From encounter to disease - Bacteriology II Flashcards
This deck contains the pneumococcal vaccine lecture and the nasal carriage of S.Aureus
Which two kinds of S.pneumoniae vaccines are there?
- Whole cell vaccines
- Polysaccharide vaccines
Disadvantage of polysaccharide vaccines
- Not effective in kids < 2 years old
- Do not generate a T cell response
Why are polysaccharide vaccines not effective in kids <2 years old?
B cells under the age of 2 really need T cell help to do anything
Why do polysaccharide vaccines don’t elicit a T cell response?
It’s a sugar instead of a protein:
- No generation of peptides –> no presentation to T cells
What does the pneumococcal conjugate vaccine consist of?
10 or 13 different purified capsular polysaccharides conjugated to carrier proteins
What are examples of carrier proteins?
Diphteria toxoid, tetanus toxoid or Haemophilus influenzae protein D
Which vaccine is recommended for elderly?
PPV23
What does aluminum phosphate do in the pneumococcal vaccine?
T helper cell 2 (Th2) adjuvant –> to increase
antibody response
Describe the mechanism of protection of PPSV
- Polysaccharide binds to BCR
- Differentiation into plasma cells
- No production of memory B cells
Describe the mechanisms of protection of PCV?
- Polysaccharide + protein antigen bind to BCR
- Polysaccharide specific B cell generates antibody- AND memory response
- Protein antigen can be presented to T cell –> T cell help
What is opsonophagocytosis?
Antibody-complement-mediated phagocytosis
Limitation of current pneumococcal vaccines (3)
- Protection against a limited number of serotypes
- Designed and based on prevalence in US and Europe
- Expensive and complex
Name the requirements of an improved vaccine (5)
- Broadly protective
- Affordable
- Target groups
- Reduction of carriage
- Identify conserved proteins required for colonization
What are the three routes of administration?
- Parental
- Intranasal (mucosal)
- Oral (mucosal)
For what kind of infections are oral vaccinations used?
Infections that infect us in the GI-tract
What are factors you have to take into account about mucosal (intranasal) vaccines? (3)
- Provides local and systemic immunity
- Prevents disease and infection
- Asymptomatic colonization causes natural immunization
Which antibody is involved in the opsonophagocytosis?
IgG, IgM, complement
Which antibody is involved in blocking the interaction with the epithelium?
IgA
Which antibody is involved in agglutination?
IgG
Describe Th17 T cell immunity against colonizing pneumococci
- Th17 cells below the epithelial surface secrete IL17A
- Recruiting/secreting AMPs, neutrophils, IgA –> killing/clearance of pneumococci
Why is it important to vaccinate mucosally?
You want to have memory T cells
Delivery systems: efficacy of intranasal vaccines depends on immune activation. How? (2)
- Penetration of epithelial barrier
- Attraction of immune cells
What can be used as particles for delivery during intranasal vaccination? (3)
- Lipids
- Immune particles
- Outer membrane vesicles
What are two characteristics of OMVs?
- Contain multiple PAMPs
- Possibility for surface display of antigens
What is the advantage of using OMVs?
Antigen delivery and adjuvanticity combined
Name examples of virulence factors of S. Aureus (4)
- PVL
- TSST
- Exfoliate toxins
- Enterotoxins
What causes toxic shock syndrome?
Enterotoxins (superantigen)
What is a superantigen?
A molecule that is able to elicit T-lymphocyte responses by circumventing normal antigen processing and presentation functions
How can viral-bacterial co-infections occur?
Influenza damages your lung epithelium, upon which bacterial co-infections can occur
Which bacteria are often involved in viral-bacterial co-infections?
- Pneumococcal
- S. Aureus
True or false: “S. Aureus can be tackled with antibiotics”
False. S. Aureus is resistant to all antibiotics
Which kind of S.Aureus strains can you encounter?
- Community-acquired MRSA
- Methilicin resistant SA
- Vancomycin resistant SA
Where can S. Aureus be found in the body?
General population:
Nasal carrier: majority in the nose
Describe the nasal carriage rate vs. age
7 min
Where is S. Aureus located if you are a nasal carrier? Why?
Border of your skin and nasal mucosa. This is because of how the setup of the epithelium is.
What happens if you eradicate S. Aureus from the nose?
It will disappear from other sites as well
What happens if you eradicate S. Aureus from the nose in a hospital setting?
Clear reduction in endogenous infections in these patients.
Replacement?
Name two kinds of carriage patterns
- Persistent (positive every time you make a nose swab)
- Non- and intermittent carriers (negative every time you make a nose swab)
How many percent of nasal carriers are persistenly colonized with one unique S.Aureus strain?
98%
How many persistent nasal carriers intermittenly carries a second S. Aureus strain?
1 in 6
What suggestsa single focus or low-grade persitent carriage?
58% of intermittent carriers are colonized with a unique
S. aureus genotype
Risk of infection amongst the carrier groups
Persistent - risk high
Intermediate/non carrier –> risk lower/risk the same between these groups
Intermittent carrier, why?
They see a persistent carrier, take up strain from the environment, but loose this strain
Name the categories of mechanisms associated with S. Aureus nasal carriage (4)
General
Exposure
Adherence
(Evading) immune response
Some examples of those categories
Describe the difference in resistance between non-carriers and persistent carriers
- Non- Carriers seem to be ‘resistant’ to colonization with S. aureus
- Persistent carriers seem to be ‘resistant’ to colonization with a different strain of S. aureus
What could cause this difference?
Host Factor or bacterial interference?
Describe the association between the proportion of persistent S. Aureus nasal carriage and the fasting serum glucose level
The sweeter the environment, the better S. Aureus can adhere
What is the role of ethnicity in nasal carriage?
Persistent carriage rates vary
between different ethnic groups
Which HLA molecule is associated with persistent carriage?
HLA-DR3
What can be said about the properties of nasal fluid from non-carriers
It is bactericidal against S. Aureus
Persistent carriers: Name a host factor involved in generating a locally immune suppressed state
Nasal secretions lacks antimicrobial activity against S. aureus
Persistent carrier: What is the contribution of S. Aureus to staying in the nose?
It induces a suppressing interaction with the local immune system
Describe the relation between pneumococcal and S. Aureus carriage
Inverse relation between pneumococcal- and S. Aureus carriage during age
Losing a-virulent bacteria could lead to elimination of S. Aureus from the nose, why?
What is ecological richness?
Diversity of different types in your microbiota
What is the level of ecological richness in hospitalized patients? Why?
Very much reduced. Treatment/surgery
True or False: “Hospitalized patients are less prone to be carrying S. Aureus.”
False. Hospitalized patients are more prone to be carrying S. Aureus
Which factors are involved in the multifactorial genesis underlying S. Aureus nasal carriage?
- Host/Human
- Microbe/Microbiota
- Host-Microbiota interaction