203 L18 Flashcards
Acute inflammation and autoimmune disease
What are the signs of inflammation?
Pain, heat, redness, swelling, and loss of function
Inflammation is a ——— response by an organism to remove the ———– stimuli and to initiate ———-.
It doesnt have to be due to an infection.
vasodilation causes ——- and increased —— flow.
Inflammation is a protective response by an organism to remove the injurious stimuli and to initiate healing.
It doesnt have to be due to an infection.
vasodilation causes swelling and increased blood flow.
Process of inflammation
The bacteria and other pathogens enter ——-.
——— from blood release blood ——– proteins at the wound site.
The bacteria produce ——- factors and ——— that causes tissue damage which signals —— cells which then release ——– and ——-. These two signal to the blood vessel causing ———- and increasing ——— so that ——- cells can leave to go to the tissue. The ——— have to first stop. They have ——- molecules that interact with the ——— on the endothelium as a response to the ——– cell signalling. This ——- them down as they interact with more until it binds to one and ——. They then penetrate through the gaps between the endothelial cells and get into the tissue.
———— secrete the chemoattractant ——- which attracts the leukocytes to the site of damage which activate cells involved in tissue ——.
The neutrophils secrete factors that kill and degrade pathogens.
——— and ———– remove pathogens by phagocytosis
Inflammatory response continues until foreign material is eliminated and the wound is repaired.
Process of inflammation
The bacteria and other pathogens enter wound.
platelets from blood release blood clotting proteins at the wound site.
The bacteria produce spreading factors and toxins that causes tissue damage which signals mast cells which then release histamine and heparin. These two signal to the blood vessel causing vasodilation and increasing permeability so that immune cells can leave to go to the tissue. The leukocytes have to first stop. They have adhesion molecules that interact with the receptors on the endothelium as a response to the mast cell signalling. This slows them down as they interact with more until it binds to one and stop. They then penetrate through the gaps between the endothelial cells and get into the tissue.
macrophages secrete the chemoattractant IL-8 which attracts the leukocytes to the site of damage which activate cells involved in tissue repair.
The neutrophils secrete factors that kill and degrade pathogens.
neutrophils and macrophages remove pathogens by phagocytosis
Inflammatory response continues until foreign material is eliminated and the wound is repaired.
How do bacteria trigger inflammation
Pathogen associated molecular patterns (PAMPs) recognised by pattern recognition receptors mostly —-.
———- cells recognise conserved structures on bacteria which have pattern recognition receptors
e.g.
Lipopolysaccharide (LPS) – found on Gram——— bacteria
Lipoteichoic acid (LTA) – found on Gram———– bacteria
Flagellin – protein part of bacterial ———-
Peptidoglycan – polymer of peptides and sugar forming bacterial —— —-
Bacterial DNA (unmethylated CpG dinucleotides)
Pathogen associated molecular patterns (PAMPs) recognised by pattern recognition receptors mostly TLR.
Immune cells recognise conserved structures on bacteria which have pattern recognition receptors
e.g.
Lipopolysaccharide (LPS) – found on Gram negative bacteria
Lipoteichoic acid (LTA) – found on Gram positive bacteria
Flagellin – protein part of bacterial flagellum
Peptidoglycan – polymer of peptides and sugar forming bacterial cell wall
Bacterial DNA (unmethylated CpG dinucleotides)
LPS or LOS- endotoxin
Has several regions
The ——- embedded in the ——- membrane of the bacterium is the part that is recognised by the ——– system
Gram ——– bacterium have an ——– membrane while gram ——– dont, so you will only see —— in gram ———- bacteria
It has regions with sugar residues - inner and outer core)
O antigen is quite variable
Has several regions
The Lipid A embedded in the outer membrane of the bacterium is the part that is recognised by the immune system
Gram negative bacterium have an outer membrane while gram positive dont, so you will only see LPS in gram negative bacteria
It has regions with sugar residues - inner and outer core)
O antigen is quite variable
LPS binding
LPS binds to ——– which are on the surface of ———- like ———–.
