vagina vs a c-section

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2
Q

What is the function of the microbiome?

A
  • energy synthesis
  • protection from pathogenic bacteria
  • Imuune system education
  • Vitamin system education
  • Drug metabolism
  • Bile salt metabolism
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3
Q

What sugar is present in breast milk that babies cannot digest?

A

Milk oliogosaccharides- promotes production of anti-inflammation molecules

B infantis contains the enzymes needed to break it down.

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4
Q

How is the microbiome involved in energy biosynthesis?

A

Starch that does not get broken down in the small intestine is broken down to small chain fatty acids.

SCFA is the main sources for enterocyte cells in the small intestine

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5
Q

How does the microbiome stop pathogenic bacteria?

A

Produce bacteriocins (toxins) that directly kill salmonella, listeria and clostidium

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6
Q

How is the microbiome involved in bile acid metabolism?

A

Microbiota produce secondary biles which can activate cell surface receptors- help reduce gut inflammation, regulate synthesis of bile acids

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7
Q

How are the microbiome and obesity linked?

A
  • bacteria are involved in ernegy production
  • they stimulate production of mediators that alter insulin/glucagon production
  • involved in satiety
  • regulate intestinal inflammation
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8
Q

What are prebiotics and probiotics?

A

Probiotics are foods or supplements that contain live microorganisms intended to maintain or improve the “good” bacteria (normal microflora) in the body. Prebiotics are foods that act as food for human microflora.

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9
Q

What is some of the advantages to taking probiotics?

A

Evidence they can lower cholesterol and have a general improvement in microbial composition and functions

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10
Q

What are some of the targeted research therapies with obesity and the microbiome?

A

Bioengineering bacteria to produce glucagon-like peptide 1 which increases insulin release and reduces hyperglycaemia

Bioengineer bacteria that effect satiety.

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11
Q

What are the two major conditions of inflammatory bowel disease?

A

Ulcerative colitis; effects the colon

Crohn’s disease; can effect any part of digestive tract from mouth to anus

Both have chronic inflammation, relapsing and remitting. Common presentation is abdominal pain, diarrhoae and weight loss

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12
Q

What is the microbiome like in patients with inflammatory bowel disease?

A

There is decreased microbial diversity, decrease of bacteria such as Firmicutes and clostridium. Some are increased such as E. coli

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13
Q

What is the current treatment for inflammatory bowel disease?

A

Anti-inflammatory treatment (glucocorticoids) and anti-tumour necrosis factor (TNF= a cytokine, induces inflammation)

There is no routine place for microbiome based therapy

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14
Q

How does colon cancer screening work?

A

Starts at the age of 50, test is for blood in stool, if there is a positive test a colonoscopy is given)

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15
Q

What increases the risk of colon cancer?

A

Obesity

Insulin resistance

Increased red meat intake

Decreased fibre intake

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16
Q

What are the microbiome protective effects against colon cancer?

A

Produce short-chain fatty acids

Phytochemicals (compounds in plants) are metabolised in colon

Both have anti-inflammatory effects

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17
Q

What are the harmful effects of the microbiome to the gut?

A

Secondary bile acids produced can promote DNA damage

Ammonia is produced- damage colonic epithelia

N-nitroso formed from certain foods which can be carcinogenic

Fermentation of of diet derived proteins to phenols

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18
Q

What bacteria do probiotics usually contain?

A

Lactobacillus and bifidobacterium, derived from cultured milk sources

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19
Q

What occurs in a helicobacter pylori infection?

A
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20
Q

What are the symptoms of peptic ulcer disease?

A

Often asymptomatic but can cause bleeding, leading to anaemia

Sometimes can cause upper abdominal pain, indigestion and heartburn

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21
Q

How is the helicobacter pylori infection detected?

A

A urea breath test, also use a stool antigen test or endoscopy or biopsy

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22
Q

How is the helicobacter pylori infection treated?

A

Proton pump inhibitor- supresses acid secretion

Antibiotics 7 day course- such as amoxicillin

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23
Q

What can a clostridiodides difficile infection cause?

A

Causes antibiotics associated colitis (bowel inflammation).

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24
Q

How does a clostridiodes difficile infection arise?

A

Comes about after taking a course of antibiotics which then kills certain bacteria in the healthy microbiome. It does not kill C diff however, which fills the void left. When antibiotics are stopped, healthy humans return to normal state.

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25
Q

What can occur if Clostridioides difficile proliferates instead of returning to normal levels after a course of antibiotics?

