Pathobiology Flashcards
What is alkaptonuria?
Homogentistic acid accumulates in joints, causing artiste damage and back pain - Kidney stones - Blackening of urine Inherited as autosomal recessive Inborn errors of metabolism
Name some autosomal recessive inherited diseases?
Alkaptonuria
Cystic fibrosis
Name some autosomal dominant inherited diseases
Brachydactyly
Huntington’s disease
Name some autosomal co-domiant inherited diseases
Sickle cell anaemia
Name some x linked inherited diseases
Duchenne muscular dystrophy
X linked mental retardation
Haemophilia
What are the symptoms and cause of sickle cell anaemia?
- Painful
- Life threatening
- Erythrocytes sickle shaped - can’t carry as much oxygen
- Caused by a single point mutation in the codon for amino acid 6 in B- global subunit
- Causes haemoglobin tetrameters containing HBs to form large insoluble polymers which distort erythrocytes shape
Where and why is the frequency of the sickle cell anaemia allele (HBs) high?
High in sub saharan countries
- Prevalence 2%
- Allele carrier is 10-40%
Heterozygous provides resistance to malaria
What has karyotyping allowed to happen?
Allows each chromosome to be distinguished
- Abnormalities in banding due to mutagens rearrangements can be associated with specific phenotypes
- Genes can be tapped to specific chromosomal locations
What is Aniridia?
An autosomal dominant phenotype caused by deletion or loss of function point mutations in one copy of the gene
What is Duchenne Muscular Dystrophy (DMD)?
Progressive muscle damage and wasting disease
Lethal in childhood or early adulthood
What gene is responsible for Duchenne Muscular Dystrophy?
- Was identified by DNA sequencing
- DNA sequence deleted form the X chromosome of DMD patients
- It is the dystrophin gene that is affected which is the largest known human gene
- Dystrophin protein is responsible of connecting each muscle fibre to the extracellular matrix - integrity
What is Huntington’s disease?
A progressive, late-onset, inherited neurodegenerative disorder
- Dementia and movement disorder
What is the pathology of Huntington’s disease?
The brain of a Huntington’s disease patient has suffered massive neuronal loss in the basal ganglia and has dilated lateral ventricles
- Caused by an expansion of the repeated CAG sequence in the Huntingtin gene
- This expansion makes the protein toxic to neurones
Name an animal virus genome the contains genes that can cause cancer ?
Rous Sarcoma Virus
- contains the v-src oncogene
- Encodes for an abnormally hyperactive version of tyrosine kinase
- Dominant gain of function
Name an example of a cancer that can be caused by a loss of function mutation
Retinoblastoma
- can be hereditary or non hereditary
- Can be bilateral or unilateral
- Caused by loss of function of a tumour suppressor gene (both alleles) - more likely to happen if inherited one mutated allele
How can chromosomal rearrangements lead to cancer?
- Disruption, eructation or the reassembling of chromosomes
How can Single Nucleotide Polymorphisms (SNP’s) be used to identify DNA sequence associated with common diseases?
- There are a total of 3x10^7 SNPs in the human genome
- Provide detailed map of DNA sequence variation across the genome
- Can compare SNP’s in a group of patients with a specific disease to the SNP’s of healthy people
- Any common differences can be associated with that disease
- These studies are called genome wide association studies (GWAS)
What is imprinting of genes in animals?
When particular regions of chromosomes have structural modifications to stop transcription e.g. methylation of DNA sequences
- The structural modification are introduced to chromosomes of the sperm and eggs and remain in somatic cells of the offspring but are removed during germ cell production
How is methylation an example of the imprinting of genes?
- Methylation of DNA on cytosine bases is a hallmark of imprinted chromatin
- Switches genes off by recruiting repressors and binding proteins
What is a paternal and maternal imprint?
