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Block 1 Partial Exam 4 > Block 1 Exam 4 Part 3 > Flashcards

Block 1 Exam 4 Part 3 Flashcards

1
Q

What does TGF-β regulate?

A

Inhibits proliferation by turning off pro-growth genes and promoting cell cycle arrest

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2
Q

Which cancers frequently have mutations in TGF-_ receptors or SMAD4?

A

Colon, stomach, endometrium, and pancreatic cancers

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3
Q

What is the role of PTEN?

A

A tumor suppressor that brakes the PI3K/AKT signaling pathway

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4
Q

What syndrome is associated with germline PTEN mutations?

A

Cowden syndrome

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5
Q

What is the function of the VHL gene?

A

Regulates cellular responses to oxygen levels by degrading HIF1_

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6
Q

Which syndrome is associated with VHL mutations?

A

Hereditary renal cell carcinoma

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7
Q

What is the role of the STK11 gene?

A

Regulates cellular metabolism

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8
Q

What syndrome is associated with STK11 mutations?

A

Peutz-Jeghers syndrome

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9
Q

What does APC regulate in colonic epithelium?

A

Negatively regulates the WNT pathway by promoting _-catenin degradation

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10
Q

What disorder is caused by germline APC mutations?

A

Familial adenomatous polyposis

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11
Q

What percentage of sporadic colon carcinomas have APC mutations?

A

About 70%

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12
Q

What role does E-cadherin play in epithelial cells?

A

Maintains cell adhesion and regulates contact-mediated growth inhibition

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13
Q

What cancer is associated with germline E-cadherin (CDH1) mutations?

A

Familial gastric carcinoma

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14
Q

What effect does loss of CDH1 expression have?

A

Increased invasiveness and WNT signaling

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15
Q

What proteins are encoded by CDKN2A?

A

p16/INK4a and ARF

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16
Q

What cancer is caused by germline CDKN2A mutations?

A

Familial melanoma

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17
Q

Which pathway does TGF-_ inhibit in normal tissues?

A

Cellular proliferation

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18
Q

What role can TGF-_ play in cancer?

A

Enhances immune evasiveness of tumors

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19
Q

What does PTEN regulate?

A

PI3K/AKT signaling

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20
Q

What disorder is associated with germline PTEN mutations?

A

Cowden syndrome

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21
Q

What does VHL encode?

A

A component of a ubiquitin ligase complex that degrades hypoxia-induced factors (HIFs)

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22
Q

What syndrome is caused by germline VHL mutations?

A

Von Hippel-Lindau syndrome

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23
Q

What is the Warburg effect?

A

Cancer cells prefer aerobic glycolysis over oxidative phosphorylation even with ample oxygen

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24
Q

How is the Warburg effect used clinically?

A

PET scans detect tumors by their high glucose uptake

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25
Q

Why do cancer cells rely on aerobic glycolysis despite it being less efficient for ATP production?

A

It provides intermediates for biosynthesis needed for cell growth

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26
Q

What is the main metabolic function of mitochondria in growing cells?

A

To generate intermediates for biosynthesis, not primarily ATP

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27
Q

What signaling pathway promotes glucose uptake and glycolysis in cancer cells?

A

Receptor tyrosine kinase/PI3K/AKT signaling

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28
Q

How does MYC support cell growth?

A

It upregulates glycolytic enzymes and glutaminase for biosynthesis

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29
Q

What is autophagy?

A

A state where cells cannibalize their own components for energy under nutrient deficiency

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30
Q

Why is autophagy often disabled in tumors?

A

It allows tumor cells to grow under poor conditions without triggering autophagy

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31
Q

How can autophagy benefit tumor cells?

A

It may allow tumor cells to become dormant and survive for long periods

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32
Q

What is oncometabolism?

A

A process where mutations in metabolic enzymes like IDH promote cancer

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33
Q

What happens when IDH is mutated?

A

It produces 2-HG, which inhibits enzymes that use _-ketoglutarate

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34
Q

What effect does 2-HG have on TET2?

A

It inhibits TET2, leading to abnormal DNA methylation

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35
Q

How does abnormal DNA methylation contribute to cancer?

A

It misregulates cancer genes, driving oncogenesis

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36
Q

What cancers are associated with mutated IDH?

A

Cholangiocarcinomas, gliomas, acute myeloid leukemias, and sarcomas

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37
Q

What is Warburg metabolism?

A

A pro-growth metabolism favoring glycolysis over oxidative phosphorylation

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38
Q

How is Warburg metabolism induced in normal cells?

A

By exposure to growth factors

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39
Q

Which proteins induce Warburg metabolism in cancer cells?

A

Oncoproteins like RAS, MYC, and mutated growth factor receptors

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40
Q

Which tumor suppressors oppose Warburg metabolism?

A

PTEN, NF1, and p53

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41
Q

What happens during autophagy?

A

Cells consume their components for energy under stress

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42
Q

How do cancer cells handle autophagy?

A

They may mutate to avoid it or corrupt it for nutrient supply

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43
Q

What is an oncometabolite?

A

A metabolite that alters the epigenome, leading to oncogenic gene expression

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44
Q

Which mutation leads to the formation of oncometabolites?

A

Mutated IDH

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45
Q

What are the two pathways leading to apoptosis?

A

Extrinsic (death receptor) and intrinsic (mitochondrial) pathways

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46
Q

What does the intrinsic pathway respond to in cancer cells?

A

Stresses like DNA damage, hypoxia, and metabolic disturbances

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47
Q

How do cancer cells evade apoptosis?

A

By mutations that disable key components of the intrinsic pathway

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48
Q

Which proteins promote apoptosis by permeabilizing the mitochondrial membrane?

A

Pro-apoptotic proteins BAX and BAK

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49
Q

What proteins inhibit apoptosis by preventing mitochondrial permeabilization?

A

Anti-apoptotic proteins like BCL2 and BCL-XL

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50
Q

What is the role of BH3-only proteins?

A

They neutralize anti-apoptotic proteins, promoting apoptosis

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51
Q

How does loss of TP53 function affect apoptosis?

A

It prevents upregulation of pro-apoptotic proteins like PUMA, allowing cells to survive

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52
Q

What is an example of cancer overexpressing BCL2 to evade apoptosis?

A

Follicular lymphoma with BCL2 translocation

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53
Q

What is the therapeutic approach for cancers with overexpressed BCL2?

A

Drugs targeting anti-apoptotic BCL2 family proteins

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54
Q

How is apoptosis initiated?

A

Through intrinsic or extrinsic pathways

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55
Q

What happens after the activation of apoptosis pathways?

A

Activation of caspases that destroy the cell

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56
Q

Which pathway is most commonly incapacitated in cancers?

A

The intrinsic (mitochondrial) pathway

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57
Q

What translocation causes BCL2 overexpression in follicular B-cell lymphomas?

