Infection Session 7 Flashcards
Under what circumstance does the virtually non-pathogenic coagulase -ve staphylococcus become pathogenic?
Upon introduction of an invasive therapy
Is Neisseria meningitidis strictly speaking a pathogen or commensal?
Commensal of the nasopharynx as it is only rarely pathogenic
What method of infection does strep pyogenes use to cause pharyngitis?
Invasion
What are the four methods of infection on surfaces?
Invasion
Migration
Inoculation
Haematogenous
Give some examples of external surface infections.
Cellulitis Pharyngitis Conjunctivitis Gastroenteritis UTI Pneumonia
Give some examples of internal surface infections.
Endocarditis Vasculitis Septic arthritis Osteomyelitis Empyema
What prosthetic surfaces can lead to surface infections?
Intravascular lines Peritoneal dialysis catheter Prosthetic joints Cardiac valves Pacing wires Endovascular grafts Ventriculo-peritoneal shunts
What is the most likely cause of prosthetic valve endocarditis
Coagulase -ve staphylococci from patient’s/surgeon’s skin
What is the pathogenesis of native valve endocarditis?
Bicuspid valve –> turbulent blood flow –> damaged endothelium –> platelets –> bacteria become lodged –> vegetation
What four process occur simultaneously in pathogenesis of infection at surfaces?
Adherence to host cells/prosthetic surface
Biofilm formation
Invasion and multiplication
Host response
Do most humans carry the same species of bacteria in the same areas as part of their microbiota?
Yes
What happens to bacterial metabolism when a biofilm is formed?
Decreases until only slime secretion continues
What induces bacteria to shrink to a spore-like state in biofilm formation?
Starvation
What turns ‘swimmers’ into ‘sinkers’ within minutes of biofilm formation starting?
Gene expression
What do bacteria that have attached to a surface do in biofilm formation?
Multiply and encase the colony w/a slimy matrix of mucopolysaccharides
What is the function of the slimy mucopolysaccharide layer in biofilm formation?
Aids sticking and protects against cellular and chemical defences
How do nutrients reach bacteria in a biofilm?
Diffusion into the matrix
What facilitates exchange of molecular signals to regulate bacterial behaviour in a biofilm?
Close proximity of cells
What relates microenvironments for different bacterial species and levels of activity within a biofilm?
Chemical gradients
What is the effect of antimicrobials on bacteria in a biofilm?
Damage outer cell layers but community is resistant
How can endocarditis lead to a brain abscess?
Shear forces propel aggregated cells to roll/ripple along a surface whilst remaining in protected biofilm
What does quorum sensing control?
Sporulation
Biofilm formation
Virulence factor secretion
How does quorum sensing control bacterial function in a biofilm?
Via autoinducers, cell surface/cytoplasmic receptors and gene expression
Why can diagnosis of causative agent in biofilm formation be difficult?
Adherent organisms, low metabolic state microbes or small colony variants can make culture difficult
What is the treatment plan for infection on a surface?
Sterilise tissue Decrease bioburden (decrease metabolic activity of biofilm)
How can an infection on a surface be prevented?
Maintain integrity of natural surfaces, prevent contamination of prosthetic surfaces and prevent/remove colonising bacteria
What is hypersensitivity?
Antigen-specific immune responses that are either inappropriate or excessive and result in harm to the host
What are the four types of hypersensitivity reaction?
I: immediate
II: antibody mediated
III: immune complex mediated
IV: cell mediated
How quickly does type I hypersensitivity occur in allergy prone individuals on exposure to environmental, non-infectious antigens?
~30 mins
How long does type II hypersensitivity take to occur after exposure?
5-12 hrs
What molecules are involved in type II hypersensitivity?
IgG or IgM
How is type III hypersensitivity different to type II?
Only takes 3-8hrs
Soluble antigens are present
Which cells are involved in type IV hypersensitivity?
T cells and macrophages
How long does type IV hypersensitivity take to occur after exposure?
24-48hrs
What initiates types II-IV hypersensitivity reactions?
Exposure to environmental infectious agents and self antigens
What is the normal process which prevents us from having allergies?
Born with TH2 phenotype
Exposure to environmental factors to educate immune system to what is safe/unsafe
Develop TH1 phenotype
What happens in response to stimulus when an individual has TH2 phenotype?
Develop increased IgE
What factors are thought to contribute to a persistence of the TH2 phenotype leading to atopy?
Small family size Stable intestinal microflora Good sanitation Low or no helminth burden Low orofaecal burden
What factors are thought to contribute to development of a TH1 phenotype?
Large family size Rural homes (inc. interaction w/livestock) Variable intestinal microflora High helminth burden High orofaecal burden
What is the implication of clinical cross-reactivity in allergy?
Degree of homology between allergens due to charged proteins therefore being allergic to one substance means you are likely to be allergic to another
It is possible to be allergic to anything?
Almost
Can any allergen have the capacity to trigger a severe allergic reaction?
Yes
Give two examples of clinically important allergens.
Medications
Latex
What is hypersensitivity?
