Week 15 - Bacterial infections, immunology Flashcards
What is an antibiotic? How are they derived
Fights bacterial infections Largely natural products of fungi and bacteria - derived by fermentation Some newer ones completely synthetic
Relationship between commensal and pathogens
Commensal organisms - live at various parts of body, but don’t cause issues Pathogen organism - when commensal organisms move and cause issues
Outline principle of selective toxicity in antibiotics
Best antibiotics target specific microorganism, but do not damage the host But can also cause loss of natural flora
What is antibiotic colitis?
Some antibiotics lead to C.diff overgrowth
What is the ‘therapeutic margin’?
Active dose vs their toxic effect Ex. narrow means low flexibility of dose before toxic effects, may need monitoring
How are antibiotics classified? (3)
Structure Target site for activity Type of activity
Key part of chemical structure in penicillins and cephalosporins - and significance
B-lactam ring Large group of antibiotics have this active component in common
What’s the difference between a gram positive and gram negative organism?
Gram positive - Large, porous peptidoglycan Gram negative - small strip of peptioglycan in periplasmic space - MORE difficult to treat
Where do antibiotics work in bacteria? TARGETS (6 with 2 examples each)
Cell wall synthesis - B-lactam, vancomycin Folic acid metabolism - Trimethoprim, sulfonamides Cell membrane - Colistin, deptomycin DNA and RNA processing - Quinolones, rifampin Protein synthesis - Erythomycin, tetracycline, doxycycline Free radicals - metronidazole, nitrofurantoin
Describe bactericidal vs bacteriostatic antibiotics
Bactericidal - kill bacteria (used when host immunity is impaired, or VERY severe infections) Bacteriostatis - inhibits bacteria (use when host defence mechanisms are intact so body can finish the job), used in many infectious diseases
Describe broad vs narrow spectrum antibiotics
Effective vs many vs few types Broad ex. cefotaxime Narrow ex. penicillin
Types of penicillins and examples
Basic - benzylpenicillin, penicillin V - fights strep,pneum, menin, treponemes BUT NOT staph aureus Anti-staph penicillin - flucloxacillin - narrow spectrum, Gram+, Broader spectrum penicillin - amoxicillin - also works on some Gram- and enterococci Antipseudomonal penicillin - piperacillin - extended spectrum for Gram+ and Gram- B-Lactam inhibitor combinations - Augmentin (clavulanic acid mixed with amoxycillin) binds and inactivates beta-lactamases (and then amoxycillin kills it)
Genetic mechanisms of antibiotic resistance (2)
Chromosome mediated / spontaneous mutation Plasmid-mediated exchange - transferable, carry genes for resistance
Examples of mechanisms by which antibiotic resistance can occur
Altered or new target Drug inactivation Metabolic by-pass Efflux pumps Overproduction of target Intrinsic impermeability
Supplementary treatments of bacterial infections (aside from antibiotics) (2)
Surgery (drainage) Immunological (rare)
Factors that inform the choice of antibacterial (5)
Sensitivity More than one agent required? Site of infection Contraindications Cost
What factors determine the dose of antibiotics?
Age, weight, renal / liver function, severity of infection
What is the minimum inhibitory concentration
Minimum amount that will inhibit or kill the organism at the site of infection
Potential routes of antibiotics (5)
Oral, intramuscular, intravenous, topical, rectal
Describe determining the duration of therapy
Depends on nature of infection, clinical response, but optimum duration is not known
Why is CSF cloudy in meningitis?
Increased protein and white cells
Shapes and gram status of most common types of bacterial meningitis (3)
Neisseria meningitidis Gram-, diplococci Hib Gram-, bacillus Strep. pneum Gram+, diplococci
What is staph aureus (gram status, shape)
gram positive cocci growing in clusters
Alpha vs beta haemolysis on blood agar
Alpha - greenish discoloration indicates Strep pneumonia Beta - clearing around colonies (looks like glowing), Strep pyogenes and some strains of Staph aureus
What are the antigen detection tests?