A

(14;18) translocation

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58
Q

What effect does overexpression of BCL2 family members have in cancer?

A

Linked to cancer cell survival and drug resistance

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59
Q

What are the three critical factors contributing to the immortality of cancer cells?

A

Evasion of senescence,evasion of mitotic crisis,capacity for self-renewal

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60
Q

How many times can most normal human cells divide before entering senescence?

A

60 to 70 times

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61
Q

What happens to cells that bypass senescence but are not immortal?

A

They enter mitotic crisis and die

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62
Q

What is the role of telomeres in mitotic crisis?

A

Progressive shortening of telomeres leads to chromosome instability and cell death

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63
Q

What enzyme is responsible for maintaining telomeres?

A

Telomerase

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64
Q

How do cancer cells maintain telomere length?

A

By expressing telomerase or using alternative lengthening of telomeres (ALT)

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65
Q

What is self-renewal in the context of stem cells?

A

The ability of a stem cell to divide and produce at least one daughter cell that remains a stem cell

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66
Q

What are cancer stem cells?

A

Cells in a tumor that have the capacity for self-renewal and are responsible for tumor persistence

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67
Q

Why are cancer stem cells thought to be resistant to conventional therapies?

A

Because of their low rate of cell division and expression of drug resistance factors like MDR1

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68
Q

What are cancer stem cells?

A

Stem cell-like cells in cancers responsible for tumor persistence

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69
Q

How do cancer stem cells arise?

A

Through transformation of normal stem cells or genetic changes in mature cells

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70
Q

What two mechanisms allow cancer cells to have limitless replicative potential?

A

Inactivation of senescence signals and reactivation of telomerase

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71
Q

What is required for tumors to grow larger than 1-2 mm in diameter?

A

The capacity to induce angiogenesis

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72
Q

What is the function of angiogenesis in tumors?

A

It provides nutrients and oxygen and removes waste products

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73
Q

What molecular event activates the angiogenic switch in tumors?

A

Increased production of angiogenic factors or loss of angiogenic inhibitors

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74
Q

What transcription factor is stabilized by hypoxia to stimulate angiogenesis?

A

HIF1_

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75
Q

Which protein upregulates the production of VEGF in tumors?

A

Mutated RAS or MYC

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76
Q

What role does p53 play in angiogenesis?

A

It stimulates anti-angiogenic molecules and represses pro-angiogenic molecules

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77
Q

What is bevacizumab used for?

A

It neutralizes VEGF to block angiogenesis in cancer

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78
Q

What has been the limitation of angiogenesis inhibitors in cancer treatment?

A

They prolong life but usually only for a few months

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79
Q

What triggers angiogenesis in tumors?

A

Hypoxia through HIF1_ activation

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80
Q

Which factor does p53 stimulate to inhibit angiogenesis?

A

Thrombospondin-1

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81
Q

Which oncogenes upregulate VEGF expression to promote angiogenesis?

A

RAS, MYC, and MAPK

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82
Q

What is the role of VEGF inhibitors in cancer treatment?

A

They prolong the clinical course but are not curative

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83
Q

What is the major cause of cancer-related morbidity and mortality?

A

Invasion and metastasis

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84
Q

What must tumor cells overcome during the metastatic process?

A

Immune defenses and adaptation to a new microenvironment

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85
Q

What are the two phases of the metastatic cascade?

A

Invasion of ECM and vascular dissemination

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86
Q

What are the four steps of ECM invasion by tumor cells?

A

Loosening of cell-cell interactions, ECM degradation, attachment to remodeled ECM, and tumor cell migration

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87
Q

What is the first step in the invasion process?

A

Dissociation of cancer cells from one another due to alterations in intercellular adhesion molecules

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88
Q

Which adhesion molecule is often altered in epithelial tumors?

A

E-cadherin

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89
Q

What is EMT (epithelial-mesenchymal transition) and which transcription factors control it?

A

A process integral to metastasis controlled by SNAIL and TWIST

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90
Q

What is the role of matrix metalloproteinases (MMPs) in invasion?

A

MMPs degrade ECM, promote tumor invasion, and release factors like VEGF

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91
Q

What happens when tumor cells change how they attach to ECM proteins?

A

They demonstrate complex changes in integrins, promoting survival and migration

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92
Q

What is anoikis?

A

A form of apoptosis triggered by loss of adhesion to ECM

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93
Q

How do tumor cells propel themselves through degraded basement membranes?

A

Via locomotion stimulated by autocrine motility factors, ECM cleavage products, and paracrine factors

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94
Q

What protects circulating tumor cells from destruction?

A

Clumping with other tumor cells or blood elements like platelets

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95
Q

What are the three factors influencing where metastases appear?

A

Location and vascular drainage, tumor cell tropism, and escape from dormancy

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96
Q

What is the “seed-soil” hypothesis in metastasis?

A

Tumor cells adapt to favorable environments in certain tissues that promote growth

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97
Q

What are the four steps involved in tissue invasion by malignant cells?

A

Loosening of cell-cell contacts,degradation of ECM,attachment to novel ECM components,and migration of tumor cells

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98
Q

How are cell-cell contacts lost during tumor invasion?

A

By the inactivation of E-cadherin through various pathways

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99
Q

What enzymes mediate basement membrane and matrix degradation?

A

Proteolytic enzymes such as MMPs and cathepsins

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100
Q

What additional effect do proteolytic enzymes have on the ECM?

A

They release growth factors and generate chemotactic and angiogenic fragments from ECM glycoproteins

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101
Q

How can the metastatic site of a tumor often be predicted?

A

By the location of the primary tumor; tumors usually arrest in the first capillary bed they encounter

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102
Q

What is organ tropism in metastasis?

A

A tumor’s preference for specific organs due to expression of adhesion or chemokine receptors whose ligands are found at the metastatic site

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103
Q

Which genes are associated with epithelial-mesenchymal transition (EMT) in metastasis?

A

TWIST and SNAIL

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104
Q

What is immune surveillance?

A

It is the process by which the immune system scans the body for emerging malignant cells and destroys them

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105
Q

What role do CD8+ cytotoxic T cells play in tumor immunity?

A

They recognize tumor antigens and kill tumor cells

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106
Q

How do tumors evade immune detection by antigen-negative variants?

A

By selecting for subclones that lose expression of immunogenic antigens

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107
Q

What happens when tumor cells lose or reduce MHC expression?

A

They avoid detection by cytotoxic T cells but may still trigger NK cells

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108
Q

What are PD-L1 and PD-L2

A

and how do they help tumors evade the immune system?,They activate PD-1 on T cells, inhibiting T-cell activation and helping tumors evade the immune system

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109
Q

What role does TGF-_ play in tumor immune evasion?

A

It is an immunosuppressive factor secreted by tumors to inhibit the immune response

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110
Q

What is checkpoint blockade therapy?

