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167 Cards in this Set
- Front
- Back
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what are the 3 patterns of response to stress and noxious stimuli of a cell
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1. adaptation: cell has an opportunity to change its fxn to achieve a NEW steady state and still preserve the health of the cell
2. cell injury: will compromise the cell integrity and / fxn. this injury is only reversible to a point 3. cell death: irreversible TOTAL loss of function |
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what patter of response to stress occur when:
1. adverse stimulus is of sudden onset and inc. sharply (no time to adapte) 2. no adaptive response is possible due to severity or nature of the stress 3. when the adaptive capability of the cell is exceeded |
CELL injury
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what patter of response to stress occur when:
there is acute severe stress or persistent stress with which the cell canNOT cope |
cell death
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what patter of response to stress occur when:
excessive physiologic or pathologic stimuli are at a relatively low level but are persistent |
Adaptation: the cell has an opp. to chnage its fxn. to achieve a new steady state and preserve heath
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what is hypoxia and what causes hypoxia
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hypoxia = oxygen deprivation, such that there is compromised aerobic oxidative
causes: -loss of O2 supply -loss of blood supply = ischemia (most important cause of hypoxia) -inadequate oxygenation of blood = from respiratory compromise - loss of O2 carrying capacity of the blood as from anemia CO poisoning |
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besides hypoxia what are some other causes of cell injury
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-chemical agents
-infectious agents -immunologic rxns -genetic defects -nutritonal imbalances -physical agents: trauma, extreme temp, radiation, electric shock, sudden changes in atmospheric press -aging |
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what is the most common physical agent that causes cell injury
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trauma
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most commonly effected during cell injury are the mitochondria and cell membranes what changes would a loss of mito's cause
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Mitochondria: if injured = compromised ATP generation without ATP Na+ pump activity is reduced = accumulation of Na+ and Ca2+ (due to failure of the Ca2+ pump) efflux of K+ causing a net gian of solute accompanied by isoosmotic gain of water (cel swelling)
you also have a compensatory increase in anaerobic glycolysis = rapidly depleted glycogen stores and accumulation of lactic acid resulting in dec. intracellular pH and enzyme activity |
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most commonly effected during cell injury are the mitochondria and cell membranes what changes would a loss of cell membrane
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integrity of cell membranes is affected in almost all situation of cellular injury!
-cell membranes are critical to normal cell fxns like transport in and out of the cell osmotic/ionic homeostasis, "messenger" receptors that control essential cell fxns. and enzyme fxns. |
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what is hypertrophy and under what conditions might you get this cond.
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increase in the size of the cells. this is due to larger numbers of organelles and other cellular components. enlargement of the cell NOT more of them. it is caused by increase functional demand or specific hormonal stimulation (inc. in organelles in response to inc. in workload)
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what is hyperplasia and when might it occur
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an increase in the number of cells in an organ or tissue due to
physiologic: 1. hormonal hyperplasia:ex breast proliferation during puberty and pregnancy 2. compensatory hyperplasia: compensates for tissue lost due to removal or disase pathologic: 1. excessive hormone or growth factor |
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compare and contrast hyperplasia and hypertrophy
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Hyperplasia and hypertrophy BOTH may be physiologic OR pathologic
BUT hyperplasia is an adaptive response in cells capable of replication whereas hypertrophy occurs when cells are incapable of dividing (ex. heart, thus hyperplasia will not occur in the heart) |
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atrophy is defined as shrinkage in the size of a cell due to loss of cell substance what causes atropy
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1. dec. workload, including immobilization
2. loss of innervation 3. diminished blood supply 4 inadequate nutrition 5. loss of endocrine stimulation 6. aging |
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these cells may have diminishe dxn they are NOT dead
they represent a retreat by the cell to a smaller size at which survival is still possible |
atrophy
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name the 2 proteolytic systems involved in atrophy
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ubiquitin: proteasome pthway, degrades proteins from nucleus and cytosol
autophagy: lysosomal enzymes degrade sequesered senescent organelles: process that a starved cell eats its own components in an attempt to find nutrients and survive |
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what is metaplasia and give one example
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a REVERSIBLE CHANGE where one adult cell type is replaced by another adult cell type. cells sensitive to a prticular stress are replace by other cell types better ale to withstand adverse environment
metaplasia involves epithelial cells most commonly squamous metaplasia in respiratory tract of smokers goes to stratified squamous |
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name 2 types of reversibel cell injury
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1. cellular swelling: when cells are incapable of maintaining ionic and fluid homeostasis
-inc in intracellular water accum. often related to inc. membrane permeability or loss of fxn of sodium pump. result of failure of energy depend. ion pumps in the plasma membrane leading to an inability to maintain ionic and fluid homeostasis 2. fatty change: ex. alcoholic liver disease occurs mainly in cells involved in and dependent on fat metabolism like hepatocytes and myocardial cells manifested by appearance of sm. or lg. fat vacuoles in cytoplasm |
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necrosis = IRREVERSIBLE CELL INJURY!!!
