MOD week 2-4 Flashcards
what is metaplasia?
the reversible replacement of one differentiated cell type with another mature differentiated cell type.
why does hypoxia causes cell lysis?
sodium-potassium pump stops working (as needs ATP)
–> more sodium diffuses into cell
–> water goes into cell by osmosis
–> cell swells –> lysis
what effect does UV light have on DNA?
causes thymine molecules which are next to each other to fuse together –> thymine dimer
normally: exonucleases cleave out thymine dimers and replace with original nucleotides
but if:
- replace with wrong nucleotides
OR
- don’t replace at all
–> when the DNA is replicated, it will be done incorrectly –> mutation –> cancer
what is involution?
the shrinkage of an organ in old age or when inactive (e.g. uterus post-menopause)
what effect does lead have in red blood cells?
blocks the synthesis of haemoglobin –> anaemia
what does cyanide do in the body?
blocks the electron transport chain –> no oxidative phosphorylation can occur and electron back up until no respiration can occur (even anaerobic as all cofactors are reduced) –> death
describe apoptosis
‘programmed cell death’ (signals cause death)
no harmful products released (so doesn’t damage adjacent cells)
takes energy
cell shrunken
describe necrosis
abnormal, unintended cell death in response to injury
causes release of harmful products (therefore there is damage to surrounding tissue) –> inflammation
does not expend energy
cell swollen
what is a FAS receptor?
‘death receptor’
a cell-surface receptor, which, if something binds to it, triggers the cell to go into apoptosis
what are caspases?
a group of enzymes which are active in apoptosis
what does the BCL-2 protein do in normal cells? what happens if it is over expressed?
a protein which inhibits apoptotic cell death
it is over expressed in follicular lymphoma –> cells accumulate
what are the 4 different types of necrosis?
coagulative
caseous
colliguative
gangrene
describe coagulative necrosis
- most common form of necrosis
- normally caused by hypoxia/ischaemia
- dead tissue becomes firm + slightly swollen
ischaemia –> reduced ATP –> increased cytosolic Ca2+ and free radical formation –> membrane damage
(nb tissue shows retention of microscopic architecture)
describe colliquative necrosis
- occurs in brain
- neural tissue has little supporting tissue, thus liquifies upon cell death
“colLIQUative necrosis is LIQUid”
describe caseous necrosis
- dead tissue lacks any structure
- often seen in granulomatous inflammation (e.g. in TB)
“looks like cheese”
describe gangrene
Gangrenous necrosis can be considered a type of coagulative necrosis that resembles mummified tissue. It is characteristic of ischemia of lower limb and the gastrointestinal tracts. If superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene)
(dry = without infection, wet = with infection)
what are the 5 physical characteristics of acute inflammation?
redness (rubor) heat (calor) swelling (tumor) pain (dolor) loss of function
what is the characteristic cell found in acute inflammation?
neutrophil polymorph
stains neutral pink colour with lobed nucleus
(2-5 lobes)
what are the 5 causes of acute inflammation?
physical agents (e.g. trauma, frostbite, sunburn etc)
infections
hypersensitivity reactions
chemicals
tissue necrosis (get inflammation around necrosis)
what is exudate?
extravascular fluid with high protein concentration, contains cellular debris
implies inflammation
what is the difference between exudate and transudate? 4
- Exudate is cloudy while transudates are clear.
- Exudate is a result of inflammation and injury while transudate is brought about by imbalanced hydrostatic and osmotic pressure (e.g. in heart failure or kwashiorkor)
- An exudate has a higher protein content compared to a transudate.
- an exudate has higher cell/cell debris content compared to a transudate
what are the 3 major components of acute inflammation?