PCR Latex agglutination tests
In suspected case of meningitis, speticaemia what is the first step?
Injection of penicillin i/m or i/v unless SEVERE reaction
What is the innate immune system?
Born with it, developed through evolution, in place before infection, responds in the same to to repeated infections, present in plants, insects, all animals
What is the adaptive immune system?
Triggered by exposure to microbes There is a lag time following exposure Combats pathogens that evade/overwhelm IIS Specific, remembers pathogens so better/faster with repeated exposure
Components of the innate immune system (barriers, cells and soluble molecules)
Barriers - physical (ex. skin and mucosa) and chemical (antibacterial enzymes in tears / saliva, antibac peptides Cells - phagocytes (neutrolphils and macrophages) and natural killer cells, mast cells, eosinophils Soluble molecules - effector proteins and cytokines
Types of granulocytes
Neutrophil, mast cell, basophil, eosinophil
Types of granulocytes / granular leucocytes (4)
Neutrophil, mast cell, basophil, eosinophil
Describe basophils
Main role in hypersensitivity type 1 reaction Blue granules when stained
Describe mast cells
Granules contain inflammatory mediators, degranulate Roles in hypersensitivity type 1 reaction and parasites
Describe eosinophils
Role in response to parasite and allergies Release granule content Pink stained
Types of phagocytes (3)
neutrophils, macrophages, dendritic cells
Describe neutrophils
Most abundant WBC in blood Early response (inflammation) Phagocytosis Killing of microbes
Define phagocytosis, roles
Cell ‘Eating’ Pathogens, damaged cells, dead cells, nutrients Very important of function of IIS to prevent infection, protect from pathogens, get rid of garbage
Steps of phagocytosis
Chemotaxis - movement to site of injury Recognition and attachment Engulfment Digestion
Describe process of chemotaxis
Movement of cells to site of infection guided by chemoattractants (that are released by bacteria, inflammatory cells such as chemokines, damaged tissues)
Types of lysosomes and their roles (4)
Proteolytic ensymes - Degrade microbes Lysozyme - break bacterial walls Lactoferrin - bind iron so not enough left for bacteria Defensins - destroy bacterial wall
Oxygen dependent vs oxygen independent killing of pathogens
Oxygen dependent - Phagocyte oxidase creates superoxide, hydrogen peroxide, hydroxl radicals, nitric oxide, peroxynitrite radicals Oxygen independent - lysosomes
Describe outputs of oxygen dependent killing pathogens
Phagocyte oxidase creates superoxide, hydrogen peroxide, hydroxl radicals, nitric oxide, peroxynitrite radicals
Describe opsonization, why is it important
Makes phagocytosis more efficient by coating pathogens with opsonins - faster recognition, faster phagocytosis Important because some microbes (ENCAPSULATED) will not be broken down without it
Describe opsonization, why is it important
Makes phagocytosis more efficient by coating pathogens with opsonins (antibodies and complements) - faster recognition, faster phagocytosis Important because some microbes (ENCAPSULATED) will not be broken down without it
Describe natural killer kills
Kill virus-infected cells Kill malignant cells (tumour cells) Express cytotoxic enzymes
What is the complement system?