A

Creates a dysbiotic environment- a more pro-inflammatory environment. After antibiotics are stopped, in some patients C diff progresses and an inflammatory environment in the colon is created. Presents as colitis- dihorrea, colon can become dilated.

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26
Q

What is the treatment for clostridioides difficile infection?

A

Most cases respond to antibiotic treatment

Avoiding antibiotics more likely to cause the infection

Faecal microbiota transplantation- oral capsule, tube or colonoscopy

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27
Q

What is an infection?

A

The invasion, multiplication and establishment of one or more pathgoens/ microorganisms in the body

Can be bacteria, viruses, yeast, parasites or prions (proteins able to bend their shape to initate another protein)

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28
Q

What does pathogenicity mean?

A

The ability of an organism to inflict damage on the host

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29
Q

What does virulence mean? And what are virulence factors?

A

The relative ability of a pathogenic organism to cause disease.

Virulence factors include genes, molecules or structures that contribute to virulence

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30
Q

What are commensals, pathogens, primary and secondary pathogens?

A
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31
Q

What type of organisms are saprophytes and zoonoses?

A

Saprophytes= organisms that live in the environemnt

Zoonoses= organisms associated with animals

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32
Q

What happens when a pathogen colonises a person?

A

When microorganisms, including those that may be pathogenic, are present at a body site (E.g. on the skin, mouth, intestines or airway) but are doing no harm and are not causing symptoms of infection.

The person colonised can also be called ‘a carrier’.

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33
Q

What are the 3 categories of the innate immune system?

A

Physical defences eg anatomical barriers, mechanical defences and microbial colonisation resistance.

Chemical defences

Cellular defences

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34
Q

What are the different types of physical barrier?

A

(lots of extra info)

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35
Q

What are the different types of chemical defenses in the innate immune system?

A

Chemicals and enzymes in the body- Acid in stomach, urine and vagina

Antimicrobial peptides that kill bacteria by attacking membranes

Plasma protein mediators (c-reactive protein)

Cytokines

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36
Q

What are examples of phagocytic cells?

A
  • Neutrophils
  • Eosinophils
  • Monocytes (natural killer cells)
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37
Q

How do host defences fail againsy protecting from pathogens?

A
  • Physical barriers= wounds
  • Flushing mechanisms- smoking causes damaged respiratory cilia, catheter in bladder
  • Chemical- decreased acidity in the stomach (H2 blockers)
  • Microbial colonisation resistance- antibiotics
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38
Q

What are the main entry points for pathogens to enter the body?

A

Break in skin; wound or infection in hair follicle

Sucking blood out of a cut= mouth

Infection at mucosal surfaces

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39
Q

Why are mucosal surfaces more prone to pathogen invasion?

A
  • have thinner epithelia due to functions
  • more prone to trauma
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40
Q

How do pathogens spread around the body?

A
  • Blood- most common
  • Lymphatics
  • Nerve cells
  • Body spaces e.g. pleura
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41
Q

What are the most common routes of transmission of pathogens?

A

Respiratory

Salivary

Faecal-oral

Sexually

Vector

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42
Q

What are virulence factors?

A

Virulence factors are the molecules that assist the bacterium colonize the host at the cellular level.

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43
Q

What is straphylococcus aureus?

A

The hospital superbug

Bacteria- half of the population is colonised with it in their noses

Causes lots of infections such as pneumonia, endocarditis, meningitis, sepsis and UTIs

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44
Q

What makes a patient more susceptible to a S aureus infection?

A

If the patient has previously been on antibiotics recently, their microbiome will be disrupted

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45
Q

What is MRSA?

A

Methicillin resistant S. aureus infection

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46
Q

What are the diseases associated with Neisseria meningitidis?

A
  • Meningitis
  • Pneumonia
  • Arthritis
  • Urethritis
  • Meningococcaemia
  • Meningoencephalitis
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47
Q

Where is streptococcus pneumonia colonised?

A

Nasopharynx and throat

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48
Q

What can strepococcus pneumoniae cause?

A

Mucosal infections such as sinusitis

Lobar pneumonia

Invasive infections such as meningitis and sepsis

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49
Q

What is the most common cause of meningitis?

A

pneumococcal pneumoniae

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50
Q

How does Streptococcus pneumoniae get past the mucosal barrier?

A

It has a negatively charged capsule, protects the bacteria from being trpped in the mucus

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51
Q

What are PAMP’s?

A

Pathogen associated molecular patterns

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52
Q

What are the steps in microbial pathogenesis?

