Infection Flashcards
Define bacteraemia
presence of bacteria in the blood
Define septicaemia
generalised sepsis
Define sepsis
SIRS + documented/presumed infection
Define severe sepsis
SIRS + organ dysfunction/hypoperfusion
shown by hypotension, decreased urine output
Define septic shock
severe sepsis + persistent hypotension despite the administration of fluids
What are the symptoms and signs of acute sepsis?
Fever nausea headache weakness general muscle aches abdominal pain pale and cool extremities fast pulse and respiratory rate low blood pressure
What does SIRS stand for?
Systemic Inflammatory Response Syndrome
What are the criteria for SIRS?
Two or more symptoms present out of: • Temperature 38 • Heart rate >90bpm • Respiratory rate >20/min • WBC 12x10⁹/l
How do microorganisms trigger the inflammatory cascade?
lipopolysaccharide endotoxins on cell wall of gram-negative bacteria trigger the inflammatory cascade
What happens in the inflammatory cascade?
endotoxin binds to macrophages
cytokines released into local environment to recruit reticuloendothelial system
cytokines released into circulation
Why does microvascular thrombosis occur as a result of the inflammatory cascade?
cytokines inititate the production of thrombin
cytokines inhibit fibrinolysis
What is the Sepsis Six?
B - blood cultures U - urine output measurement F - IV fluids A - empirical IV antibiotics L - measure serum lactate O - high flow oxygen
What kind of organism is Neisseria meningitidis?
gram negative
diplococcus
What are the symptoms of meningitis?
- a fever, with cold hands and feet
- vomiting
- drowsiness and difficulty waking up
- confusion and irritability
- severe muscle pain
- pale, blotchy skin, and a distinctive rash (although not everyone will have this)
- a severe headache
- stiff neck
- sensitivity to light (photophobia)
- convulsion or seizures
What are the features of innate immunity?
fast
lacks specificity
lacks memory
no change in intensity
What are the main types of phagocyte?
macrophage
monocyte
neutrophil
How are pathogens recognised by host cells?
PAMPs on microbial structures
recognised by PRRs on phagocytes
How is the attachment of phagocytes to microbes enhanced?
opsonisation
C3b
What processes are cytokines involved in?
chemoattraction
phagocyte activation
inflammation
How is the complement system activated?
alternative pathway
MBL pathway
Describe the alternative pathway of complement system activation
C3b deposits on microbial surface
Bb protein binds to form Alternative Pathway C3 Convertase
Which complement proteins are involved in phagocyte (neutrophil/monocyte) recruitment?
C3a
C5a
Which complement proteins are involved in opsonisation of pathogens?
C3b - C4b
Which complement proteins are involved in killing pathogens and the membrane attack complex?
C5 - C9
Define a health care infection
infection arising as a consequence of providing healthcare
neither present or intubating at the time of admission
onset at least 48 hours after admission
What kind of organism is Clostridium difficile?
anaerobic
gram positive
bacillus
What are common causes of a C diff infection?
antibiotic treatment with clindamycin, ampicillin and cephalasporins
What toxins are produced by C diff?
What is their effect?
Toxin A - enterotoxin causing excessive fluid secretion and inflammatory response
Toxin B - cytotoxin. disrupts protein synthesis. causes disorganisation of cytoskeleton
What is the treatment for C diff infections?
not severe = ten day oral metronidazole
severe = ten day oral vancomycin
What kind of organism is Staphylococcus aureus?
gram positive
coccus
facultative anaerobic
What kind of organism is Norovirus?
single stranded
RNA
non-enveloped
Which type of immunity is activated for extracellular microbes?
humoral immunity
antibodies
Which type of immunity is activated for intracellular microbes?
cell dependent immunity
cytotoxic T cells
What are MHC molecules?`
molecules inside cells coded for by HLA genes
Selectively bind to peptides produced when proteins are processed inside the host cell
present peptides on the cell surface to T cells with the appropriate TCRs
Which cells express MHC Class I molecules?
all nucleated cells
Which cells express MHC Class II molecules?
antigen presenting cells
Which cells do MHC Class I molecules interact with?
CD8+ - cytotoxic
Which cells do MHC Class II molecules interact with?
CD4+ - T helper
What kind of microbes do MHC Class I molecules present peptides from?
intracellular
What kind of microbes do MHC Class II molecules present peptides from?
extracellular
What is the function of CD4+ cells?
Release cytokines that regulate the proliferation and differentiation of T cells into helper, memory and regulatory T cells
Cooperate with B cells to enhance the production of antibodies.
induce the migration and activation of monocytes and macrophages, leading to inflammation
What is the function of CD8+ cells?
On contact with their target cell, they are able to kill the cell.
use granzymes and perforins
Which cytokines induce the proliferation of CD4 cells?
TNF-alpha
IL-6
Where does B cell activation occur?
Secondary Lymphoid Organs - spleen, lymph nodes
What is the function of plasma cells?
antibody production
Relate the structure of the spleen to its function
red pulp - removal of dead or damaged cells
white pulp - lymphoid tissue
What kind of bacteria does the spleen specifically protect against?
encapsulated
Describe the structure and function of IgA
monomer in blood
dimer in secretions
neutralisation on mucosal surfaces (first contact!) and in blood
Describe the structure and function of IgG
monomer
opsonisation
complement activation
neutralisation
crosses placenta
most abundant
Describe the structure and function of IgM
pentamer
initial response (Thinking)
Describe the structure and function of IgE
monomer
mast cell degranulation in parasitic infections and allergic response
Describe the structure and function of IgD
B cell antigen receptor on cell surface
What initiates the production of TH1 Helper cells?
