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Infections and Defence > Corina Cotoi > Flashcards

Corina Cotoi Flashcards

1
Q

What are telomeres?

A

Protective caps at the end of eukaryotic chromosomes that safeguard chromosome degradation.
These become shorter after each division.
Means that cells cannot divide forever.

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2
Q

What is the function of telomerase?

A

This enzyme keeps the telomeres long in cells that need to keep dividing.
eg. stem cells, skin cells, leukocytes, intestinal epithelial cells, reproductive tissues.

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3
Q

Outline the 5 stages of the cell cycle

A

1) G1 PHASE
2) S PHASE
3) G2 PHASE
4) MITOSIS
5) CYTOKINESIS

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4
Q

What occurs during the G1 phase?

A

The new cells grows, duplicates its organelles, and produces proteins that are needed for DNA replication.

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5
Q

What happened between the G1 phase and the first checkpoint?

A

The G0 phase

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6
Q

What occurs in the G0 phase?

A

Cells arrest temporarily (quiescence) or permanently (senescence).
The cells do not divide but they differentiate and fulfil their purpose.
They may re enter cell cycle if triggered by a stimulus.

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7
Q

When does the first checkpoint occur?

A

After G1 phase

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8
Q

What is the purpose of the first checkpoint?

A

Internal mechanisms check the DNA before S phase.

Cell cannot proceed unless the DNA quality checks are passed and cell is ready for replication.

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9
Q

What occurs during S phase?

A

The cell replicates its genome. DNA polymerase and other replication complexes synthesis a double strand of DNA. It is assembled into a pair of sister chromatids that are joined at a centromere.

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10
Q

What occurs after S phase?

A

Cell goes straight into G2 phase.

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11
Q

When is the second checkpoint?

A

After G2 phase, before mitosis.

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12
Q

What is the purpose of the second checkpoint?

A

DNA is checked before mitosis begins, make sure all DNA has been replicated and is intact.

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13
Q

What occurs after the second checkpoint?

A

Mitosis begins.

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14
Q

Outline the process of mitosis

A

1) Prometaphase
2) Metaphase
3) Anaphase
4) Telophase

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15
Q

What happens in prometaphase?

A

The nuclear envelope breaks down, so the microtubules from the spindle can attach to the chromosomes.

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16
Q

What occurs during G2 phase?

A

Cell further grows and produces proteins needed for mitosis.

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17
Q

What happens in metaphase?

A

Mitotic spindle makes the chromosomes line up at the equator of the cell.

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18
Q

What happens in anaphase?

A

The centrioles on opposite poles of the cells pull each sister chromatid to each pole of the cell using the mitotic spindle.

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19
Q

What happens in telophase?

A

The mitotic spindle is disassembled and a nuclear membrane reforms around each set of chromosomes.

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20
Q

When does the third checkpoint occur?

A

It occurs before the cell enters anaphase.

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21
Q

What is the purpose of the third checkpoint?

A

To make sure the mitotic spindle has properly formed. Mitosis will not continue if this is not properly configured.

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22
Q

What stages does interphase consist of?

A

G1, S phase and G2

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23
Q

What 4 genes are required for regulation of DNA replication?

A

1) Proto oncogenes
2) Tumour supressor genes
3) Genes that regulate apoptosis
4) Gene involved in DNA repair

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24
Q

What is the function of proto oncogenes?

A

Promotes growth. Codes for transcription factors, signal transducers.
Allows cells to progress from one stage of the cell cycle to the next.
Positive cell growth regulation.

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25
Q

What happens to proto oncogenes when they are mutated?

A

They promoted uncontrolled cell growth.
These are called oncogenes.
They code for oncoproteins that are involved in independent tumour cell growth.

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26
Q

What is the function of tumour suppressor genes?

A

Inhibits growth.

eg. RB1, P53

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27
Q

What are the roles of the 2 types of genes that safeguard the cell cycle?

A

1) Gatekeepers

2) Caretakers

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28
Q

What is the function of gatekeepers?

A

They regulate cell proliferation and prevent cell from passing thought her cell cycle checkpoints.
They trigger apoptosis.

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29
Q

What is the function of caretakers?

A

They maintain the genome.
Are involved in DNA repair and prevent mutations accumulating.
This occurs through DNA base excision repair, prevention of pathologic chromosomal rearrangement, mismatch repair, or telomere maintenance.
(tumour suppressor genes)

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30
Q

What other mechanisms are in place to limit cell division?