what 2 processes account for the morphologic appearance of necrosis |
1. autolysis: hydrolytic enzymes derived from dead cells themselves
2. heterolysis: enzymes dervied from lysosomes of leukocytes (outside of the cell) =macrophages |
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the microsocopic hallmarks of necrosis are seen in the nucleus what are they
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1. karyolysis: major pattern = fading of the nucleus due to enzymatic digestion
2. pyknosis: shrinkage and darkening of the nucleus 3. karyorrhexis: fragmentation of the pyknotic or partially pyknotic nucleus (not as common = subtype of pyknosis) |
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this type of necrosis is characteristic of hypoxic cell death in all tissues except the brain, it is classically seen in myocardial infarction
-will make tissue very firm and white in color -characterized by denatuation of proteins, component cells are dead but basic tiss architecture is preserved |
coagulative necrosis
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this type of necrosis is a progressive catalytic degradation of cell structures as a result of autolysis or heterolysis. it is characteristic mainly of focal (localized) bacterial infections and characteristic also of hypoxic death of CNS
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liquefactive necrosis
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this type of necrosis when necrosis of a limb ocurs ans a result of compromised blood supply
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gangrene
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what is the difference btw dry gangrene and wet gangrene
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dry: coagulative necrosis predominates, dries out and turns black
wet: liquefactive necrosis predominates due to a secodary bacterial infection -this was coagulative necrosis that progressed to wet |
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what type of change in nucleus would you see in coagulative necrosis compared to to liqueactive necrosis
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coagulative: pyknosis and/or karyorrhexis= shrinkage and darkening of nucleus, fragmentation of pyknotic nucleus
liquefactive karyolysis |
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this form of coagulative necrosis is encountered in tuberculosis
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caseous necrosis: completely obliterates tissue architecture and cell outlines
gross appearance: dry, white and cheesy |
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what is the cause of fat necrosis
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results from the abnormal release of activated pancreatic enzymes into pancreatic tissue or peritoneal cavity. accompanied by severe abdominal pain
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this special form of necrosis usually occurs with immune mediated reactions involving blood vessels
-antigen-antibody complex complexes with fibrin to form a pink amorphous layer in the blood vessel wall |
Fibrinoid necrosis
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this is a morphologic pattern of cell death that has a distinctive mode of programmed cell death that is referred to as cell suicide
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Apoptosis
mechanism: is activation of caspase family of enzymes that cleave after aspartic residues that breakdown both nuclear and extranuclear cell proteins |
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name the morphologic characteristics of apoptosis
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1. cell dev. intensely eosinophilic cytoplasm and condensed nuclear chromatin
2. cell fragments into apoptotic bodies 3. chromatin frags. are taken up and degraded by adj. phagocytic cells |
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this process is commonly used in cells undergoing atrophy to dec. the number of organelles that are in abundance
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autophagy
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what is the mechanism by which autophagy occurs
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1. organelles and portions of cytosol are sequestered in an autophagic vacuole
2. autophagi vacuole fuse with lysosome = autophagolysosomes 3. cellular debris not totally digested by autolysosomes persists as membrane bound resdiual bodies -undigested residual pigment persists as lipofuscin pigment |
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this is known as "wear and tear" pigment
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lipofusion pigment: undigest residual pigment that persistes following autophagy
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what are the subcellular responses to injury
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1. autophagy
2. mitochondrial alterations 3. cytoskeletal abnormalities 4. induction of SER |
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when is an intracellular accumulation referred to as a storage disease
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when missing enzyme is due to a genetically determined inborn error or metabolism
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true or false?
