Lecture 1: Acute & Chronic Infections Flashcards
What role do N-formylated peptides have in Neutrophil Signalling?
They play a major role as potent chemoattractants
What are N-formylated peptides recognised by?
Recognised by the macrophage
Where do N-formylated peptides originate from?
Degraded bacterial proteins
What changes occur in macrophages to allow for engulfing?
Changes in actin filaments
How do antigen presenting cells act?
Presenting antigenic determinants to T cells via MHC II proteins
(communication between T-helper and macrophage)
How do antigen presenting cells become effective ‘killers’?
They become up-regulated
What is involved in the acute response to infection?
Hypothalamus - fever, re-setting body temperature
Brain - somnulence
Vascular permeability changes - hypotension & shock
(tight junctions between blood capillaries opening up)
Mobilisation of WBC - neutrophilia
(from the bone marrow)
Enhancement of neutrophil killing mechanism
Release of acute phase proteins from liver
What are the characteristics of the chronic response to infection?
Muscle and fat mobilisation - weight loss
(chronic bacterial infections are a catabolic process)
Fibroblasts stimulated - healing and repair
(continued release of acute phase proteins)
What are the components of acute phase proteins and what is the role of each?
C-reactive protein, mannose binding lectin and fibrinogen
Mannose binding lectin: binds non-specifically to the surface of bacteria - aids phagocytic process
C-reactive protein: marker of the response to infection
Fibrinogen: increases erythrocyte sedimentation rate
What is the cause of the increased erythrocyte sedimentation rate in the acute response to infection?
Fibrinogen binds to red blood cells and causes them to sediment faster
What are the differences between the 3 complement activation pathways?
Classical pathway: antigen-antibody complexes (pathogen surfaces)
MB-lectin pathway: mannose-binding lectin binds mannose on pathogen surfaces
Alternative pathway: pathogen surfaces
What marker drives a pathogen for phagocytosis?
C3b
What do C3a and C5a do in the complement activation pathway?
Peptide mediators of inflammation
Phagocyte recruitment
What does C3b do in the complement activation pathway?
Binds to complement receptors on phagocytes
Opsonization of pathogens
Removal of immune complexes
What do the terminal complement components do?
Membrane-attack complex
Lysis of certain pathogen and cells
What do Mannose binding lectin binding sites recognise?
D-mannose
L-fucose
N-acetylglucosamine
What does Mannose binding lectin bind with?
MBL binds with high affinity to mannose and fucose residues with correct spacing
How much do C-reactive protein levels increase within hours of inflammation? And what it the increase induced by?
Increase up to 10,000 fold
Indue by infection or injury
What are the rough baseline levels of C-reactive protein naturally circulating?
Low levels
What is bacteraemia?
The presence of bacteria in the blood
What are the 3 types of bacteraemia?
Transient: lasts less than 20 mins
Intermittent: implying an extravascular source
Continuous: implying intravascular source (growing within circulatory system)
What is the normal range of bacteria in a bacteraemic patient?
20-50/ mL
How are blood cultures taken?
- Inform patient of procedure
- Apply tourniquet and select vein for puncture
- Wash hands using alcohol hand rub and clean puncture site with alcohol wipe
- Enter being within palpating site again
What are the different types of growth media for blood cultures?
Blood in 5% CO2
Blood agar anaerobic
Chocolate agar in 5% CO2
Enteric agar for coliforms
Sensitivity agar (antimicrobial sensitivity)
What is the process of gaining a positive blood culture sample?
Sample is inoculated into bottle and incubated.
Signal received of a positive test (changes in pH, CO2 production, absorbance)
Sample removed from positive bottle
Sample gram stained
What would be an indication of a gram-positive cocci?
Dark blue/ violet in colour
What type of bacteria is gram positive?
Streptococcal
What type of bacteria is gram negative?
Meningococcus
What would be an indication of a gram-negative bacteria?
Pink in colour
What is bacterial endocarditis?
Physical damage to the value endothelium
What is bacterial endocarditis caused by?
Occurs by blood turbulence or the impact of micro-particles
What is deposited in the blood as a result of bacterial endocarditis? What can occur as a result of the deposits?
Fibrin and platelets
Bacteria passing by in the blood can attach to and colonise the deposits
What do bacteria in a valve give rise to?
Local pathology (local tissue damage)
Distant pathology due to septic emboli
Immune response (continued bacteraemia)
Untreated can cause death
What is prosthetic valve endocarditis?
Bacteria can be introduced at the time of operation
The infection may manifest weeks or months after the opeation
What can prosthetic valve endocarditis be divided into?
Early: < 1 year
Late: > 1 year
What is the process of blood culturing for endocarditis?
3-4 blood sets are collected from different sites
How is a positive test identified with continuous bacteraemia?
When 7/8 bottles are positive within 2 days
Antibiotic sensitivity tests are then conducted
What antibiotics are commonly used in endocarditis?
Bacteria commonly sensitive to penicillin
Benzylpenicillin (4-hourly) AND Gentamicin (2-4 weeks)
Vancomycin and teicoplanin (glycopeptides): streptococcal and staphylococcal endocarditis (penicillin allergy)
What ae the signs bacterial endocarditis is being overcome?
Patient’s temperature returns to normal
Return of C-reactive protein and erythrocyte sedimentation rate
