Learnt in past papers Flashcards

1
Q

Role of BUB

A

Is dissociated from chromatid to commence anaphase

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2
Q

Role of CENPE

A

Senses tension in chromatid

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3
Q

Role of CHKE1 and 2

A

Anticancer therapy arresting cell at G2

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4
Q

How can carcinoma prognosis and invasive ability be assessed

A

Degree of cell-cell adhesion

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5
Q

When to give platelet concentrations

A

haematology patients with bone marrow failure (if platelets <10 x 109/L)
Massive bleeding or acute DIC
If very low platelets and patient needs surgery
If for cardiac bypass and patient on anti-platelet drugs

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6
Q

When to not give platelet concentrations

A

Autoimmune thrombocytopenia

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7
Q

2 examples of reduced survival of platelets

A

Autoimmune thrombocytopenia

DIC

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8
Q

Presentation of beta thalassaemia

A

○ Profound anaemia thalassaemia
○ Failure to thrive
○ Malaise
○ Splenomegaly

All in first year of life

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9
Q

Treatment for beta thalasaemia major

A

Lifelong transfusion

iron chelating agent

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10
Q

Risks of life long infection

A

Viral infection in particular Hep C

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11
Q

Causes of liver cancer

A
Hep C.
Chronic Hep. B
Alcoholism
Aflatoxin B1 (aspergillus flavus)
Haemochromatosis
Diabetes
Obesity
Drugs &amp; Medication
Steroids
Oestrogens
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12
Q

Liver cancer pathophysiology

A

Hepatitis infection > becomes chronic if untreated > inflammation > cirrhosis > dysplastic lesions >clonal selection > hepatocellular carcinoma

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13
Q

Example of initial signalling protein

A

Grb2

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14
Q

How do cells go from benign to malignant

A

Disassembly of the cell-cell contact
Loss of polarity
Increased motility
Release of MMP to break down the extracellular matrix

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15
Q

Problems with metastases

A

Worse prognosis

Hard to resect

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16
Q

5 steps for investigating outbreak

A
Preliminary Investigation
Case definition and identification
Descriptive study
Analytic study
Control
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17
Q

Drugs given with transplant

A

Tacrolimus - inhibit t lymphocyte signal transduction (CNI inhibitor)
Cyclosporin - inhibit t lymphocyte signal transduction (CNI inhibitor)
Rapamycin - inhibit t lymphocyte signal transduction (mTOR inhibitors
Azathioprine - antiproliferative agent - purine synthesis inhibitor
Corticosteroids

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18
Q

Risks of immunosuppression

A

1) Increase risk of getting infection both conventional infections and opportunistic
2) Activation of dormant pathogen such as TB due to immunosuppression
3) Cardiovascular morbidity and mortality
4) Azathioprine - side effects include nausea, vomiting anaemia and Cyclosporin - side effects include convulsions, pancreatitis, kidney and liver dysfunction
5) Increase risk of malignancy

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19
Q

Blood film iron deficiency anaemia

A

Anisocytosis, Poikilocytosis, Hypochromasia, Pencil Shaped RBC

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20
Q

Drugs that cause iron deficiency anaemia

A

NSAIDS

Fluoroquinalone

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21
Q

Advantages and disadvantages of PCR, electron microscope, cell culturing and immunofluorescence

A

PCR; advantage; able to work out viral load. Also highly sensitive method (low rate of false negatives) used to detect specific sequences of nucleic acids. Disadvantage; prone to contamination
Electron microscope; able to visualise the viral structure disadvantage; expensive? Not highly specific?
Cell culture; able to see viral susceptibility to drugs ( useful for phenotypic antiretroviral susceptibility testing) disadvantage;slow and time-consuming
Immunofluorescence - useful for direct detection of viral antigens in clinical setting. used for typing and cell culture confirmation, rapid and inexpensive. Disadvantage - subjective and dependant on skill of technician and quality of sample

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22
Q

Advantages and disadvantages of molecular techniques and culture

A

Culture: advantage; figure out which antibiotic to use (test for antimicrobial resistance). Disadvantage; it takes about 24 hrs to grow the bacteria and another 24 hrs to do the susceptibility testing.
Molecular techniques: advantage; rapid and sensitive (low level of false negatives). Disadvantage; myriad of resistance genes.

