Health and Disease Week 19 Flashcards
What is the immune system?
the body’s tool for preventing or limiting infection
What is the immune system made up of?
a complex network of cells, organs, proteins and tissues that defend the body from pathogens
What does the immune system recognise?
pathogens and abnormal cells, such as cancer cells
What are the two organs of the immune system?
thymus and spleen
What is the lymph system?
an organ system that white blood cells circulate in
What is the lymph system made up of?
lymphatic vessels and lymph nodes
What are the 2 types of immunity?
innate and acquired (adaptive)
What is innate immunity also known as?
natural immunity
What are the features of innate immunity?
- non-specific
- needs minimal energy
- fast response
- present from birth
What is innate immunity?
the initial response of the body to eliminate microbes and prevent infection
What are the 4 main components of innate immunity?
- physical and structural barriers
- chemical barriers
- protective cells
- also sneezing, coughing, vomiting
What are some examples of physical and chemical barriers?
skin, mucus membranes, tears, digestive enzymes in mouth, stomach acid, blood-brain barrier
What are the 3 main cell types of innate immunity?
- macrophages, neutrophils and mast cells
- natural killer (NK) cells
- dendritic cells
What is the role of macrophages, neutrophils and mast cells?
involved in the removal of pathogens by phagocytosis
What is the role of natural killer (NK) cells?
to eliminate infected or abnormal host cells
What is the role of dendritic cells?
have direct microbicidal activity, and secrete chemicals that recruit and activate other immune cells
When does innate immunity trigger inflammation?
when physical barriers are broken or infection occurs
What does inflammation do?
helps eliminate pathogens and promotes tissue repair
What happens in inflammation?
there is a release of signalling molecules including cytokines and chemokines and this recruits cells to the site of infection
What are the 4 classic signs of inflammation?
heat, pain, redness, swelling
What is the complement system?
essentially a cascade of plasma proteins involved in innate and adaptive immunity
What is the complement system made up of?
over 30 different plasma proteins
What does the complement system do?
- helps destroy pathogens
- active immune cells
- clears immune complexes
- bridge between innate and adaptive immunity
When is adaptive immunity triggered?
when innate immunity fails to clear a pathogen
What are the features of adaptive immunity?
- long-term immunity
- slow response
- antibodies produced by B cells
- detects SPECIFIC antigens on the pathogen
What are the 2 branches of acquired/adaptive immunity?
cellular immunity and humoral immunity
Which 4 cells types does cellular immunity involve?
- cytotoxic T cells (T killer)
- helper T cells
- regulatory T cells
- memory T cells
What do dendritic cells do?
present antigen to T cells to trigger a response
What do cytotoxic T cells do?
directly attack and kill infected or abnormal cells
What do helper T cells do?
help B cells with antibody production and active other immune cells
What do regulatory T cells do?
help maintain immune balance and prevent excessive response - shuts down immune response after pathogen removed
What do memory T cells do?
retain a ‘memory’ of previously found pathogens, allowing a faster and more effective immune response when exposed again
What 2 types of cells are involved in humoral immunity?
plasma cells and memory B cells
What do B cells do?
produce antibodies in response to antigens
What are antibodies?
proteins that neutralise pathogens, mark them for destruction by phagocytes, or trigger other immune response
define immunisation
when the immune system is stimulated to produce an immune response against specific pathogens
How can immunisation be achieved?
natural infection OR vaccination
define vaccination
a specific form of immunisation
What do vaccines contain?
weakened, killed or parts of pathogens
What is the point of vaccination?
to enable the immune system to remember and quickly eliminate a specific pathogen when re-exposed
What are the steps of vaccination?
- introduction of antigens
- immune response activated
- memory formation
- protection against disease
What are the 4 main types of vaccines?