A
  1. Entry
  2. Niche establishment
  3. Multiply
  4. Spread
  5. Exit the host
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53
Q

What mechansims so pathogens use to move and stick to cell walls once in contact with an organism?

A

Flagella or chemotoxis to move

Uses adhesives to adhere to epithelium walls

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54
Q

What diseases put you more at risk of infection?

A
  • Diabetes
  • Chronic renal disease
  • COPD
  • Malignancy
  • Immnosupression e.g. congenital, drugs or HIV
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55
Q

What is a common cause of UTIs?

A

E. coli

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56
Q

How do you stop the chain of infection?

A

Controlling or eliminating the agent at the source

Hand washing, decontamination of environment- stopping transmission

Intervening aginst portals of entry= PPE

Increase host defences= vaccines, herd immunity

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57
Q

What are important healthcare-associated infections?

A

Straphylococcus aureus

Clostridium difficile

COVID-19

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58
Q

What are the standard infections control precautions?

A
  • Hand hygiene
  • PPE
  • linen managment
  • equipment managment
  • patient placement
  • respiratory and cough hygeine
  • fluid spillage management
  • waste management
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59
Q

How is Neisseria meningitidis transmitted?

A

Person-to-person

Inhaling respiratory secretions or direct contact e.g. kissing

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60
Q

What diseases can neisseria meningitidis cause?

A

Meningitis and bacteraemia

Can be severe and sometimes fatal

Notifiable to public health

61
Q

What is a genome?

A

A complete set of genetic info, provides all the info an organism requires to function

Stored in long molecules of DNA, within chromosomes. In eukarytoic cells contained within the nucleus

62
Q

What charges are DNA and histone proteins?

A

DNA= negative

Histone proteins= positive

63
Q

What is the name given to the base, sugar and phosphate group in DNA?

A

NUCLEOTIDE

64
Q

How many carbon is the sugar in DNA?

A

5

65
Q

What makes up the backbone of DNA?

A

Sugar and phosphate

66
Q

What is the sugar present in DNA?

A

2-deoxyribose

67
Q

What are the different types of bases in DNA?

A
68
Q

What is the name given to a base and sugar in DNA?

A

Nucleoside

69
Q

What is the start and the end of a DNA chain?

A

5’ end is the start and 3’ is the finish

70
Q

What is a nucleosome?

A

A nucleosome is the basic repeating subunit of chromatin packaged inside the cell’s nucleus.

71
Q

What is the structure of histone proteins?

A

The DNA strand winds around the octo-histone structure. Each histone also has a long amino acid tail which extends out from the nucleosome core particle. The tails are subject to reversible chemical reactions that help to control many aspects of chromatin structure.

72
Q

How many pairs of chromosomes do humans posses?

A

Humans have 23 pairs of chromosomes- 22 pairs of autosomes and one set of sex chromosomes

73
Q

Why is DNA replication semiconservative?

A

It is known as semi-conservative because in each round of replication, half of the parent strand is kept within the daughter strand.

74
Q

Where does DNA replication occur?

A

The replication origin- either direction is known as a replication fork

75
Q

In what direction is DNA synthesised?

A

5’ to 3’ direction

76
Q

How are bases added to replicating DNA?

A

DNA polymerase adds nucleotides to the 3’ end of the growing chain. Added as deoxyribonucleotide triphosphates (dNTPs). Base pairing dictates which nucleotide is added. Energy required for synthesis reactions comes from hydrolysis of the dNTPs high energy phosphate bond.

77
Q

What is the leading and lagging strands?

A
78
Q

What enzyme joins up the Okazaki fragements?

A

DNA ligase

79
Q

What is the functions of DNA and RNA polymerase?

A

DNA polymerase can only continue an existing strand, not initiate new ones.

And RNA polymerase known as primase makes an RNA primer first (later removed) that is around 10 bases long. DNA polymerase can then extend the RNA chain.

80
Q

What enzyme helps to unwind the double helix?

A

DNA helicase

81
Q

What process proofreads DNA replication?

A

DNA polymerase proofreads

Then DNA mismatch repair

82
Q

What are the differences between mitochondrial DNA v nuclear DNA?

A
83
Q

What are the steps of PCR reactions?

A
84
Q

How do COVID tests work?

A

Sample taken on a swab

In lab, the RNA is isolated and everything else is removed from the sample

The RNA is mixed with enzymes, nucleotides, co-factors, primers and probes.