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23
Q

Tacrolimus side effects

A

side effects include cardiac damage, nephrotoxicity, lung damage, increased chance of malignancy

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24
Q

Side effects rapamycin

A

Lung toxicitiy

Diabetes M

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25
Side effects azothyoprine
nausea, vomiting anaemia
26
Side effects corticosteroids
Cushings
27
Side effects cyclosporin
side effects include convulsions, pancreatitis, kidney and liver dysfunction
28
How can proto-oncogene become oncogene
Amplification of gene Point mutation Insertion Creation of fusion gene
29
Classes of proto-oncogenes
Cyclin D C-myc Ras/raf EGFR
30
Why do you need 2 mutations for TSG
Even with 1 the other can still function
31
Features of thrombocytopenia
Superficial bleeding into skin, mucusoal membranes, spontaneous bleeding, epistaxis, easy bruising, petechiae
32
How are platelets formed
Granulation of megakaryocytes
33
Aspirin MOA
Irreversible COX 1 inhibitor - prevents thromboxane from being produced by platelets as platelets don’t have nuclei so can’t make more enzyme.
34
Uses of aspirin
Use as antithrombotic in arterial thrombosis, acute coronary syndrome -STEMI and NSTEMI, atrial fibrillation
35
Why give red blood cells rather than full bood
1) Avoid fluid overload (potential heart failure) 2) More efficient - less is wasted because patients may not need all the components 3) Some components degenerate quickly if stored as whole blood ● Putting blood in the fridge is NOT good for the coagulation factors ● The fridge is also not good for preserving platelets
36
Why are red blood cells stored at 4 degrees
Preserve them | Reduced infection
37
What are ESCAPE bacteria
Cause hospital acquired infections
38
3 things causing anaphylaxis
Food Insect bite Medicine
39
Describe f actin structure
Filamentous | Soluble chain of G actin monomers
40
What happens in anaphylaxis
Allergens stimulate anaphylaxis via IgE antibodies. Type 1: Immediate hypersensitivity ○ IgE antibody produced ○ Antigen cross-links IgE on the mast cells and basophils ○ This leads to degranulation of IgE sensitised mast cells and release of inflammatory mediators Cardiovascular collapse, vomiting, diahorrea. Respiratory effects are bronchospasm and laryngeal oedema - contraction of bronchial smooth muscle and constriction of the muscles around the throat and endothelial cells within the membranes of the blood vessels move apart so you get a lot of fluid moving into the tissues Skin effects are vasodilation, erythema, urticaria and angioedema
41
How does fluoride oxalate work
Inhibits glycolysis preventing glucose uptake
42
Things looked for when grading a tumour
Abnormal growth pattern Loss of uniformity Deeply staining nuclei Variation in shape/size
43
Things for when staging a tumour
Site of tumour Size of tumour Sites of metastases Lymph node involvement
44
Sequence to carcinogenesis
There is damage or random mutation in the cells that affect cell proliferation pathways. They become permanently switched on (oncogenes)and lose the ability to apoptose (tumour suppressor genes). They proliferate uncontrollably, even without external stimulation, and often remain poorly differentiated. They can also gain the ability to become invasive via loss of anchorage-dependence and can spread away from the primary cancer site.
45
4 common resp infections
``` Mycobaterium tuberculosis (Gram +ve) streptococcus pneumoniae (Gram +ve) Haemophilus influenzae (Gram -ve) Legionella pneumophila (Gram -ve) ```
46
2 types of cervical cancer
Squamous cell carcinoma | Adenocarcinoma
47
ESCAPE bacteria
``` Enterococcus faecium (+) Staphyloccocus aeureus (+) C. Difficile (+) Clostridium Difficile Acinetobacter baumannii (-) Pseudamonas aeruginosa (-) E. coli (-) Escherichia ```
48
Things done with stool sample
``` Naked eye examination Culture for bacteria on agar Microscopy to look for cysts Parasite staining Toxin detection Antigen detection (EIA) PCR Test for Salmonella: XLD (xylosine lysine deoxycholate) agar goes bright pink or red colour and bacteria produces hydrogen sulfide so forms black colonies on agar. Campylobacter: incubate sample at 42 degrees ```
