Sepsis Flashcards
What are 2 challenges of vaccine production
- Pathogenic strains can mutate, and become resistant
- Route of transmission of the disease can be difficult
- Some diseases only affect humans, so animal models cannot be used
True or false: ROS activate nuclear receptors such as NF-KB, HIP or p53.
True
What are antibiotics
used to treat bacterial infections, by killing the pathogens, or preventing them from spreading
What are pro-inflammatory cytokines
a communication mechanism which cause inflammation.
What are the symptoms of a cytokine storm
Fever Vomiting/Diarrhoea Rash Increased body temp Tachycardia Hypertension Tachypnoea resp failure
What are the 4 types of cytokine
- lymphokines
- monokines
- interleukins
- chemokines
What are monokines produced by
mononuclear cells
What are defensins
Cationic proteins able to form ion pores in membranes
What are MHCs
genes encoding cell surface glycoproteins required for antigen presentation to T cells
Give 3 effects of T reg cells
- Release inhibitory cytokines
- Release anti-inflammatory cytokines
- Cause cytolysis of effector cells
- Act in competition with APC cells
- Cause cytokine deprivation
- Turn off dendritic cells
How is meningitis diagnosed
It is diagnosed via CSF analysis (from a lumbar puncture)-
Describe COX-2 enzymes
induced by inflammation. COX2 inhibitors are selective and have less GI effects
PRR activation leads to what
proteasome degradation of IkB.
Describe MHC1 complexes
Present on nucleated cells
Interact with cytotoxic T cells
Is IL-10 pro or antiinflammatory
antiinflammatory
What are typical symptoms of meningitis
headache, fever, neck pain and a non-disappearing rash.
Which of the following are Interleukins responsible for:
- Antiviral
- Leukocytes
- Mediate chemotaxis
- Different effects, depending on cell picked up by
-Leukocytes
Which of the following are Chemokines responsible for:
- Antiviral
- Leukocytes
- Mediate chemotaxis
- Different effects, depending on cell picked up by
-Mediate chemotaxis
In missing self-hypothesis, what are two enzymes which destroy the cell
perforin and granzymes
What are interleukins produced by
a leukocyte
True or False: STAT are always present in the cytoplasm waiting to be activated by JAK
True
proteasome degradation of IkB leads to what
NF-KB transcription factor translocates to the nucleus and causes gene transcription of key parts of the immune response
what processes does JAK activation stimulate
cell proliferation
cell differentiation
cell migration
apoptosis
True or false:
ROS may have regulatory effects on numerous signalling pathways
True
Which cytokine causes the activation of CD8 cells
IFN-y
Role of eosinophils
Granules release enzymes to kill pathogens.
Describe the nitric oxide pathway of bacteria killing
o Highly toxic to bacteria and inhibits viral replication
o NO can bind to iron and deprive bacteria of this element
What does bacterial meningitis show in CSF
- Increase in leukocytes
- Elevated protein
- Less than 50% blood glucose
- Gram staining needed
- PCR if available
- Bacterial culture needed
Describe MHC2 complexes
Present on antigen presenting cells
Interact with T helper cells
Which of the following are Cytokines responsible for:
- Antiviral
- Leukocytes
- Mediate chemotaxis
- Different effects, depending on cell picked up by
-Different effects, depending on cell picked up by
What are alarmins
endogenous molecules released after infection or tissue damage (aka DAMPs).
What are lymphokines produces by
activated T cells
What are the two layers of gram-negative bacteria
peptidoglycan layer
lipopolysaccharide
What are cytokines
proteins are secreted into the bloodstream to regulate the immune response
What are commensal microorganisms
the beneficial microorganisms present on the body surfaces which are covered by epithelial cells such as the GI and respiratory tract
What is CRP
C reactive protein. a non-specific serum marker of acute inflammation, appearing hours after damage or infection.
Explain the mechanism of JAK/STAT signalling
- ligand binds (e.g. cytokine)
- receptor dimerisation activates JAK phosphorylation of receptor
- STAT binds to phosphorylated receptor
- JAK phosphorylates STAT
- STAT dimer forms
- STAT dimer travels to nucleus
- STAT dimer binds DNA and changes gene expression
Define pleiotropic effect of cytokines
One cytokine has many effects on different cells
Hypochlorous acid is produced from what?
hydrogen peroxide and chlorine
What are vaccinations
an injection containing a version of the pathogen. They trigger an immune response in the body so that if you encounter the pathogen again, then the secondary immune response is faster and more effective.
In bacterial infections, how do dendritic cells activate T helper cells
by presenting a peptide part of the pathogen to the T Helper (TLR) on the MHC 2 surface molecule
when does non-canonical NFKB signalling pathway occur
during the development of lymphoid organs responsible for generating B and T lymphocytes
Role of natural killer cells
Induce apoptosis in virus. Release perforin, which ruptures the viral membrane
What are the 5 types of vaccines
Live attenuated Dead Toxoid Conjugate DNA
True or false: a cytokine storm is a negative feedback loop of cytokine and immune cell signalling.
False- positive feedback loop
What is the function of chemokines
create a chemotactic gradient for immune cells to follow to the required site
Which of the following are Interferons responsible for:
- Antiviral
- Leukocytes
- Mediate chemotaxis
- Different effects, depending on cell picked up by
-Antiviral
What are the 5 basic mechanisms of antibiotic action
- Inhibition of Cell Wall Synthesis (most common mechanism)
- Inhibition of Protein Synthesis (Translation) (second largest class)
- Alteration of Cell Membranes
- Inhibition of Nucleic Acid Synthesis
- Anti-metabolite Activity
What is an cytokine storm
a severe immune reaction and can have devastating consequences.