fatty change is an indicator of a lethal injury |
FALSE! NON-lethal
fatty change = steatosis appearance of fat vacuoles represents an absolute inc. in intracellular lipids = reversible cell injury |
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this intracellular accumulation is due to accumulation of Carbon dust. it is seen in the lungs of ALL city dwellers where it does not seem to cause problems. Causes a black colorit may greatly reduce respiratory fxn in "coal worker's pneumoconiosis
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Anthracosis = CARBON = exogenous pigment!
carbon is black and inhert thus usuall dec. disease prod. but in coal worker's pneumoconiosis there are very heavy carbon diposits that may greatly reduce respiratory fxn. |
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this exogenous pigment results in a a grey/white color. breathing it in in sm. doses still results in significant lung disease
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Silicosis = Silicon
* this is the only inhaled pigment that causes lung disease |
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what exogenous pigment is accumulated in silicosis
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Iron
regional to places with lots of iron in environment... no major prob. assoc. |
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true or false amalgam tattoo is an iatrogenic problem
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true! iatrogenic = caused by physicians = alloy embedded in soft tiss. = black staining of tiss.
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name the endogenous pigments (synthesized within the body) that may accumulate
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1. lipofuscin: "wear and tear pigment" undigested residual pigment persisting following autophagy
2. melanin 3. hemosiderin: yellow-brown color derived from hemoglobin breakdown |
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true or false hemosiderosis is more severe than hemochromatosis
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FALSE!
hemosiderosis: results from systemic overload of iron hemochromatosis : extreme iron overload |
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what is the difference between dystropic calcification and metastatic calcification
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dystrophic calcification: forms in deadt tissue! if necrotic debris is NOT rapidly removed by scavenger cells, calcium and other minerals salts are deposited
* this occurs when serum calcium levels are normal Metastatic calcification: depositon of calicum salts in LIVING (vital) tissue. it is due to abnormal serum calcium hypercalcemia (to get Ca2+ levels down it is thrown off into the soft tissues |
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calcinosis refers to large areas of metastatic calcification will you see this in dystrophic or metastatic calcification
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Metastatic calcification!
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what are the main characteristics of acute inflammation
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exudation of plasma fluid and proteins and aggregation of leukocytes (predominantly neutrophils)
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this inflammation is universal, immediate and early response to tissue injury. Is relatively short duration
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Acute inflammation: fundamentally a protective response whose ultimate goal is to eliminate both the initial cause of cell injury and the consequence of the injury
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this type of inflammation is typically an immune mediated response and is longer duration days to years
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chronic inflammation: characterized by presence of lymphocytes and macrophages
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What are the 3 major stimuli for acute inflammation (triggers)
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infections- most common
physical injury tissue necrosis |
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what are the characteristic vascular and cellular changes and events of acute inflammation
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vascular changes: vasodilation and inc. vascular permeability
cellular events: recruitment and activation of leukocytes at the site of injury= provide neutralization of the assult and clean-up |
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I am a hallmark of early hemodynamic changes in acute inflammation and I am the cause of rubor and calor (cardinal signs) of acute inflammation
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hyperemia = increase/excess blood flow
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what is the difference between transudate and exudate
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transudate= pure edema fluid= water and electrolytes + sm. molecules (glucose)
* transudate escapes due to changes in hydrostic and osmotic pressure exudate: inflammatory fluid = plasma + proteins! ***exudate escapes dut to changes in permeability |
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I am a type of exudate that consists of H2O+e-+sm. plasma proteins
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Serous exudate
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I am a type of exudate that consists of H2O + e- + sm and larger plasma proteins + contain fibrinogen (lg. plasma protein
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fibrinous exudate
characteristic is the large plasma protein b/c fibrinogen is also a lg. plasma protein remember that fibrinogen becomes activated to fibrin in clotting |
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I am an exudate that is also known as pus
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purulent exudate
H2O + e- + S/L plasma proteins + WBC's |
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what is characteristic of serosanguineous exudate
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RBC's they give it a characteristic pink/red color
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name the sequence of cellular events that occur during phase 3 of acute inflammation
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1. margination + rolling
2. adhesion + transmigration 3. chemotaxis and activation of leukocytes 4 phagocytosis MAC P |
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rolling and loose adhesion is mediated by what family of molecules
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selectins which are expressed on the endothelial cells and leukocytes
here the blood flow slows and WBC's tumble out of the central column and move towrd the periphery (margination and roll along the endothelium |
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Firm adhesion is mediated by endothelial cell adhesion molecules of the immunoglobulin super family which bind to what expressed on leukocytes
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Integrins are expressed on leukocytes (WBC's) allowing them to firmly adhere to the blood vessel wall
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after the WBC adheres to the blood vessel wall how does it transmigrate
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transmigrate is the leukocyte crawling between the endothelial cells. collagenases allow it to pass through the basement membrane = diapedisis
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what is diapedesis and what is the main mediator of diapedesis
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process of WBC walking through the loosened endothelial cell basement membrane
PECAM-1 is the main mediator |
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true or false chemotactic factors can be both endogenous or exogenous.
