Strep, Staph and pathogens Flashcards
Name the 3 stages of the innate immune function
- recognition of microbes and damaged cells
- activation of mechanisms
- elimination of unwanted substances
Explain the role of PRRs
They are pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and activate other parts of the immune system
Compare PAMPs and DAMPs
PAMPs are molecular structures of a pathogen that the pathogen requires for survival
DAMPs are molecular patterns released by injured and necrotic cells that are recognized by leukocytes
Name 3 types of PRRs found on different types of immune cells
- Intracellular (cytosolic)
- Endosomal (membrane-bound molecules used to tag and induce the complement system)
- Extracellular
Explain the role of Toll like receptors
They recognize pathogens and through transmembrane sections cause signalling to occur, many pick up DAMPs and PAMPs
What do PRRs trigger? Name 6 of their functions…
OI PAPI
Trigger the innate immune response:
- initiate opsonization
- Induce inflammatory mediators
- induce complement proteins
- Induce apoptosis
- Induce phagocytosis
- Secrete inferno cytokine pro cytokines
Name 2 common examples of PRRs
Toll like receptors and nod like receptors
What happens when TLR receptors are activated? How are they activated?
TLR engagement starts by bacterial or viral molecules
Initiates a cascade of events that activates 3 main transcription factors:
1. NF kappa beta: makes pro-inflammatory cytokines like TNFa (enhances immune response and induces apoptosis) and interleukin (IL-1b and Pro-IL18, enhances immune response through chemotaxis effect)
- AP=1 adaptor protein causing differentiation, proliferation and apoptosis of cells
- IRFs: Interferon regulatory factor stimulating the production of type 1 interferon (anti-viral cytokines)
Describe what happens when a TLR is activated by a bacteria vs virus?
Bacteria: Recruits proteins that activate NF kapa beta that makes proinflammatory cytokines
Virus: Produces IRFs (interferon regulatory factors) that stimulate the production of type 1 interferon (antiviral cytokines)
What are Nod like receptors and where are they? List the 3 main types and identify their structural difference
Cytosolic receptors that recognize cell walls of pathogens.
All NLRs contain nucleotide oligomerization domain (NOD) but different N-terminal domains
3 main types: NOD-1,2 and NLRP3
Describe the function of the 3 main types of NLRs
NOD 1 and 2 activate NF kappa beta
NLPR3 oligomerizes with an adaptor protein and an inactive form of caspase-1 to form an inflammasome.
Once formed the caspase-1 within the inflammasome becomes active and cleaves IL-1b into its active form which recruits leukocytes and induces fever
What receptor is responsible for the painful reaction in gout?
NOD like receptors recognize the buildup of uric acid crystals as DAMPs and initiate a cascade producing inflammasomes - leading to inflammation
Name 4 other cellular receptors asides from TLRs and NOD like receptors
- C-type lectin receptors
- RIG like receptors
- Cytosolic DNA sensors
- GPCRs
Where are C type lectin receptors expressed and what do they do?
On the PM of macrophages and dendritic cells, they detect fungal glycans and initiate an immune response to fungi
Where are RIG like receptors located, what do they detect and what does their activation lead to?
Cytosol of most cells, detect nucleic acids or viruses that replicate in the cytoplasm of most infected cells and induce a cascade leading to the production of type-1 interferons
What can cytosolic DNA receptors recognize and induce?
Recognize viral DNA and induce type 1 IFN
Where are GPCRs, what do they recognize and stimulate
Neutrophils, macrophages and most leukocytes recognize short bacterial peptides and stimulate a chemotactic response of cells
What are the 2 main mechanisms the innate immune response uses to eliminate microbes?
- Inflammation
2. Anti viral defences
Name the 5 basic steps of a typical inflammatory reaction
- extravascular pathogen recognized by host cells
- leukocytes and plasma proteins recruited
- recruited cells are activated and destroy the pathogen
- reaction is controlled and terminated
- damage tissue is repaired
Describe what happens once viral nucleic acids are recognized and the two immediate ‘anti-viral’ effects
When viral nucleic acids are recognized by TLRs the infected cells or dendritic cell will secrete cytokines part of the type 1 interferon family: this has 2 effects
- Activates enzymes that degrade viral nucleic acids and inhibit viral replication (also producing RNAase - degrades RNA and some viral nucleic acid is destroyed)
- enhance the ability of NK cells
What are the 3 pathways of the complement system? How are they each activated?
