Inflammation Flashcards
What is inflammation
Causes
-vascular and cellular response of the body to injury or invasion by pathogens
- physical trauma
- chemical trauma
- hypersensitivity reaction
- microorganisms infection
What is gram negative outer layer that’s bad to people
What molecules can make antigens
- endotoxins lipid A
- a liposaccharide
- proteins
- sugars
- glycoprotein
Conditions to classify substance as antigen
- immunologic : must stimulate immune response in specific cells
- reactive : must stimulate plasma cells to produce specific antibodies
Describe how incomplete antigens are converted to compete and their incomplete name
How does cell membrane damage come about ( pathogens and physical )
-haptens bind to skin surface and become compete antigens
/bacteria release endotoxins which damage cell membrane
-physical trauma damages
How are mast cells activated by bacteria and how they respond
-endotoxins produced by bacteria bind to receptors on mast cells ( immunoglobulin E ) and this activates them
/release inflammation molecules
- histamine
- prostaglandins
- leukotrines
Describe how bradikirins are formed
/in plasm are proteins called factor 7
- enzyme coverts them to prekalikarin
- enzyme converts to kalikarin
- kalikarin converts kinenogen in tissue into bradikirins
Other route for leukotrine and prostaglandin acquisition besides mast cells
/when membrane is damaged it releases enzyme phospholipase AC and it breaks down phospholipids into arachadonic acid
- lipo-oxygenase ( LPO ) converts arachadonic acid into leukotrines
- Cox 1 and 2 ( cyclo-oxygenase) coverts arachadonic acid into prostaglandins
Hallmarks of acute inflammation
1 edema ( swelling ) 2 pain 3 joint immobilized 4 redness ( erythema ) 5 heat
What do the mast cell molecules do to the endothelial
-activates them for inflammation
1 bind to receptor causing wiebel palade bodies inside cell to migrate to membrane and place p selectins
2 bind to receptors causing endothelial cells to contract and create gaps
How does edema come about
-after vasculature has been increases in permeability, plasma ( mainly water ) leaks into interstitial tissue , accumulates and causes swelling
How does pain come about in inflammation
- the edema applies pressure on pain receptors in interstitial tissue and this activates them producing pain
- bradikirins bind to pain receptors activating them and causing pain
What happens to smooth muscle during inflammation and the effects ( how does redness and heat come about )
Benefits of the heat
- mast molecules bind to smooth muscle causing relaxation
- allows vasculature to expand ( vasodilation)
- more blood flows to site of inflammation ( erythema )
- more heat present is vasodilated vessels ( heat )
/to increase metabolic processes to fight against inflammation
List the 3 steps of how WBC enter tissue at site of inflammation
1 margination
2 diapedesis
3 chemotaxis
Describe margination
-WBC have ligands on surface which bind to p/selectins on endothelial causing them to roll slowing
Describe how diapedesis occurs
-endothelial cells have PCAM which are expressed after cytokines and leukotrine influence which bind to WBC integrins to aid them in squeezing through vasculature openings
Describe chemotaxis
Types of chemoattractants and examples
-mast molecules stimulate WBC to migrate to site of inflammation
- exogenous ( molecules from bacteria )
- endogenous ( IL-8 , arachadonic metabolites , components of contemporary system )
What secretes IL-1 and TNF-alpha and their functions
- macrophages
- bind to endothelial to produce e-selectins which WBC bind to
Function of IL-8
-chemotaxis
- binds to endothelial to stimulate ICAM and VCAM production
- binds to endothelial receptors and activates WBC integrins so they can bind to ICAM and VCAM during diapedesis
How does fever come about and its function
/IL-1 and TNF-alpha migrate to brain ( hypothalamus )and causes release of PGF-2 which resets body temps and causes fever
-increase body metabolism
/heat detrimental to some organisms
Effect of IL-1 and TNF-alpha at liver and it’s uses
Which other chemokine the same effect
- cause production of acute phase reactant proteins ( APRP )
- if blood test done and ARPR shows up as C-reactive protein aids in deduces presence of inflammation in body
- IL-6
Effect of IL-1 and TNF-alpha on bone
Name of the process
- stimulates production of WBC’s
- leukocytosis
How does WBC fight infection
Describe
What remains !? Or can’t be digested
/engulf bacteria with pseudopodia into membrane bound vesicle inside cell ( phagocytosis)
- phagosome membrane and lysosome membrane fuse forming phagolysosome
- hydrolytic enzymes of lysosome degrade bacteria wall and cell components
-Antigens
What are antigen presenting cells and list them
/cells that present antigens on membrane
- macrophages
- b lymphocytes cells
- dendritic cells
How do neutrophil extrude antigens
-phagolysosome membrane fuses with with membrane and antigen released via exocytosis
How do neutrophils deal with bacteria resistant to lysosomes
-they sacrifice themselves
/intake O2 and converts it into reactive oxygen species ( superoxide , peroxide , hypochlorite acid ) which kill the bacteria but with cell also ( oxidative respiratory burst )