Maternal - When maternal gene has a structural modification so is not expressed - Paternal gene is expressed - Gene carries a maternal imprint - During oogenesis Paternal - When paternal gene has a structural modification so is not expressed - Maternal gene is expressed - Gene carries a paternal imprint - During spermatogenesis
Explain UBE3A and SNORD116 as an example of gene imprinting
Maternal imprint on SNORD116
Paternal imprint on UBE3A
An example of reciprocal imprinting
Only SNORD116 expressed form paternal and UBE3A from maternal
- Maintained in somatic tissue
- Removed in germ cell development and reestablished
What disease occurs when maternal copy of SNORD116 is imprinted and paternal copy mutated?
No functional copy of SNORD116 Prader-willi syndrome - Low muscle tone - Cognitive disability - Morbid obesity
What disease occurs when paternal copy of UBE3A is imprinted and maternal copy mutated?
No functional copy of UBE3A Angelman syndrome - Cognitive disability - Sleep disturbance - Seizures - Frequent smiling
What is epidemiology?
Basics science concerned with the patterns of disease frequency in human population
What extrinsic and intrinsic factors can cause disease?
Extrinsic - Physical - Socioeconomic Intrinsic - Age - Sex - Behaviour - Immunisation
Give an example of a migrant study that shows environmental factors causing disease?
Prevalence of certain cancers e.g. stomach and lung are substantially higher in Japan than America
- Decreases if the people from japan migrate to America
- Decreases further in the offspring of the immigrants
=> suggests environmental over genetic factors
How is cholera shown to show environmental causes of disease?
- There was poor access to safe water
- Caused by vibrio cholera
- prevalence 50% in unprepared communities but only 1% well organised
- Kills 6 million a year
What is the mortality associated with smoking?
320+ UK deaths every day from smoking
1/5 all deaths across all ages
7.5 years average loss of life expectancy
What are the major health consequences of smoking?
- Cancer (lung, mouth, bladder, pancreas)
- Respiratory disease (COPD)
- Vascular disease (Coronary heart disease, stroke, peripheral vascular disease)
- Pregnancy and birth complications (premature birth)
- Pulmonary emphysema
What is pulmonary emphysema?
- Breakdown of extracellular matrix in lungs
- Alveoli burst
- Macrophages secrete chemotactic factors and secrete proteases which digest lungs
- Oxidants and free radicals in smoke release antitrypsin making proteases more active
- Increased risk of infection
Discuss the addictive quality of smoking
- Heroin and cocaine users say smoking is harder to quit
- 70% want to quit
- 50% with a removed lung smoke again
- Social influence
- Associates with memories
- Nicotine is the driving force behind addiction
What are the two broad responses of different occupational lung diseases?
- Allergic
- Pneumoconiosis
What is Pneumoconioses?
- Lung disease caused by inhaled dust
- Dust can be organic or inorganic
- Could cause inert reactions
- May aggravate co existing disease
What is asbestosis?
- Asbestos fibre + iron and calcium causes a ferruginous body
- Macrophage fibre ingested increased fibrogenic response (collagen deposition by fibroblasts)
What are the different types of pathogens?
Obligate pathogens - Can only survive in host usually very specific to host species
Facuitative pathogens - Present in the environment waiting for host
Opportunistic pathogens - Normally benign but cause disease in compromised host
Discuss the life cycle of fungi and how it utilises the host
- In its solid form its mold
- In warm body - switches to the yeast morphology
- Consumed by macrophages in host
- Once consumed fungus responds by growing a ‘germ tube’
- This projection eventually pierces the macrophage from inside killing it
Discuss the life cycle of protozoa and how it utilises the host
- Often has more than one host
Malaria - Mosquito picks up gamete which fertilise and invade the gut and move to the the salivary gland
- Mosquito injects this into the blood of another host, it replicates and infects red blood cells
Can two closely related species be virulent or non pathogenic?
Yes - only takes a differ of a few genes (virulent genes) to make them pathogenic
e.g. Vibrio cholerae needs to be infected by a certain bacteriophage to become virulent - the bacteriophages transfer genes that encode cholera toxin to the bacteria
What external barriers need to be overcome by pathogens to enter a host?
