Immunology and Cancer Flashcards
Describe acute inflammation
- sudden onset, short, usually resolves
* neutrophil reaction
Describe chronic inflammation
- slow onset (may follow acute inflammation), long, may never resolve
- lymphocyte and macrophage reaction
3 main cells from the inflammatory response
- neutrophils - pus cells
- macrophages - phagocytic
- lymphocytes - immunological memory
- (endothelial cells)
- (fibroblasts)
Describe neutrophils
- short lived
- first response for acute inflammation
- granular cytoplasm - contain lysosomes (enzymes) that digest bacteria
- usually does at the scene - become yellow
- release chemicals that attract other inflammatory cells
Describe macrophages
- live weeks to months
- phagocytic
- May present antigen to lymphocytes
- a few die at the scene
- (many types of macrophage, this is the generic name)
Describe lymphocytes
- live for years
- control inflammation - produce chemicals that attract other inflammatory cells
- immunological memory for past infections/antigens
Describe endothelial cells
- become sticky during inflammation so inflammatory cells stick to them
- become porous so inflammatory cells can pass into tissue
Describe fibroblasts
- long lived
- particularly present in chronic inflammation
- responsible for scarring (form collagen)
Define:
• B lymphocytes
• T lymphocytes
B lymphocytes - produce antibodies
T lymphocytes - memory cells that produce chemicals to draw other inflammatory cells in
Define
• regeneration
• repair
Regeneration - initiating factor removed OR damaged tissue can regenerate
Repair - initiating factor still present OR damaged tissue is unable to repair
(Tissue replaced with fibrous tissue and scarring)
2 types of skin wound healing
Healing by 1st intention - best possibility
• incision fills with fibrin and blood
• fibroblasts make collagen
• repair + scar
Healing by 2nd intention
• if can’t suture smoothly
• can grow across eventually, but repair is not upwards
• larger scar, paler tissue
Define:
• thrombosis
• embolus
Thrombosis - solid mass of blood constituents formed within intact vascular system during life
Embolus - mass of material in vascular system able to become lodged within a vessel and block it
Describe thrombus formation
- damaged endothelium of artery
- collagen underneath exposed
- positive feedback loop - placement activation factor makes more platelets stock
- disruption of laminar flow - RBCs may stick too
- fibrin deposited (positive feedback loop of fibrin from fibrinogen)
3 parts of Virchow’s triad
Any 1 or combination increases risk of thrombosis
Changes to:
• vessel wall
• blood flow
• blood constituents
4 potential outcomes if thrombus is not treated?
- lysis and resolution - thrombus breaks down, but still need to consider what that vessel was supplying
- organisation - repair and scar tissue (vessel becomes stuck to itself)
- recanalisation - return of blood flow after previous occlusion (scar and residual thrombus at site)
- embolism - usually if part of the thrombus breaks off and spreads to other places
3 ways to prevent thrombus formation
- exercise
- elastic circulation stockings - squeezes blood out of leg veins
- aspirin - inhibits platelet aggregation
Causes of embolus
- atheroma with thrombus
- atrial thrombus
- valve vegetation - growth of bacteria on a heart valve causing infection
- thrombus from old/recent myocardial infarct
Define:
• ischaemia
• infarction
Ischaemia
• reduction in blood flow
Infarction
• reduction in blood flow that causes cell death (subset of ischaemia)
What is reperfusion injury?