- attenuated vaccines
- inactivated vaccines
- subunit vaccines
- nucleic acid vaccines
define attenuated vaccine
using a weakened virus to trigger an immune response
define inactivated vaccine
using a killed virus to trigger an immune response
define subunit vaccine
using only a portion of a virus to allow the immune response to recognise the whole virus
define nucleic acid vaccine
using virus DNA or RNA to enable human cells to manufacture portions of a virus to trigger an immune response
What is an allergy?
an overreaction of the immune system to a normally harmless substance
How are allergies encountered?
through inhalation, ingestion, contact with skin
What are symptoms of an allergic reaction?
anaphylactic shock, itching, sneezing, rash
What is autoimmunity?
when the immune system mistakenly attacks the body’s own cells and tissues
What is autoimmunity caused by?
genetic predisposition
What can autoimmunity be triggered by?
environmental factors
What are examples of autoimmunity?
rheumatoid arthritis, ulcerative colitis, psoriasis, diabetes, multiple sclerosis
What are 4 examples of microbes?
prokaryotes, eukaryotes, viruses, prions, bacteria
What are features of prokaryotes?
1-5 mCM, haploid, asexual reproduction, unicellular, no true nucleus, cell wall*
What are features of eukaryotes?
over 10 mCM, diploid, sexual reproduction, uni and multicellular, true nucleusW
What are examples of prokaryotes?
bacteria and archaea
What are examples of eukaryotes?
fungi, protozoa, helminths, slime moulds, algae
What are features of viruses?
no cellular structure - they are genetic material surrounded by protein
What are features of prions?
no nucleic acid - just pieces of infectious protein
What is an example of a prion?
Bovine Spongiform Encephalopathy (BSE)
What are features of bacteria?
unicellular, huge diversity, majority harmless or even beneficial, some are pharmaceutical contaminants
How do we name bacteria?
italics - give genus + species - genus is capital, species is lower case
Which 3 ways can bacteria be classified?
morphology, metabolism and molecular characteristics
How is morphology used in bacterial classification?
cell shape, size, motility, spore forming
How is metabolism used in bacterial classification?
use of energy sources/nutrients
How are molecular characteristics used in bacterial classification?
protein, lipid structure, sequence of gene encoding 16S RNA
What are 2 examples of specific bacterial classification?
bacterial shape and 16S ribosomal RNA gene sequencing
What 3 main shapes can bacteria have?
coccus (balls), rods, spirals
What is a single coccus called?
coccus
What is a double coccus shape called?
diplococcus
What is a chain of cocci called?
streptococcus
What are clusters of cocci called?
staphylococcus
Which two ribosomal subunits do bacteria have?
50S and 30S
What does the 50S subunit contain?
23S rRNA, 5S rRNA + proteins
What does the 30S subunit contain?
16S rRNA + proteins
What is special about the 16S rRNA gene?
it is an ESSENTIAL GENE and is highly conserved, but contains hypervariable regions
define hypervariable region
short sections of DNA which are different
How can bacteria be identified by their 16S rRNA gene?
there is big variation in the hypervariable regions between species
What is the function of the plasma membrane of bacterial cells?
selectively permeable, site of secretion and respiration, site of environmental response regulators
Where is the cytoplasm of bacteria located?
between the plasma membrane and nucleoid
What is also located in the cytoplasm?
ribosomes (70S) and inclusion bodies
What are inclusion bodies?
structures in the cytoplasm that contain important nutrients and float around (C, P, N, S)
What do bacteria NOT have?
mitochondria - energy production occurs on cytoplasmic (plasma) membrane
What 2 parts make up the nucleoid?
double stranded DNA (dsDNA) and plasmids
What are the features of the dsDNA?
- NOT enclosed by a nuclear membrane
- usually a single closed circular chromosome
- DNA is supercoiled to make it compact
- 1 copy of each gene - haploid
What are the features of plasmids?
- extrachromosomal
- small, circular DNA
What is different about plasmids compared to dsDNA?
they replicate independently of the chromosome
What do plasmids encode?
auxiliary functions e.g. antibiotic resistance
What is the function of the prokaryotic cell wall?
protects bacteria from the environment and provide rigidity and strength
What is the prokaryotic cell wall made of?
peptidoglycan cross-linked to form a mesh
What is a glycan backbone made of?
a chain of sugar residues joined by glycosidic bonds
What is every other sugar linked to?
a short peptide sidechain that crosslinks to a peptide on an adjacent glycan backbone
What does its mesh-like structure enable?
molecules to pass in and out
What 2 types of bond make the peptidoglycan cell wall strong and rigid?
peptide bonds and glycosidic bonds
Why are bacteria easily targeted by antibiotics?
the peptidoglycan cell wall is unique to bacteria
What are the 2 types of peptidoglycan structure?
gram positive and gram negative
Which colour stain do gram positive bacteria produce?
purple
Which colour stain do gram negative bacteria produce?
pink
What are the main features of gram positive peptidoglycan?
