Bacterial pathogens and disease II (exotoxins) Flashcards
What’s the Difference between gram positive and gram negative bacteria?
- Gram positive: Thick peptidoglycan layer + no outer lipid membrane
- Gram negative: Thin peptidoglycan layer + has outer layer lipid membrane
What is the main component of cell walls in gram negative bacteria?
- Contains Lipopolysaccharide (LPS) as gram negative
- Has a outer lipid membrane whereas gram positive doesn’t
- Signal for the immune system VD
Describe the 3 major components of lipolysaccharide (LPS)?
- LIPID A. - Phosphorylated glucosamines attached to long chain fatty acids. - Number and type of fatty acid vary by species. - Hydrophobic (interacts with outside of membrane)
- POLYSACCHARIDE CORE - Ketodeoxyoctanoic acid (KDO) and heptose. - Relatively constant between species - Hydrophilic (interacts with water)
- O - SIDE CHAIN - Repeat units of tri, tetra or penta-saccharide sugars. Highly variable between species - Hydrophilic (interacts with water)
State the major characteristics of endotoxin?
- Endotoxin is lipopolysaccharide (LPS)
- Lipid A is the active component. - not immunogenic (unable to produce an immune response against it)
- O antigen is highly immunogenic and immune specific.
- Found only in gram negative bacteria.
- Heat stable
- Not converted to toxoids - vaccines can’t be made
- Occurs due to being very diverse + difficult to inactivate
- Major initiator of the sepsis pathway - Lipid A drives the pathway
What is sepsis?
“Life threatening organ dysfunction caused by a dysregulated host response to infection”
Describe the process behind sepsis?
- Sepsis is the dysregulation of the normal process where innate immune cells are recruited via DAMPs and PAMPs to recruit pro-inflammatory mediators
- VD
Describe the pathway of endotoxin detection which activates immune response? VD
- CD14 detects the fatty acid chains + long chains of LPS
- MD2 then recognises the lipid A component of the endotoxin and transfers it to TLFR-4
- Binding of LPS to TLR-4 causes dimerisation of TLR-4 inducing an intracellular signalling pathway
- Leads to production of pro-IF cytokines - Innate immune response caused and acute inflammation
State the major effects of pro-inflammatory cytokines? (PART 1)
- Increase number, lifespan and activation state of innate immune cells.
- Increase adhesion molecule and chemokine expression by endothelial cells.
- Increase acute phase protein such as complement, fibrinogen and CRP.
- Cause fever
- Causes neutrophils to release extra-cellular traps (NETs) made of DNA and antimicrobial proteins that forms a scaffold for platelet activation.
State the major effects of pro-inflammatory cytokines? (PART 2)
- Cause release of microparticles by activated platelets
- Increase tissue factor expression by blood monocytes
- 5+6+7 - formation of a thrombus (immunothrombosis)
- Microbes trapped within this. - attracts and activate further leucocytes (a colourless cell which circulates in the blood and body fluids and is involved in counteracting foreign substances and disease)
Describe how systemic injury can occur via sepsis?
- Normally process achieves rapid control of localised and minor infections
- However the process may pass a threshold -> systemic injury
- If threshold is so high, the mechanism of regulation is not established (disproportionate amount of help) -> dysregulated immune response
What is the Systemic inflammatory response syndrome?
An exaggerated defense response of the body to a noxious stressor (infection, trauma, surgery, acute inflammation, ischemia or reperfusion, or malignancy, to name a few) to localize and then eliminate the endogenous or exogenous source of the insult
State the effects of sepsis dysregulation?
- Production of reactive oxygen species (ROS) - Hydroxyl and nitric oxide - damages cellular proteins, DNA and lipids and impairs mitochondria.
- Complement activation (esp. C5a) - increase ROS, granulocyte enzyme release, endothelial permeability and tissue factor expression.
- Widespread immunothrombosis leading to disseminated intravascular coagulation (DIC) with impaired microvasculature function and organ dysfunction.
Describe how sepsis is usually resolved from the body?
- This resolution is impaired when overrun with endotoxins
- Autophagy means destruction
- VD
Describe meningococcal sepsis?
- Type of endotoxin-induced sepsis
- Caused by Neisseria meningitidis
- Gram negative diplococcus
- Serotypes A, B,C, Y, W135
- Can cause disease ranging from meningitis to life threatening meningococcal sepsis.
What makes meningococcus so effective in sepsis?
- It is very effective at inducing sepsis as its LPS is different from a standard LPS. It has an O-antigen on the surface that is very short (lipooligosaccharide) and this is unique to this species. This O-antigen has a potent immunostimulant effect.
- This bacteria contains blebs (protusions) of the membrane filled with PS and specifically the lipid A component. This causes an overwhelming cytotoxic response.