What are the receptors which phagocytes possess to bind to antibodies
FcR
State two roles of commensal microorgansims
mucosal immune system
metabolic role
Protective functions
Structural function
Why is it bad to miss an antibiotic dose
can lead to bacterial resistance, as the weaker pathogens are killed first, and the stronger ones are killed last. If the course is not finished, these stronger ones remain, causing more serious infection
Does the activation of T reg cells up or downregulate the immune response
Downregulate
What is the function of DAMPs/Alarmins
They stimulate signalling pathways which initiate innate and adaptive immune responses, triggering inflammation or tissue repair, and directly sense and report damage by signalling to the environment when released from live cells undergoing physiological stress.
How can an increase in immune signalling lead to death
immune signalling leads to inflammation, which causes the destruction of tissue, and loss of organs resulting in death.
Role of neutrophils
Locate pathogens through chemotaxis. Granules contain enzymes which kill engulfed pathogens
When arachidonic acid is turned into cyclooxygenase, what is this turned into?
Endoperoxides- COX1 and COX2
What is meningitis
An inflammation of the meninges and subarachnoid space
When arachidonic acid is turned into lipoxygenase, what is this turned into?
Leukotrienes
Describe missing self-hypothesis
Cells that express self-MHC class I molecules are protected from NK cells, but those that lack this self-marker are eliminated by NK cells.
Give two ROS involved in the oxidative burst
Nitric oxide
Superoxide
Hydrogen peroxide
Hydroxyl radical
What are prostanoids
tissue specific isomerases
What can a cytokine storm be treated by
corticosteroids- which bind to cytoplasmic and nuclear receptors on the cell surface
Role of dendritic cells
Engulf the pathogen, process antigens, and present them on the CSM using MHC II molecules
Phospholipase A2 –> ?
Arachidonic Acid
What is the respiratory burst
After opsonin/ligand binding to cell surface receptors, the active NADPH oxidase is assembled to generate superoxide (O2*) in phagocytes.Superoxide spontaneously dismutates into hydrogen peroxide (H2O2), which may then react with chloride ions to form hypochlorous acid (HOCl), in a reaction catalysed by myeloperoxidase.
Give 2 classes of antibiotics
- B-lactam
- Glycopeptides
- Sulphonamides
- quinolones
- tetracyclin
- aminoglycosides
- macrolides
- amphenicols
In viral infections, the virus is released into the tissue. The epithelial cells present a peptide portion of rhe virus on which MHC
MHC1
What in addition do the cell walls of gram-positive bacteria have
peptidoglycan with 2 additional acids: alternating N-acetylglucosamine and N-acetylmuramic acid
What does viral meningitis show in CSF
- Lymphocytes increased
- Elevated protein
- Usually normal blood glucose
- PCR if available
- IgM needed
Explain the steps of NF-KB pathway
- a ligand binds to the receptor on the cell surface membrane causing conformational change
- this phosphorylates iKK activating it
- IkK phosphorylates iKB
- IkB is tagged with ubiquitin and sent to the proteasome to be degraded
- ikb dissociates from NF-KB
- NF-KB translocates to the nucleus where it starts transcription
- when negative feedback occurs, iKBa is transcribed and inhibits NF–KB
What are PAMPS
exogenous molecules found on pathogens which can be recognised by pattern recognition receptors (PRR)
When the effector T cell is activated (bacterial), which cytokine is released
IL-2
Describe the process of neutrophil attraction to a damaged site
- Damage occurs, and bacteria enters the tissue
- PRR on macrophages binds to the PAMPS on the bacteria and then phagocytosed
- Cytokines are released to surrounding tissues
- Mast cells are activated and degranulate, which causes blood vessels to become leaky
- Neutrophils enter through the gaps (drawn by cytokines) and cause phagocytosis
If TNFa pro or antiinflammatory
proinflammatory
Give three examples of prostanoids
prostaglandins
Prostacyclin
Thromboxane
Describe COX-1 enzymes
- constitutive. Synthesise prostaglandins and inhibit gastric acid secretion, promoting mucus secretion
Role of monocytes/macrophage
Phagocytes engulf pathogens and hydrolytic enzymes destroy the pathogen
Explain the steps of phagocytosis
- Phagocytes extend their membrane round the microbe.
- forms a phagocytic vacuole.
- Microbe then exposed to lysosomal-independent killing mechanisms.
- The phagosome may also fuse with a lysosome, forming a phagolysosome.
- The microbe is then exposed to lysosomal-dependent killing mechanisms.
What are the binding sites for STAT proteins
phosphotyrosine residues on the receptor proteins
State 3 pro-inflammatory cytokines
IL-1B
IFNY
IL-6
TNFa
What types of general effects may cytokines have
- pleiotropic
- synergistic
- antagonistic
- cascade
What is the Arachidonic Acid Pathway
Inflammation mediated by unsaturated fatty acids- pain fever, vascular permeability, and chemotaxis.
What can cause meningitis
may result from infections, other disorders, or reactions to drugs
In missing self- hypothesis, if cells express MHC 1 molecules, what happens?
protected from NK cells, but those that lack this self-marker are eliminated by NK cells