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TRUE!
exogenous = bacterial products particularly peptides with N-formyl-methionine termini |
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name all of the chemotactic factors
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bacterial products
Il-8 (cytokine) C5a (complement sys) leukotriene B4 |
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what cell is know to be back up for neutrophils
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MONOCYTES (Macrophages)!
neutrophils predominate durin the first 6-24 hrs. they are the first to arrive but undergo apoptosis w/in 24-48 hrs. MONOCYTES predominate in 24-48 hurs arrive later and live longer persist for longer periods as macrophages |
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what are the 3 distinct steps in phagocytosis
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1. recognition and attachment: accomplished via oposin.
2. engulfment: opsonins bind sp. leukocyte receptors. their binding triggers formation of phagosome 3. killing and degradation: pahgosome fuses with lysosome to form phagolysosme |
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name cells capable of phagocytosis. what cells are incapable of phagocytosis
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capable MEN
Macrophages = professionals (called monocytes when circulating in blood) Eosinophils Nneutrophils non-phagocytic = lymphocytes and plasma cells |
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name the substances that act as opsonins
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1. C3b
2. IgG 3. collectins identify things to be phagocytosized |
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the ultimate step in phagocytosis is killing and degradation what accomplishes this task
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ROS and NO
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what are the cardinal signs of acute inflammation
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Heat (calor)
redness (rubor) swelling (tumor) pain (dolor) loss of function: due to pain, swelling or nature of injury |
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what two cardinal signs of acute inflammation are caused by hyperemia and what 2 are result of mediators
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calor and rubor = hyperemia
dolor = PGE2, bradykinin |
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what are the outcomes of acute inflammation
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resolution, progression to chronic, scarring or fibrosis
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what is the major source of histamine
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Mast cells (not found in the brain
other sources: basophils and platelets |
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what is the principal mediator of the immediate phase of inc. vascular permeability in acute inflammatory response
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Histamine
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what 4 plasma protease systems does the Hageman factor initiate
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1. Kinin system: bradykini = pain
2. clotting system 3. fibrinolytic system 4. complement system |
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what initiates the Hageman factor
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exposure to collagen, basement membrane or activated platelets
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what are the actions of Bradykinin
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1. arteriorlar vasodilation
2. inc. permeability 3. PAIN fxns are almost the same as histamine it is also quickly available histamine instead of pain is chemotactic for eosinophils |
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what is the complement system
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plays important role in both immunity and inflammation serves primarily in the defense agains microbes. the end prod. is cell lysis!
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name the anaphylatoxins and what are their main fxns
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C3a and C5a both inc. vascular permeability by stimulating histamine release
C5a is also a strong chemotactic factor for granulocytes and monocytes |
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C3b is also a complement system mediator what is its fxn
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OPSONIN for phagocytosis
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true or false the cyclooxygenase pathway produes the prostaglandins and thromboxane
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true
PgD2, I2 and E2 = vasodilators PGE2 = pain and fever thromboxane TXA2 = vasoconsriction and platelet aggregaton (step zero in acute inflam. vascular changes) |
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How do NSAID's work and which arachadonic acid pathway do they affect
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NSAID's inhibit cyclooxygenase thus blocking pain by inhibiting PgE2
*** the lipoxygenase pathway is not affected = leukotrienes still prod. |
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these mediators prod. from arachadonic acid increase vascular permeability 1000X potency of histamine
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leukotrienes LTC4, D4, E4
LTB4 = chemotactic |
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corticosteriords are powerful anti-inflammatory agents how do they work
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they block both the cyclooxygenase and the lipooxygenase pathways of arachadonic acid which are most important in the later sustain phase of acute inflammation
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what cells characterize chronic inflammation
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mononulear leukocytes: macrophages, lymphocytes and plasma cells
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what cell participates in both acute and chronic inflammation
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macrophages: mediate tiss. destruction, angiogenesis and fibrosis
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what mediators induce macrophages to fuse into lg. multinucleated giant cells
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IL-4 and INF gamma
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morphological patterns of inflammation mimic those of exudate what is the pattern
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like exudate where the smallest substances leak out first you also will see the accumulation of the smallest.