49
Things included in report to doctor from microbiologist
Any abnormalities - Appearance, culture results, any sensitivity test results Tests carried out and findings of each test If there was an infection and if so the type of bacteria How much infection there was (number of bacteria).
50
Early effect of chemotherapy
Nausea
51
Delayed effect of chemotherapy
Lethargy
52
Late effect of chemotherapy
Immunosuppression
53
Psycological effect of chemotherapy
Anticipatory vomitting
54
What is a gray
1j of energy per kg of tissue
55
2 examples of biotic anti cancer therapy
Cisplatin – adds a platinum group to guanine, causing DNA interlinks and intralinks. The DNA is unable to uncoil at replication and therefore undergoes apoptosis. Bevazizumab - VEGF-R
56
Effects of GTPases and their effects on motility
Cdc42 promotes filopodia – polarised activity and actin polymerisation Rac promotes lamellipodia – actin polymerisation and branching. Rho promotes stress fibres – tension and contraction Lammellipodia are thin like sheets of polymerised actin that are used to project the front of the cell forward. Filopodia are finger like projections that also move forward and are used in combination of lamellopodia to extend the cell. Stress fibres are contracted and are used to drag the cell forwards. They are anchored on focal points (ie points of anchorage at the front of the cell).
57
Difference in migration of normal and tumour cells
Tumour cells lose their anchorage dependent and cell-cell adhesion and are consequently able to migrate and invade uncontrollably.
58
When would take liver sample
To check for primary liver cancer To investigate for cirrhosis To check for liver infection To detect presence of metastasis
59
Why give anaemics RBC not whole blood
Whole blood may cause fluid overload Only need RBCs There’s a shortage of blood, so why give clotting factors when they’re not needed.
60
Concept of universal donor
A universal donor has blood type O-. This means they have no A or B antigens or Rh-D antigens so it can be given to any blood type as there are no antigens in the blood so it will not cause a haemolytic reaction in the recipient that may contain antibodies (anti-A or anti-B or anti-D) Potential problems with this - there are hundreds of red cell antigens on membranes (C, c, E, e etc) and 12-15% of them are clinically significant but are not matched for when giving transfusions. Therefore, a patient on a prior transfusion may have developed an antibody to one or more of these antigens. This can lead to a delayed haemolytic reaction
61
Immunological occurences of asthma
Allergen presentation via dendritic cell to Th 2 cells. These then cause degranulation of eosinophils by releasing IL-5 Th2 cells also release IL-4 and IL-13, which stimulate the production of IgE by plasma cells The IgE then becomes mobilised onto the surface of mast cells The antigens then cross-link with the IgE on the surface of the mast cells and cause degranulation Degranulation causes histamine, cytokines, toxic proteins, leokotrienes and prostaglandins to be released. These cause vascular leakage → airway oedema, mucus secretion and smooth muscle contraction arounf bronchi → bronchoconstriction
62
Clinical features of asthma
SOB Mucous production leading to cough Wheezing Chest tightness
63
Features of thrombocytopaenic bleeding
Spontaneous bleeding Nosebleeds Prolonged bleeding
64
How can infection predispose to hypersensitivity/allergy
1) Molecular mimicry of other molecules 2) induction of co-stimulatory molecule or inappropriate MHC class II expression -> proinflammatory environment, 3) failure in regulation -> effects on regulatory T cells, 4) immune deviation -> shift in type of immune response eg Th1 to Th2
65
Why is suppression used in faecal testing
Many other flora bacteria in faeces
66
Features on blood film for megaloblastic anaemia
``` Macrocytosis Hyper-segmented Neutrophils Anisocytosis and poikilocytosis Low Hb, platelets and WCC Giant Metamyelocytes Howell Jolly bodies ```
67
When do you give DDAVP
