microbiology and pathology Flashcards
give an example of ectopia
normal tissue forming in the wrong place, merkels diverticulum - epithelium at small intestine
give an example of atrophy
break down of tissue, if not being used or in disease, osteoporosis - decreased bone density
what is hypertrophy and describe a disease in which this is a factor
increase size of cells - muscle cells have reduced mitotic ability so increase in size instead of dividing. heart failure, increased load on heart so muscle bulk increases - ventricular hypertrophy
what is hyperplasia and what can cause it
increase number of cells, tissue becomes much thicker , can be caused by medications - gingival hyperplasia by epilepsy medication.
what is metaplasia and give an example of this
change of one differentiated tissue to another, change in epithelial type - barrett’s oesophagus, in response to GORD, change from stratified squamous to simple columnar
what is the difference between metaplasia and dysplasi
metaplasia is controlled change, dysplasia is uncontrolled, cells dividing all through the tissue, not just at bottom - could become malignant
describe 3 differences between benign and malignant tumours
benign tumours are encapsulated, keeping their growth localised. malignant tumours have no capsule, can invade other tissues (metastases). benign tumours have fewer mitotic bodies so have a slower growth rate, malignant tumours have several mitotic bodies so grow much faster. benign tumour cells all look relatively normal and are all similar from same tissue of origin. malignant tumour cells are difficult to see where they come from, all very different and pleumorphic
name the 3 types of carcinogens
chemical - tobacco, alcohol
physical - ionising radiation, UV light
viral - HPV
how can carcinogens result in tumour formation
initiation - mutating gene of cell giving it neoplasmic potential, another factor then required to cause division and formation of tumour (promotion), then progression, as division continues, malignancy is developed
what is the role of proto-oncogenes
produce proteins involved in cell division, growth factors, growth factor receptors, signal transducer
how can proto-oncogenes play a role in cancer
one genetic mutation in this gene causes the production of oncogenes which produce oncoproteins - this stimulate cell proliferation, which if uncontrolled can result in tumour formation
what are tumour suppressor genes
genes which control cell division, prevents uncontrolled growth
how can tumour suppressor genes play a role in cancer
two mutations to this gene results in cells dividing and proliferating in an uncontrolled manner
what is P53 and how is this involved in tumour formation?
as cells undergo mitosis, they have check points to check for defective DNA, if this is detected, the P53 can send the cell for DNA repair. If this is not possible, P53 sends the cell into apoptosis, this prevents any mutation being passed down cell lineage. In cancer, this protein is not produced, so mutated genes are passed to all cells, forming more tumour cells
what are the 6 main hallmarks of cancer
self-sufficient growth signals, insensitive to anti-growth signals, limitless replicative potential, production and maintenance of angiogenesis, evade apoptosis and metasises and invade other tissues
what is the difference in spread between epithelial cancers and connective tissue cancers
epithelial spread via lymph nodes and then blood vessels, connective tissue (sarcomas) spread via blood vessels first
what is tumour grading?
looking at a tumour down a microscope, at the histological appearance of the tumour cells - high grade cells are very different to cells of origin (pleomorphic) and many mitotic bodies
what is tumour staging?
determining the extent of spread of the tumour, if it is localised or metastised
what staging mechanism is used for oral cancers?
TNM - tumour size, lymph node involvement and metastasis
what are the 3 E’s in cancer immunology and what do they mean?
Elimination - immune system is removing cancer cells
Equilibrium - immune system and cancer cells are balanced but immune system coping and controlling
Escape - due to immunosuppression or another disease, the cancer cells can escape the immune system and spread to other areas
describe the process of the gram stain
stain cells with crystal violet, then iodine. then treat cells with alcohol - if gram negative, this will wash away the iodine stain, if gram positive the stain will remain. then counter stain with safrinin, this will stain colourless gram negative cells pink.