Co receptor ——– is always associated with ——–
——– ——- protein circulating in the bloodstream can catch the ——— and bring it to the ——- and facilitate the binding.
Once the ——- region of —— binds to the ——— there is signalling within the cell that ends up in the ——–.
The transcription factor ——— starts the expression of ————– ———–.
Other TLR signal to the same place therefore —— the signal and expression of the ——–.
LPS binds to TLR4 which are on the surface of phagocytes like macrophages.
Co receptor CD14 is always associated with TLR4
Lipid binding protein (LBP) circulating in the bloodstream can catch the LPS and bring it to the receptor and facilitate the binding.
Once the Lipid A region of LPS binds to the TLR4 there is signalling within the cell that ends up in the nucleus.
The transcription factor NF-KB starts the expression of proinflammatory cytokines.
Other TLR signal to the same place therefore amplifying the signal and expression of the cytokines.
Sepsis
If the bacteria are in the ——-, get attacked and —— they can release the ———–. If there is a lot of the ——– there will be a lot of the signalling of the ——- and as a result increased ——-. This can result in uncontrolled ———— that leads to sepsis (blood poisoning)
If the bacteria are in the bloodstream, get attacked and they can release the endotoxin. If there is a lot of the endotoxin there will be a lot of the signalling of the TLR4 and as a result increased cytokines. This can result in uncontrolled inflammation that leads to sepsis (blood poisoning)
The progression of meningococcal disease
The bacteria are gram ——– and have ——- instead of ——
Meningococcal disease starts in the ———. The bacteria are ——– there and can invade the ——– and ——– and end up in the ———-. If they proliferate in the ——- there can be damage due to abundant ——-. The bacteria can also go through the blood —— barrier and cause inflammation in the outer lining of the brain (Meningitis)
The bacteria are gram negative and have LOS instead of LPS
Meningococcal disease starts in the nose. The bacteria are attached there and can invade the tissue and mucosa and end up in the bloodstream. If they proliferate in the bloodstream there can be damage due to abundant LOS. The bacteria can also go through the blood brain barrier and cause inflammation in the outer lining of the brain (Meningitis)
Damage
Major mediator of damage is the response to ——– component of ——-.
The extensive ————- response causes most of the damage
Damage is not due specifically to the activities of the ——–, it’s our ——— system that overreacts and causes the damage.
Blebs of outer membrane containing ——- are released as immune decoys during growth in the body. The —— is picked up by the —— binding protein and is actively transported to —— and —– co receptor. Signalling occurs resulting in the ——– transcription and excessive secretion of pro-inflammatory ———.
So the damage is a result of an overreaction of our immune system, but the bacteria contribute to it.
Damage
Major mediator of damage is the response to Lipid A component of LOS.
The extensive inflammatory response causes most of the damage
Damage is not due specifically to the activities of the bacteria, it’s our immune system that overreacts and causes the damage.
Blebs of outer membrane containing LOS are released as immune decoys during growth in the body. The LOS is picked up by the lipid binding protein and is actively transported to TLR4 and CD14 co receptor. Signalling occurs resulting in the NF-KB transcription and excessive secretion of pro-inflammatory cytokines.
So the damage is a result of an overreaction of our immune system, but the bacteria contribute to it.
Damage
Major mediator of damage is the response to ——– component of ——-.
The extensive ————- response causes most of the damage
Damage is not due specifically to the activities of the ——–, it’s our ——— system that overreacts and causes the damage.
Blebs of outer membrane containing ——- are released as immune decoys during growth in the body. The —— is picked up by the —— binding protein and is actively transported to —— and —– co receptor. Signalling occurs resulting in the ——– transcription and excessive secretion of pro-inflammatory ———.
So the damage is a result of an overreaction of our immune system, but the bacteria contribute to it.
Damage
Major mediator of damage is the response to Lipid A component of LOS.
The extensive inflammatory response causes most of the damage
Damage is not due specifically to the activities of the bacteria, it’s our immune system that overreacts and causes the damage.