- changes in vessel calibre
- increased vascular permeability –> fluid exudate formation
- cellular exudate formation
what changes in vessel calibre occur in acute inflammation? and what 2 things is this mediated by?
local vasodilation (initial transient vasoconstriction)
- -> increased blood flow
- -> heat + redness
mediated by histamine and NO on vascular smooth muscle
how is the fluid exudate formed in acute inflammation?
increased permeability of microvasculature results in escape of protein-rich fluid into tissue
caused by:
- chemical mediators (e.g. histamine, NO, leukotriene)
- direct vascular injury (eg in trauma)
- endothelial injury - bacteria and toxins
what effects does the presence of fluid exudate have? 6
dilution of toxins
increased entry of antibiotics
increased transport of drugs to area
increased fibrin formation (acts as a scaffold for later granulation)
delivery of nutrients and oxygen
stimulation of the immune response
ie FLUID EXUDATE IS USEFUL!!
how does the cellular exudate form?
ie neutrophil emigration and accumulation
loss of fluid into tissues and increased calibre of vessels
- -> slower blood flow + increased viscosity of blood
- -> stasis
–> neutrophils line up along vascular endothelium, stick to endothelium + migrate through walls into tissues
what is the role of selectins in cellular exudate formation?
as the neutrophil rolls along the blood vessel wall, the selectin binds to certain carbohydrate groups presented on proteins on the neutrophil, which slows the cell and allows it to leave the blood vessel and enter the site of infection.
The low-affinity nature of selectins is what allows the characteristic ‘rolling’ action attributed to neutrophils before they exit the blood vessels
what are the 5 cell-derived mediators of acute inflammation?
histamine (vasodilator)
prostaglandins (vasodilator)
lysosomal components
leukotrines (produced by leukocytes)
cytokines
what common respiratory condition is associated with inappropriate leukotrines?
asthma
leukotrines trigger contractions in the smooth muscles lining the bronchioles; their overproduction is a major cause of inflammation in asthma
Leukotriene antagonists are used to treat asthma by inhibiting the production or activity of leukotrienes.
what are the 4 plasma-derived mediators of acute inflammation?
complement system
kinin system
coagulation system
fibrinolytic system
what is a kinin
family of polypeptides which induce vasodilation and contraction of smooth muscle
eg bradykinin
what are the 4 systemic effects of acute inflammation?
pyrexia
lymph node enlargement
nausea, malaise, anorexia
leukocytosis (high white blood cell count)
what is a non-specific marker of inflammation picked up in blood tests?
c-reactive protein (CRP)
What happens is there is excessive exudate formed as a result of acute inflammation?
suppuration (aka formation of abscess, due to accumulation of pus) occurs
what happens if there is excessive necrosis?
repair and organisation –> fibrosis
what happens is the causal agent of acute inflammation persists?
develops into chronic inflammation –> fibrosis
what is chemotaxis?
transportation of something (neutrophils, in case of acute inflammation) to correct place due to chemical stimulus
what can acute epiglottitis cause?
respiratory distress
what is diapedisis?
endothelial cells contract, so gaps form between them, so neutrophils can pass –> tissue
how do you treat an abscess?
drain it
can’t use antibiotics as they can’t reach middle of abscess
what 3 things does granulation tissue consist of?
- lots of blood vessels
- fibroblasts
- white blood cells
what are the three things that pus consists of?
living + dead neutrophils
bacteria
cell/tissue debris
what part of the lung does TB normally occur in?
top of the lungs
what’s another name for neutrophils?
polymorphic neutrocytes
what are the 7 causes of cell injury?
hypoxia (most common)
physical agents (e.g. trauma)
chemical agents (incl. drugs + poisons)
infections
immune-mediated cell injury
genetic disorders
nutritional imbalances
what is an area affected by coagulative necrosis called?
infarct
what causes pain in acute inflammation? 3
release of mediators (e.g. histamine)
tissue damage by neutrophils
physical pressure on nerves from swelling
what are the 4 possible outcomes of acute inflammation?
resolution
fibrosis
chronic inflammation
suppuration
what is margination?
accumulation and adhesion of leukocytes to the epithelial cells of blood vessel walls at the site of injury in acute inflammation
what are the 3 different types of selections and where do they originate from?