A

A treatment that removes inhibitory signals (such as CTLA-4 or PD-1) on T cells, enhancing the immune response against tumors

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111
Q

What is the role of CD8+ CTLs in tumor immunity?

A

They recognize tumor antigens on MHC class I molecules and kill tumor cells

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112
Q

What types of tumor antigens exist?

A

They include mutated proto-oncogenes, tumor suppressor genes, overexpressed proteins, and viral antigens

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113
Q

How do tumors avoid immune detection?

A

They can lose antigen expression, reduce MHC molecules, or secrete immunosuppressive factors like TGF-_ and PD-L1

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114
Q

What is the link between immunosuppression and cancer risk?

A

Immunosuppressed patients have a higher risk of cancers caused by oncogenic DNA viruses

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115
Q

How do immune checkpoint inhibitors work?

A

They block tumor immune evasion mechanisms, making the immune system more effective against cancer

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116
Q

What are the main contributors to genomic instability in cancer cells?

A

Loss of p53 function, DNA repair factor mutations, and DNA polymerase mutations

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117
Q

What is the role of DNA mismatch repair proteins?

A

They correct replication errors, and defects in these proteins can lead to microsatellite instability

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118
Q

What syndrome is associated with defective mismatch repair genes?

A

Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome

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119
Q

How does UV radiation affect DNA

A

and how is it repaired?,It causes pyrimidine cross-linking, which is repaired by the nucleotide excision repair system

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120
Q

What is the significance of homologous recombination repair?

A

It fixes double-stranded DNA breaks and cross-links; defects increase cancer risk

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121
Q

What is the function of the BRCA genes?

A

They are involved in homologous recombination repair, and mutations lead to increased risk of breast, ovarian, and other cancers

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122
Q

How do DNA polymerase mutations contribute to cancer?

A

They cause loss of proofreading function, leading to an accumulation of mutations

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123
Q

What role does regulated genomic instability play in lymphoid cells?

A

It allows antigen receptor diversification but can cause lymphoid neoplasms through errors in recombination

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124
Q

What increases the risk of cancer development in persons with inherited mutations in DNA repair systems?

A

Increased genomic instability

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125
Q

What syndrome is caused by defects in mismatch repair

A

leading to colon carcinomas?,Hereditary nonpolyposis colon cancer (HNPCC)

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126
Q

What condition is associated with defective nucleotide excision repair and high skin cancer risk?

A

Xeroderma pigmentosum

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127
Q

What disorders are characterized by defects in homologous recombination DNA repair?

A

Bloom syndrome, ataxia-telangiectasia, and Fanconi anemia

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128
Q

Which genes are involved in familial breast cancer due to DNA repair defects?

A

BRCA1 and BRCA2

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129
Q

What happens in cancers with defective DNA polymerase proofreading?

A

Genomic instability leads to increased mutation rates

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130
Q

How do T and B cells undergo regulated genomic instability?

A

Through somatic gene rearrangements, which can cause lymphoid neoplasms

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131
Q

What type of reaction do cancers provoke?

A

Chronic inflammatory reaction

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132
Q

How can inflammatory cells promote tumor proliferation?

A

By secreting growth factors like EGF and releasing proteases that liberate growth factors from the ECM

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133
Q

How do inflammatory cells contribute to removing growth suppressors?

A

Proteases degrade adhesion molecules, removing barriers to growth

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134
Q

What protects tumor cells from anoikis?

A

Tumor-associated macrophages express adhesion molecules like integrins

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135
Q

How do inflammatory cells induce angiogenesis?

A

By releasing factors such as VEGF

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136
Q

How do inflammatory cells activate invasion and metastasis?

A

By releasing proteases that remodel the ECM and stimulating tumor cell motility

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137
Q

What factors help tumor cells evade immune destruction?

A

Soluble factors like TGF-_ and PD-L1 produced by macrophages

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138
Q

What are the most common chromosomal abnormalities in cancer?

A

Chromosomal translocations

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139
Q

How can translocations activate proto-oncogenes?

A

By promoter/enhancer substitution or by forming fusion genes

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140
Q

What is an example of a fusion gene in cancer?

A

BCR-ABL in CML

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141
Q

How can chromosomal deletions contribute to cancer?

A

By leading to the loss of tumor suppressor genes

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142
Q

What are two patterns of gene amplification seen in cancer?

A

Double minutes and homogeneous staining regions

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143
Q

What is chromothrypsis?

A

A chromosomal shattering event that creates multiple rearrangements

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144
Q

What are the types of oncogenic mutations found in cancer?

A

Point mutations, translocations, deletions, and gene amplifications

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145
Q

How do translocations contribute to cancer?

A

By overexpressing oncogenes or creating fusion proteins with altered signaling

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146
Q

What effect do deletions have in cancer?

A

They cause loss of tumor suppressor genes and can activate proto-oncogenes

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147
Q

How does gene amplification contribute to cancer?

A

It increases the expression and function of oncogenes

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148
Q

What is chromothrypsis?

A

A process where a chromosome is shattered and reassembled haphazardly

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149
Q

What is epigenetics?

A

Regulation of gene expression by mechanisms other than changes in DNA sequence

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150
Q

How can tumor suppressor genes be silenced in cancer?

A

By local hypermethylation of DNA

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151
Q

What effect do global changes in DNA methylation have in cancer?

A

They alter the expression of multiple genes

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152
Q

How do changes in histones affect cancer cells?

A

They modify gene expression that influences cellular behavior

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153
Q

What role does epigenetic therapy play in cancer treatment?

A

Drugs target enzymes responsible for reversible epigenetic modifications, like DNA methylation inhibitors and histone deacetylase inhibitors

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154
Q

What is initiation in chemical carcinogenesis?

A

It is the process by which exposure to a carcinogenic agent causes permanent DNA damage

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155
Q

What are promoters in chemical carcinogenesis?

A

They induce tumor formation in initiated cells but are not tumorigenic by themselves

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156
Q

How do promoters contribute to cancer?

A

They stimulate proliferation and clonal expansion of mutated cells

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157
Q

What is the role of unopposed estrogenic stimulation in cancer?

A

It acts as a promoter by stimulating proliferation of cells in the endometrium and breast

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158
Q

What is the nature of chemical carcinogens?

A

They are highly reactive electrophiles that react with DNA, RNA, or proteins

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159
Q

What is the difference between direct-acting and indirect-acting chemical carcinogens?

A

Direct-acting carcinogens cause cancer without metabolic conversion, while indirect-acting carcinogens require metabolic activation to become carcinogenic

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160
Q

What are direct-acting carcinogens?

A

They do not require metabolic conversion to become carcinogenic

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161
Q

What is a key example of a direct-acting carcinogen?

A

Alkylating agents used in cancer chemotherapy

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162
Q

What are indirect-acting carcinogens?

A

They require metabolic conversion to become active carcinogens

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163
Q

What are ultimate carcinogens?