- Flora, epithelia and mucous
- Epithelia is densely packed with flora
- Held together by tight junctions
- Epithelia secrete mucus
- Bacteria have p pili - stick proteins that anchor them to epithelia
- Breaks in epithelia are quickly recognised by white blood cells
Why do pathogens need to breach the cell membrane?
Cell membrane needs to be breached so pathogens can inject toxins into the host cell or replicate inside it
Toxins are often used to kill host cells to provide the pathogen nutrients and killing white blood cells help the pathogens invade the immune system
What is an actin pedestal?
E.coli form an actin pedestal on a host cell to hold them in place
- E.coli inject TIR through type 3 secretion into the host cell
- Causes growth of actin filaments from the host which holds the e.coli in place and stops it from being flushed away into the gut
- TIR is sufficient to change cells morphology
Why do bacteria hide in cells?
Pathogens can evade the immune system by hiding in a cell
e. g.. Legionnaires disease
- bacteria phagocytose by macrophages but replicate inside
How does listeria enter the cell?
- Uses adhesions to enter the host cellls
- Engulfed in a phagosome
- Secretes hemolysin, a protein that breaks down the membrane of the phagosome
- The protein is broken down by the PEST amino acid sequence
- They then assemble actin tails to push them into the neighbouring cells
How do antibiotics work?
They disrupt cellular processes that are different to ours
-eg. protein synthesis, RNA polymerase, cell wall synthesis
What is one way to overcome antibiotic resistance?
Addition of different side chains to the antibiotics
What is the basic structure of a virus?
A simple genome encapsulated in a coat protein (capsid)
What is type 1 class of virus and how does it replicate?
- Adenoviruses such as conjunctivitis and respiratory disease
- Herpes viruses
- Papilloma viruses - genital warts, cervical cancer
Replicates similar to normal cells
What is type 2 class of virus and how does it replicate?
Small - single stranded DNA
- Parvoviruses: fifth disease
Replicated via DNA polymerase making the single strand double stranded
What is type 3 class of virus and how does it replicate?
RNA virus
-Rotavirus: Acute gastroenteritis
Replicated via RNA transcriptase unique to virus and replicates RNA - produces proteins
What is type 4 class of virus and how does it replicate?
- Polio viruses, yellow fever
- SARS viruses
Replicated via mRNA making polyproteins that are cleaved
What is type 5 class of virus and how does it replicate?
Single stranded RNA
- Ebola viruses, influenza viruses, measles
Replicated via RNA transcriptase (from virus)
What is type 6 class of virus and how does it replicate?
Retroviruses
- Leukaemia, AIDS
Replicated via reverse transcriptase - converts RNA to DNA
What is type 7 class of virus and how does it replicate?
Double stranded DNA
- Hepatits B virus
Replicated via reverse transcriptase - DNA is made into genomic RNA
How can a virus form a tumour?
Proteins produced by the viral genome unregulated DNA replication and proliferation by the host cell to allow more production of the viral genome
Accidental integration of the virus can result in too much proliferation and is the first step in malignant tom out formation - E6 and E7 bind to Rb and p53 proteins and inactivate them taking of the constraints on DNA replication
Causes 6% of cancers
What type of viruses cause cancer?
Papilomaviruses contain several oncogenes
How do retroviruses cause cancer?
by incorporating human proto-oncogenes into their genome
How does the presence of proto-onogenes cause tumour formation in retroviruses?
Proto-oncogenes are proteins involved in cell proliferation
What are the bodies physical barriers?
- Skin epithelia - hairy skin (prevents organisms reaching the skin), tight junctions
- Chemical defences (sweat, lactic acid, sebum, lysosomes, Stomach pH
What is the roll of defensins?
They are positively charged peptides
- Act on viruses, microbes and parasites
- Target their membranes and create channels and secrete cryptdin
What is a weak point of the epithelia (to let pathogens in)?
Most membranes - Eye - Respiratory system - GI system - GU system Can lead to conjunctivitis, TB, Syphilis
What are the principle cells, tissues and organs if the immune system?