- THICK peptidoglycan layer which makes up 6-80% of cell wall
- X- linked to form a thick mesh
What are the main features of gram negative peptidoglycan?
- THIN peptidoglycan layer which makes up 10-20% of cell wall
- surrounded by an outer membrane
Which 2 structures do gram positive cell walls contain?
teichoic acids and lipoteichoic acids
What are teichoic acids?
acidic polysaccharides bonded to peptidoglycan
What do teichoic acids do?
transport metal cations
What are lipoteichoic acids?
teichoic acids bonded to membrane lipids
What do lipoteichoic acids do?
trigger inflammatory responses
When are lipoteichoic acids released?
released by killed bacteria during infection
What does the outer membrane of gram negative cell walls contain?
lipopolysaccharides and porins
What is special about gram negative cell walls?
the outer membrane is impermeable to large molecules - more resistant to antibiotics
What do the lipopolysaccharides do?
stabilise the membrane structure
What are porins?
water-filled channels
What is another name for a lipopolysaccharide?
endotoxin
What are features of lipopolysaccharides (endotoxins)?
- strongly immunogenic
- extremely toxic to animal cells
- heat resistant (difficult to get rid of)
What are 2 examples of pathogenic bacteria that are NOT classified by gram stains (atypical)?
acid-fast bacilli and bacteria lacking peptidoglycan
What is an example of an acid-fast bacilli?
mycobacteria tuberculosis - cell wall is a thick waxy lipidic layer
What is a common feature of bacteria lacking peptidoglycan?
often cause intracellular infections
What is an example of bacteria lacking peptidoglycan?
mycoplasma pneumoniae
What are 3 examples of bacterial cell components associated with some bacterial cells?
- bacterial endospores
- capsules and slime layers
- P-pili (fimbriae) and F-pili
What are bacterial endospores?
highly resistant dormant structures which form inside a bacterium in response to adverse conditions
What are 3 features of endospores?
dormant, non-reproductive, tough
What are capsules and slime layers?
a network of polysaccharides secreted outside of the peptidoglycan cell wall
What is the function of capsules and slime layers?
protection, aiding attachment and contributing to virulence
What are P-pili and F-pili?
hair-like structure composed of protein subunits
What do P-pili do?
aid attachment to surfaces - forming biofilms?
What is the function of F-pili?
they are used in bacterial conjugation
define bacterial conjugation
the transfer of genetic material between cells
How do bacteria usually live?
in biofilms
define biofilm
a group of microorganisms that attach to a surface and are encased in a matrix of extracellular polymeric substances (EPS)
Where can bacteria form biofilms?
on any surface where there is moisture
What actually is a biofilm?
when bacteria attach to surfaces, grow and become enveloped in an extracellular matrix composed mostly of polysaccharides, proteins and DNA
What are the 5 stages of biofilm formation?
- initial formation
- irreversible attachment
- maturation 1
- maturation 2
- dispersal
initial attachment
individual bacteria attach weakly to a surface
irreversible attachment
- attachment becomes irreversible using fimbrae and pilli
- bacteria multiply and also attract other microbes to attach
maturation 1
- bacteria secrete a sticky, protective extracellular matrix (ECM)
- bacteria continue to join and multiply
maturation 2
biofilm grows in size and structure to form a large 3D colony
dispersal
- sections of the biofilm break off
- these cells can go and colonise new areas
What is the ECM made up of?
polysaccharides, proteins and DNA
What does the biofilm do for bacteria?
acts as a protective coat and protects them from harm
What is the main issue with biofilms?
the biofilm makes bacteria very resistant to antibiotics
What 3 things to biofilms protect bacteria against?