why do certain bacteria retain the gram stain
gram positive cells have a lipid bilayer and an outer cell wall of peptidoglycan, between these layers is the periplasmic space. it is in here that the gram stain is retained, as alcohol cannot penetrate through the cell wall to get to here so it is not washed away
describe the structure of gram negative bacteria
has a lipid bilayer, peptidoglycan wall and periplasmic space between. but it also has an outer most lipopolysaccharide layer. there is then another periplasmic space between the LPS and peptidoglycan, this is where the iodine is trapped. however, as cells are treated with alcohol, this can penetrate through the LPS and wash away the stain, making it gram negative
what medication can be given for gram positive infections
penicilin - breaks down cross-link bonds in peptidoglycan wall
what is the difference between an endotoxin and exotoxin
exotoxin - peptides produced within the bacteria, normally gram positive, much more potent and lethal. endotoxin - embedded in LPS in gram negative bacteria, large amount required to be lethal
give an example of a gram positive cocci bacteria
in bunches like grapes - stauphlococcus aureus, in chains - streptococcus mutans
give an example of a gram positive bacilli bacteria
closstridium difficile
give an example of a gram negative cocci
n. meningitis
give an example of a gram negative bacilli
prevotallus intermedium
what people are more at risk for fungal infections
immunocompromised
what are the 3 types of fungi
candida, asperilligus, cryptococcus
how do candida get into the blood stream
have hypha that extend from spore, these hypha can get between cells, releasing enzymes to break down the attachments
how are fungal infections treated
main aim of treatment is to attack the cell membrane - ergostril, nystatin breaks this down so the cytoplasm leaks out, fluconazol prevents the production of the membrane
describe the structure of a fungi membrane and cell wall
wall - beta glucans and chitin, membrane - ergostril
describe structure of a virus
nuclei acids, protein coat, some have a lipid envelope, have HA and NA on outside - HA for entrance to a cell, NA for leaving a cell
what effects can a virus have on a cell
death, transformation (HPV changes epithelial cell to tumour cell) or latent infection - stays in cell, embeds its DNA into cellular DNA so it is always being replicated, when a person is stressed or immunocompromised, this breaks out of cell
name the steps in the chain of infection
infectious agent, reservoir, portal of exit, mode of transmission, portal of entry, susceptible host
what is a differential diagnosis
the diagnosis after a medical history and examination, determining what diseases could be linked to the symptoms and signs, but special tests required to determine which one
what are the 2 cell lineages for defence cells
myeloid and lymphoid
what defence cells contain granulocytes and what are these
granulocytes - vesicles of destructive enzymes and anti-microbial peptides. neutrophils, basophil, eosophil, mast cells
what is the role of the dendritic cell in immunity
dendritic cell is in the blood, has long processes which can extend into tissues when detect an infection. their main role is antigen presenting - runs from the site of infection to lymphoid tissue to present antigens to B and T cells
describe antigen presentation
dendritic cells internalise and degrade antigen into linear peptides. these are then attached to MHC proteins - either I or II. T cells then bind to these proteins - CD4 to MHC II, CD8 to MHC I
what is the role of natural killer cells
respond to cells infected with virus or tumour, tries to kill these whilst waiting for adaptive immunity to kick in
what is koch’s postulates
the theory that one bacteria or organism causes one disease. can be proved by taking a sample of those with the disease and growing in culture, showing the organism is present, then putting this organism in an animal model, showing the disease will form, then removing this again and culturing to show its present
how can bacteria attach to surfaces
pilli - projections of the outer wall, allow for adhesion, or are capsulated - capsule is thick and sticky
give an example of an infection in which pilli are required
UTI - need to stick on to mucosal membrane so they are not washed away by urine
how are capsulated bacteria more dangerous
the capsule allows them to hide from the immune system, they are not phagocytosed or attacked therefore they replicate in large numbers and can then be fatal
what are non-professional immune cells
epithelial cells and fibroblasts
what are the 3 divisions of innate immunity
physical barrier, cellular mechanisms, plasma factors
how do antimicrobial peptides work
