MoD lectures 1-7 Flashcards
Define hyperplasia
increase in cell number
Define hypertrophy
cell size increase
Define atrophy
cells decrease in size and number
Define metaplasia
Cells change their morphology
Define hypoxia
not enough oxygen, often caused by ischaemia
Define anoxia
no oxygen
What is ischaemia?
lack of blood flow
What can cell injury be due to? (5)
- insufficient oxygen availability
- physical trauma
- chemical agents
- infectious organisms
- exposure to radiation
What is the difference between exo-toxins and endo-toxins?
bacteria can produce toxins which are secreted by the cells, these are exo-toxins. The endo-toxins are toxins that are present inside the bacterial cell and is released when the cell disintegrates
What tissues have a high sensitivity to free radicals?
Bone marrow as it is high proliferating.
The uterus and pancreas have a low turnover so are not as sensitive
What does damage to the mitochondria cause?
oxidative phosphorylation is damaged so there is less ATP causing:
- the sodium pump is reduced causing an influx of calcium, water and sodium into the cell and increase efflux of potassium –> osmotic gain of water, and acute cellular swelling
- anaerobic glycolysis increases to generate ATP from glycogen, this lowers the pH due to the increased lactic acid
What is lethal cell death?
when cells are unable to achieve a new steady state following environmental insults
due to irrreversible breakdown of energy-dependent interactions between DNA, MEMBRANES AND ENZYMES
How does free radial toxicity damage cells?
some escape from the electron transport chain and damage important cellular processes or characteristics e.g. cell membrane. They can react with molecules to produce more free radicals
Which enzymes work together to diffuse oxygen based free radicals?
superoxide dismutase and catalse
How does an increase in calcium cause membrane defects?
it activates a number of enzymes: ATPases (causes atp depeletion), phospholipases (causes membrane damage), proteases (breakdown membrane and cytoskeletal problems) and endonucleases (DNA fragmentation)
What is necrosis?
cell death as a result of lethal cell injury
Is necrosis or apoptosis a passive process?
necrosis
How does necrosis incite an inflammatory reaction?
when the cells die they release small effector molecules that cause an inflammatory response
What are the 4 types of necrosis and what tissues do they affect?
Coagulative: most sorts of solid tissue except brain
caseous: tuberculosis (tissues loses all structure and looks like cottage cheese)
colliquative: brain
fat: the fat become necrotic when it is traumatized, free chain fatty acids are released when the fat breaks down which chelates calcium
What replaces the necrosis tissue in the brain?
due to the lack of collagen in the brain it liquidifies and causes a cyst
What necrosis is a sub-group of coagulative?
gangrene: there are two types wet and dry
What is apoptosis?
programmed cell death, if there is DNA/protein damage the body will stimulate apoptosis
How does chemo/radioherapy work?
agents stimulate apoptosis through DNA
How do tumours affect apoptosis?
they knock off p53 which allows the cells to recognise it has damage (also affcets bl-2)
What is a neutrophil polymorph?
neutophils that have lobed nuclei and granualar cytoplasm and function as phagocytes
What is an inflammatory exudate?
a fluid that filters from the circulatory system into lesions or areas of inflammation
What are inflammatory mediators?
molecules that are released by immune cells during times when harmful agents invade our body
What is endothelium?
the tissue which forms a single layer of cells lining various organs and cavities of our body, it is formed from embryonic mesoderm
What is resolution?
The arrest of an inflammatory process without suppuration: the absorption or breaking down and removal of the products of infloammation
What is fibrosis?
the thickening and scarring of connective tissue, usually as a result of injury
What is suppuration?
the formation or discharge of pus
What is an abcess?
a swollen area within body tissue, containing pus
What is pyogenic?
pus producing
What are the 4 cardinal features of inflammation?
heat (calor), redness (rubor), pain (dolor), swelling (tumor)
Name 4 types of inflammation?
serous: outpouring of serous fluid
fibrinous: formation of fibrin
prulent: formation of pus
psuedomembranosus:
What is the vascular reaction to acute inflammation?
dilatation
initially the flow increases then decreases due to increased permeability
What mediates the increased permeability in the vascular reaction?
histamine, bradykinin, NO, leukotriene B4 and complement components
How does the exudative reaction defeat the initial cause of inflammation?
the exudate is constantly turning over so it tends to diltue the noxius agents and it transports clumps of them to lymph nodes, it also increases the supply of oxygen and nutrients
Why does the endothelium become protein rich?
it become leaky so immunoglobins and fibrinogen leak out
What ways can you quantitate how severe the process of acute inflammation is?
measuring pyrexia and acute phase reaction proteins
What acute phase reaction proteins are usually measured?