A

They are the active carcinogenic products formed after metabolic conversion of indirect-acting carcinogens

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164
Q

What is an example of an indirect-acting carcinogen found in tobacco?

A

Benzo[a]pyrene

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165
Q

How are most indirect carcinogens metabolized?

A

By cytochrome P-450-dependent monooxygenases

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166
Q

What is a factor that influences susceptibility to carcinogenesis from indirect-acting carcinogens?

A

Polymorphic variants of P-450 genes that affect enzyme activity

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167
Q

What do most chemical carcinogens target?

A

DNA

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168
Q

What type of mutations do chemical carcinogens typically cause?

A

Mutations in oncogenes and tumor suppressor genes like RAS and TP53

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169
Q

What is a mutational hotspot associated with aflatoxin B1 exposure?

A

p53 gene at codon 249

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170
Q

Where is aflatoxin B1 commonly found?

A

Improperly stored grains and nuts

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171
Q

What type of cancer is associated with aflatoxin B1?

A

Hepatocellular carcinoma

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172
Q

What is a common mutation pattern in lung cancers caused by smoking?

A

Skewed base substitutions caused by carcinogens in cigarette smoke

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173
Q

What are some examples of other potential environmental carcinogens?

A

Vinyl chloride, arsenic, nickel, chromium, insecticides, fungicides, and polychlorinated biphenyls

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174
Q

What do chemical carcinogens typically damage?

A

DNA

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175
Q

What is the difference between direct-acting and indirect-acting carcinogens?

A

Direct-acting agents do not require metabolic conversion, while indirect-acting agents must be metabolized into an ultimate carcinogen

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176
Q

What influences the activity of indirect-acting carcinogens?

A

Polymorphisms of endogenous enzymes like cytochrome P-450

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177
Q

What role do promoters play in tumorigenesis?

A

They stimulate proliferation of mutated cells after exposure to a mutagen or initiator

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178
Q

What are some examples of direct-acting human carcinogens?

A

Alkylating agents used in chemotherapy

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179
Q

What are examples of indirect-acting human carcinogens?

A

Benzo[a]pyrene, azo dyes, and aflatoxin

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180
Q

What are examples of promoters that enhance tumorigenesis?

A

Agents causing hyperplasias of the endometrium or regenerative activity in the liver

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181
Q

What type of radiation causes skin cancer?

A

UV rays

182
Q

What is the primary wavelength range responsible for skin cancers?

A

UVB (280-320 nm)

183
Q

How do UVB rays cause DNA damage?

A

They cause pyrimidine dimers to form in DNA

184
Q

What happens if pyrimidine dimers are not repaired properly?

A

Error-prone repair mechanisms can lead to mutations and cancer

185
Q

What hereditary disorder is associated with defective nucleotide excision repair and increased cancer risk?

A

Xeroderma pigmentosum

186
Q

What types of radiation are carcinogenic aside from UV rays?

A

Electromagnetic (x-rays, _ rays) and particulate radiation (_ particles, _ particles, protons, neutrons)

187
Q

What type of cancer is most common after radiation exposure?

A

Myeloid leukemias

188
Q

What increases the risk of cancer from medical radiation exposure?

A

Frequent CT scans, especially in children

189
Q

What does ionizing radiation cause?

A

Chromosome breakage, translocations, and point mutations

190
Q

How do UV rays cause cancer?

A

By inducing the formation of pyrimidine dimers within DNA, leading to mutations

191
Q

What disorder increases the risk of skin cancer due to UV exposure?

A

Xeroderma pigmentosum

192
Q

What increases cancer risk in children exposed to imaging procedures?

A

Exposure to radiation during CT scans

193
Q

What does HTLV-1 cause?

A

Adult T-cell leukemia/lymphoma (ATLL)

194
Q

What cancers are associated with high-risk HPVs?

A

Squamous cell carcinomas of the cervix, anogenital region, and head and neck

195
Q

What is the role of EBV in Burkitt lymphoma?

A

EBV acts as a polyclonal B-cell mitogen and facilitates the acquisition of mutations like MYC translocations

196
Q

What role does chronic HBV or HCV infection play in hepatocellular carcinoma?

A

Chronic infection causes liver cell injury, compensatory proliferation, and genomic damage

197
Q

What bacterial infection is linked to gastric cancer?

A

Helicobacter pylori infection

198
Q

What causes adult T-cell leukemia/lymphoma?

A

HTLV-1

199
Q

What viral proteins are encoded by HTLV-1?

A

Tax and HBX

200
Q

Which viral oncoproteins are responsible for neutralizing p53 and Rb in HPV?

A

E6 and E7

201
Q

What is required for the development of HPV-related cancers?

A

Integration of HPV into the host genome and additional mutations

202
Q

Which virus is linked to Burkitt lymphoma and nasopharyngeal carcinoma?

A

EBV

203
Q

What effect does chronic HBV and HCV infection have on liver cells?

A

Chronic inflammation, hepatocellular injury, and reparative proliferation

204
Q

What bacterial infection is associated with gastric adenocarcinoma and MALToma?

A

H. pylori

205
Q

What are the critical determinants of clinical effects in tumors?

A

Location and hormonal effects

206
Q

What is cancer cachexia?

A

A hypercatabolic state with muscle loss that can’t be explained by reduced food intake

207
Q

What cytokines are implicated in cancer cachexia?

A

TNF, IL-1, and IL-6

208
Q

What are paraneoplastic syndromes?

A

Signs and symptoms in cancer patients that are not directly caused by the tumor’s location or normal hormone production

209
Q

What is the most common paraneoplastic endocrinopathy?

A

Cushing syndrome

210
Q

What protein is responsible for hypercalcemia in many cancers?

A

Parathyroid hormone-related protein (PTHRP)

211
Q

Which cancers are commonly associated with paraneoplastic hypercalcemia?

A

Breast, lung, kidney, and ovarian carcinomas

212
Q

What is Trousseau syndrome?

A

Migratory thrombophlebitis often seen in cancers like pancreatic or lung carcinoma

213
Q

What skin condition is associated with stomach cancer?

A

Acanthosis nigricans

214
Q

What is hypertrophic osteoarthropathy?

A

A disorder with periosteal new bone formation, arthritis, and clubbing of digits seen in lung cancer patients

215
Q

What is grading of a tumor based on?

A

The degree of differentiation and sometimes the number of mitoses or architectural features

216
Q

What does tumor grading assess?

A

How much tumor cells resemble normal cells

217
Q

What are the general categories in tumor grading?

A

Typically two to four categories (low grade to high grade)

218
Q

What is staging of a tumor based on?

A

The size of the primary lesion, regional lymph node involvement, and presence or absence of metastases

219
Q

What does T in the TNM staging system represent?

A

The size of the primary tumor

220
Q

What does N in the TNM staging system represent?