they are cationic, so are attracted to negatively charged membranes - bacteria. this brings them close to bacteria, then they have a water loving and lipid loving part. the lipid loving part tries to get through bacterial membrane as the water loving part stays outside, creates a pore through which the cell cytoplasm of bacteria leaks through and the cell is lysed
what proteins in saliva have antimicrobial peptides
cystatin, lactoferrin, lysosome
how can secretory IgA provide immune defence
it is found on mucosal membranes, binds to flagella of bacteria, prevents it moving, stops bacteria from adhering to surfaces and binds to antigens
give an example of a pattern recognition receptor
toll-like receptor
what binds to pattern recognition receptors
microbial associated molecular patterns - cell wall or membrane or nucelic acids specific
what is the result of activation of pattern recognition receptors
activates phagocytosis, alters gene transcription to produce chemokines and cytokines
what is the role of chemokines in innate immunity
sets up a chemokine concentration gradient to recruit immune cells to the site of infection
how can leukocytes be recruited in from the bloodstream
cytokines activate the endothelial cells to produce selectins - these can bind to carbohydrates in the leukocytes. slows the movement of leukocytes so they are not travelling as fast - neutrophil rolling. integrins are then activated which stop the neutrophils from moving so they can then be pulled through the gap junctions in endothelial cells by CD31
how do neutrophils attack foreign cells
has neutrophil extracellular traps, these hold the bacteria close to the neutrophil, it then degranulates releasing antimicrobial peptides to kill the infection
explain phagocytosis
the phagocyte engulfs the bacteria so it is in a vesicle in the cell - phagosome, this then fuses with a lysosome to form a phagolysosome, this then breaks the infection down to residual bodies and waste
how does phagocytosis differ to antigen presentation
antigen presentation also engulfs the cell and then fused with a lysosome - phagolysosome but instead of waste being produced, it is broken down to smaller peptides these are then paired with MHC proteins
what co-receptor is required for activation of CD4 or CD8
CD3, anchors TCR and antigen
describe the basic structure of the TCR
two chains, one alpha, one beta, each with a constant region and a variable region
how many gene segments make up the variable region in the alpha chain of the TCR
2, joining segment and variable segment
how many gene segments make up the variable region in the beta chain of the TCR
3, joining, diversity and variable segment
how is diversity of the TCR generated
due to gene re-arrangment, many possible combinations of genes which results in different proteins structures
how is it decided if a t cell will be a helper cell or cytotoxic in thymic education
the epithelial cells of the cortex of the thymus express either MHC I OR II, if the T cell binds to I it will become CD8, if it binds to II, it will become CD4
what is positive selection in thymic education
only t cells that bind to an MHC protein will develop further, those that do not will be sent for apopotosis
what is negative selection in thymic education
if t cells bind to self-antigens, they are sent for apoptosis
what is required for t cell activation
binding of TCR to antigen, binding of co-receptors on APC to T cell (CD28 - CD80), and release of cytokines from APC for the T cell to develop into a subtype effector cell
what is the role of Th1 cells
activates macrophages and produce IgG
what is the role of Th2 cells
activates B cells - normally IgE
what is the role of Tfh cells
activates B cells and support humoral immunity
what is the role of T17 cells
produce IL-17, supports innate immunity
what is the role of treg cells
regulate t cells, reduces the immune response, apoptosis of T cells and inhibits dendritic maturation
how are t memory cells generated
when effector T cells are produced, most are short lived but some remain - these are memory cells for a second infection
how do CD8 cells generate cytotoxic
after binding, causes release of granules which contain granzymes, these can get through the membrane of the infection and then stimulate apoptosis pathways in the cell
what is the general structure of the antibody and where does the antigen bind
two chains - one light and one heavy, antigen binds to the fab region - fc region is the constant region
what segments make up the heavy chain of the antibody
one variable gene segment, one constant, followed by a hinge segment, after this follows 2 more constant segments
what segments make up the light chain of the anitbody
just one variable and one constant
how does the antibody generate diversity
different antibody for each antigen, due to a number of genes to choose from, several combinations of these genes are possible, so different structures able to be formed
what are the main classes of antibody and what are their functions?