Ischaemia-reperfusion injury, IRI
- when tissue is damaged by return of blood supply after a period of ischaemia or lack of oxygen
- induces comas can help prevent this
Define
• end artery supply
• dual supply
End artery supply
• only one way in
• e.g. the heart is mainly end arteries (not watershed though)
Dual supply
• if one is blocked, blood can still get to the organ
• few organs have this
• (e.g. lungs and liver, therefore rarely get infarction in these organs)
Describe watershed areas/territories
- region of the body that receives dual blood supply from the most distal branches of 2 large arteries
- if blood supply is decreased in either vessel, this can be problematic (despite being dual supply)
- can cause watershed strokes in the brain
Define and describe atherosclerosis
- buildup of plaque on artery walls which can restrict blood flow - also comes with inflammation and fibrosis
- can be fats, cholesterols and other substances
- the plaque can burst, leading to thromboses
- almost all >70s will have it
Describe the distribution of atherosclerosis in the body
- very prevalent in systemic arteries (i.e. derive from aorta)
- often occurs at bifurcation of arteries
• does not occur in veins or pulmonary arteries - low pressure so thrombus forms rather than plaque
Risk factors for atherosclerosis
- smoking
- hypertension
- diabetes mellitus - only if poorly controlled
- hyperlipidaemia - high cholesterol
- more prevalent in more deprived, industrial areas
- more prevalent in men with ischaemic heart disease
Atherosclerosis formation theory
Endothelial damage theory
• based on risk factors also damaging endothelial cells
• endothelial cells are delicate and very metabolically active
• recurrent endothelial cell injury - microthrombi formation, healing and haemorrhaging over years to form atherosclerosis
(Note, lipid insudation theory is incorrect)
Treatment of atherosclerosis
- lower risk factors
* aspirin - antiplatelet
Complications of atherosclerosis
- blocked arteries
- infarctions
- weakened aorta - aneurism (excessive, localised swelling of an artery wall)
2 types of cell death
- apoptosis - falling off, one cell at a time
* necrosis - killing, traumatic cell death in large areas of cells
Describe apoptosis
- programmed cell death
- something, usually DNA damage, indicates to resting cell that it’s time to die
- cell releases enzymes that cause it to shrink, nucleus shrivels too
- organelles go into membrane bound vesicles
- macrophages eventually digest fragments
Gatekeeper of genome
Effectors of apoptosis
P53 protein - detects DNA damage and produces other chemicals which cause apoptosis
Caspases
• internal (within cell) - apoptosis inhibited by Bcl-2 proteins
• internal (within cell) - apoptosis stimulated by BAX proteins
• external - Fas receptor on surface of cells. It switches on caspases if Fas ligand binds
Use of apoptosis
- stop damaged cells from reproducing in disease
- development - e.g. unwebbing fingers
- normal function - tissue with high cell turnover need to remove cells at end of useful life
- lack of apoptosis in cancer (i.e. cancer isn’t too much growth, but too little cell death)
- too much apoptosis in HIV
4 clinical examples of necrosis
- frostbite
- cerebral infarction
- avascular necrosis of bone - many bones have poor blood supply, e.g. scaphoid
- pancreatitis
Word roots
- hyper-
- meta-
- dys-
- a-
- -trophy
- -plasia
- hyper- = excess
- meta- = change
- dys- = bad, not right
- a- = without
- -trophy = nourishment
- -plasia = formation
Names for tissues getting bigger
- hypertrophy - increase in size of cells (usually in cells that can’t divide, e.g. muscle)
- hyperplasia - increase in the number of constituent cells (cells stay the same size, e.g. smooth muscle)
• can have a mixture of hypertrophy and hyperplasia - occurs in pregnant uterus smooth muscle
Name for tissues getting smaller
- atrophy - decrease in size of cells OR decrease in number of constituent cells
- e.g. muscular atrophy - muscles become smaller when not used, but number of cells is constant
- a term for both of what could be called ‘hypotrophy’ or ‘hypoplasia’…but aren’t
Define metaplasia
change in differentiation of a cell from one fully differentiated type to another fully differentiated type
2 examples of metaplasia
- bronchus - ciliated columnar epithelium becomes squamous when exposed to cigarette smoke. Consider chronic bronchitis and smokers’ cough
- Barret’s oesophagus - stratified squamous epithelium to simple columnar with goblet cells due to GORD
Define dysplasia
imprecise term for morphological changes seen in cells in the progression to becoming cancer (i.e. not yet cancer)
What is spina bifida?
- formation of tube but failure to close
* exposed spinal cord
3 main types of spina bifida
- spina bifida oculta - missing spinus process, asymptomatic
- meningocele - meninges bulge out and may be repaired and function normally
- myelomeningocele - parts of spinal cord and cauda equina comes out, often paralysis of lower limbs
Types of genetic abnormality
- chromosome - autosomal/sex chromosome
- single gene inheritance - Mendelian
- polygenetic (most common)
Define:
• inherited
• acquired
Inherited
• due to genetic abnormality, which may or may not be present at birth
Acquired
• caused by non-genetic (environmental) factors, may be congenital, e.g. foetal alcohol syndrome
Why don’t adult cells divide as much?
Telomeres
• are at end of chromosome to allow replication of DNA for cell division
• telomere becomes shorter after each division
• eventually it can’t replicate anymore
• paternally inherited