C-reactive protein (produced in the liver), ESR (erythrocyte sedimentation rate) and plasma viscosity
How do neutrophils phagocytose bacteria?
Oxygen dependent myeloperioxidase and oxygen independent (lysozyme, lactoferrin cationic proteins) mechanisms
What do pattern recognition recepetors do?
recognize foreign cells, just recognises a pthogen, it can’t distinguish a type from another
What are cytokines?
chemical messengers that the cells of the immune system use to tell each other what they should be doing, allows for communication
Name 5 pattern recognition receptors
toll-like receptors (TLR) NOD-like receptors (ɴʟʀ) rigl-like receptos (ʀʟʀ) C-type lectins (Clr) scavenger receptors
Which receptor recognises
a) ʟps
B) Flagellin
a) toll-like receptor 4
b) Tlr5
how does complement interact with the pathogenʔ
- it induces the inflammatory response
- binding of the anitbody with the complement at the surface of the pathogen that produces very effective immune response (same mechanism that hypersensitivity reactions can occur)
Which cytokines makes you feel unwell and is the first to be producedʔ
ɪʟ1- it incxreases coagulation, inflammation, acute phase proetins and fever
What cells are the Prr onʔ
plasma
What are the primary and secondary lymphoid organsʔ
primaryː bone marrow and thymus (lymphocyte development and selection.
secondaryː spleen, lymph nodes, mucosal surfaces (where the immune response takes place)
how are B and T cells receptors codedʔ
they are coded by genes that are fragmented that can be combined to produce specificity
What human leucocyte antigens does MʜC class 1 molecules displayʔ And to what kind of T cellsʔ
ʜʟa-a
ʜʟa-b
ʜʟa-C
cytotoxic T cells
What human leucocyte antigens does MʜC class 2 molecules displayʔ And to what kind of T cellsʔ
ʜʟa-dp
ʜʟa-dq
ʜʟa-dʀ
helper T cells
What is immunosuppressionʔ
a natural or artificial process which turns off the immune system, partially or fully, accidentally or on purpose
What is immunodeficiencyʔ
the lack of an efficient immune system- susceptibility to infection
if you have a lack of or damage to neutrophils or macrophages, what infections are you more susceptible toʔ
staphylococcus aureus, salmonella, aspergillus
ones that are killed off using macrophages etc/.
if you have damage to or lack of Prr what infections are you more susceptible toʔ
pneumococcus or hSV
What are you more susceptible to if you have a problem with complementʔ
neisseria meningitis
What does a lack of B cell make you more susceptible toʔ
recurrent pulmonary problems/infections mainly
What is hypersensitvityʔ
undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host
includes allergy and utoimmunity
What are the 4 types of hypersensitivity reactionʔ
type 1ː ɪgE mediated reaction
ʇype 2ː cytotoxic reaction
type 3ː immune complex reaction
type 4ː cell mediated reaction (DTh)
What is the allergic/anapylactic responseʔ
igE Ab mediated mast cell and degranulation- release of inflammatory mediators
What occurs in an inflammatory responseʔ
hypotension, bronchospasm, mucous glands produce alot of secretions, diarrhoea
What are the pre-formed mediators that are released during degranulation as part of the intial response after the allergen binds to the mast cell (cell filled with basophil granules)ʔ
histamine (stimulation of irratant nerve receptors, smooth muscle contraction and increase in vascular permeability)
kallikrein (activates bradykinin)
tryptase E
What are the end products from the late-phase reaction of an allergic responseʔ lipid mediators
leukotrienes and prostoglandins
they are arachidionic acid derivatives
name 4 examples of an allergic response
astham
rhinitis
dermatitis
food allergy
What occurs during a type 2 hypersensitivity reactionʔ
antibodies produced by the immune response bind to antigens on the patient’s own cell surfaces.
These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.
how is the complement pathway initiated in type 2 hypersensitivity reactionsʔ
IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens. e.g. if penicillin were to bind to rBC then the rbc would be destroyed
What are type 3 hypersensitivity reactionsʔ
overproduction of immunoglobulin G (IgG) and IgM to a foreign or self‐antigen can lead to the formation and deposition of excessive amounts of insoluble intermediate‐sized immune complexes, which can be difficult to remove from various tissues by phagocytosis. This in turn may trigger classical complement activation, leading to overproduction of other inflammatory mediators
What is the end consequence of type 3 hypersensitivity reactionsʔ
tissue damage (vasculitis) due to attempted phagocytosis of complexes causing the release of enzymes and free radicals
name a condition that is an example of type 3 hypersensitivity reaction
systemic lupus erythematosus
What hypersensitivity reaction is T cell mediated and give examples?
type 4. Examples: contact dermatitis (nickel, poison ivy), mantoux test, multiple sclerosis
What type of hypersensitivity reaction is graves disease and myasthenia gravis a part of?
type V (can also be classed as being in type II) Instead of binding to cell surface s, the antibodies recognise and bind to the cell surface receptors, which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling.