E-selectin (from endothelium)
P-selectin (from platelets + endothelium)
L-selectin (from leukocytes)
what molecules allow for leukocytes to transmigrate out of blood vessels? (i.e. diapedesis)
up regulation of integrins (role is to attach cells to extracellular matrix)
what do you call a reduction in the number of blood cells?
cytopenia
what do you call an abnormal increase in the number of cells?
cytosis
what do you call inflammation of the rectum?
proctitis
what is the term used to describe secondary pathological conditions arising from a disease?
sequelae
what are pattern recognition receptors (PRR)?
what part of the immune system are they a part of?
antigen recognition receptors
2 types:
- cell surface+ intracellular recptors
- fluid-phase soluble molecules
not specific - just tell immune system that there’s danger in the vicinity (is the fastest response)
innate system
what does the PRR TLR4 recognise?
lipopolysaccharides
(ie on gram -ve bacteria)
it triggers cell to produce inflammatory cytokines
what do the PRRs TLR7 and TLR9 recognise?
single-stranded DNA molecules
this indicates presence of virus
(cell produces cytokines in response)
nb TLR7+9 are intracellular
name a large ‘family’ of fluid-phase recognition molecules
C-type lectin family
(eg collectins, such as mannan(aka mannose)-binding lectin + surfactant protein A + D)
- they recognise microbial complex carbohydrates
- then bind to them, via carbohydrate-recognition domains (CRDs)
roles:
- neutralisation of pathogen
- recruitment of adaptive response
what do plasmacytoid dendritic cells (DCs) produce large amounts of?
what does this do?
interferon (IFN-)
antitumour + antiviral properties
what do myeloid (aka interstitial) dendritic cells produce large amounts of?
interleukin 10 + 12
what type of organism do eosinophils act against?
eosinophils
what is the function of primary lymphoid organs?
what are the 2 found in humans?
lymphocyte development and selection
bone marrow (b cells) thymus (t cells)
what is the function of secondary lymphoid organs?
what are the 3 found in humans?
to produce an immune response
- spleen
- lymph nodes
- mucosal surfaces
what is the name of the process which results in such a great variety in t and b cell receptors being transcribed?
V(D)J recombination
what is the mechanism of antigen presention on an APC?
antigen bind to specific innate (or B) cell receptor on cell membrane (basically an antibody embedded in membrane)
antigen is internalised (so signal is transmitted into cell)
antigen is broken down -> peptides
peptides are bound to newly-synthesised class 2 molecules + bought to cell surface
if peptide is foreign, it is recognised by helper T cells which are then activated
helper T cells produce cytokines needed by B cells, T cells, etc
what are major histocompatibility complexes?
what are they also known as?
glycoproteins on cell surface membranes of cells
Human Leucocyte Antigens (HLAs)
(unique to each person but vary more the less you are related to a person, eg diff ethnic groups)
- if endemic disease in an area people become more resistant as their HLAs adapt (via darwinian evolution)
diff HLAs are better at recognisisng diff diseases
- also play a role in certain autoimmune diseases (eg RA)
what are the two types of MHC/HLAs?
what’s the difference?
class 1
- found on ALL cells
- presents peptides to cytotoxic T cells
class 2
- found only on Antigen Presenting Cells
- presents peptides to helper T cells
what are the 4 ways in which the binding of antibodies to antigens inactivates said antigens?
1) neutralisation
2) agglutination of microbes
3) precipitation of dissolved antigens
1, 2 + 3 enhance phagocytosis by macrophages
4) activation of complement system
4 leads to cell lysis
what is perforin produced by? and what does it do?
cytotoxic T cells
creates cores in infected host cells
The pores formed allow for the passive diffusion of a family of pro-apoptotic proteases, known as the granzymes, into the target cell -> apoptosis
what is the difference between a basophil and a mast cell?
Mast cells are fixed in the tissues while basophils circulate in the blood
“MASTs are firmly FIXED onto boats”
what is the function of mast cells/basophils?
regulation of vascular permability
(a protective response to pathogens)
allergic responses
what is the definition of a hypersensitivity reaction?
undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against INNOCUOUS ANTIGENS) in a PRE-SENSITISED (immune) host
what are the 4 types of hypersensitivity reactions?
1 - IgE mediated
2 - cytotoxic
3 - immune complex
4 - cell-mediated
describe type 1 hypersensitivity reaction
classic anaphylaxis + allergic reactions
(incl hayfever, allergic asthma)
(common antigens incl: pollen, bee venom etc)
- happens fast (15-30mins)
sudden degranulation of mast cells + basophils
-> release of inflammatory mediators
FINISH TYPE 1!!!!