The primers can recognise the viral DNA

Called reverse PCR as the RNA first has to be transcribed into a DNA copy

85
Q

What are the differences between DNA and RNA?

A
86
Q

What enzyme makes an RNA copy of one DNA strand?

A

RNA polymerase II

87
Q

How does transcription occur?

A

Transcription produces an RNA copy of the coding strand of DNA. (except U not T).

RNA polymerase II synthesis in 5’ to 3’ end direction, does not require a primer

88
Q

What is a promoter?

A

Promoter= made up of the sequence elements found immediately 5’ to the gene that interact with RNA polymerase and other compnenets of the transcription machinery

89
Q

What are enhancers?

A

Increase transcription from a nearby gene can can operate over considerable distances

90
Q

What are transcription factors?

A

Proteins which bind d to specific DNA sequences within the promotor or enhancers so as to increase or decrease gene expression.

91
Q

How do transcription factors change myosin gene transcription in muscle and skin cells?

A
92
Q

What are the different ways that a gene can be controlled to give various different products?

A
  1. Alternative promotion
  2. Alternative splicing
  3. Alternative polyadenylation
93
Q

What are exons and introns?

A

Exons contain coding sequences, introns are founnd between exons

94
Q

What is splicing?

A

introns can be removed to give a functional RNA molecule. Different variations of splicing can occur. Exons can be skipped or included, but their order cannot be changed.

95
Q

What are the RNA processing steps that RNA must undergo before it can be exported from the nucleus?

A
  1. slicing
  2. capping
  3. polyadenylation
96
Q

What is RNA capping?

A

It modifies the 5’ end of a RNA transcript. The cap contains an atypical neucleotide, a guanine nucleotide that has a methyl group- protects the ways mRNA is protected from degradation

97
Q

What are the different types of RNA?

A
98
Q

What is polyadenylation?

A

A polyA tail is a string of adenylate residules added to the 3’ end of an mRNA

It is only found on mRNAs

Transcript is cleaved past the polyA site

99
Q

What are codons?

A

Groups of 3 nucleotides

100
Q

What is the start codon?

A

AUG

101
Q

What are the 3 stop codons?

A

UAA

UGA

UAG

102
Q

Where are the places on tRNA molecules that are not base paired and are unbound?

A

At the anticodon region

The 3’ end at the top where the amino acid will bind

103
Q

What eznyme is involved in attaching tRNA to an amino acid?

A

aminoacyl tRNA synthetases

energy for reaction given by ATP hydrolysis

104
Q

What is a tRNA after it has given up it’s amino acid?

A

spent tRNA

105
Q

What are ribosomes made of?

A

Made of rRNAs and proteins

106
Q

What are the 3 tRNA docking sites?

A
107
Q

What are the 4 steps of translation at a ribosome?

A
108
Q

How do some antibiotics work in terms of protein synthesis?

A

Some antibiotics work by inhibiting prokaryotic proteins synthesis

109
Q

What are genes that code for proteins found in most cells called?

A

‘Housekeeping genes’

Include ribosomal genes which are essential for the production of proteins

110
Q

What changes are there in the genes of specialised cells?

A

All cells in a multicellular organism have a full complement of genes. Cells are specialised because of differences in gene activity and not gene content.

111
Q

What are transcriptional regulators?

A

Switch genes on and off

112
Q

What is an operon?

A

An operon is a cluster of genes that are transcribed together to give a single messenger RNA (mRNA) molecule, which therefore encodes multiple proteins

113
Q

What is an example of bacteria switching on and off based on resources?

A

E. coli has 5 genes that code for enzymes tryptophan biosynthesis pathway.

When trytophan is low the genes are switched ON, and when it is abundant they are off.

114
Q

Where do transcription factors bind to?

A

Enhancer regions

115
Q

What is the role of a transcription factor?

A

It influences the activity of RNA polymerase by switching genes on or off

116
Q

What is MyoD?

A

Binds to DNA and ultimately leads to the development of muscles

117
Q

What is a chromatin?

A

DNA is packaged into nucleosomes. DNA is associated with proteins: histones and other nonhistone chromosomal proteins, this DNA-protein complex is known as a chromatin

118
Q

What can transcription factors attract in nueclosomes?

A

Histone modification enzymes

Chromatin remodelling complexes

Histone chaperones

119
Q

How do transcription factors cause nucleosomes to unwind and become more accessible?

A

Change the composition of the histones

This unwinds the chromatin

These combine to histones and remove them from the nucleosome, exposing the DNA.

120
Q

What are differentiated cells that never divide?