A

1) Cells are sensitive to signals from neighbouring cells, causes contact inhibition
2) Some cells are anchored to the basal membrane and the surrounding cells. Means can only divide when space permits.
3) Cells cannot grow indefinitely on top of each other. This preserves the tissue architecture.

31
Q

What are physical agents that can cause cell damage?

A

Low and high temperatures, electromagnetic radiation, charged radiation (alpha and beta), UV

32
Q

What are chemical agents that can cause cell damage?

A

Alkylating agents, aromatic amines, amides, polycyclic hydrocarbons.

33
Q

What are microbial agents that can cause cell damage?

A

Helicobacter pylori (bacteria), HPV (virus), Human T cell Leukemia Virus, Hep B, EBV.

34
Q

What is dangerous about injurious agents that affects the checkpoint protection mechanisms in the cell cycle?

A

They can interfere with the protective mechanisms, so apoptosis isn’t triggered.
These cells may go on to divide when they are not supposed to.

35
Q

What is the name given to cells that bypass the protective mechanisms of the cell cycle?

A

Neoplastic cells

36
Q

What are the characteristics of neoplastic cells?

A

1) Independent of anchorage
2) Lacks contact inhibition so will grow in a chaotic fashion on top of each other.
3) They have the capacity to grow and divide in the absence of external growth and survival factors.

37
Q

What is a neoplasm?

A

Synonym for tumour.

Swelling/mass of abnormal growth made from neoplastic cells.

38
Q

Define the word benign

A

Mass that grows at a slower rate, doesn’t invade neighbouring tissues.
Can cause clinical symptoms.

39
Q

Define the word malignant

A

Able to invade and destroy adjacent structures and spread to other sites.
Fast growth rate.
Cancer is also used to describe this.

40
Q

What 2 things have to be present for neoplasia to occur?

A

1) Initiators - substances that causes a heritable change in DNA eg. carcinogens
2) Promoters - substance that induces cellular division, such as a growth factor.

41
Q

What are the 2 main components of a neoplasm?

A

1) Parenchyma - neoplastic cells

2) Stroma - connective tissue with blood vessels and inflammatory cells, mostly macrophages and lymphocytes

42
Q

Define carcinogenesis

A

Also oncogenesis.

Transformation of normal cells into cancer cells. Can be caused by internal or external factors.

43
Q

List some risk factors of cancer

A

1) Tobacco
2) Obesity
3) Alcohol
4) Radiation
5) Age
6) Chronic inflammation
7) Immunodeficiency
8) Genetics
9) Precursor lesions

44
Q

Outline the 3 stages of carcinogenesis

A

1) Initiation - exposure to the carcinogenic agent that targets DNA, RNA or proteins

2) Promotion - when promoting agents can cause cell proliferation and accumulation of pre neoplastic cells.
Doesn’t target DNA directly.

3) Progression - Further genetic and phenotypic changes with tumour growth and spread.

45
Q

What tumour is formed when the proto oncogene KRAS becomes an oncogene?

A

Tumours of the lung, colon and pancreas

46
Q

What tumour is formed when proto oncogene BRAF becomes an oncogene?

A

Melanoma

47
Q

What tumour is formed when proto oncogene RET becomes an oncogene?

A

Leukemia

48
Q

What tumour is formed when proto oncogene KIT becomes an oncogene?

A

GI stromal tumours, leukemias

49
Q

What tumour is formed when proto oncogene C-MYC becomes an oncogene?

A

Burkitt lymphoma

50
Q

What tumour is formed when proto oncogene Cyclin D becomes an oncogene?

A

Mantle cell lymphoma

51
Q

What tumour is formed when the p53 tumour supressor gene is mutated?

A

Most - has a function of DNA repair, cell cycle.

52
Q

What tumour is formed when the RB1 tumour suppressor gene is mutated?

A

Retinoblastoma, tumours of the lung, colon and breast

53
Q

What tumour is formed when the BRCA1 and BRCA2 tumour suppressor gene is mutated?

A

Tumours of the breast and ovary

54
Q

What tumour is formed when the MLH1 and MLH2 tumour suppressor gene?

A

Many tumours and hereditary cancers

55
Q

Describe the process of the formation of a benign tumour

A

1) There is a mutation in a tumour suppressor gene, this could be acquired or inherited.