System of plasma proteins (C1-C9) activated by microbes, helps to coat them and stimulates inflammation
Components of adaptive immune system
Cells - T lymphocytes, B lymphocytes Soluble molecules - antibodies, cytokines
Types of T cells and role
Cellular immunity T Helper - express CD4, activate macrophages, help B cells produce antibodies Cytotoxic - express CD8, attacks microbes / tumour cells Regulatory - inhibit function of other T cells and immune cell / control of immune repsonse
Types of B lymphocytes (3)
Follicular B Cells - spleen, lymph nodes, IgG high-affinity, PROTEIN Marginal zone B cells- spleen, lymph nodes, IgM, LIPID B-1 cells - Peritoneal cavity, mucosa, IgM low affinity, LIPID
What is needed to ensure protection? (4 steps)
Recognise danger Act (effector function) Control (regulation) Remember (memory)
Describe Pathogen Associated Molecular patterns (PAMPs)
Patterns that are recognised on pathogens / microbes generally. Such as lipoteichoic acid, LPS Recognised by Pattern recognition receptors
Describe pattern recognition receptors and list examples (4)
Part of innate immune system, recognise molecules on pathogens / detect invaders Toll-like receptors C-type lectin receptors NOD-like receptors RIG-like helicase receptors Scavenger receptors
Describe process of immune recognition in adaptive immune system
Antigen receptors on B and T cells can recognise microbial structures (failure can lead to autoimmune diseases)
Summary of cells, response, receptors, range, specificity, memory of IIS and adaptive IS
What is acute inflammation?
Initial QUICK response to tissue injury Minutes/hours to develop Short duration Innate immune response Relatively non-specific (several types of injury)
Triggers of acute inflammation
Infection Tissue damage - physical (frost bite, burns), chemical (chemical burns, irritants), mechanical & ischaemia (trauma, reduced blood flow) Foreign bodies - splinters, dirt, sutures
What is the purpose of acute inflammation?
Alert Limit spread of infection / injury Protect from infection Eliminate dead cells/ tissue Create conditions for healing
The process of acute inflammation (the 5 Rs)
Recognition of injury Recruitment of leucocytes Removal of injurious agents Regulation Resolution /repair of affected tisuse
5 signs of acute inflammation
Redness (rubor), swilling (tumor), heat (calor), pain (dolor), loss of function
Systemic changes in response to acute inflammation
Fever (caused by endogenous or exogenous pyrogens), neutrophilia (high neutrophils) Increase in acute phase reactants - CRP, fibrinogen, complement, serum amyloid A protein RARE = sepsis
What are the vascular responses to acute inflammation? (3)
Vasodilation of small vessels Increased blood flow Increased vessel permeability to allow leucocytes and plasma proteins to enter inflammation site
Inflammatory exudate vs transudate
Exudate - water, salts, small plasma proteins, inflmmatory celsl and RBCs that go to site of inflammation Transudate - fluid leak due to altered osmotic / hydrostatic pressure, not due to inflammation
Types of inflammatory exudate (4)
Serous - few cells, plasma based, often seen in skin blisters (burns, viral) Purulent (fibrino-purulent) - Pus ex. acute appendicitis and abscess Fibrinous - Fibrin deposition, large vascular leaks, can lead to scarring Haemorrhagic - RBC predominate offten following blood vessel rupture, trauma
Describe the series of cellular events in acute inflammation (3)
Migration and accumulation of cells Removal of pathogens / injured / dead cells Migration and accumulation of monocytes
Steps of neutrophil recruitment during acute inflammation (5)
Margination Rolling Integrin activation by chemokines Firm adhesion to endothelium Transmigration through endothelium into tissue Chemotaxis to inflamed site
Describe Integrin activation by chemokines
chemokines released by activated endothelium which act on integrins to make them higher affinity so the neutrophil is now much more stronlgy bound to cell
Describe margination and rolling
Margination - neutrophil moves closer to endothelium Rolling - selectins bind to ligand of cells which roles them along endothelium (P-selectin always there and e-selection appears in response to inflammation)
Describe Chemotaxis to inflamed site
Chemoattractants (largely proteins) released to lead cell to site (like bread crumbs)
How do the types of cells at inflammation site change over time?
Neutrophils (6-24hr) Monocytes (change into macrophages in tissues) (24-48hr)
What kind of cells show up in allergies or parasite infection?
Eosinophils
What type of cells show up in viral infections
lymphocytes
Different mechanisms to destroy pathogens (4)
Release of granule content Phagocytes Generation of reactive oxygen / nitrogen species Formation of Neutrophil Extracellular Traps (NETs)
What are the outcomes of acute inflammation?