serous inflammation = water + electrolytes (Protein poor) fibrinous inflammation: more severe greater vascular permeability = water,electrolytes, sm. + lg. proteins and fibrin suppurative = pus (WBC) Ulcer: granulomatous inflammation |
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what is the difference btw. an abscess and cellulitis
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Both are examples of suppurative (purulent inflammation)
Abscess = caused by staphylococci, localized b/c staph do not posses the ability to break down the extracellular matrix. instead they have coagulase which protects the bacteria from phagocytosis by walling off the infection cellulitis: caused by group A (beta hemolytic) streptococcus... they possess hyaluronidae and fibrinolysin that break down the extracellular matrix allow the infection to spread!!! |
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there are many diff. types of morphologic patterns of inflammation which ones are related to chronic vs. acute inflammation
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granulomatous inflammation= exclusively chronic inflammation, they are aggregates of activated macrophages
ulcers = both suppurative, fibrinous and serous = acute inflammation only |
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what pathologic state is granulomatous inflammation characteristic
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Tuberculosis!
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repair of lost or destroyed cells can be accomplished in one of 2 ways name them and what is the difference
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1. regeneration by parenchymal cells: specialized cells of that organ prod. the same type of cells lost
2. replacement by connective tissue: fibrosis results in a scar |
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these are tissues that are continuously dividing where will you find them
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labile tissues: have ability to repeatedly multiply b/c of the lg. population of stem cells
ex: epithelial surfaces=skin, mucosa, GI tract and urinary tract, ductal epithelium, hematopoietic sys. |
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name an example of a stable tissue (quiescent tissue). have the latent capacity to regenerate but normally do not actively replicate
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mesenchymal cells: fibroblasts endothelial cells and smooth muscle cells
parenchymal cells of solid and glandular organs: liver, pancreas, kidney, parotid, thyroid gland |
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neurons, cardiac muscle and skeletal muscle are all types of what type of dividing tissues
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permanent or non-dividing tissue they have no regenrative capacity
*** notice that smooth muscle but NOT skeletal muscle have the ability to regenerate |
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the progression of cells through the cell cycle are controlled by what family of proteins
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Cyclin family
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what is angiogenesis and what growth factors promote it
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growth of new blood vessels that orginate by budding from preexisting vessels
growth factors that stim. angiogenesis=VEGF, FGF-2 |
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This type of scarring occurs in people with a gentic defect for enzymes needed for collagen breakdown.
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Keloid formation: there is an inadequate rate of lysis of bibrous proteins that leave excessive amts. of collagen = protruding scar
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What are some extrinsic variables that modify wound healing
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INFECTION!!! (most important cause of delayed healing
nutrition, glucocorticoids (stress hormones inhibit collagen syn), mechanical factors (pulling wound open), poor perfusion, foreign bodies |
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what are some intrinsic variable that modify wound healing
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larger volume of injured tiss. type of tissue involved (permanent tiss = no option for repair except scarring)
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this is an immediate hypersensitivity response to an antigenic challenge. it means away from protection
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Anaphylaxis
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this is the most extreme form of a type I hypersensitivity that is considered life threatening
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anaphylatic shock
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what are the major components responsible for a type I hypersensitivity
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IgE, mast cells/basophils
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what defects/imbalances appear in someone with a type I hypersensitivity
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type I:
1. immunization/exposure to the antigen: pollen, animal hair,smog, insect venom 2. Production of IgE: requires Th2 subset to secrete IL-4 and IL-13 3. IL-4 and IL13: promote B-cells to switch to IgE normally Th1 subset would then perform a counter reaction by producing IL2 and IFN-gamma which suppress IgE and Th2 development. those with hypersensitvity have an imbalance of Th2 and Th1 functions |
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both mast cells and basophils are important in type I hypersensitivity what is the diff. btw the 2
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both: have high affinity for IgE, both have granules filled with histamine
Mast cells: more important, found in tissues (skin, nasal mucous memb. lungs, GI tract) may remain sensitized for up to 12 wks. basophils: found only in circulation |
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in type I hypersensitivity there is a immediate response and a late phase response what is happening in ea. of these phases
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1. immediate response is due to granule contents of mast cells being released and membrane phospholipids like PAF and PD2 : vasodilation, vascular leakage and smooth muscle spasms
late phase is due to leukocyte infiltration (LTB4,C4,D4)epitheial damage and broncho spasm |
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what is the most abundant and fastest acting preformed mediator of type I hypersensitivity
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histamine rapidly binds to H1 and H2 receptors
H1=smooth muscle = contraction and endothelial cells = inc. vascular permeability H2 = mucous membranes=inc. mucus and acid secretion |
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name the secondary mediators of a type I hypersen.