A

Neurons and skeletal muscle

121
Q

How can histone tails be modified?

A

Histone tails can be reversibly chemically modified to make the chromatin more or less accessible e.g. to increase or decrease gene expression.

122
Q

What reinforces a cell’s memory and passes the memory onto daughter cells?

A

Histone modification

DNA methylation

123
Q

What is DNA methylation?

A

DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence

124
Q

How are different cell types produced based on intracellular signals?

A

When a cell is about to divide, if there is an uneven distribution of a particular molecule e.g. a transcription factor on one side of cell, it will produce two cells that have inherited different amounts of TF.

125
Q

What extracellular signals allow different cells to be produced?

A

If the TF tells the cell to produce a signal and if the TF blocks the production of the receptors signal, this will mean the blue cell does not have the receptor and the grey does. Cells can signal but only cells close to it can pick it up, which leads to a third cell type.

126
Q

What is Waddington’s landscape?

A

Waddington prosed a landscape made of ridges and valleys down which a marble could roll. As it moves it could make choices until it found its resting place. Similar is a cells path towards being specialised.

127
Q

What is the fist step in the differentiation of blood cells?

A

A multipotent hematopoitic stem cell differentiate into lymphoid or myeloid fate

128
Q

What is commitment to proginotors regulated by in hematopoietic stem cells?

A

Specific TF e.g. GATA1

129
Q

Where would erythropoieten act on the following pathway?

A

Create more erthyroblasts

130
Q

What is the haematopoitic stem cell niche?

A

Stromal cell signals regulate stem cell regulate stem cell differentiation. Progenitor cells are surrounded by protective tissue cells called stromal cells- niche

131
Q

What is stemness?

A

Stemness refers to the molecular processes underlying the fundamental stem cell (SC) properties of self-renewal and generation of differentiated daughter cells

132
Q

How are stem cells able to differentiate?

A

They maintain their stemness by contact between receptor on stem cell and ligand in stromal cell

When a stem cell divides one daughter will lose contact with the receptor and will differentiate

133
Q

When is erythrocyte production selectively increased?

A

Anaemia (lack of Hb)

Blood loss

Accclimatization at high altiude

134
Q

What is the hormone produced in response to lack of O2/ shortage of erthrocytes?

A

Erythropoiten- produced by kidney

Acts on erythrocyte precursor cells to increase their proliferation/survival

135
Q

A GATA1 knock out mouse would have a deficit from which step?

A
136
Q

What is GATA1?

A

The GATA1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and helps control the activity of many other genes. On the basis of this action, the GATA1 protein is known as a transcription factor.

137
Q

What stimulates neutrophil and macrophage differentiation from precursor cells?

A

Infection

Colony stimulating factors are released by fibroblasts, endothelial cells, fibroblasts and lymphocytes in response to tissue factor

CSFs act on precursor cells

138
Q

What are kinases and what do they do?

A

Kinases are enzymes that control whether or not a cell divides. They need to be activated in a specific order to allow to replicate

These kinases are activated by external signals known as mitogens

139
Q

What are mitogens?

A

Extracellular signals that stimulate cell division by triggering a wave of G1/S-Cdk activity tht relieves intracellular negative controls blocking the cell cycle.

140
Q

What is a signal that specifically inhibits the growth and proliferation of fibroblasts?

A

Myostatin

141
Q

What is the experiment with mice being implanted with 5 foetal spleens and 5 foetal thymus glands?

A

What this suggests is that thymus gland is regulated by local mechanisms, whereas the spleen controlled by feedback mechanisms which senses the size of the spleen in comparison to the body as a whole.

142
Q

What are the defining characteristics of a stem cell?

A
  1. Is not itself terminally differentiated
  2. It can divide without limit
  3. Upon division each daughter has a choice: stem cell or terminal differentiation.
143
Q

Where do cells from the small intestine come from?

A

Cells lining the villi live for an approximate 5 days. They are replaced by cells found in the crypts.

The daughters of some cells will remain stem, but some will differentiate and move up the villi in a conveyer belt fashion.

144
Q

What is the intestinal stem cell niche?

A

Stem cells fate is induced by signals from Paneth cells and connective tissue surrounding the crypt

145
Q

What is produced by Paneth cells?

A

WNT

146
Q

How does WNT influence intestinal cells?

A
147
Q

Why is mitochondrial DNA more sussceptible to damage?

A

Not protected by histone proteins

148
Q

What contributes to loss of cell function and death?

A

Sem 2 Year 1 (12 decks)

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