- Lymphatic and cardiovascular systems
- Effector and signalling molecules
- Lymphatic system - vessels, thymus gland (t lymphocytes), lymph nodes , lymphoid tissue, bone marrow (B cells)
- Phagocytes
- Natural killer cells
- Interferons
- Complement
- Inflammation
What are the differences between general recognition and pattern recognition of pathogens?
General recognition - pathogen associated immunostimulants - e.g. prokaryote proteins - F met - Lipopolysaccharides - from gram negative - enough to recognise as foreign - Foreign nucleic acids Pattern recognition receptors - Soluble - Membrane - bound
What are collectins?
- Soluble plasma components (and surfactant)
- Bind to specific carbohydrates and phagocytes
- Interact with complement
- Are pattern recognition receptors
- From a family of collagenous Ca2+ dependant defence lectins
What is the complement system?
- Part of the immune system that enhances the ability of antibodies and phagocytic cells, promotes inflammation
- 20+ soluble proteins
- Evoke lysis, phagocytosis and inflammation
How does C3 cleavage in the complement system attack pathogens?
- Binding to lectin can cause C3 to cleavage - triggers membrane attack
- Creates water channels - osmosis - cells burst
How do phagocytes attack a pathogen?
Phagocytes
- Macrophages and microphages
- Surface of macrophages have own receptors - PRR’s and FC receptors (part of an antibody)
- If receptors triggered then phagocyte engulfs and destroys
What are interferons?
They are secreted by lymphocytes and macrophages
- Can inhibit viral replication
- Interferon a attracts natural killers
- Interferon b slows inflammation ]
- Interferon y stimulates t-cells
- Secretion evoked by double stranded RNA
What are natural killer cells?
- Destroy bacteria, virus infected cells and tumour cells
- Target cells have low MHC 1
- Doesn’t have a memory
What is inflammation?
Part of the bodys innate response to damage or infection
- Its unregulated and active
What are the characteristics of inflammation?
- Readness
- Heat
- Swelling
- Pain
What is the difference between acute and chronic inflammation?
Acute - Short duration - Neutrophils Chronic - Long duration - Lymphocytes, plasma cells, macrophages
What are the roles of megakaryocytes in inflammation?
- Break up to form platelets - blood clotting
- Produce pro-inflammatory cytokines and chemokines
What are the roles of monocytes/macrophages in inflammation?
- Monocytes differentiate into macrophage
- Their function Is phagocytosis, antigen presentation and cytokine production
What are the roles of basophils in inflammation?
- Least common white blood cell
- Releases histamines and prostaglandins to cause dilation and permeability of capillaries
What are the roles of mast cells in inflammation?
- Role in allergy and anaphalaxis
- Contains granules of heparin and histamines as well as as pro-inflammatory cytokines such as TNFalpha, IL4
What are the roles of eosinophils in inflammation?
- Role in anti-parasite responses
- Present antigens to their adaptive immune system, generate cytokines and kill cancer cells
What are the roles of neutrophils in inflammation?
- 50-60% of white blood cells
- Leave circulation to some on a site of injury and inflammation where they die and form puss
- They phagocytose microbes
- Secrete cytokines that recruit macrophages
What blood vessels are involved in inflammation?
Continuous - Only permeable to small molecules - e.g. muscles Fenestrated - Small molecules and proteins - fit though pres Sinusoid - Allow blood cells to cross - e.g. bone marrow, lymph nodes
What is a cytokine storm?
- In extreme cases postitive feedback of cytokines on WBCs can turn a localised inflammation into a cytokine storm
- Often fatal consequences e.g. anaphylaxis
What is impact in the release of histamine?
Increase in permeability - fluid influx into tissue increases which can cause oedema (swelling)
During inflammation, what does the reduction in blood velocity promote?
- Margination
- Diapedesis (passage of blood cells through the intact walls of the capillary)
What are some indicators of infection?
- C-reactive protein
- Neutrophils (bacterial), lymphocytes (viral), eosinophils (allergy, parasites)
- HPA hormones e.g. growth hormones - consequence of biological stress
What conditions can lead to chronic inflammation?