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arachidonic acid metabolism leukotrienes LTC4,D4,E4 cause slow prolonged contraction of smooth muscle play important role in asthma
prostaglandin D2 = unsaturated FA results in smooth muscle contraction |
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name the genetic factors that predispose someone to allergic response
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IL4 gene cluster: controls total IgE levels
some HLA genes control allergen sp. IgE responses Hyper IgE syndrome |
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What are some diagnostic tests done to determine allergies
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skin prick: a reaction of induation and erythema = + test = "wheal and flare"
radioallergosorbent Test (RAST) uses radiolabeled anti-IgE to quantify serum IgE ELISA- aslo quantifies serum IgE but does not require radioactivity |
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what would be the treatmet for a systemic allergic rxn. compared to a localized rxn
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systemic: administer epinephrine=opp. effect of histamine
localized: avoid the allergen, anti-histamines compete with histamine for H1 and H2 receptors, corticosteriods (immunosuppressive) |
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how do allergy shots = hyposensitization work
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you give an injection of allergen over a period of weeks form low does to rel. high.
this causes IgE to decrease and IgG and IgM to increase IgG intercepts the allergen before it reaches sensitized cells this would activate the complement system promoting phagocytosis IgG also stimulates TH1 helper cells that secretes IL2 and IFN gamma = down regulates allergic reaction |
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what are some chemical mediators of hypersensitivity type I that down regulate the reaction
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eosinophils: may release histaminase and arylsulfatase which degrade histamine and leukotrienes down reg. rxn
heparin inhibits tryptase |
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what are the major components in antibody mediated Hypersensitivity
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type II hypersensitivity!
antigen is on cells or tissues -IgG, IgM = antibodies involved they cause disease by activating the complement system, targeting cells for phagocytosis, and interfering with normal cellular fxns. |
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name the examples of type II hypersensitivity
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transfusion reactions
hemolytic disease of the newborn and drug induced reactions |
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what is the major cause of transfusion rxns
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ABO incompatibility: based on the presence of antigens (carbohydrates) on the surface of RBC's
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in HDN (hemolytic disease of newborn) how is this scenario prevented
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Rh- mother Rh+ fetus.... mother dev. antibodies to the Rh+ fetus and subsequent pregnancies the blood of the fetus is attacked by the mother.
prevention = Rhogam test= anti-Rh antibody is administered to all Rh- mothers at 7mos. and at time of delivery |
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what test is done to diagnose Hemolytic disease of the newborn
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1. direct coombs test
RBC's of infant + Coombs reagent 2. indirect coombs test: serum from mom + Rh pos. RBC's + coombs reagent agglutination indicates pos. test (antiRh antibody is present) |
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what are the 3 ways that a drug may induce a reaction
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1. act as a hapten: binding to lg. carrier molecule = cell surface. this induces antibody to bind the drug = lysis
2. drugs induce the antibody first and then bind to cell = lysis 3. drugs adsorb to cells and change its existing antigens resulting in new antigen = body no longer recognizes this antigen and tolerance is broken = lysis |
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what type of cells are destroyed in type II hypersensitivity wehn penicilin, chloramphenicol, or sedormid are involved
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penicilli: erythrocytes = hemolysis
chloramphenicol = leukocytes sedormid: platelets |
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what type of hypersensitivity involves INTERMEDIATE SIZE soluable antigen-antibody IgG, IgM complexes + complement activation
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Type III
remember type II also involves IgG and IgM but here intermediate size ocmplexes are most likely to persist and lodge in walls of blood vessels. this loding activates the complement system = creates MAD neutrophils |
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in type III immune complex hypersensitivity what is happening that is allowing the immune complexes to build up and lodge in the walls of blood vessels
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If immune complexes are made in excess or for a prolonged period of time CR1 receptors on erythrocytes become depleted (CR1 has a receptor for C3b and transports opsonized immune complexes to be engulfed) this results in a decline in efficiency of removal
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what is creating the damage in type III hypersensitivity
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the immune complexes that are lodging on the vessel walls activate the complement system generating C3a and C5a = strong neutrophil chemotactic factors
the attracted neutrophils attempt to phagocytize the complexes but get frustrated and instead release ROS and enzymes from granlues = damage |
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type III hypersensitivity can result in Arthus reaction or serum sickness what is the diff. btw the 2
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Arthus : around sm. blood vessels of the skin and is localized. results at injection sites in diabetics, insect bites, due to the substantial supply of antibodies that the body has against the antigen
serum: results from soluble circulating immune complexes: it is a systemic rxn. causing a generalized rash. the antigen could persist in kidney and other filter organs |