- phagocytosis
- antibiotics
- disinfectants
Why are biofilms a huge issue in healthcare?
they grow on medical devices and implants
What are the 5 factors affecting bacterial growth?
- nutrients
- iron
- oxygen
- temperature
- pH
Why do bacteria need nutrients?
for cellular biosynthesis and energy respiration
What are examples of macroelements that bacteria need?
carbon, hydrogen, oxygen, nitrogen, water, sulfur etc
What are examples of trace elements bacteria need?
zinc, cobalt, nickel, copper, manganese, molybdenum
Where do bacteria get nutrients from?
their host (aka us)
Why is iron crucial for bacteria?
it is used for energy generation
Why is iron in our body NOT available to bacteria?
it is complexed with another molecule
How is iron stored within mammalian cells?
- 90% stored in ferritin or as haem group
- 8% stored in other cellular proteins e.g. myoglobin
Where is iron stored outside mammalian cells?
- 1-2% attached to transporters e.g. transferrin in serum, lactoferrin in mucosal secretions
- no complexed iron exists as Fe3+ which is insoluble and not absorbed into the blood
What are siderophores?
low MW compounds produced by bacteria with a high affinity for iron
When are siderophores produced by bacteria?
when concentration of iron is low
What do siderophores do?
bind iron and allow uptake into the cell
What is an example of a siderophore?
enterobactin
How does enterobactin work?
they remove the iron complexed with transferrin and this enables uptake into the bacterial wall
How do humans use siderophores to treat infection?
we trick bacteria into taking up antibiotics instead of iron
define aerobe
requires oxygen for growth
define anaerobe
does not require oxygen for growth
What are the 2 types of anaerobe?
obligate and facultative
define microaerophile
can grow in low concentrations of oxygen
What is an example of a microaerophile?
Streptococcus pyogenes
define obligate anaerobe
cannot grow in the presence of oxygen
What is an example of an obligate anaerobe?
Clostridioides difficile
Why is C. diff an issue in hospitals?
it produces spores which spread as bacteria are under stress - very hard to get rid of
define facultative anaerobe
can grow if oxygen is available, but can also grow without oxygen
What is an example of a facultative anaerobe?
E. coli
What are 3 different types of temperature-suited bacteria?
- psychrophiles
- mesophiles
- thermophiles
define psychrophiles
grow at -40 to 20 degrees, so can grow in cold conditions, however optimum is greater than 15
What is an example of a psychrophile?
Listeria
define mesophile
grows at 20-40 degrees (body temperature)
define thermophile
grows at 40-100 degrees
What is an example of a thermophile?
Thermophilus aquaticus - produces enzymes used in molecular biology at 100 degrees
define neutrophile
a bacterium that grows best at body pH (6.5-7.5)
define acidophile
bacteria that can grow in acidic conditons
What is an example of an acidophile?
Helicobacter pylori
What are the 2 ways of culturing bacteria?
suspensions, colony
define suspension
bacteria are grown in a complex liquid as a batch culture
What are bacterial suspensions used for?
to determine growth rate or effect of antimicrobial agents
define colony
when bacteria are grown on complex media solidified with agar
What are colonies used for?
obtaining a pure culture, performing a viable count, assessing diversity, aiding identification
Which method do bacteria divide by?
binary fission
When does bacterial cell division continue until?
nutrients run out or the environment changes to unfavourable
How do bacteria increase in numebers?
exponential growth
What is the time taken for bacteria to divide called?
generation time
What is the rate of cell division determined by?
time needed for DNA replication AND the conditions
What are the steps of binary fission?
- cell elongates to approx. double length
- cell about to divide copies its chromosome
- a septum begins to form
- the 2 copies of the chromosome are pulled apart
- septum formation continues until two daughter cells are pinched off
What kind of growth curve do batch cultures have?
a unique one
What are the 4 stages of the growth curve?