- TB
- Syphilis
- Arthritis
May not have an acute preceding phase
What is osteomyelitis?
- Chronic infection of bone
- Poor vascularisation means poor recovery
What are the major features of adaptive immunity?
Specificity
Memory
Tolerance
What is the difference between innate and adaptive immunity?
Adaptive is learned
What are the major players in adaptive immunity?
Lymphoid tissue Antigen - presenting cells Follicular dendritic cells T-lymphocytes B-lymphocytes
What are the structures and role of antigen presenting cells?
- They display fragments of invading pathogens on their surface
- Present them to immune system cells - t lymphocytes
- Fixed and free macrophages e.g. Kupffer cells, monocytes and microglia
- Epithelia
- B lymphocytes
What are the differences between T and B lymphocytes?
T lymphocytes - mature in the thymus and attack directly
B lymphocytes - mature in bone and make antibodies
What are MHC’s?
Major histocompatibility complex proteins
- Cell surface glycoproteins that bind antigens and present and present them to passing immune cells
- How T cells recognise a pathogen
What is the difference between MCH 1 and MCH II’s?
MHC 1 - In all nucleated cells - Constitutive - Activates cytotoxic T cells MHC II - Inducible in many cells - Activates helper T cells
What is the role of T cells?
- Receptor binding evokes T helper cell activation and division
- Activate and form cytotoxic and memory T cells
- Cytotoxic T cell - cause apoptosis
- Memory T cells - rapid response
What causes lymphocytes to be attracted to a site?
The release of chemokines
What are the types of immunoglobulins?
igG - Most common in the blood IgM IgE IgA - Technically most common in body IgD
How does antibody mediated death occur?
Immunoglobulins bound to surface activated the complement
- Causes cell lysis
- Phagocytosis
- Inflammation
- Caused cleavage of C3 - insertion of water channels
Immunoglobulins recognised by phagocytes
What is acquired immunotolerance?
Developmental loss of self - reactive lymphocytes in thymus (clonal deletion)
Give an example of autoimmune diseases?
Myasthenia gravis, crones disease
What are the differences in first and secondary responses?
First response
- After injections of first antigen, antibodies start to produce after a few days
- Not a high conc of antibodies produced
Second response
- After second injection, antibodies produced immediately
- Much higher conc of antibodies produced - due to memory cells
What is clonal expansion?
B cells divide into plasma and memory cells
Plasma cells release antibodies
What is necrosis?
- Uncontrolled cell death
- Characterised by a loss of cell components by lysis, inflammation and autolysis
- Associated with physical damage, infections, acute toxicity and acute hypoxia
What is apoptosis?
- Controlled cell death
- Characterised by shrinkage, nuclear breakdown, phagocytosis, requires protein synthesis
- Associated with developmental cell loss, chronic toxicity and removal of growth factors
Give some examples of apoptosis?
In c.elegans - 131 cells doe during development Metamorphosis - Tadpole --> frog - Cells need to die for this transformation Digit formation - Cells in between digits die
What are CED genes?
Genes that provide recognition for engulfment
- 4 key genes: EGL-1, Ced3, Ced4, Ced9
How do CED genes work?
- Decrease in Ced 3 or 4 gives access adult cells (increase causes cell death)
- Ced 9 decrease causes massive cell death
How does EGL-1 trigger apoptosis?
EGL-1 –| Ced9 –| Ced4 –> Ced3
Ced3 triggers cell death
What is the role of caspases in cell death?
They are the executioners of cell death
- Caspase 3 important in development - break down DNA repair enzyme, Lamina A, Huntingtin
How is apoptosis activated?
Indirectly active caspases Intrinsic pathway - Cyctochrome C release from mitochondria - Binds to apaf-1 and caspase 9 - Triggers caspase cascade - Triggers Cy-c
What causes apoptosis in red blood cells?
- Precursors stimulates by colony stimulating factors to produce many offspring - RBC
- Withdrawal of colony stimulating factors (CSF’s) causes apoptosis
What are the risk factors of increasing chance of HIV?