Haemophilia | Type 1 vWb disease
68
Common cancers giving vertebral metastases
Breast, Prostate, Lung
69
Cytological features looked for in staging
Degree of differentiation, number of mitotic bodies, pleomorphism, integrity of cells, necrosis
70
Cancers leading to physiological functioning changes
Lung cancer - can secrete ACTH -> cushing's | Thyroid cancer - secrete thyroxine -> thyrotoxicosis
71
Non enzyme substances looked for when doing lLFTs
Bilirubin | Albumin
72
How configuration of Hb helps oxygen delivery
A lower pH, as in metabolically active tissues, lowers the oxygen affinity of Hb and facilitates the downloading of O2 to tissues. HbA can carry up to 4 oxygen molecules. This is referred to as different liganded states. The main function of Hb is the carriage of oxygen from the lungs to metabolically active tissues. To facilitate this, the Hb can exist in two spatial configurations. Deoxy haemoglobin exists in a tight configuration and has a relatively low affinity for oxygen. Oxygen molecules are taken up sequentially by the 4 haem groups. At some point the partially liganded Hb molecule switches to a relaxed configuration which has a markedly higher affinity for oxygen.
73
Universal donor
O neg, no A, B or D antigens on RBC surface
74
Other uses of tamoxifen
Infertility | Gynaecomastia
75
Why is PSA elevated in blood in prostate cancer
PSA is normal part of seminal fluid, only released into serum upon damage to prostate, such as in prostate cancer, thus causing elevated levels PSA
76
3 genomic causes of androgen independence
Mutation allows the prostate to respond to anti-androgens and oestrogen. Upregulation of androgen receptors in response to low levels of circulating androgen and other weak androgens or by co-stimulatory molecules. Also decreased levels of co-repressors of the prostate.
77
G1 checks on cell
Assesses chromosome stability ext environment cell size
78
G2 checks on cell
cell size ext environment correct and complete DNA replication
79
Vaccinated bacterial infections
``` Hemophilus influenzae (Gram -) Neisseria meningitidis (Gram -) Streptococcus pneumoniae (Gram +) clostridium tetani corynebacterium diphtheriaea ←is this not clostridium diptheriae? Salmonella typhi Bacillus anthracis Bordetella pertussis ```
80
What causes high Hb and Hct
Polycythaemia
81
Advantage of diagnosing sickle cell at birth
Penicillin ● Should be started at 3 months of age to reduce the risk of life-threatening pneumococal infection Vaccination ● Against the organisms that individuals with hyposplenism are susceptible to Monitor Spleen Size ● Splenic sequestration is a potential cause of death in young people (repetitive vaso-occlusive damage from infarction from early life) ● Parents can be taught how to monitor spleen size Prophylaxis against pneumococcal infection ● Risk of recurrent stroke in children with sickle cell anaemia is very high so they should keep having regular transfusions Induction of HbF HYDROXYUREA (Hydroxycarbamide) ● This is cytotoxic - it is a ribonucleotide reductase inhibitor ● It induces the production of red cells in the bone marrow that mainly contain HbF ● This means that, over time, there will be an increase in the number of red cells that are UNABLE to sickle ● It will also have other effects such as reducing the adhesion to the vascular endothelium
82
Reason for elevated Hb in sickle cell
Low affinity for oxygen so releases it to tissues meaning less EPO released Free Hb from intravascular haemolysis
83
How can ALL cause hyperuricaemia. Is this clinically significant? How?
Hyperuricaemia esult of the release of cellular contents of dying cells into the bloodstream from breakdown of cells after cytotoxic therapy or from cancers with high cell turnover and tumor proliferation rates result in nausea and vomiting, acute kidney failure, seizures, cardiac arrhythmia, death
84
Reason for bone pain in ALL
Increased pressure in bone marrow
85
Reason for anaemia in ALL
Reduced production of other cells
86
Reasons against prostate screening