- Classical: initiated by antigen-antibody complexes
- Alternative: C3 a and b parts are constantly dissociating into active-inactive state, in a perchance active state C3b binds
- Lectin binding pathway: activated by a particular glycoprotein on the surface
Name the 3 major components of acute inflammation
- DILATION of small vessels= increased blood flow
- INCREASED PERMEABILITY (so plasma proteins and leukocytes can leave circulation)
- EMIGRATION of leukocytes so they accumulate in the area of injury and eliminate the offending agent
What happens once any one of the complement system pathways are activated?
Once C3 has split into active C3a and C3b…
C3b is a binding protein and attaches onto bacteria, viruses and fungi: once attached it becomes C3 convertase which activates more C3 proteins (restarting the cycle), therefore it aids in opsonization.
C3a is active: recruits phagocytes to the area, the C3b receptor helps to attach and anchor the phagocytes to the pathogen
C3 convertase becomes a C5 convertase that recruits proteins into making a structure known as membrane attack complex (donut on the stem). The stem punches holes in the pathogen; so fluid rushes in (osmotic lysis) and the pathogen “bleeds out”
In viruses: complement system can grab viruses in circulation and guide them to immune cells
Why does activation of the complement system result in inflammation?
C5a and C3a are chemoattractants for leukocytes
Explain the role of a second signal
The innate immune system can stimulate the adaptive immune system using second signals, they also help produce the correct type of adaptive immune response i.e., cellular or humoral (ensures lymphocytes don’t respond to harmless non-infectious substances)
*Can also be useful during vaccinations so that a complete immune response is induced
Describe the mechanism of action of Tetanus toxin
Clostridium tetani has an AB neurotoxin inhibiting the release of glycine and Gaba. This increases chemical signals to the motor neurones causing continuous tightening and muscle contractions = spastic paralysis
How do staphylococci grow? Name their most pathogenic species and 3 factors they have with the potential to interfere with host defense mechanisms
They grow in clusters.
The most pathogenic species is S. aureus; capsular polysaccharide, protein A and leukocidin
What protein toxins can S aureus express that causes symptoms during infection?
(4 things)
- Membrane damaging toxins
- Superantigens: enterotoxins and toxic shock syndrome toxins
- extracellular proteins like coagulase and staphylokinase
- Epidermolytic exfoliative toxin (ET)
What are the 2 ways staphloccoci cause diseases?
- Direct tissue invasion (invasins like panton-valentine leukocidin)
- exotoxins (sometimes produced by staph)
Name 3 toxin mediated staphylococcal diseases
- TSS
- Staphylococcal scalded skin syndrome
- Staphyloccocal food poisoning
Name 3 similarities and 2 differences between strep and staph
Similarities: gram-positive, non-spore forming and nonmotile
Differences:
- Staph is catalase-positive (strep isn’t)
- Staph grows in clusters while strep grows in chains and pairs
Name 3 most common acute diseases by strep
- pharyngitis
- Scarlet fever
- skin infections
How do bacterium use coagulase to aid their invasion?
Coagulase converts fibrinogen in plasma to fibrin:
The bacterium forms a protective clot around itself and produces kinase when it’s ready to dissolve the clot and release itself into the bloodstream
Name 5 diseases caused by direct tissue invasion of staph
- skin infections
- pneumonia
- endocarditis
- osteomyelitis
- Infectious septic arthritis
Name 4 ways the skin protects the body from pathogens entering
- Keratinised
- sebaceous glands produce antibacterial peptides
- langerhan cells detect pathogens
- Structure: multilayered, hardened and flattened
What determines the type of skin infection that can occur (staph)?
The depth of the infection in the skin layer
What is cellulitis? What commonly causes it, who is most at risk, and where on the body does it occur commonly in adults and children?
Bacterial infection of the skin and subcutaneous tissue commonly caused by strep or staph. Most at-risk people include those with a weak immune system and those who handle fish/meat/poultry or soil without gloves.
In adults: legs, face and arms
Children: face, anus
What could a cellulitis infection of the face lead to?
A dangerous eye infection
Name the 3 (major) classes of strep and what differentiates them?