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why does serum sickness occur today
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antilymphocyte globulin (immunosuppressive therapy)
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what is farmer's lung disease
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type III hypersenstivity
from exposure to moldy hay resulting in Arthus like vasulitis (localized) the continued inhalation of the spores leads to localized immune complex in the alveoli |
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this typer of hypersensitivity is slowly-developing cell mediated response that involves no antibodies and no activation of the complement system
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type IV hypersensitivity, delayed type
instead involves T-lymphocytes-Th1 subset, cytokines, monocytes/macrophages remember that Th1 releaes IL2 and IFN gamma = upregulators of macrophages and down regulators of IgE |
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formation of granulomas is a unique feature of this form of hypersensitivity
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type IV hypersensitivity
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describe the mechanism of type IV hypersensitivity
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DELAYED RESPONSE:
controlled by T-lymphocytes especially the Th1 subset: prod. IFN gamma = potent activator of macrophages, IL2 and TNF beta both enhance macrophage fxn. these prod. released in an attempt to phaocytize and/or destroy the foreign invader (normal) the difference is that the antigen persists resulting in an intense prolonged rxn. = destructive to tissues |
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what are the sequence of events that occur in type 4 hypersens.
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1. sensitization phase: langerhan's cells are specialized APC' in the skin expressing high levels of MHC class II molecule, they internalize the hapten-carrier complex migrate through lymphatics present to CD4 and Th1 cells and memory Th1 helper cells gen
2. elicitation phase: Langerhan's and memory Th1 cells meet in dermis and Langerhans' presents antigen again, lg. amts of cytokines are secreted, lymphocytes and many macrophages are recruited into the skin |
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what is the clinically most serious form of type 4
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granulomatous results from a persistent agent within macrophages granuloma core consist of:
1.epithelioid cells=lg. flat nucleus, look like epithelial cells but are activated macrophages under chronic stimulation of TNF gamma 2. giant cells 3. macrophages all of these cores are macrophages |
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what infectious disease will elict a type 4 hypersens.
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tuberculosis
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what test would you perform to detect cutaneous hypersensitivity
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patch test: effective test for contact dermatitis
antigen si spread onto the skin and dressing applied induration and erythema indicates + rxn |
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what is tolerance
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inability of the immune sys. to react to antigens (self or foreign antigens
OR physiological process that allows immune system to recognize self and non-self antigens |
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name the 3 types of tolerance
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1. central tolerance
2. peripheral tolerance 3. acquired tolerance |
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this tolerance is the result of B and T cells reacting with self antigens in the bone marrow and thymus
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central
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this is a process that allows us to develop self tolerance: the ability of the immune sys. NOT to react with self antigens
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negative and positive selection
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what is positive and neg. selection
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T-cells dev. from hemopoetic stem cells in thymus and express CD4 or CD8 ++
pos: in the cortical region of thymus T-cell precursors are exposed to epithelial cells class I and II MHC. those that recognize self MHC are selected and undergo apoptosis negative selection: those T-cells that bound to self MHC in positive selection now pass on to the medulla. they differeentiat to CD3+ or CD8+ they are again exposed to self MHC those that bind with HIGH affinity are deleted via apoptosis |
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this tolerance is acquired by B and T cells after entering the peripheral circulation
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peripheral circulation
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what organs is peripheral tolerance taking place
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lymphoid tiss, peyer's patches, spleen, lymph nodes
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is B-cell neg. and + selection diff. than T-cells
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yes
B-cells selected for in bone marrow in neg. selection when B cell binds too tightly the receptor undergoes editing to allow for less tightly binding after editing if still binds to tightly it will become anergy = non-fxnal or apoptosis |
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this tolerance is acquired by non-reaction to antigens that would normally elict a humoral or cell mediated response. immune systems adaptation to external antigens
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acquired tolerance
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name some examples of acquired tolerance
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organ transplant, oral tolerance, pregnancy
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why is oral tolerance so important
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it evolved to prevent hypersensitivity to food proteins and bacterial antigens of mucosal flora
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what is the driving force for tolerance induction
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the antigen. tolerance induction is dept. on the size route of admin.