A

Regional lymph node involvement

221
Q

What does M in the TNM staging system represent?

A

Presence or absence of metastases

222
Q

What is T0 in the TNM system?

A

An in situ lesion

223
Q

What does M0 signify in the TNM system?

A

No distant metastases

224
Q

What additional prognostic information is becoming important in cancer staging?

A

Molecular features of tumors

225
Q

What is cachexia?

A

Progressive loss of body fat and lean body mass, accompanied by weakness, anorexia, and anemia caused by factors released by the tumor or immune cells

226
Q

What are paraneoplastic syndromes?

A

Symptom complexes in cancer patients not explained by tumor spread or release of hormones from the tumor’s origin

227
Q

What are examples of paraneoplastic syndromes?

A

Endocrinopathies, neuropathic syndromes, skin disorders, skeletal abnormalities, hypercoagulability

228
Q

What is grading based on?

A

Cytologic appearance and the idea that poorly differentiated tumors behave more aggressively

229
Q

What is staging based on?

A

Size, local and regional lymph node spread, and distant metastases

230
Q

What is the purpose of immunohistochemistry in cancer diagnosis?

A

Immunohistochemistry is used to identify specific proteins in tumor cells to determine the tumor’s origin, type, and potential treatment options.

231
Q

What is the role of flow cytometry in cancer diagnosis?

A

Flow cytometry is used to detect cell surface markers on blood-related cancers like leukemia and lymphoma to identify and classify cancer cells.

232
Q

How is molecular diagnostics useful in cancer diagnosis?

A

Molecular diagnostics helps identify specific mutations or genetic alterations in tumors, aiding in diagnosis, prognosis, and guiding targeted therapy.

233
Q

What is the TNM staging system used for?

A

The TNM system is used to stage cancers based on tumor size (T), lymph node involvement (N), and metastasis (M).

234
Q

What are the different sampling approaches used for tumor diagnosis?

A

Sampling approaches include excision, biopsy, fine-needle aspiration, and cytologic smears.

235
Q

How do immunohistochemistry and flow cytometry aid in cancer diagnosis?

A

They help classify tumors by identifying distinct protein expression patterns specific to different cancer types.

236
Q

What are molecular analyses used for in cancer diagnosis?

A

Molecular analyses are used to determine diagnosis, prognosis, detect minimal residual disease, and assess hereditary predisposition to cancer.

237
Q

How does molecular profiling help in cancer treatment?

A

Molecular profiling helps in stratifying tumors for targeted treatment and predicting outcomes based on specific genetic alterations or mutational signatures.

238
Q

What is the role of proteins like PSA in cancer diagnosis?

A

Proteins like PSA can be used to monitor cancer recurrence but are not ideal for screening due to low sensitivity and specificity.

239
Q

What are assays of circulating tumor cells and tumor DNA used for?

A

They are being developed for early detection, monitoring treatment response, and assessing minimal residual disease.

240
Q

What mediates humoral immunity?

A

Secreted antibodies

241
Q

What is the primary function of humoral immunity?

A

Defense against extracellular microbes and microbial toxins

242
Q

How can humoral immunity be transferred between individuals?

A

Through the serum containing antibodies from an immunized individual to a naive individual

243
Q

Where are antibodies produced?

A

In plasma cells in secondary lymphoid organs,inflamed tissues,and bone marrow

244
Q

What mediates the effector functions of antibodies?

A

The Fc regions of immunoglobulin (Ig) molecules

245
Q

What is the role of the Fab region of an antibody?

A

It confers specificity to its target (antigen binding)

246
Q

What is the role of the Fc region of an antibody?

A

It drives the biological function of the antibody

247
Q

What are the four major mechanisms of antibodies?

A

Neutralization,opsonization,complement activation,and antibody-dependent cellular cytotoxicity (ADCC)

248
Q

How do antibodies neutralize microbes and toxins?

A

By blocking their binding to cellular receptors and interfering with their ability to infect cells

249
Q

What does opsonization involve?

A

Coating microbes with antibodies to promote their phagocytosis

250
Q

Which immune cells express receptors for the Fc portions of IgG antibodies?

A

Mononuclear phagocytes and neutrophils

251
Q

How do antibodies promote phagocytosis through opsonization?

A

By binding to Fc receptors on phagocytes

252
Q

What role does IgG play in opsonization?

A

It coats microbes and promotes their phagocytosis by phagocytes

253
Q

What is Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)?

A

NK cells and macrophages bind to antibody-coated cells by Fc receptors and destroy these cells

254
Q

Which receptor on NK cells binds to IgG molecules during ADCC?

A

Fc_RIIIA

255
Q

What activates NK cells in ADCC?

A

Clustered IgG molecules displayed on target cells

256
Q

What do NK cells secrete during ADCC?

A

IFN-_ and the contents of their granules

257
Q

What cells cooperate in the antibody-mediated clearance of helminths?

A

Eosinophils and mast cells

258
Q

Why can’t helminths be engulfed by phagocytes?

A

They are too large

259
Q

What toxic protein do eosinophils use to kill helminths?

A

Major basic protein

260
Q

What immune response is involved in defense against helminths?

A

Th2 cell activation,IgE antibody production,and eosinophilia

261
Q

What pathway is involved in complement activation?

A

Classical pathway

262
Q

What is the primary protective mechanism of convalescent plasma?

A

Pathogen neutralization

263
Q

What additional roles might convalescent plasma play?

A

ADCC and opsonization

264
Q

What is molecular mimicry?

A

When a lymphocyte receptor recognizes both a foreign pathogen antigen and a self-protein due to structural similarity

265
Q

What is bystander activation?

A

When autoreactive immune cells become activated due to the liberation of self-antigens that are normally not exposed to the immune system

266
Q

What are monogenic traits?

A

Monogenic traits are determined by a single gene and are also known as Mendelian traits, named after Gregor Mendel.

267
Q

What is the principle of segregation?

A

It states that sexually reproducing organisms possess genes that occur in pairs, and only one member of this pair is transmitted to offspring.

268
Q

What does the principle of independent assortment state?

A

It states that genes at different loci are transmitted independently, meaning the transmission of one allele does not affect the transmission of another.

269
Q

How do Mendel’s principles relate to chromosomes and meiosis?

A

Mendel’s principles describe the behavior of chromosomes during meiosis, where genes segregate and are transmitted as distinct entities.

270
Q

What is the genotype?

A

An individual’s genetic constitution at a specific locus.

271
Q

What is the phenotype?

A

The observable physical or clinical traits of an individual.

272
Q

Can two individuals with different genotypes have the same phenotype?

A

Yes, for example, a dominant homozygote and a heterozygote can share the same phenotype.

273
Q

How can the same genotype result in different phenotypes?

A

The phenotype can change based on environmental factors, as seen in phenylketonuria (PKU), where a low-phenylalanine diet can prevent severe brain damage in affected individuals.