What is their subsequent classification
Differentiated based on their appearance in sheep agar plate:
- alpha; surrounded by green due to incomplete hemolysis
- beta; surrounded by clear hemolysis
- gama; nonhemolytic
Subsequent classification is the Lansfield characteristic: study of glycoproteins on the surface
Name 4 virulence factors of group A strep
- Hyaluronic acid capsule inhibiting phagocytosis
- Extracellular products like pyrogenic toxin (causing the rash in scarlet fever)
- M protein and lipoteichoic acid acid for attachment
- streptokinase, (streptodornase and streptolysins)
Name 3 most common acute diseases caused by strep
- Pharyngitis
- scarlet fever
- skin infections
How can you distinguish between strep and staph?
What is the significance of this?
Performing a catalase test: flood an agar slant with several drops of 3% hydrogen peroxide, catalase-positive cultures bubble immediately.
Catalase converts peroxide into water and oxygen and thus protects the bacteria from the toxic byproduct of oxygen metabolism
What causes necrotizing fasciitis and what is it?
How is the prognosis and what does treatment involve?
Highly toxic infection that can be caused by strep pyogenes releasing exotoxin B and MRSA. Since the bacteria rapidly spreads up the fascial planes (not muscles) prognosis is poor without early and aggressive treatment.
Treatment includes antibiotics, surgery and amputation
Name 4 main upper resp tract defence mechanisms
- mucociliary escalator
- mechanical barriers: glottis and nasal turbinates
- Reflexes: cough, sneeze
- Maintenance of oropharyngeal flora (Saliva, local immunoglobulins, etc)
What is sinusitis?
Bacteria initiates an immune response causing a buildup of fluid in the sinuses - causing pressure and pain
How can pharyngitis cause otitis?
Due to a connection between the ear and pharynx bacteria can move into the eustachian tube causing bulging of the tympanic membrane (and possible rupture)
Define otitis media
General term for infection or inflammation of the ear (fluid, exudate, pus in middle ear)
What is pathogen that causes the classic pharyngitis infection? How does the pathogen cause symptoms?
Strep throat caused by strep pyrogenes: contains M proteins which inhibits phagocytosis and pyrogenic toxins which cause symptoms
What can the coagulase test be useful for?
This test can distinguish S. aureus from other staphylococci (Other staphylococci do not produce
coagulase)
List 6 possible virulence and pathogenic factors associated with S aureus.
- Adhesins – adhere to host cells (fibrin / fibrinogen (clumping factor attaches to blood clot), fibronectin, and collagens)
- DNAase - hydrolyzes
- DNA Lipase - lipolytic
- Coagulase – Fibrinogen to fibrin
- Fibrinolysin - digests fibrin
- Protein A – anti phagocytic (bind
What is staphylococcal Toxic shock syndrome?
What are the criteria for a ‘confirmed’ and a ‘probable’ case?
Hint: criteria acronym FRHM-hmmggrf
Staphylococcal toxic shock syndrome (TSS) is a rare, life-threatening systemic bacterial intoxication
The confirmed case meets all 6 criteria, a probable one meets 5.
Criteria:
1. Fever: temperature > 38.9 C
2. Rash: diffuse macular erythroderma (“sunburn”)
3. Hypotension: systolic blood pressure < 90 mm Hg or orthostatic hypotension, dizziness or syncope
4. Multisystem dysfunction- at least three of the following:
a. Gastrointestinal: vomiting or diarrhoea at onset of illness
b. Muscular: severe myalgias, or serum creatine phosphokinase level (CPK) >
twice the upper limit of normal
c. Mucous membranes: vaginal, oropharyngeal, or conjunctival hyperemia
d. Renal: blood urea nitrogen (BUN) or creatinine > twice the upper limit of normal, or pyuria (> 5 leucocytes per high power field), in the absence of urinary tract infection
e. Hepatic: total serum bilirubin or transaminase level > twice the upper limit of normal
f. Hematologic: Platelets< 100,000 per L
g. Central nervous system: disorientation or alteration in consciousness but no focal neurological signs at a time when fever and hypotension are absent
Name 2 mediators of the effects of TSS toxins
- interleukin 1
2. tumour necrosis factor
What is TSST-1’s mechanism of action?
Since it is a superantigen it is capable of binding to both the MHC2 complex and T cell receptors resulting in massive T cell proliferation and cytokine production capable of initiating the body’s shock response
What are 3 principles of management of TSS?
- fluids
- antibiotics
- remove the toxin