2) If both copies of the tumour suppressor gene are damaged then the phenotype of no suppression is expressed.
Indirectly this gives a survival advantage to cells.

This results in a benign tumour.

56
Q

What are the characteristics of a benign tumour?

A

1) Dysplasia
2) Loss of cell uniformity
3) Disorganised architecture
4) Always above the basement membrane
5) Where cells have already differentiated.

57
Q

How does a benign tumour become a malignant tumour?

A

1) If the mutation in the tumour suppressor gene occurs in the cells the divide to replace other cells (those with active telomerase), it forms an adenocarcinoma.
2) Further mutations of proto oncogenes becoming oncogenes result in inhibited growth. This allows the cells to cross the basal membrane and invade tissues.

58
Q

Will an adenocarcinoma be formed if the mutation of tumour suppressor genes occurs at the top of the CSM?

A

Cells have already differentiated and began the cell cycle. This means that it will remain as an adenoma and will make no difference.

59
Q

What is dysplasia?

A

It is the presence of atypical cells in a tissue. There is a loss of cell uniformity and a disorganised structure = pre cancerous condition.
It is above the basement membrane, so is not invasive.

60
Q

What are the characteristics of malignant tumours?

A

1) Atypical cells
2) Loss of nuclear polarity - the position of the nucleus in the cell, it is usually in the bottom area of the cell.
3) Back to back glands.
4) Desmoplastic (dense connective tissue) stroma.
5) Necrosis (death of cells).
6) Variation in size and shape of cells and nuclei.
7) Dark nuclei, hyperchromasia.

61
Q

What alteration to genes is an indication of cancer?

A

1) Proto oncogenes become oncogenes, results in promotion of growth.
2) Mutations of tumour suppressor genes mean the cell becomes insensitive to growth inhibition.
3) The cell becomes insensitive to growth inhibition signals.

62
Q

What alteration to metabolism is an indication of cancer?

A

1) Increased level of glucose uptake.
2) Cell can evade apoptosis through pro and anti apoptotic proteins.
3) Potential for continuous replication due to telomerase.
4) Ability to invade and metastasise.
5) Ability to evade host immune responses.

63
Q

What enables the continuous delivery of blood to the cancer cells?

A

Sustained angiogenesis - migration, growth and differentiation of endothelial cells that line the inside wall of blood vessels.

64
Q

What are the 3 major ways that metastases can develop?

A

1) Direct spread through the lining of the body cavities.
2) Lymphatic spread through the lymphatic vessels and lymph nodes/
3) Haematogenous spread through blood vessels, typical of soft tissue neoplasms.

65
Q

What type of tumour is a small mass of fibrovascular cores lined by squamous epithelium with focal acute inflammation, with no epithelial atypia?

A

A benign squamous cell papilloma

66
Q

What is the suffix of epithelial and mesenchymal benign tumours?

A

“oma”

67
Q

What is the suffix of epithelial malignant tumours?

A

“carcinoma”

68
Q

What is the suffix of mesenchymal malignant tumours?

A

“sarcoma”

69
Q

What type of tumour has irregular glandular structures with nuclear atypia, desmoplastic stroma and necrosis. There is invasion of lymphatic vessels, and there is lack of the MLH1 promoter methylation?

A

Epithelial carcinoma

70
Q

What is the function of the MLH1 promoter tumour suppressor gene?

A

Caretaker involved in DNA mismatch repair.
Can be due to somatic inactivation of the gene, germline mutation (Lynch syndrome), autosomal dominant inheritance, genetic predisposition.

71
Q

Why is regular cancer testing important?

A

Abnormalities can be picked up quickly, from hereditary cancer syndrome.

72
Q

What is the difference between sporadic and hereditary cancers?

A

Sporadic cancers can affect anyone and depends on the genetic changes that occur during the lifetime of that individual.
Hereditary cancers only occur in individuals that have inherited mutations.

73
Q

What is an example of a hereditary cancer syndrome from a mutated allele of MLH1 tumour suppressor gene?

A

Lynch syndrome.
It is an autosomal dominant disease.
People with a defective copy of the gene have a higher risk of developing cancers, BUT only if there is inactivation of the second copy of the gene will lead to cancer formation.
This “second hit” is dependent on the environment.

Infections and Defence (8 decks)

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