274
Q

What influences phenotype?

A

The interaction of genotype and environmental factors, including genetic environment.

275
Q

What is a pedigree?

A

A tool used in medical genetics to show family relationships and whether members are affected by a genetic disease.

276
Q

Who is the proband in a pedigree?

A

The first person in the family diagnosed with the genetic disease.

277
Q

What are first-degree relatives?

A

Parents, offspring, or siblings.

278
Q

What are second-degree relatives?

A

Grandparents, grandchildren, aunts, uncles, nieces, or nephews.

279
Q

What are third-degree relatives?

A

First cousins, great-grandchildren, or great-grandparents.

280
Q

What is the inheritance pattern of autosomal dominant diseases?

A

A disease caused by a dominant allele, typically seen in each generation, with males and females equally affected.

281
Q

What is the recurrence risk for a child of an affected heterozygote and an unaffected parent?

A

1/2 or 50%.

282
Q

What does father-to-son transmission in a pedigree indicate?

A

The trait is autosomal, not X-linked.

283
Q

What does it mean that each birth is an independent event?

A

The recurrence risk for each child remains the same regardless of the outcomes of previous births.

284
Q

What is the recurrence risk for an autosomal dominant disorder?

A

50%What is the inheritance pattern of autosomal recessive diseases?,Observed in one or more siblings but not usually in earlier generations

285
Q

What proportion of offspring of two heterozygous carriers will be affected?

A

One-fourth

286
Q

Why is consanguinity more common in autosomal recessive pedigrees?

A

Related persons are more likely to share the same disease-causing alleles

287
Q

What is a key characteristic of autosomal recessive inheritance?

A

Clustering of the disease among siblings but not in parents or ancestors

288
Q

What is the typical gender distribution in autosomal recessive inheritance?

A

Equal numbers of affected males and females

289
Q

Why might consanguinity be present in autosomal recessive inheritance?

A

Related individuals are more likely to share the same disease-causing alleles

290
Q

What is the recurrence risk for the offspring of two heterozygous carrier parents for an autosomal recessive disease?

A

25%

291
Q

What is the recurrence risk if a carrier of a recessive disease-causing allele mates with a person homozygous for the allele?

A

50%

292
Q

What happens when two individuals affected by a recessive disease mate?

A

All their children will be affected

293
Q

What is the typical recurrence risk for autosomal recessive diseases?

A

25%

294
Q

When does quasidominant inheritance occur?

A

When an affected homozygote mates with a heterozygote

295
Q

What is the recurrence risk in quasidominant inheritance?

A

50%

296
Q

What is a de novo mutation?

A

A new mutation that occurs in a gene transmitted by one parent without any prior family history of the disease

297
Q

How does a de novo mutation affect recurrence risk for the parents’ future children?

A

The recurrence risk is not elevated above the general population

298
Q

What is the recurrence risk for the offspring of a child with a de novo mutation in an autosomal dominant disease?

A

50%

299
Q

What is germline mosaicism?

A

It is when a mutation occurs during the development of the parent’s germline, affecting only the germline cells but not the somatic cells.

300
Q

How does germline mosaicism affect the recurrence risk for offspring?

A

The parent can transmit the mutation to multiple offspring even though they don’t express the disease themselves.

301
Q

What is an example of a disease where germline mosaicism has been observed?

A

Osteogenesis imperfecta type II

302
Q

Can germline mosaicism occur in diseases with no family history?

A

Yes, it can cause multiple offspring to have the disease even when there is no family history.

303
Q

What does reduced penetrance mean?

A

Reduced penetrance occurs when a person has a disease-causing genotype but does not show the disease phenotype

304
Q

What is an example of a disease with reduced penetrance?

A

Retinoblastoma is an example of a disease with reduced penetrance

305
Q

What percentage of obligate carriers of retinoblastoma do not show the disease?

A

10% of obligate carriers do not show the disease

306
Q

What is age-dependent penetrance?

A

A delay in the onset of a genetic disease until adulthood

307
Q

What effect does age-dependent penetrance have on natural selection?

A

It reduces natural selection against a disease-causing allele

308
Q

What does variable expression refer to?

A

The degree of severity of a disease phenotype

309
Q

What is a well-known example of an autosomal dominant disease with variable expression?

A

Neurofibromatosis type 1

310
Q

What factors can influence the expression of a genetic disease?

A

Environmental factors, modifier genes, and allelic heterogeneity

311
Q

What does allelic heterogeneity refer to?

A

Different mutations at the same disease locus causing variable expression

312
Q

What is a modifier gene?

A

A gene that influences the severity of a disease caused by another gene

313
Q

What is locus heterogeneity?

A

A condition where a single disease phenotype can be caused by mutations at different loci

314
Q

What is an example of locus heterogeneity in an autosomal dominant disorder?

A

Adult polycystic kidney disease (APKD)

315
Q

Which genes are involved in locus heterogeneity for APKD?

A

PKD1 on chromosome 16 and PKD2 on chromosome 4

316
Q

What is another example of locus heterogeneity?

A

Osteogenesis imperfecta

317
Q

What is pleiotropy?

A

A condition where a gene has more than one discernible effect on the body

318
Q

What is an example of pleiotropy in an autosomal dominant disorder?

A

Marfan syndrome

319
Q

What causes the pleiotropic effects in Marfan syndrome?

A

Mutations in the gene encoding fibrillin

320
Q

What is consanguinity?

A

The mating of individuals who are related by blood

321
Q

Where is consanguinity most common?

A

In many Middle Eastern countries and some parts of India

322
Q

Why does consanguinity increase the risk of recessive diseases?

A

Relatives are more likely to share the same disease-causing mutation

323
Q

What is the typical inheritance pattern for most metabolic disorders?

A

Autosomal recessive

324
Q

Does the carrier state of metabolic disorders usually cause health problems?

A

No

325
Q

What is the most common method for detecting metabolic disorders in newborns?

A

Screening blood for elevated metabolite levels

326
Q

What do enzymes act as in biochemical reactions?

A

Catalysts

327
Q

What are the four primary groups of biomolecules?

A

Nucleic acids, proteins, carbohydrates, and lipids

328
Q

Which pathways are included in major metabolic pathways?

A

Glycolysis, citric acid cycle, pentose phosphate shunt, gluconeogenesis, glycogen and fatty acid synthesis and storage

329
Q

What is the most abundant organic substance on Earth?

A

Carbohydrates

330
Q

Which three monosaccharides are carbohydrates metabolized into?

A

Glucose, galactose, and fructose

331
Q

What is the most common monogenic disorder of carbohydrate metabolism?

A

Galactosemia

332
Q

What enzyme is most commonly mutated in classic galactosemia?

A

GAL-1-P uridyl transferase

333
Q

What symptoms are typically seen in newborns with untreated galactosemia?

A

Poor sucking, failure to thrive, jaundice

334
Q

What is the primary treatment for classic galactosemia?