Antigen-specific immune responses that are either inappropriate or excessive and result in harm to the host
What are the four types of hypersensitivity reaction?
I: immediate
II: antibody mediated
III: immune complex mediated
IV: cell mediated
How quickly does type I hypersensitivity occur in allergy prone individuals on exposure to environmental, non-infectious antigens?
~30 mins
How long does type II hypersensitivity take to occur after exposure?
5-12 hrs
What molecules are involved in type II hypersensitivity?
IgG or IgM
How is type III hypersensitivity different to type II?
Only takes 3-8hrs
Soluble antigens are present
Which cells are involved in type IV hypersensitivity?
T cells and macrophages
How long does type IV hypersensitivity take to occur after exposure?
24-48hrs
What initiates types II-IV hypersensitivity reactions?
Exposure to environmental infectious agents and self antigens
What is the normal process which prevents us from having allergies?
Born with TH2 phenotype
Exposure to environmental factors to educate immune system to what is safe/unsafe
Develop TH1 phenotype
What happens in response to stimulus when an individual has TH2 phenotype?
Develop increased IgE
What factors are thought to contribute to a persistence of the TH2 phenotype leading to atopy?
Small family size Stable intestinal microflora Good sanitation Low or no helminth burden Low orofaecal burden
What factors are thought to contribute to development of a TH1 phenotype?
Large family size Rural homes (inc. interaction w/livestock) Variable intestinal microflora High helminth burden High orofaecal burden
What is the implication of clinical cross-reactivity in allergy?
Degree of homology between allergens due to charged proteins therefore being allergic to one substance means you are likely to be allergic to another
It is possible to be allergic to anything?
Almost
Can any allergen have the capacity to trigger a severe allergic reaction?
Yes
Give two examples of clinically important allergens.
Medications
Latex
Is the sensitisation phase of allergy clinically silent or pathological?
Silent
What must happen for the effector phase of allergy to be clinically pathological?
Re-exposure to same antigen from sensitisation phase
What is directly activated in the first exposure to an allergen?
Mast cells
C3a
C5a
What is the effect of plasma cells (B cells) on 2nd exposure to an allergen?
Produce antigen-specific IgE to bind to allergen
What leads to degranulation of granular cells upon second exposure to an allergen?
Cross linking of allergen bound to IgE and granular cell
What granule contents are released both in the sensitisation and effector phases of allergy?
Histamine
Leukotrienes
Prostaglandins
What are the effects of granule contents release in the immune mechanism of allergic reaction?
Increased vascular permeability
Vasodilation
Bronchial constriction
How can granule contents from mast cells be used in diagnosis of allergy?
Measure blood/serum levels to see if they are raised
What is the result of mast cells activation in the epidermis?
Urticaria
What is the effect of mast cell activation in the deep dermis?
Angioedema
When does angioedema become a medical emergency?
When the upper respiratory airways are involved
What are the results of systemic mast cell activation?
Hypotension CV collapse Generalised urticaria Generalised angioedema Breathing problems
What are the characteristics of S/S of anaphylaxis?
Sudden onset and rapid progression involving more than one organ system due to circulatory collapse
What is the treatment for anaphylactic shock?
Immediate IM adrenaline
Which receptors does adrenaline act on to reverse peripheral vasodialtion, decreases oedema and alleviate hypotension in anaphylactic shock?
Via alpha-1-adrenoceptors
Which receptors does adrenaline act on to reverse airway obstruction in anaphylactic shock?
Via beta-2-adrenoceptors
What is the action of adrenaline treatment on beta-1-adrenoceptors in anaphylactic shock?
Increase force of myocardial contraction
What action does immediate adrenaline treatment have on mast cells in anaphylactic shock?
Inhibit is activation
Will only one dose of adrenaline be required to treat anaphylactic shock and why?
No, likely to need further doses due to biphasic allergic response
How are chronic allergic diseases treated?
With steroids to reduce immune mechanism of response
What four methods can be used to diagnose allergy?
Clinical Hx
Blood tests
Skin prick tests
Challenge tests
What features of a clinical Hx will lead to a diagnosis of allergy?
Atopy
Allergen
Seasonality
Route of exposure
What is measured in blood tests looking for allergy?
Serum allergen-specific IgE
Serum mast cell tryptase
Serum/urinary mast cell histamine
How is a skin prick test performed?
Stop antihistamine Tx 48hrs prior to test
Try to activate mast cells in epidermis –> wheal&flare >3mm=+ve
Use saline as a control
What types of allergens are challenge tests used to investigate?
Food and drug
What risks are associated with skin prick and challenge tests for allergy?
Anaphylaxis in highly sensitised pts
How can allergy be managed?
Avoid/eliminate allergen Education of pt of S/S, triggers and Tx Medic alert ID Short/long acting drugs Allergen desensitisation
How do short and long acting histamines differ apart from their duration of action?
Short are sedating
Long are non-sedating
What causes wheezing in allergic reaction?
Mast cell activation in the lung
What is lacking when only the sensitisation phase of allergic reaction takes place?
IgE