PSA not only released by prostate cancer, elevated levels can be due to other reasons so this may cause undue anxiety while they wait for further, invasive, investigations A raised PSA will cause further invasive tests to occur, and cause acute anxiety for patient. If cancer is detected will undergo treatment - has unpleasant side effects - decrease quality of life. However if leason was left alone may not have affected man in his lifetime.
87
Most probable cause of high lymphocytes and normal other cells
T cell hodgkins lymphoma
88
Causes of eosinophilia
Parasites | Autoimmune
89
Test for hodgkins lymphoma
TCR gene recombination
90
Test for B12 deficiency
Schilling | Romberg
91
Example of antigenic shift
Influenza
92
Example of antigenic drift
Rhinovirus
93
Why do blood samples sometimes show abnormally high potassium levels
Haemolysis of RBCs
94
What differentiates serum from plasma
Plasma contains clotting proteins, serum does not contain clotting proteins
95
Diagnosing viral infection
1. Cell culture 2. Electron microscopy 3. Immunofluorescence (IF) 4. Enzyme immuno assays (EIA) 5. Viral genome detection and quantification – PCR
96
What observations on urine sample
Bedside examination with the naked eye: is the specimen clear, cloudy, haemorrhagic etc. ● Microscopy: the cell types that may be present include white blood cells (high concentrations indicate infection), red blood cells, epithelial cells etc. Crystals and casts may also be present. ● Culture on agar: urine should be sterile so any growth may suggest infection. ● Quantitative colony count: for significant bacteruria of >105 bacteria/mL. ● Antibiotic sensitivity testing: for any bacterial growth.
97
4 benefits of autopsy
1. To determine the cause of death of a patient. 2. To explain why treatment for the patient was unsuccessful. 3. To show the spread of disease. 4. To educate doctors regarding disease processes.
98
3 ways to generate commercial antibodies
1. Antisera from immunised animals. 2. Monoclonal antibodies. 3. Genetically engineered antibodies.
99
When do you find smear cells
CLL
100
Use of thrombin clotting time
Detects abnormalities in the fibrinogen to fibrin conversion
101
Differentiating between primary and reactive lymphocytosis
1. Immunophenotyping – test for light chain restriction. | 2. Test for gene rearrangement using Southern Blot analysis.
102
Prophylactic measures for sickle cell
1 Folic acid 5mg / day To compensate for the short RBC lifespan, RBC turnover may be increased, depleting stores of folic acid. 2 Vaccination To protect against pneumococcal infection (normally dealt with by the spleen; hyposplenism is a feature of sickle cell anaemia). 3 Penicillin prophylaxis To prevent some of the infections caused by hyposplenism 4 Monitoring spleen size To check for future splenic sequestration
103
Example of bacteria and their virulence factor
● Capsule - S.pneumoniae ● Endospores - clostridium, bacillus ● Biofilms - pseudomonas aeruginosa, staphylococcus epidermis ● Neurotoxins - tetanus, botulinum ● Enterotoxins - infectious diarrhoea (V. cholera, E. coli, C. Jejuni, etc ...), food poisoning (S. aureus, B. cereus) ● Pyrogenic exotoxins - S. Aureus, S. pyogenes ● Tissue invasive exotoxins - S. Aureus, S. pyogenes, C. perfringens ● Endotoxins - any gram negative bacteria
104
Resistance to vancomycin, methicillin, cephalosporins and carbapenems
``` Cephalosporins Inhibit peptidoglycan synthesis by inhibiting the activity of penicillin binding proteins Extended spectrum beta lactamase cleaves cephalosporins Carbapenems Inhibit peptidoglycan synthesis by inhibiting the activity of penicillin binding proteins Carbapenemase enzyme encoded on a transposon which cleaves carbapenem Methicillin Inhibit peptidoglycan synthesis by inhibiting the activity of penicillin binding proteins Expression of additional penicillin binding proteins such as PBP2A 13 Vancomycin Inhibit peptidoglycan synthesis by binding to a peptidoglycan precursor Multiple proteins synthesised by genes carried on a plasmid or transposon resulting in the synthesis of different peptidoglycan precursors ```
105
7 ways viruses can evade interferon system