A

Elimination of dietary galactose

335
Q

What long-term disability is often seen in females with galactosemia?

A

Primary ovarian failure

336
Q

What enzyme deficiency causes hereditary fructose intolerance (HFI)?

A

Fructose 1,6-bisphosphate aldolase

337
Q

What dietary component triggers symptoms in hereditary fructose intolerance?

A

Fructose or sucrose

338
Q

What enzyme deficiency impairs gluconeogenesis and causes hypoglycemia in fructose metabolism disorders?

A

Fructose 1,6-bisphosphatase

339
Q

What are the most common errors of carbohydrate metabolism?

A

Glucose metabolism disorders

340
Q

What is type 1 diabetes mellitus (T1DM) characterized by?

A

Reduced or absent plasma insulin levels

341
Q

What is type 2 diabetes mellitus (T2DM) characterized by?

A

Insulin resistance

342
Q

What condition is associated with mutations in the insulin receptor gene?

A

Insulin resistance and acanthosis nigricans

343
Q

What is lactase-phlorizin hydrolase (LPH) responsible for metabolizing?

A

Lactose

344
Q

What geographic regions have high lactase persistence?

A

Northwestern Europe and certain parts of Africa

345
Q

What symptoms do individuals with lactase nonpersistence experience after ingesting lactose?

A

Nausea, bloating, and diarrhea

346
Q

What is the consequence of mutations that abolish lactase activity?

A

Congenital lactase deficiency with severe diarrhea and malnutrition

347
Q

How are glycogen storage disorders classified?

A

Numerically according to the chronological order of their enzymatic discovery

348
Q

What organs are most affected by glycogen storage disorders?

A

Liver and skeletal muscle

349
Q

What is the most common defect in amino acid metabolism?

A

Phenylalanine metabolism

350
Q

What is the most common inborn error of fatty acid metabolism?

A

MCAD deficiency

351
Q

What system is responsible for energy production from substrates like glucose and fatty acids?

A

OXPHOS system

352
Q

Where are the polypeptides of the OXPHOS system located?

A

Inner mitochondrial membrane

353
Q

How many OXPHOS polypeptides are encoded by the mitochondrial genome?

A

Thirteen

354
Q

What type of inheritance pattern do OXPHOS disorders caused by mitochondrial DNA mutations follow?

A

Maternal inheritance

355
Q

What disorder is caused by defects in electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO)?

A

Glutaric acidemia type II

356
Q

What are common symptoms of glutaric acidemia type II?

A

Hypotonia, hepatomegaly, hypoglycemia, and metabolic acidemia

357
Q

What is the main metabolic end product in tissues with high glycolytic activity and reduced OXPHOS capacity?

A

Lactic acid

358
Q

What is the most common disorder of pyruvate metabolism?

A

Pyruvate dehydrogenase (PDH) deficiency

359
Q

What is immunologic tolerance?

A

Unresponsiveness to an antigen induced by exposure to that antigen

360
Q

What are antigens that induce tolerance called?

A

Tolerogens

361
Q

What is self-tolerance?

A

Tolerance to self antigens, preventing immune reactions against one’s own tissues

362
Q

What is the result of the failure of self-tolerance?

A

Autoimmunity

363
Q

What term is used for diseases caused by immune reactions against self-antigens?

A

Autoimmune diseases

364
Q

What are the two main types of tolerance?

A

Central tolerance and peripheral tolerance

365
Q

Where does central tolerance occur?

A

In the generative lymphoid organs (thymus for T cells, bone marrow for B cells)

366
Q

Why is peripheral tolerance necessary?

A

To prevent activation of self-reactive lymphocytes that escape central tolerance

367
Q

What is central tolerance?

A

The process where immature lymphocytes in generative lymphoid organs are exposed to antigens, leading to cell death or receptor editing

368
Q

Where does central tolerance occur?

A

In the thymus and bone marrow

369
Q

What types of antigens are encountered in the generative lymphoid organs?

A

Mostly self antigens

370
Q

What is peripheral tolerance?

A

The process where mature lymphocytes become incapable of activation or die when they encounter self antigens in peripheral tissues

371
Q

What role do regulatory T cells (Tregs) play in peripheral tolerance?

A

They suppress activation of lymphocytes specific for self antigens and other antigens

372
Q

How are some self antigens sequestered from the immune system?

A

By anatomic barriers such as the testes and eyes

373
Q

What is T lymphocyte tolerance?

A

The process by which T cells become unresponsive to self antigens

374
Q

Why is T cell tolerance important in therapy?

A

T cells mediate many inflammatory reactions and help B cells produce harmful antibodies

375
Q

What types of cells promote potentially harmful antibodies?

A

CD4+ helper T cells

376
Q

What happens to immature T cells that recognize antigens with high avidity in the thymus?

A

They die by a process called negative selection or deletion

377
Q

What is negative selection?

A

The process where T cells with high-affinity receptors for self antigens die by apoptosis

378
Q

Where does negative selection occur?

A

In the thymic cortex and medulla

379
Q

What determines if a self antigen induces negative selection?

A

The presence of the antigen in the thymus and the affinity of T cell receptors (TCRs) for the antigen

380
Q

What are the peripheral tissue antigens in the thymus produced by?

A

Medullary thymic epithelial cells (MTECs)

381
Q

Which protein controls the expression of peripheral tissue antigens in the thymus?

A

Autoimmune regulator (AIRE) protein

382
Q

What disease is caused by mutations in the AIRE gene?

A

Autoimmune polyendocrine syndrome type 1 (APS1)

383
Q

What happens to T cells in the absence of functional AIRE?

A

They escape deletion and attack target tissues

384
Q

What do patients with APS1 commonly develop?

A

Autoantibodies and mucocutaneous candidiasis

385
Q

What role does the AIRE protein play in the thymus?

A

It promotes the expression of tissue-restricted antigens

386
Q

How do high-affinity TCR signals affect immature T cells?

A

They trigger apoptosis

387
Q

What happens to some self-reactive CD4+ T cells in the thymus?

A

They differentiate into regulatory T cells (Tregs)

388
Q

What are the three mechanisms of peripheral T cell tolerance?

A

Anergy, suppression by Tregs, and deletion

389
Q

What happens to T cells during anergy?

A

They become functionally unresponsive to an antigen

390
Q

What signals are required for full T cell activation?

A

Recognition of antigen (signal 1) and costimulation by B7-CD28 (signal 2)

391
Q

What happens when T cells recognize antigens without costimulation?

A

They may become anergic or unresponsive

392
Q

What enzyme is involved in targeting TCR-associated proteins for degradation in anergy?

A

Ubiquitin ligase CBL-b

393
Q

How does CBL-b deficiency affect T cells?

A

It leads to spontaneous T cell proliferation and autoimmunity

394
Q

Which receptors inhibit T cell responses during self antigen recognition?