- Number of sexual partners
- Recreational drug use
- Haemophiliacs
How is HIV transmitted?
- Blood and blood products
- Vaginal mucus and secretions
- Semen
- Any body fluid that is mixed with infected blood
- Sometimes breast milk
What is the bodies response to HIV?
- Person will feel and look completely healthy
- Latent period can last up to 15 years but will normally end within 10 years
- Reduce immune system (can cause lip warts, shingles,PCP, thrush, kaposis sarcoma
- Viral load in an untreated patient
- T cell depletion
How does the genetic make up of people affect their likely hood of HIV developing into AIDS?
HIV uses CD4 protein found on T cells to invade them
- CD4 serves important functions in the immune system - binding of macrophages to T helper cells
- CCR5 is a co receptor to CD4 and people with mutant copies of it are less likely to develop AIDS (common in Europe)
Why do we have vaccines?
- Protect from infectious disease
- Produce risk less immunity
- 1.5 million children under 5 die from vaccine preventable disease a year
What is active immunity?
- Protection produced by persons own immune system
- The more similar a vaccine is to the natural disease, the better the immune response to the vaccine
- Usually killed micro-orgs and live pathogens weakened
What is passive immunity?
- Protection transferred from another person or animal as antibodies
- Temporary protection
- Important in infancy
Why was the small pox eradication programme successful?
- Used cowpox (a weaker version) as a vaccine
- Life long immunity
- Major commitment by governments
- Subclinical cases are rare
How does vaccination compare to the immune response?
The vaccination acts as the first immune response
Memory cells produced
Next time infected - rapid response
What is hypertension?
High blood pressure
What is thrombosis?
Local coagulation/ blood clots Involves - Endothelial cells - Platelets - Coagulation cascade
What is an embolism?
Obstruction of an artery, typically by a clot of blood or an air bubble
What is atherosclerosis?
Deposition of fatty material on their inner walls
What is the difference between arterial and venous thrombosis?
Arterial - Often middle - age or elderly - May have circulatory disorders - Diabetic or smokers Venous - May be any age - Immobility - leeds to narrowing/occlusions
What are the major components of plaques?
- Cells (smooth muscle, macrophages and other WBC)
- ECM (collagen, elastin and proteoglycans)
- Lipid (cholesterol)
What are the major processes in plague formation?
- Intimal thickening (smooth muscle cells proliferate and ECM synthesis)
- Lipid accumulation
What are the consequences of thrombosis?
Thromboembolism
- Obstruction of blood vessel by blood clot that has become dislodged from another site in the circulation
Myocardial infarctions
Aortic aneurysms
What drugs can be used to treat thrombosis?
Streptokinase
- Promotes formation plasmid - which breaks down the clot
Aspirin
- Inhibits thromboxane - so inhibition clot formation
What is atherosclerosis?
Atherosclerosis is a disease of the tunica intima
Causes damage to endothelium which may lead to
- Narrowing of vessel
- Obstructions
- Thrombosis
What s the difference between atherosclerosis and arteriosclerosis?
Atherosclerosis - Disease of the tunica intima - Leads to obstruction, thrombosis Arteriosclerosis - Disease of the tunica media - May increase wall thickness - Decreased elasticity - Hypertension
Describe the appearance of atheromatous plague
In the intima layer
- fatty macrophages surround a necrotic core
What is ischaemic heart disease?
- Commonest death in the western world
- Often symptomless
- 31000 prematures deaths in uk
What causes ischeamic heart disease?
Age, male, family history
Hyperlipidaemia, smoking, diabetes mellitus, obesity, hypertension
Lack of exercise, high alcohol consumption, type A personality, soft water
What causes restricted blood flow?
- Blockage
- Decrease in oxygenated blood flow (anaemia, CO poisoning, hypotension)
- Increased demand (increased cardiac output)
What is a stent?
To treat percutaneous coronary interventions (PCI) Keeps blood vessels open
What is restenosis?
The renarrowing of a treated blood vessel
What is hyperplasia?
Enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells
What is hypertrophy?