IgG - most numerous, small, exists in tissues, responsible for resistance, IgE - recruits mast cells and basophils, involved in parasitic infections and allergy, IgM - immature antibody, produced initially until IgG can be produced, IgD - main receptor on the B cell, IgA - secretory, found on mucous lining, important innate
describe B cell maturation and development
mainly just gene rearrangment to produce a specific B cell receptor. at first, IgM expressed as BCR but as matured, replaced with IgD although the cell can still secrete IgM
what is negative selection in B cell development
presents the B cells with self-antigens, if any B cells bind to them, they are removed and sent for apoptosis
name 3 roles of antibodies
opsonisation for phagocytosis, natural killer cells and mast cell degranulation, neutralises bacterial toxins, activates complement
what is the main goal of B cell activation
differentiation to plasma cells, which then generate a large number of the specific antibody
what are the two ways in which B cells can be activated
within lymphoid tissue with T cells - thymus dependant
outwith the lymphoid tissue, not requiring T cells - thymus independant
how do T cells activate B cells
B cells and T cells bind to same antigen, when T cell binds and is activated, the subtype effector cell is produced (Th2 or Tfh), B cell binds to this along with co-receptors (CD40). Cytokines are then released from the effector cell and these cause the B cells to differentiate into plasma cells which then produce antibodies
what is avidity
class switching in thymus dependant activation, when plasma cells first produced, initially they produce IgM but then they produce IgG for a stronger response, these are also required for generation of memory cells
How do B cells produce memory cells
when plasma cell produces IgG antibody, some of these remain once the infection passes, then at a second infection, the IgG cells can bind directly to the antigen for a much faster response - IgM stage is not required
what is affinity
the strength of bond between antibody and antigen, this increases with more infections, affinity at the second infection will be stronger than the first, this will then leave memory cells with a stronger affinity
describe thymus independant activation of B cells
something released from microbe that the B cell can bind to - LPS from gram negative bacteria binds to BCR - this then activates the B cell, producing plasma cells and releasing antibodies - but only IgM produced with no memory cells left
what is meant by tolerance
when b and t cells do not respond to normal cells, when an immune response is not desired - e.g. self-antigens
what is central tolerance
tolerance that is made in either the thymus or the bone marrow. for T cells this is the positive and negative selection they undergo in thymic education. For b cells, this is the negative selection in b cell maturation
what is peripheral tolerance
tolerance that is made out with the bone marrow or thymus, in lymph nodes. For t cells, when they are activated they require 3 steps. without one of these, anergy occurs and cell sent for apoptosis, even if antigen binds to TCR. For B cells, most of these need to bind to T cells for activation, unlikely a B and T cell will bind to same self-antigen
give an example of breach of tolerance
sjorgen’s syndrome, autoimmune against salivary ducts
what 3 processes are involved in acute inflammation
vascular dilation, vascular permeability and neutrophil migration
what is the vascular response to acute inflammation
increased vascular dilation and calibre - more capillaries recruited to increase flow to the area. also increase the permeability to become leaky
how is inflammatory exudate formed
when the capillaries increase permeability, immune cells can enter the area along with fluid and salts from the blood vessel
what is inflammatory exudate composed of
immune cells, fluid and salts, glucose, complement protein, fibrin
name 2 chemical mediators of acute inflammation
histamine and prostaglandins
how is histamine released
through degranulation of mast cells and basophils in response to complement
what is the role of histamine
vascular dilation and permeability, neurotransmitter for itch
what is the role of prostaglandins
regulate cytokines and chemokines, vascular dilation, tissue remodelling, activates pain pathway
how can prostaglandins be inhibited
NSAID like ibruprofen will ihibit COX-II to prevent production of prostaglandins