- lag phase
- exponential phase
- stationary phase
- death phase
lag phase
- when first inoculated
- length of phase depends on conditions e.g. fridge
exponential phase
- bacteria start doubling
- cells behave in a constant predictable way
- the generation time will be constant (straight line on graph)
- this is the ideal phase to use the bacteria for research
stationary phase
- bacteria are running out of resources
- no increase or decrease in number of cells
- some cells are dying, other still dividing
- the cells are behaving unpredictably
death phase
- decline in cell numbers
- some cells called persister cells don’t die but stay dormant
What are persister cells?
bacterial cells that don’t die in the death phase, but stay dormant until conditions are made more favourable - known as viable but non-culturable cells
define generation time
the time required for cells to double in number
Where is generation time read from?
ALWAYS the exponential phase of the growth curve
What is the equation for the number of bacterial cells present at time T?
NT = N0 x 2^n
N0 = number of cells initially present
N= number of generations
What is the equation for generation time?
generation time (g) = time (T) / number of generation (n)
What is the equation for calculating the number of generation?
Log10Nt = Log10N0 + nLog102
Test yourself:
* A population of Escherichia coli increases from 103 to 109 cells in 10 hr.
* What is the generation time?
30 minutes or 0.5 hours
What is a direct measure of bacterial number?
viable count
What are the steps of a direct measurement of bacterial number using a viable count?
- dilute a sample of bacteria
- spread on agar plate
- incubate overnight at 37 degrees
- count colonies
- express as colony forming units (CFU) / mL
What can’t this method be used for?
clumps or chains of cells
What is a indirect method of measuring bacterial cell number?
optical density
How does optical density work?
optical density increases with increasing cell number over time - essentially how easy it is for light to go through bacteria
What are the axes of the optical density graph?
optical density vs cell number or time
Which stage must cells be in to use the optical density method?
exponential phase
define microbiota
groups of microorganisms living in a SPECIFIC ENVIRONMENT
define microbiome
all the microorganisms living on almost all of our body surface
What does each microenvironment have?
a set of common microorganisms
What does a person’s microbiota depend on?
age, diet, lifestyle, time of year, disease etc
What are the microorganisms colonising our body surfaces called?
indigenous human commensals
define commensal
living on us without causing harm
What are indigenous human commensals needed for?
- they are beneficial for bacteria and the host
- they provide some protection against pathogen
How do indigenous human commensals protect us against pathogenic bacteris?
they make it harder for pathogenic bacteria to adhere to surfaces to gain nutrients from the host and they now have to compete
When does the human microbiota develop?
from birth - it takes about 2-3 years for stable biome to form
What is the gut microbiome crucial for?
- breakdown of food
- synthesising essential vitamins B12 and K
When can indigenous human commensals become opportunistic pathogens?
when our natural barriers to infection are broken
define opportunistic pathogen
pathogens that usually don’t cause infection but will if they get a chance
What is an example of an opportunistic pathogen?
E. coli when it gets into urinary tract from gut - causes a UTI
What are the 6 major regions with normal human microbiota?
- skin
- upper respiratory tract
- lower respiratory tract
- digestive system
- urinary tract
- adult female genital tract
Which 3 microenvironments is the skin divided into?
dry skin, moist skin areas, areas rich in sebaceous glands
What are the natural colonisers of the skin?
gram positive bacteria as they have a thick cell wall and are resistant to drying e.g. Staphylococcus, Streptococcus
When can natural colonisers on the skin become an issue?
when skin wound lead to infection by bacteria getting into bloodstream
What is the upper respiratory tract made up of?
the nose and throat
What are examples of natural colonisers in the nose and throat?
Streptococcus, Staphylococcus, Neisseria, Haemophilus
Which of these can cause issues?
Streptococcus, Neisseria, Haemophilus as most people have these living at the back of the throat
What is important about the lower respiratory tract?
it is usually sterile - but can be a common site for infection
What are bacteria that cause infections in the lower respiratory tract?
haemophilus, streptococcus, Mycobacterium tuberculosis
Which areas is the mouth divided into?
different microenvironments depending on how aerobic they are
What type of bacteria inhabits the cheeks + gums?
facultative anaerobes e.g. Streptococcus
Which bacteria inhabit the gingival groove (where teeth and gums meet)?
anaerobes - can cause gum disease e.g. Bacteroides
Which bacteria inhabit the tooth enamel?
facultative anaerobes e.g. Streptococcus
Which bacteria inhabit the stomach?
very few due to acidic environment - however, Helicobacter pylori can survive here and cause gastric ulcers
What bacteria inhabit the duodenum?
very few due to acidity and high numbers of enzymes
Which bacteria inhabit the ileum?
an increase in number due to less acidity
Which is the most heavily colonised part of the digestive system?
the large intestine
What is unique about the large intestine?
there is very little oxygen - so bacteria are either anaerobes or facultative anaerobes
What are the 3 most common examples of bacteria in the large intestine?