/as it is dying in release it’s chromatin which binds to bacteria and actives enzymes ( cathepsin G ) wc degenerate bacteria ( NETS ) neutrophil extracellular trap
How is antigen presented to membrane
When is a cell now called an antigen presenting cell
Which chromosomes codes for MHC molecules
- MHC-2 molecules complimentary to antigen transport it to membrane via binding
- when MHC-2 bound to antigen is at membrane
- chromosomes 6
Diff of MHC 1 and 2 and what does 1 have
/1 is found in all nucleated cells and 2 only on antigen presenting cells
-2 has a self antigen present
How many genes code for MHC molecules, name them and how do they cater for numerous antigen structures
What is recombination
- MHC 1 : A B C
- MHC 2 : DP , DR , DQ
/through recombination ( shuffling of nucleotides to produce diff proteins accommodate for numerous antigen structures )
Where do antigens go
-released into lymph nodes
Characteristics of acute inflammation
/short duration
- rapid onset
-remove injurious agent
/prevent spread
/initiate healing
-remove all necrotic tissue and cells
What happens to lymphatic vessels during acute inflammation
/increased lymph flow to accommodate all excess interstitial fluid
/proliferation of lymph cells to handle increased load
List briefly cellular response and vascular response of acute inflammation
/increased blood flow
-increased permeability
- recruiting of cells
- recognition of foreign pathogen
- removal of foreign pathogen
How do WBC dissolve basement membrane
-release collagenases
How do leukocytes recognize foreign pathogen. List the receptors involved
1 toll receptors - recognize bacterial lipopolysaccharides , proteoglycans and RNA
2 GPCR - substances produced by host cells ( leukotrines , PDGF , short bacteria polypeptides
3 opsinon receptors- recognize opsinon proteins ( lectin , antibodies , complement proteins )
4 cytokines receptor - cytokines ( IL-8 )
What is opsinosation
-coating of bacteria during inflammation with proteins to increase phagocytosis activity
How is acute response terminated after injurious agent removed
1 stimulus for inflammation no longer persists
2 mediators for response have short half life
3 neutrophils have short duration after leaving circulation
4 leukotrines converted into anti/inflammation lipoxins
5 macrophages release anti-inflammation cytokines IL-10 and TGF
6 neural impulses inhibit inflammation response
4 characteristic properties of chronic inflammation
1 ongoing tissue destruction
2 ongoing attempt to repair tissue by fibrosis
3 prolonged duration
4 has significant morbidity due to ongoing tissue damage
Causes of chronic inflammation
1 Persistent infection 2 persistent indigestible matter 3 immune mediated responses 4 following acute inflammation 5 repeated acute inflammation episodes
What causes persistent infection , examples and what does it evoke
-organism difficult to remove
/mycobacterium tuberculosis
/mycobacterium leprde
-evokes hypersensitivity reaction type 4 ( containment of infection for long time by chemical mediators)
2 Types of persistent indigestible matter and examples
-exogenous
/ silica , asbestos fibers
-endogenous
/ necrotic bone , urid acid deposits
Types of immune mediated responses that causes chronic inflammation
/auto immune reaction
-organ transplant reaction
/unregulated immune response
-hypersensitivity reactions ( body fighting harmless antigens )
How does a acute abscess cause chronic inflammation
- if it cannot be removed by body or surgically it causes chronic abscess
Macroscopical changes due to damage via chronic inflammation
- ulcers on epithelium
- cavitatory lesions On parenchyma tissue
- chronic abscess
- formation of sinuses
- formation of fistula
What is an abscess
How is a sinus formed
How is a fistula formed
- pus filled cavity surrounded by pyogenic membrane
- formed when abscess evades and corrodes surrounding tissue towards surface to try and drain abscess
- 2 epithelium surfaces connected by chronic damage
List and describe macroscopic changes due to fibrosis of chronic damage
/hollow organs thicken causing stricture ( hallowing of tube )
-distortion of organ : fibrous tissue tends to contract due to myofibroblasts to reduce size of scar but excessive contraction causes distortion
List what is seen microscopically due chronic inflammation
1 mononuclear cell infiltration
2 tissue necrosis
3 tissue regeneration
4 multi nucleic giant cells
Clinical manifestations of chronic inflammation
1 fistula
2 stricture
3 distortion of organs
4 ulcers
5 cavitatory lesions
6 chronic abscess
7 sinuses
8 end artery oblicans ( end arteries closing up )
9 metaplasia of epi surface
10 low grade long term fever due to cytokines
11 loss of appetite and weight due to inhibitatory effect of TNF-alpha
How are macrophages recruited to site of chronic inflammation
1 via blood by TGF ( transforming growth factors ) , PDGF
2 proliferation of macrophages at site of inflammation
3 immobilized macrophages at site via MIF ( migration inhibition factors ) from T lymphocytes
What does TFN/gamma do
What secretes it
/activate macrophages so that they can perform their function
-t cells and pathogen endotoxins
What do macrophages do at site of chronic inflammation
/released destructive agents 1 reactive oxygen species 2 nitric oxide 3 proteases 4 arachnoid metabolites 5 growth factors PDGF and VEGF to promote repair