IL-12 release by APCs
What is the function of TH1 Helper Cells?
release of cytokines!!!
produce INF-gamma, TNF beta and IL2
activates macrophages
promotes cytotoxic CD8+ and NK cells
promotes phagocytosis
What initiates the production of TH2 Helper cells?
IL-4 and IL-5
What is the function of TH2 Helper Cells?
produce IL-4 and IL-5, IL-10, and IL-13
promotes antibody production by plasma cells
promotes eosinophil recruitment
What type of hypersensitivity reaction are TH1 Helper Cells seen in?
Type IV
What type of hypersensitivity reaction are TH2 Helper Cells seen in?
Type I
What happens when a macrophage is activated?
increased phagocytic ability
increased respiratoty burst activity
increased MHC expression
increased release of cytokines
Describe the action of granzymes
enter cells
initiate apoptosis
Describe the action of perforins
form a pore in cells
What is the cause of chronic granulomatous disease?
unable to produce ROS due to defect in NADPH oxidase
no oxidative burst
phagocytized bacteria cannot be destroyed so granulomas form
What is hereditary angioedema caused by?
autosomal dominant disease
low levels of the plasma protein C1 inhibitor
inflammatory system activated
episodic swelling of subcutaneous tissue
What causes a malaria infection?
Plasmodium: falciparum, vivax, ovale Malariae
What are the presenting features of malaria?
six days to six months post exposure anaemia fever chills sweats splenomegaly hepatomegaly headache cough jaundice
Describe the pathogenesis of a malaria infection
mosquito bite EXOERYTHROCYTIC sporozoites enter blood stream dormant in liver = hypnozoite mature and release merozoites ERYTHTROCYTIC invade red blood cells asexual reproduction inside cell mosquito bites and ingests sexual reproduction inside mosquito to from sporozoites
What are the risk factors for malaria?
poor young children pregnancy elderly non-immune eg. travellers
Explain, in relation to time of presentation, the most likely causative organism of malaria
falciparum = 7-14 days vivax = 12-17 days ovale = 15-18 days malariae = 18-40 days
Explain, in relation to the fever cycle, the most likely causative organism of malaria
falciparum = daily vivax = tertian (relapse due to dormant parasites in liver) ovale = tertain malariae = quartan
How is malaria diagnosed?
thin blood film
State the treatment of malaria
Non-falciparum = chloroquine, primaquine
Falciparum = quinine
What organism causes typhoid fever?
Salmonella enterica serovar Typhi
What kind of organism is Salmonella enterica?
gram negative
bacillus
facultative anaerobic
fimbriae
Why is lymph node enlargement seen is Typhoid fever?
Ingested salmonella enter the small intestinal cells via endocytosis.
The bacteria then pass through the endothelial cells to the submucosa
taken up by macrophages which carry the salmonella to the reticuloendothelial system where bacteria multiply intracellularly,
What are the symptoms of typhoid fever?
• Systemic disease – bacteraemia • Severe fever • Abdominal discomfort • Constipation • Dry cough • Chills and sweats • Faint rash on trunk anaemia lymph node enlargement raised LFTs
What is the incubation period for Typhoid?
10-20 days
How is Typhoid treated?
axithromycin
ceftriaxone
What kind of organism is influenza?
RNA negative strand segmented spherical enveloped
Type A B and C
What type of influenza is the most common cause of major outbreaks?
A
What type of influenza is the most common cause of yearly oubreaks?
B
How are Influenza A serotypes categorised?
H - facilitates entry of virus into host cell
N - facilitates release of virions from infected host cells
What is antigenic drift?
minor mutations to one or both of its surface antigens
What is antigenic shift?
major and sudden changes in the H and N antigens to produce a new virus subtype
What is the incubation period for influenza?
1-3 days
What are the presenting features of influenza?
Anorexia. Malaise. Headache (retro-orbital). Fever. Myalgia. Non-productive cough and sore throat.
How is influenza managed?
Conservative
Oseltamivir and zanamivir reduce replication of influenza A and B
what does it mean if a patient is immunocompromised?
the patient’s immune system is unable to respond appropriately and effectively ot infectious organisms
What organism is often the cause of infection in those with cystic fibrosis?
why?
Pseudomonas aeruginosa
produces mucopolysaccharide, forming a biofilm, making it hard to phagocytose.
What is the difference between a primary and secondary immunodeficiency?
primary = intrinsic secondary = underlying disease or condition affecting the immune components. Decreased production or increased loss/catabolism.
What are the causes of neutropenia because of deceased production?
b12/folate deficiency malignancy infiltrating bone aplastic anaemia drugs viruses congenital disorders
What are the consequences of neutropenia?
severe life threatening bacterial or fungal infections
Name infections that patients with a neutropenia get
catalase positive staphylococcal
invasive Aspergillus
What leads to suspicion that a patient immunocompromised?
Infections that are: Severe Persistent Unusual Recurrent
If a patient is T cell deficient, what kind of infections are they susceptible to?
viral and fungal infections
PCP, VZV, CMV and EBV
How are patients with T cell deficiency managed?
no live vaccines
CMV- blood products
prophylactic antibiotics
bone marrow/stem cell transplants
If a patient is B cell deficient, what kind of infections are they susceptible to?
frequent LRT and URT infections GI complications (Giardia).
How are patients with B cell deficiency managed?
antibiotic prophylaxis
Ig replacement
If a patient is phagocyte deficient, what kind of infections are they susceptible to?
prolonged and recurrent infections
catalase positive staphylococcal
invasive Aspergillus
SEPSIS
How are patients with phagocyte deficiency managed?
prophylactic antibiotics
interferon-g (increases phagocyte activity)
stem cell transplant