Complete resolution Repair (scarring, fibrosis) Chronic inflammation - cannot be resolved
Describe regeneration ability of cells (how good are different types of cells at regenerating)? (3 types)
High regeneration - labile like skin Intermediate regeneration - Stable tissues are normally in G0/G1 but may regenerate when injured *liver, kidney, pancreas) No/little regeneration ability - permanent tissues with heal with fibrosis, loss of function - neurons, myocardium, skeletal muscles
Factors that favour tissue resolution (7)
Minimal destruction Minimal cell death Good regeneration ability of injured tissue Fast clearance of infection Quick removal of dead tissue Removal of foreign materials Immobilisation of wound edges
Factors that prevent tissue healing (10)
Infection Diabetes Poor general health / nutrition Old age Drugs (steroids) Extensive injury Poor vascular supply Extensive bleeding Foreign bodies Pressure / torsion / movement of wound
Outline GREEN warning signs (low risk) - colour, activity, resp, hydration
PICTURE
Outline AMBER warning signs (intermediate risk) - colour, activity, resp, hydration, other
PICTURE
Outline RED warning signs (high risk) - colour, activity, resp, hydration, other
PICTURE
What is included in a septic screen?
Blood, urine, CSF, swabs
In what cases would you not do an LP? (2)
Signs of high intercranial pressure, low platelet count
Treatment for Septicaemia and meningitis
IV ceftriaxone (slightly higher dose for suspected meningitis) Also give IV dexamethasone for meningitis to protect hearing
What do you give children with underlying disease?
TAZ plus gentamicin (or vancomycin)
How do you treat a child with pneumonia?
Oxygen FLuid IV anitibiotics - or oral amoxycillin if possible (if not IV Augmentin or IV Cefuroxime)
Describe epiglottitis and treatment
Swollen epiglottis, often bracing and drooling Do not examine, keep them calm, waft oxygen, get ENT to intubate if necessary, IV antibiotics
Describe Kawasaki disease and treatment
Persistent high temperature, rash, cracked lips, swollen lymph nodes High dose IVIG, Aspirin (despite risk of Reye’s), echo to rule out coronary artery aneurysms In young babies or children who don’t respond, give high dose steroids
Potential complications of varicella (5)
Secondary bacterial infection Pneumonitis Encephalitis Severe haemorrhagic varicella (when immunocompromised) Reye’s
Most common organisms under three months
Group B Streptococcus E Coli Other Listeria
What should you consider in a child with a fever over 5 days?
Kawasaki disease
Aims of clinical diagnostic microbiology (5)
Presence / absence of pathogen AMR testing Pathogenic potential Rationale for treatment Public health concerns
How do we look for a pathogen? (3)
Look for presence of pathogen itself Look for presence of product of pathogen (antigen, polysaccharide, toxins, DNA) Patients immune response to pathogen
How to take a proper sample
Aseptic techniques Correct specimen (s) Timing (during disease) Handling the specimen Quick transport of specimen Transport medium (temp, preserve viability and sterility) Communication between lab/Dr
Type of stain used for TB
Ziehl Nielsen Auramine is better to determine severity as you can more easily count the bacteria
Gram negative, gull wing shape - what is it?
campylobacter
What type of tests need to be done under selective atmosphere?
Anaerobic culture for Clostridium tetani, botulinum, difficile
Difference in urine samples for STIs vs UTIs
STIs - first catch urine UTIs - mid stream urine
Describe staph aureus
Gram positive cocci that clumps Lives on skin Different staph infections have different significance, severity
What is staph aureus - How do you identify staph aureus in the lab - and best antibiotic to treat it?
Gram-positive cooci that vlumps, aerobic Produces coagulase enzyme (most other staphs do not) Lives in nose / skin normally and can be AMR