1. Hide the PAMP to avoid detection 2. Interfere with host gene expression/protein synthesis no ISGs made 3. Blocking interferon induction cascades 4. Inhibiting interferon signalling 5. Block the action of individual interferon induced antiviral enzymes specifically 6. Activate SOCs genes 7. Replication strategy insensitive to IFN, i.e. too quickly for IFN to work
106
How knowledge of evasion of interferon system can be used in future therapies
1) Vaccines: if we block the ability of viruses to control the interferon response they become attenuated, and thus can be used in vaccinations. 2) Influenza therapy: interferon lambda receptors are only present on epithelial surfaces. Since this is where influenza grows, interferon lambda could potentially be used as influenza therapy with lesser systemic side effects than type 1 interferons, which bind to many cell types. 3) Cancer therapy: cancer cells are deficient in interferon so viruses are able to grow well in them. Viruses could therefore be used to lyse cancer cells, without harming healthy cells.
107
Differences between protozoa and metazoa
Protozoa Metazoa Single-celled Multicellular Do not produce eosinophilia in the host Forms which invade the blood often cause eosinophilia
108
Acute and chronic immunopathophysiology of asthma
``` Acute ● Mast cell activation and degranulation ● Release of preformed histamine and newly formed prostaglandin and leukotriene ● Features: o Vascular leakage o Mucosal oedema, mucous secretion and smooth muscle contraction leads to acute, reversible airway narrowing Chronic ● Th2 lymphocyte and eosinophil activation ● Features: o Inflammatory cellular infiltration o Tissue damage o Epithelial cell shedding o Sub-epithelial fibrosis o Smooth muscle hypertrophy o Mucus pluggin ```
109
Tissues transplanted and reasons for transplants
Failed organ / tissue Reason for failure 1. Cornea 2. Skin 3. Kidney 4. Liver 5. Heart 6. Lungs 7. Pancreas 8. Bone marrow 9. Small bowel 1. Degenerative disease, infections, trauma 2. Burns, trauma, infection 3. Diabetes, hypertension, glomerulonephritis, hereditary conditions 4. Cirrhosis, acute liver failure 5. Coronary artery/valve disease, cardiomyopathy, congenital defects 6. COPD, interstitial fibrosis, cystic fibrosis, pulmonary hypertension 7. Type I diabetes 8. Tumours, hereditary diseases 9. ‘Short gut’, Crohn’s, vascular disease etc
110
Define tolerance
Acquired inability to respond with an immune reaction to an antigen to which the organism usually responds
111
Name and describe 3 tolerance mechanisms
1. Anergy: an absence of costimulation for naïve T cells results in a refractive state so that cell proliferation and factor production cannot proceed. 2. Ignorance of antigen: occurs in immunologically privileged sites where immune cells cannot normally penetrate, such as the eye. 3. Suppression by regulatory T cells: autoreactive T cells are present but controlled by ‘regulatory’ T cells to prevent them from responding to autoantigen.
112
Example of diseased caused by central tolerance issue
APCED
113
Example of disease casued by peripheral tolerance issue
IPEX
114
How can infection lead to issue with tolerance
1. Molecular mimicry of self molecules 2. Induction of co-stimulatory molecules 3. Induction of inappropriate MHC II expression 4. Failure of regulatory T cells 5. Shift in the immune response from Th1 to Th2 6. Tissue damage at immunologically privileged sites leading to ‘leakage’ of antigen
115
Genomic causes of oncogenes
● A mutation in the coding sequence (point mutation or deletion) leading to an aberrantly active protein. ● Gene amplification leading to multiple gene copies and overproduction of the normal protein. ● Chromosomal translocation: an inappropriate piece of one chromosome is joined to another chromosome e.g. a ‘strong enhancer’. ● Insertional mutagenesis: a virus inserts its genome into the host, which fuses to actively transcribed gene leading to overproduction of a protein or the fusion protein itself is overactive.
116
Angiogenesis in disease
``` Cancer ● Chronic inflammatory diseases ● Diabetic retinopathy ● Cardiovascular disease ● Psoriasis ● Vascular malformation ```
117
Angiogenesis physiological
Wound healing Embryo Menstrual cycle