what activates the fibrin, coagulation and kinin system
hageman factor (factor XII)
describe the activation of bradykinin
hageman factor converts prekalikrien to kalikrien, this then activates kininogen to bradykinin
what is the role of bradykinin
activates complement, causes vascular permability, increases cytokines and chemokines for inflammation, activates pain pathway
how is the fibrinolytic pathway activated
plasminogen converted to plasmin which converts fibrin to soluble fibrin particles
what is the role of the fibrinolytic pathway
to reduce blood clots when they are no longer required to prevent clotting to death, also plasmin activates the complement pathway
what is suppuration
formation of an abscess
what is an abscess
a collection of dead neutrophils and bacteria, encompasses in pyogenic membrane - prevents it from travelling to anywhere
what is required for resolution of acute inflammation
limited tissue damage, rapid elimination of causative agent and a tissue that is able to regenerate
how does chronic inflammation differ from acute
less neutrophils, more macrophages and lymphocytes, productive producing more new fibres rather than exudative
what are the types of chronic inflammation
non-specific, specific and granulomatous
when does non-specific chronic inflammation occur
when acute inflammation has failed to resolve, get bouts of inflammation followed by resolution, changing between tissue damage and tissue formation
what is specific chronic inflammation
when a specific causative agent causes the chronic inflammation
what are granulomas and how are they formed
when macrophage presents antigen and activates T cell, Th1 cell causes macrophage to form epitheliod macrophages, these then fuse together to form giant cells - forms a wall against the infective agent
what is oro-facial granulomatous
when granulomas are found on the soft tissues in the mouth, may exist along with crohn’s disease - known as oral crohn’s
what are the subsets of macrophages
M1 - inflammatory, causes inflammation
M2 - anti-inflammatory, growth factors for tissue production
how can chronic inflammation cause destructive damage
inflammatory macrophages activated at one area whilst anti-inflammatory cells in the adjacent, causes tissue production at one area but this is dysregulated, more destructive than productive
What contributes to the destruction of gingiva in periodontal disease
MMP’s, lack of TIMP’s and NOS and ROS
how does the function of MMP’s differ in health and disease
in health - MMP’s remodel ECM to allow cells to flow through the tissue or for angiogenesis. These are regulated by TIMP’s.
In disease - cytokines and plasmin upregulate MMP’s so they remove more ECM, they also inhibit the production of TIMP’s so the removal of ECM is unregulated
in health, how is osteoblastogenesis and osteoclasogenesis balanced
osteoclasts are activated by RANKL binding to RANK, this is then turned off and osteoblasts activated by osteoprotogerin
in periodontal disease, what contributes to the alveolar bone loss
macrophages activate RANKL which stimulates osteoclasts for bone resorption. Due to high levels of RANKL, OPG is down-regulated, therefore nothing controlling osteoclasts or activating osteoblasts
what is the difference between regeneration and repair
regeneration occurs when the tissue damage is minimal and the inflammation is resolved, allowing cells of the same function to be produced. Repair involves wound healing and scar tissue formation, function is not regenerated
what are the different cell types of proliferative capacity
labile, stable and pernament
name the steps involved in wound healing
haemostasis, inflammation, proliferation and remodelling
what is involved at the haemostasis step of wound healing
vasoconstriction, platelet aggregation and coagulation to prevent blood loss
what occurs at the inflammation stage of wound healing
vasodilation, influx of immune cells removing an infection or debris. causes wheal and flare
what occurs at the proliferation stage of wound healing
granulation tissue formation. vascular permeability and angiogenesis to allow nutrients to enter site of infection. then get fibroblasts entering and laying down collagen to form the wound
what occurs at the remodelling stage of wound healing
the collagen fibres are rearranged to improve the strength of the tissue, as it reaches the epithelial level, epithelial cells are laid down and the wound contracts to close by myofibroblasts.