Enlargement of an organ or tissue caused by an increase in the size of the cells
What is metaplasia?
Abnormal change in the nature of a tissue
What is dysplasia?
The presence of cells of an abnormal type within a tissue, which may signify development of cancer
What is a neoplasm?
A new and abnormal growth of tissue in a pert of the body
Define benign
Not harmful, does not spread
Define malignant
Harmful, breaks through basement membrane, spreads usually poorly differentiated
Where is the world is cancer most prominent?
Geographical location
- Most common in Eastern Asia
- Followed by western Europe
- Much lower in Africa
- Study showed that certain cancers were more prominent in Japanese compared to Americans which moved to California it decreased and when had children decreased again
Give an example of a viral infection that causes cancer?
Rous sarcoma virus
Name some inherited cancers
- Retinoblastoma
- Li fraumeni
- Wilms tumour
- Gorlins syndrome
- Breast cancer
- Familial adenomatous polposis (FAP)
How is chronic myeloid leukaemia (CML) an example of genetic instability causing cancer?
- Philadelphia chromosome (chromosome 22)
- Translocation occurs due to the fusion of two genes (ABL and BCR)
- ABL is a proto - oncogene which encodes a uncle tyrosine kinase protein
- This increased activity causes increased proliferation and malignant growth
How common is cancer?
1 in 3 people will develop cancer
- A single mutation is not enough to cause cancer
- Most cancers derive from a single abnormal cell
What capabilities must cells acquire before they can become cancerous?
- Self- sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potenial
- Sustained angiogenesis
- Evading apoptosis
How are malignant neoplasms graded?
1 = Well differentiated 2 = Moderately differentiated 3 = Poorly differentiated 4 = Nearly anlaplastic - 4 is most unique normal cells and likely to develop into cancer
What is a retinoblastoma and how is it acquired?
Tumour in the retina
- First mutation inherited in germ cell
- Second mutation in somatic cell
- Loss of function of tumour suppressant gene
- People without an inherited mutation would require two mutations in somatic so unlikely
- Most people with inherited retinoblastoma get it in both eyes
What is cryogenic analysis used for?
To identify retinoblastoma gene
What are the difference between oncogenes and tumour suppressant genes?
Oncogenes - Gain of function, dominant - Only 1 allele required for effect - Enhance protein production Tumour suppressant genes - Loss of function, recessive - Two alleles required for effect - Reduced protein production
How can apoptosis cause a tumour?
if normal cell decision but decreased apoptosis
What is the role of the P53 protein?
It arrests cells when DNA is damages and turns on transcription for DNA repair
If it fails it turns on apoptosis
How do cancer cells avoid apoptosis?
- B cell leukemias express high levels of Bcl-2 which is an apoptotic regulator
- Lung and colon cancer secretes substances that destroy MHC receptors stopping T site recognition
How does tumour spread?
- Into surrounding cells
- Via lymphatics - lymph node
- Bloodstream
What is metastasis?
The spread of cancer to other parts of the body
How does metastasis occur?
It breaks though the basal lamina and enters the capillary and spread through the bloodstream
What promotes metastasis?
- Decrease in adherence between cells
- Synthesis of defective basement membrane
- Tumour angiogenesis
- Increase in cell motility
- Secretion of growth factors, ECM and proteases
- Evade host immune system
What are some treatments for cancer?
- Surgery
- Radiotherapy
- Chemotherapy
- Endocrine - related treatment
- Immunotherapy (interferons, vaccination)
- Molecular mechanism based therapies
What is a leading cause of breast cancer?
25-30% of breast tumours have Her2 amplification
- It is a receptor for tyrosine kinase which regulated cell growth
- Responds to Herceptin
What should have effective screening process be?
- Affordable to the healthcare system
- Be acceptable to all social groups
- Have good discrimination between benign and malignant lesions
- Show a reduction in mortality from the cancer
What is Herceptin and how does it work?
A drug that releases monoclonal antibodies that bind to erbB2 receptor sites which inhibits receptors function
- Causes cell cycle arrest (blocks G1)
- Suppresses angiogenesis