What are granulomas?
masses of immune cells that form at sites of infection or inflammation
What is CGD?
chronic granulomatous disease
This is when phagocytes are unable to kill some types of bacteria and fungi. This disorder leads to long-term (chronic) and repeated (recurrent) infections.
it is sex-linked
What is granulation tissue?
an important component of healing and compromises of small blood vessel in a connective tissue matric with myofibroblasts
What are monocytes?
newly formed cells of the mononucelar system
What are macrophages?
monocytes which have entered tissue (after being in the blood) and then undergo further differentiation in macrophages. Kupffer cells ad histocytes are examples
What does caseating mean?
necrosis with conversion of damaged tissue into a soft substance
What are fibroblasts?
type of cell that synthesizes the extracellular matrix and collagen and plays a cricial role in wound healing. They are the most common cells of connective tissue in animals
What are the dominant cells in chronic inflammation?
lymphocytes (b and t cells), plasma cells and macrophages
What can result in primary chronic inflammation (5)?
- some infection - TB, leprosy
- endogenous tissue
- exogenous material
- some autoimmune diseases e.g. rheumatoid arthritis, SLE, pernicious anaemia
- primary granulomatous diseases e.g. crohn’s, sarcoidosis
What is pernicious anaemia?
auto-antibodies to intinsic factor and gastric parietal cells leads to no B12 absorption causing anaemia
What is sarcoidosis?
granulomas collecting in organs, often lungs and lymph nodes, viewed as an immune response to an infection usually
What is the most common acute inflammation that can become chronic inflammation?
supportive (pus forming)
How does acute inflammation become chronic inflammation?
If the pus forms as abscess cavity that is deep seated, and drainage is delayed or inadequate, then by the time the drainage occurs the abscess will have developed thick walls composed of granulation and fibrous tissues
The rigid walls of the abscess cavity will therefore fail to come together after drainage, and the stagnating pus within the cavity becomes organised by the ingrowth of granulation tissue, eventually to be replaced by a fibrous scar
Recurrent cycles of acute inflammation and healing can lead to chronic
Name an example of acute becoming chronic inflammation
cholecystitis (gall bladder inflammation)
This is usually due to gall stones. Multiple episodes of acute inflammation can lead to the replacements of the gall bladder by fibrous tissue and the predominant cell type becomes the lymphocyte rather than the neutrophil polymorph
What are 5 macroscopic appearances of chronic inflammation?
- chronic ulcer
- chronic abscess cavity
3 thickening of the wall of a hollow viscus (singular of viscera- organs in abdo) by fibrous tissue in the presence of a chronic inflammatory cell infiltrate - granulomatous inflammation changes
- fibrosis
What are microscopic features of chronic inflammation?
the cellular infiltrate consists of lymphocytes, plasma cells and macrophages.
Exudation of fluid is not a prominent feature
there may be production of new fibrous tissue rom granulation tissue
What does histamine do and where does it come from?
increases permeability of blood vessels to white blood cells and proteins. they are from mast cells
What are Polymorphonuclear leukocytes?
granulocytes.
Types include neutrophils, basophils, eosinophils, mast cells
produced in bone marrow
What do macrophages induce and what are they stimulated by?
induce: angiogenesis (development of blood vessels in embryo), cells to re-epthelialise the wound and create granulation tissue, angiogenesis factors for bood vessel formation in granulation tissue
What do macrophages do if they cannot kill myocabacterium?
hold and contain viable organsisms
they are long lived
What is granulation tissue?
new connective tissue and blood vessels that form on the surface of a wound during healing. consists of connective tissue cells and ingrowing young cells, it ultimately forms cicatrix
What is fibrosis?
formation of excess fibrousw connective tissue during repair of damaged tissue. it is called fibroma if arises from 1 cell line
What is a granuloma?
aggregate (nodule) of epithelioid histiocytes (macrophages when they are in cells) and other cells; lymphocytes and histiocytic giant cells
Name examples of granulmatous disease arising from these different causes:
a) bacterial
b) parasitic
c) fungal
d) synthetic material
e) unkown
a) TB, leprosy
b) schistomiasis
c) cyrtococcal in immunocompromised
d) scilicosis
e) sarcoidosis, Crohn’s