what controls angiogenesis in wound healing
growth factors released from cytokines, VEGF is main one
what stages are involved in fracture healing
inflammation, soft callus, hard callus and remodelling
what occurs at the initial stage of fracture healing
inflammation, influx of immune cells to remove any infection, vascular dilation and permeability
how is the soft callus formed in fracture healing
due to influx of chondrocytes and fibroblasts, results in formation of fibrocartilage
how is the hard callus formed in fracture healing
once soft callus laid down, mineralisation of this occurs to produce woven bone, not in any structure
what occurs at the remodelling stage of fracture healing
over time, the hard callus is changed into cortical bone in lamellae arrangement, but this takes time
what is fibrosis
extensive deposition of collagen fibres, scar tissue laid down but dysregulated due to ongoing inflammation
what causes fibrosis
M2 cells releasing anti-inflammatory cells and growth factors to deposit collagen fibres, despite the ongoing inflammation. results in more destruction rather than productive
what is a hypersensitivity reaction
an exaggerated reaction to an antigen
describe sensitisation in type 1 hypersensitivity reaction
antigen binds to t cell - t cell produces Th1 effector cell, this binds to B cell, b cell produces plasma cells which produce IgE antibodies - these antibodies then bind to mast cells and basophils at the Fc region
what happens in a type 1 hypersensitivity reaction at the second exposure
antigen binds to the IgE antibody on the mast cells and basophils, this then causes degranulation of these cells - results in release of histamine, vascular dilation, can cause mucous secretions
what is localised degranulation in type 1 reaction called
atrophy, normally has a genetic component
how can a type 1 reaction be fatal
widespread degranulation, results in vascular dilation and oedema, laryngeal oedema and bronchial constriction
what is a hapten
a small allergen that has to bind to a carrier protein to exert its effect, penicillin is a hapten
how can a type 1 reaction be treated
anti-histamine - blocks release of histamine, reducing the symptoms, hydrocortisone cream inhibits histamine, epinephrine through an EpiPen - reverses effects of anaphylatic shock
give an example of a type 2 hypersensitivity reaction
in blood transfusion, if wrong blood type delivered, antibodies in patients blood will attack the antigens on the donor blood - result in haemolysis
how do type 3 hypersensitivity reactions occur
antibody-antigen complexes that are intermediate in size, not phagocytosed, in blood vessel causes complement release and attracts neutrophils, results in inflammation of the blood vessel - vasculitis, arthur reaction
what is serum sickness
when the type 3 reaction is not localised, more widespread, can cause a rash and fever, can result from penicillin
what are type 4 reactions also known as and why
delayed hypersensitivity due to recruitment of T cells as this requires more time
give an example of a type 4 reaction
contact dermatitis - release of macrophages
what determines if cell injury is reversible or not
the tissue that is damaged - its ability to generate repair, how susceptible it is and how it can adapt
the extent of damage - once past a certain point, repair unable regardless of factors
what can cause cell injury
hypoxia, ischaemia, chemical damage, ionising radiation, infections, nutritional imbalance
what are 2 mechanisms of cell injury that is reversible
cloudy swelling and fatty change
how does cloudy swelling occur
lack of oxygen results in lack of ATP so carriers across membrane altered, allows Na to enter cell, water follows this causing a swelling of the cell
how does fatty change occur
triglycerides build up in cells, causing an increase in lipid vacuoles, occurs in liver after alcohol
what is blebbing
when parts of the cell break away from the membrane, as this becomes uncontrollable, cell passes point of no return
what occurs in necrosis
blebbing uncontrollable, cytoplasm leaks out of cell, get an immune reaction to this, increase inflammation and phagocytosis of the cell
define necrosis
cell death in response to tissue damage
how can you tell a cell is necrotic
the nucleus becomes black, then smaller fragments then it disappears
what is the effect of necrosis
functional effect is dependant on the area, always get inflammation which then results in scar production
what are the types of necrosis and give examples of each
coagulative - structure remains but becomes fibrotic, myocardial infarction, liquefactive - cells are lysed producing a puss, bacterial infections, caseous - mass lysis of tissue, normally granulomas are broken down - TB
when is apoptosis required
if DNA damage detected in cells, cells infected with viruses, to immune cells when immune reaction no longer required, epithelial cells when dead
what are some differences between apoptosis and necrosis
inflammation with necrosis, not with apoptosis, apoptosis requires ATP, cells shrink with apoptosis, enlarge with necrosis, cell membrane intact and nucleus contained with apoptosis
what is amyloidosis
deposition of amyloid protein by abnormal plasma cells, blocks tissue and organ, can cause organ failure, result of chronic inflammation or multiple myeloma