A

Inhibitory receptors of the CD28 family

395
Q

What are the two main inhibitory receptors involved in T cell tolerance?

A

CTLA-4 and PD-1

396
Q

How does CTLA-4 inhibit T cell activation?

A

It competes with CD28 for binding to B7 and removes B7 from APCs

397
Q

What happens in mice lacking CTLA-4?

A

They develop severe systemic inflammation and lymphoproliferation

398
Q

What is the mechanism of PD-1 inhibition?

A

PD-1 recruits phosphatase SHP2, which removes phosphates and blocks TCR and CD28 signaling

399
Q

What types of conditions is checkpoint blockade (blocking CTLA-4 or PD-1) used to treat?

A

Cancer, especially advanced melanomas

400
Q

What are the side effects of checkpoint blockade therapies?

A

They can cause autoimmune reactions

401
Q

What is the primary function of regulatory T cells (Tregs)?

A

To suppress immune responses

402
Q

What transcription factor is critical for Treg development and function?

A

FOXP3

403
Q

What syndrome is caused by loss-of-function mutations in the FOXP3 gene?

A

IPEX syndrome

404
Q

Which cytokine is essential for the generation and maintenance of Tregs?

A

IL-2

405
Q

How does CTLA-4 contribute to the function of Tregs?

A

It inhibits T cell responses by reducing B7 availability on APCs

406
Q

Where are Tregs generated?

A

In the thymus and peripheral tissues

407
Q

What cytokine is crucial for Treg generation alongside IL-2?

A

TGF-_

408
Q

How does CTLA-4 on Tregs inhibit T cell activation?

A

By binding to B7 molecules on APCs and reducing costimulation

409
Q

Which two immunosuppressive cytokines do Tregs produce?

A

IL-10 and TGF-_

410
Q

What is the effect of Tregs consuming IL-2?

A

It deprives other cells of IL-2, reducing their proliferation and differentiation

411
Q

What role does TGF-_ play in Treg development?

A

It stimulates expression of FOXP3

412
Q

What cytokines are involved in the generation and functions of Tregs?

A

TGF-_ and IL-10

413
Q

What is the primary role of TGF-_ in the immune system?

A

Inhibiting T cell proliferation and macrophage activation

414
Q

Which antibody isotype is stimulated by TGF-_?

A

IgA

415
Q

How does TGF-_ contribute to tissue repair?

A

By stimulating collagen synthesis and promoting angiogenesis

416
Q

What immune cells primarily produce TGF-_1?

A

CD4+ Tregs and activated macrophages

417
Q

What is the primary role of IL-10 in the immune system?

A

Inhibiting activated macrophages and dendritic cells

418
Q

What cytokine does IL-10 inhibit the production of in macrophages and dendritic cells?

A

IL-12

419
Q

What immune reactions are suppressed by IL-10’s inhibition of IL-12?

A

Cell-mediated immune reactions against intracellular microbes

420
Q

How does IL-10 inhibit T cell activation?

A

By reducing costimulator and class II MHC expression on macrophages and dendritic cells

421
Q

What is the role of Tregs in self-tolerance and autoimmunity?

A

Maintaining self-tolerance and preventing autoimmune responses

422
Q

What syndrome is caused by mutations in the FOXP3 gene?

A

IPEX syndrome

423
Q

How does CTLA-4 on Tregs regulate immune responses?

A

By inhibiting costimulation via B7 on APCs

424
Q

What cytokine is crucial for the generation and function of Tregs?

A

IL-2

425
Q

What autoimmune disease results from mutations in FAS or FASL?

A

Autoimmune lymphoproliferative syndrome (ALPS)

426
Q

What is the purpose of B lymphocyte tolerance?

A

To maintain unresponsiveness to self antigens

427
Q

What is receptor editing in B cells?

A

A process where self-reactive B cells change their antigen receptor specificity

428
Q

What happens if receptor editing fails in self-reactive B cells?

A

The B cells undergo apoptosis (deletion)

429
Q

What happens when immature B cells recognize self antigens weakly?

A

They become functionally unresponsive (anergic)

430
Q

What happens to mature B cells that recognize self antigens in the absence of helper T cells?

A

They become functionally unresponsive or die by apoptosis

431
Q

What is required for anergic B cells to survive?

A

Higher than normal levels of the growth factor BAFF

432
Q

What happens to B cells that bind with high avidity to self antigens in the periphery?

A

They undergo apoptotic death by the mitochondrial pathway

433
Q

How do inhibitory receptors prevent B cells from responding to self antigens?

A

They set a threshold for B cell activation

434
Q

What is the role of T follicular regulatory (Tfr) cells?

A

They help limit T cell help to germinal center B cells during antibody responses

435
Q

What factors contribute to the development of autoimmunity?

A

Genetic susceptibility and environmental triggers

436
Q

What can infections and tissue injury promote in autoimmunity?

A

Influx and activation of autoreactive lymphocytes

437
Q

How can susceptibility genes contribute to autoimmunity?

A

They may disrupt self-tolerance mechanisms

438
Q

What role do pro-inflammatory cytokines play in autoimmunity?

A

They lead to failure of self-tolerance and activation of self-reactive lymphocytes

439
Q

What term is often used for diseases where immune reactions accompany tissue injury?

A

Immune-mediated inflammatory diseases

440
Q

What determines if an autoimmune disease is systemic or organ-specific?

A

The distribution of the autoantigens

441
Q

What type of immune response leads to systemic autoimmune diseases like SLE?

A

Formation of circulating immune complexes

442
Q

Which autoimmune disease is associated with muscle function?

A

Myasthenia gravis

443
Q

What causes tissue injury in autoimmune diseases?

A

Immune complexes, circulating autoantibodies, and autoreactive T lymphocytes

444
Q

Why are autoimmune diseases often chronic and self-perpetuating?

A

Self antigens persist and immune amplification mechanisms perpetuate the response

445
Q

What is epitope spreading?

A

A process where tissue injury releases other antigens, activating more lymphocytes and worsening the disease

446
Q

What do polymorphisms in non-HLA genes often affect?

A

The development and regulation of immune responses

447
Q

Which gene variant is associated with rheumatoid arthritis and type 1 diabetes?

A

PTPN22

448
Q

What disease is associated with polymorphisms in NOD2?

A

Crohn’s disease

449
Q

What is the function of NOD2 in the immune system?

A

Cytoplasmic sensor of bacterial peptidoglycans

450
Q

Which complement proteins are associated with SLE when deficient?

A

C1q, C2, and C4

451
Q

What is the role of IL-23 in autoimmune diseases?

A

Development of Th17 cells and stimulation of inflammatory reactions

452
Q

What autoimmune disease is associated with polymorphisms in CD25 (IL-2R_)?

A

Multiple sclerosis (MS)

Block 1 Partial Exam 4 (4 decks)

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