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what is the best and least effective routes of inducing tolerance
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least = subcutaneous and intramuscular due to abundance of langherangs cells
best is oral route |
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what is the consequence of breaking tolerance
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autoimmunity
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how is tolerance broken by alteration of sel/autoantigens
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self antigens can be altered by drugs (hypersen. II) infectious agents and genetic mutation
-the body no longer see antigen as self |
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how is tolerance broken by super antigen activation
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super antigen there is no antigen present but the super antigen pulls together the antigen presenting cell and T-cell receptor this results in non-sp. overexuberant response
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rheumatic fever is an example of this breaking of tolerance
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moleular mimicry: some bacterial antigens are similar to those found in huma tissue. result is an inappropriate reaction to self antigens as a consequence of infection
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what are immunologically privileged sites and how can they break tolerance
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eyes, brain, testes, pregnant uterus these tissues are sequesterd from the immune system. if they are expose to the immune system via trauma they will illict an immune response b/c they are seen as foreign antigens
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there are 4 types of grafts which ones have a less probability of rejection
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autograft: graft moved fomr one sit to another site in same indiv
isograft or syngraft: graft moved from one indv. to another of the same genetic comp. ie twins or inbred strains of animals |
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there are 4 types of grafts which ones have a more probability of rejection
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Allograft: graft moved from one indiv. to another w/in same species
xenograft: graft from indv. of one species to another indv. of diff. species |
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in preggers the fetus is a combo of both maternal and paternal gene. yet fetus is not seen as foreign. What mechanisms are at work protecting the fetus
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1. mucoprotein that coats the fetal cells
2. immunosuppressive hormones like HCG and progesterone 3. prod. of IgG4 antibodies that block immune recognition |
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this type of rejection occurs via preformed antibodies against the graft antigens activating the complement system, reaction occurs within minutes to hours
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hyperacute rejection
this is the only rejection that is irreversible |
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this type of rejection T-lymphocytes dominate the reaction Antibodies generated may kill or assist the graft (IgG4), this rejection episode occurs 7-21 days after and may be reversible
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Acute rejection
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in acute rejection you get t lymphocytes that dominate and also antibodies prod. how may these antibodis block rejection
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IGg4 may block rejection by competing with T-cells for graft antigens
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this type of rejection may occur months to years after the graft survives and has assumed normal fxn. it is characterized by narrowing of blood vessel lumen and excessiv proliferation of endothelial cells. It si known for being slowly progressing and may be reversible very early but becomes irreversible later
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chronic rejection
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name the examples of host vs. graft rejections
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hyperacute, acute, and chronic rejection
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what is graft vs. host disease
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When the graft attacks the reciient: there must be immunocompetent cells present in the graft and the patient is immunodeficient
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in this graft reaction/disease you will have a rash is the first sign that may look like a second deg. burn
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graft vs. host disease a dec. immunocompetence in the host
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what is the chance of an HLA match btw siblings
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25%
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true or false MHC proteins provoke the strongest rejection response
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true
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what is the function of cyclosporine A
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novel immunosuppresant
cyclic peptide inhibits the synthesis and secretion of IL2 by activated T helper lymphocytes thus indirectly inhibits expansion of graft sp. cytotoxic T-cells |
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what are the main complications of cyclosporin what would be an alternative drug
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kidney and liver damage
alternative would be Tacrolimus (FK506) similar to cyclosporine but more potent w/o side effects |
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what are the major infiltrating cells in cutaneous basophil hypersensitivity
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basophils
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what is the function of C5-9 complement fragments
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"membrane attack complex" to inc. the permeability
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what is the function of LTB4
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chemotaxis and leukocyte adhesion
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what autoimmune disease are systemic
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rheumatoid arthritis, Systemic Lupus, Systemic sclerosis, pemphigus vulgaris, bullous pemhigoid
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what autoimmune disease are localized
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graves disease, hashimoto's, addison's disease, myasthenia gravis, autoimmune hemolytic anemia
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