Blebs of outer membrane containing LOS are released as immune decoys during growth in the body. The LOS is picked up by the lipid binding protein and is actively transported to TLR4 and CD14 co receptor. Signalling occurs resulting in the NF-KB transcription and excessive secretion of pro-inflammatory cytokines.
So the damage is a result of an overreaction of our immune system, but the bacteria contribute to it.
Super antigens - non enzymatic activity
Are ——— that are released into the environment by Staphylococcus ——- and Streptococcus ——–.
Normally the bacteria is taken up by ——- cells, degraded, processed and the ——– is presented on the phagocytic cell via —— class 2 to the — cell receptor causing a normal inflammatory response
The superantigen binds to the — cell receptor as well as the —— activating increased amounts of —– cells due to low specificity resulting in a strong ———– response.
The outcome of the signalling of the superantigen is the same as the ——-, NF-KB starts the transcription of pro-inflammatory cytokines.
So if there are endotoxin and superantigens it promotes inflammation even more.
Leads to systemic acute inflammation, toxic shock syndrome
Are exotoxins that are released into the environment by Staphylococcus aureus and Streptococcus pyogenes
Normally the bacteria is taken up by phagocytic cells, degraded, processed and the peptide is presented on the phagocytic cell via MHC class 2 to the T cell receptor causing a normal inflammatory response
The superantigen binds to the T cell receptor as well as the MHC activating increased amounts of T cells due to low specificity resulting in a strong inflammatory response.
The outcome of the signalling of the superantigen is the same as the TLR, NF-KB starts the transcription of pro-inflammatory cytokines.
So if there are endotoxin and superantigens it promotes inflammation even more.
Leads to systemic acute inflammation, toxic shock syndrome
Acute rheumatic fever
Acute rheumatic fever is triggered by group A streptococcus ———-
It starts with a ——– infection, there is an initial ——– response then an ——— immune response.
Sometimes you have bacterial and host ——– that are completely different except for a small part. If this is the part of the ——— then the antibody will recognise it as well. This leads to antibody cross reaction with human antigen
If the antibody recognise the bacterium the normal reaction would be it opsonise it (sticks to the bacterium and targets it to the immune cells to act) , the ——— with the receptor for the ——— recognise it and when they engage they ———– it and kill it.
In rheumatic fever there is an antibody that recognises the tissue in the ——-. The ———- recognize the antibody but the tissue is too big to ——– so the ——— releases toxic substances like —— or ——- which then causes ———- on the heart epithelial cells.
Group A strep starts with ——-. If this isn’t treated it can lead to acute rheumatic fever. If there are several episodes of acute rheumatic fever it can cause ——- disease. At this stage it is no longer ——— but rather an ——— response.
In our ——– tissue there is a ——— protein which has a small region similar to the —— protein so the antibodies can cross react and bind to —— tissue. At this stage it is an autoimmune disease not an infection
Acute rheumatic fever is triggered by group A streptococcus pyogenes)
It starts with a bacterial infection, there is an initial immune response then an adaptive immune response.
Sometimes you have bacterial and host proteins that are completely different except for a small part. If this is the part of the epitope then the antibody will recognise it as well. This leads to antibody cross reaction with human antigen
If the antibody recognise the bacterium the normal reaction would be it opsonise it (sticks to the bacterium and targets it to the immune cells to act) , the macrophages with the receptor for the antibody recognise it and when they engage they phagocytose it and kill it.
In rheumatic fever there is an antibody that recognises the tissue in the heart. The macrophages recognize the antibody but the tissue is too big to phagocytose so the macrophage releases toxic substances like ROS or elastase which then causes inflammation on the heart epithelial cells.
Group A strep starts with pharyngitis. If this isn’t treated it can lead to acute rheumatic fever. If there are several episodes of acute rheumatic fever it can cause heart disease. At this stage it is no longer inflammation but rather an autoimmune response.
In our heart tissue there is a myosin protein which has a small region similar to the bacterial protein so the antibodies can cross react and bind to heart tissue. At this stage it is an autoimmune disease not an infection