- Bacteroides fragilis - most common cause of appendicitis
- Enterococcus faecalis - doesn’t cause issues in intestine but can move to heart
- E. coli - can move to urethra
What bacteria inhabit the kidneys, bladder and ureters?
none- they are usually sterile in a healthy adult!
Which bacteria colonise the urethra?
lower part is lightly colonised but upper kept mostly sterile due to flushing effect - E. coli can cause UTIs
What is unique about the adult female genital tract microbiome?
acidic environment
What does the microbiome in the adult female genital tract depend on?
age, menopausal status, diet, childbirth, stage in cycle etc
Which bacteria colonise the adult female genital tract?
Lactobacillus grows
What causes vaginal thrush?
Candida albicans (a yeast) when it overgrows - exists normally
What are the main non-specific defences against infection?
indigenous microbiota, physical barriers, blood and tissues
How do commensals protect against pathogenic infection?
a pathogen must compete with natural microflora for adhesion sites for food
define probiotics
live microorganisms that prevent or treat conditions - in tablets and yoghurt
define prebiotics
chemicals that induce growth / activity of microorganisms
What are the 3 main layers of skin acting as defence?
epidermis, sebaceous glands and sweat glands, skin associated with lymphoid tissue (SALT)
How is the epidermis a barrier?
dry and acidic and the upper layer is constantly shed - hard for pathogenic bacteria to colonise
How are sebaceous glands and sweat glands a defence?
they both secrete an enzyme called lysozyme, which breaks down the peptidoglycan cell wall - gram positive are more susceptible
How is the skin associated with lymphoid tissue (SALT) a barrier?
invading pathogens are detected by lymphoid tissue which induces a local inflammatory response
What are the 3 main barriers in mucosal surfaces?
mucus, epithelium, mucosal associated lymphoid tissue (MALT)
How is mucus a physical barrier?
- contains mucin and is produced by the submucosal glands
- mucin traps bacteria
- lysozyme kills gram positive bacteria
- lactoferrin binds iron
- lactoperoxidase kills bacteria
How is the epithelium a physical barrier?
cilia waft mucus, also contains indigenous bacteria
How is the mucosal associated lymphoid tissue (MALT) a barrier?
responds to any invading pathogens which breach this layer by inducing a local inflammatory response
What are polymorphonuclear (PMN) leucocytes?
a group of leucocytes that circulate in the blood and recongise and remove invading pathogens
What are the 3 types of PMN leucocytes?
- neutrophils
- eosinophils
- basophils
What is the role of neutrophils?
phagocytosis
What is the role of eosinophils?
releasing cytotoxic substances which kill bacteria
What is the role of basophils?
when stimulated, release inflammatory mediatories like histamine which induce inflammation
What is the role of macrophages?
phagocytosis, producing cytokines, presenting antigens to T cells for acquired immunity
What do lysosomes contain?
digestive enzymes, defensins, enzymes of respiratory burst
What is the complement system?
a biochemical cascade involving over 30 proteins activated by infection
What are the 4 main functions of the complement system?
- lysis
- opsonisation
- activation of inflammatory response
- clearance of immune complexes
What is the role of transferrin?
it binds iron so it is unavailable for bacteria to use in growth and energy release
What is mannose binding lectin?
a soluble factor produced by the liver following an infection
What is the role of mannose binding lectin?
- it binds to patterns on the surface of bacteria cells
- one end binds to the bacteria and the other end binds to receptors on the macrophage
- the macrophages can now recognise and phagocytose the bacteria
- also increases the activation of the complement system - positive feedback
