Infection Session 3- Sepsis And Innate Immunity Flashcards
What is sepsis?
Life threatening organ dysfunction due to dysregulated host response to infection- septic shock is persisting hypotension requiring treatment to maintain blood pressure despite fluid rescue situation
What is bacteraemia?
Presence of bacteria in the blood
What is the sepsis six bundle?
Oxygen Blood cultures IV antibiotics Fluid challenge Lactate Measure urine output
What urgent investigations can be done for sepsis?
FBC Urea and electrolytes ECTA bottle for PCR Blood sugar Liver function tests CRP Coagulation studies Blood gases Other microbiology samples
Which pathogen causes meningococcal meningitis?
Neisseria meningitidis
How is meningococcal meningitis spread?
Direct contact with respiratory secretions
How can the inflammatory cascade cause sepsis?
Endotoxins binds to macrophages so cytokines locally stimulate inflammatory response to promote wound repair and recruit RE system.
Cytokines released into circulation stimulating GF, macrophages and platelets.
Infection not controlled cytokines lead to activation of humoral cascades and RE system
CIRCULATORY INSULT
How can cytokines cause shock and multi organ failure?
Cytokines initiate production of thrombin and promote coagulation and inhibit fibrinolysis. Coagulation cascade leads to macrovascular thrombosis and organ ischaemia, dysfunction and failure
What supportive care can be offered for sepsis?
Early referral to ITU
Sepsis six
Regular monitoring and reassessment
What antibiotic is used to treat meningitis and why?
Ceftriaxone- penetrates into CSF
Not used for neonates/elderly
What are some of the life threatening complications of sepsis?
Irreversible hypotension Respiratory failure Acute kidney injury Raised intracranial pressure Ischaemic necrosis of digits/hands/feet
What type of bacteria is neisseria meningitidis?
Gram -ve diplococcus
What are the serogroups of neisseria meningitidis based on?
Polysaccharide capsular antigen- evades immune response by preventing phagocytosis
Outer membrane acts as endotoxin
What percentage of young adults carry meningococcal disease?
25%
How is meningococcal disease spread?
Aerosols and nasopharyngeal secretions
How many cases of meningococcal disease per year and which type?
1000 cases per year, mainly group B
What is the fatality rate of meningococcal disease?
About 10%
What are the 2 ways to prevent meningococcal disease?
Vaccination-ACYW or men C
Antibiotic prophylaxis
Define immune system
Cells and organs that contribute to immune defences against infectious and non-infectious conditions
Define infectious disease
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What are the 4 main parts of the immune response?
Pathogen recognition- cell surface and soluble receptors
Containing/eliminating the infection- killing and clearance mechanisms
Regulating itself- minimum damage to host
Remembering pathogens- preventing disease from recurring
What are the main differences between innate and adaptive immunity?
Innate = immediate protection, adaptive = long lasting protection Innate = fast, adaptive = slow Innate = lack of specificity, adaptive = specificity Innate = lack of memory, adaptive = immunologic memory Innate = no change in intensity, adaptive = changes in intensity
What are the 4 barriers of innate immunity?
Physical barriers
Physiological barriers
Chemical barriers
Biological barriers
What physical barriers exist within the body?
Skin
Mucous membranes (mouth, resp tract, GI tract, urinary tract)
Bronchial cilia
What are the physiological barriers in innate immunity?
Diarrhoea - food poisoning
Vomiting- food poisoning, hepatitis, meningitis
Coughing- pneumonia
Sneezing- sinusitis
What chemical barriers exist in the innate immune system?
Low pH- skin 5.5, stomach 1-3, vagina 4.4
Antimicrobial molecules- IgA, lysozyme, mucus, beta defensins, gastric acid and pepsin
What are the biological barriers of innate immunity?
Normal flora- non pathogenic microbes, strategic locations, absent in internal organs/tissues
Benefits- compete with pathogens for attachment sites and resources, produce antimicrobial chemicals, synthesise vitamins
How can normal flora be displaced from its normal location to sterile location?
Breaching skin integrity = skin loss, surgery, injection drug users, IV lines
Fecal-oral route = foodborne infection
Fecal-perineal-urethral = UTI
What is the main way normal flora is displaced from its normal location (not to a sterile location)?
Poor dental hygiene/dental work - common cause of harmless bacteraemia
When can normal flora overgrow and become pathogenic?
When host is immunocompromised- diabetes, AIDS, malignant diseases and chemotherapy
Give 2 examples of diseases that can be caused by normal flora being depleted by antibiotics
Severe colitis in intestine caused by clostridium difficile
Thrush in vagina caused by candida albicans
What are the second line of defence in innate immunity?
Phagocytes and chemicals
What are the main types of phagocytes?
Macrophages
Monocytes
Neutrophils
Where are macrophages found and what is their function?
Present in all organs
Function is phagocytosis (and presenting microbial antigens to T cells in AI)
Produce cytokines and chemokines
Where are monocytes found and what is their function?
Present in blood (5-7%)
Recruited at infection site and differentiate into macrophages
Where are neutrophils found and what is their function?
Present in blood (60% of blood leukocytes)
Increased during infection
Recruited by chemokines to the site of infection
Ingest and destroy pyogenic bacteria: staph aureus and strep pyogenes
What other cells are important in innate immunity and what is their function?
Basophils/mast cells- early actors of inflammation, important in allergic response
Eosinophils- defence against multicellular parasites
Natural killer cells- kill all abnormal host cells
Dendritic cells- present microbial antigens to T cells (acquired immunity)
What does PAMPs stand for?
Pathogen associated molecular patterns
Give some examples of PAMPs and what they relate to
Lipopolysaccharides- gram -ve bacteria
Peptidoglycan- gram +ve bacteria
Mannose rich glycine- all mycobacteria
Flagellum- bacterial flagella
What is opsonisation of microbes?
Opsonins bind to the microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes
Give some examples of opsonins
Complement proteins- C3b
Antibodies- IgG
Acute phase proteins- CRP
What are the two phagocyte intracellular killing mechanisms?
Oxygen dependant pathway
Oxygen independant pathways
Describe the oxygen dependant pathway (respiratory burst)
Toxic O2 products for the pathogens- hydrogen peroxide, hydroxyl radical, nitric oxide, singlet oxygen , hypohalite
What molecules are used in oxygen independant pathways?
Lysozyme
Lactoferrin/transferrin
Cationic proteins
Proteolytic and hydrolysis enzymes
Describe the 2 activating pathways in the complement system
Alternative pathway- initiated by cell surface microbial constituents
MBL pathway- initiated when MBL binds to mannose containing residues of proteins found on many microbes
What are the microbial actions of complement and which serum proteins are responsible?
Recruitment of phagocytes- C3a and C5a
Opsonisation of pathogens- C3b to C4b
Killing of pathogens, membrane attack complex- C5 to C9
What are the anti-microbial actions of macrophage-derived TNF/IL-1/IL-6 and where do they occur?
Liver (opsonins)- CRP and MBL (complement activation)
Bone marrow- neutrophil mobilisation
Inflammatory actions- vasodilation, vascular permeability, adhesion molecules = attraction of neutrophils
Hypothalamus- increased body temp
What can result in reduced phagocytosis and what causes this?
Decreased spleen function- asplenic and hyposplenic patients
Decreased neutrophil number- cancer chemotherapy, certain drugs, lymphoma and leukaemia
Decreased neutrophil function- chronic granulomatous disease, chedial-hiyashi syndrome (no phagolysosomes formation)
