Session 2 Flashcards
How do bacteria reproduce?
Binary fission
1>2>4>8
so exponential growth
When does bacterial reproduction enter the stationary phase?
When nutrients have run out and toxic waste products accumulate
Benefits of flora?
- Produce antimicrobials against harmful bacteria
- Gut flora produce vitamin K, aid digestion and absorption
- Outcompete invading pathogens for receptors and nutrients
- Establishment of a microbiome in newborns stimulates the immune system to develop
Negatives of flora?
- Become harmful if displaced. E.g. E.coli from colon can causes cystitis
- If numbers reduce (immunocompromised), then pathogenic/ opportunistic bacteria can cause harm. E.g. Candida albicans overgrowth when lactobacilis numbers reduce.
- Colon flora (sulfatases) can convert food into carcinogenic derivatives. E.g. Cyclamate sweetner > cyclohexamine (bladder carcinogen)
Where does our microbiome come from?
- Birth canal through delivery
- Mother’s and other caregivers’ skin
- Breast milk (delivers microbes, vitamins, antibodies and nutrients into the baby’s gut).
- external environment (water, soil, animals, etc.)
Physical barriers of the innate immune system?
Skin
Mucous membranes
Ciliated epithelium in the bronchi
Physiological barriers of the innate immune system?
Diarrhoea - food poisoning
Vomiting - fp/ meningitis
Coughing - pneumonia
Sneezing - sinusitis
Chemical barriers of the innate immune system?
- low pH in the stomach (2), skin (5), and vagina (4.4)
Antimicrobials:
- pepsin in stomach
- lysozyme in sebum (oil), sweat and urine
- IgA in tears, saliva and mucous membranes
- beta defensins of the epithelium (antmicrobial peptide)
Biological barriers of innate immune system?
Flora
Monocyte vs macrophage
Monocytes circulate in the blood for up to 3 days before migrating into tissues where they become macrophages.
How do macrophages recognise pathogens?
Pattern recognition receptors on the pahgocyte surface recognise/bind either:
- opsonins
- PAMP’s, pathogen- associated molecular patterns
‘PRR’s recognise PAMP’s’
Explain
Pattern recognition receptors (TLR’s) on the surface of (phagocytes) neutrophils, macrophages etc. bind pathogen-associated molecular patterns on the microbe surface. (LPS, peptidoglycan).
Match the pattern recognition receptor (PRR) and PAMP;
- LPS
- Lipoproteins
- Peptidoglycan
- Flagellin
LPS = TLR4 Lipoproteins = TLR2
Peptidoglycan = TLR2
Flagellin = TLR5
Examples of Opsonins
Antibodies (IgM 1st, IgG chronic)
CRP (acute phase)
MBL, mannose binding lectin (acute phase)
C3b
IgM :IgG ratio
IgM is the first antibody to appear at a foreign antigen
IgG is only present if the infection has occurred before
3 ways the complement system can be activated?
Classical pathway
Alternative pathway
Lectin pathway
What is MBL, mannose binding lectin?
MBL is a lectin (protein that binds carbohydrates) which binds D-mannose on pathogen membranes. It acts as an opsonin and initiates the complement cascade via the lectin pathway.
It binds to Candida albicans (yeast), HIV (virus) and Salmonella (bacteria) etc.
What initiates the alternative pathway of the complement cascade?
Binding endotoxin (on E.coli)
What initiates each?
Classical pathway
Alternative pathway
Lectin pathway
1) antigen antibody complex (IgM/IgG)
2) endotoxin
3) mannose binding lectin, MBL
Roles of each:
C3a, C4a, C5a
C3b (+ C4b)
C5-C9
1) stimulate vascular leakage and attract neutrophils to site of injury (chemotaxins)
2) opsonins
3) membrane attack complex; punches holes in bacterial cell membranes
Cytokines released from macrophages?
Il-6, TNF-alpha. Il-1
What are the systemic and local effects of cytokine release from macrophages?
TNF-alpha, Il-1, Il-6
Local effects are vasodilation of arterioles, vascular permeability and upregulated adhesion molecules within vessels to allow neutrophil migration into the tissues (selectins and integrins)
Systemic effects are upon the;
- liver (stimulate CRP and MBL production)
- hypothalamus (raise body temperature)
- bone marrow (increase neutrophil mobilisation [release])
Asplenic pateints are particularly susceptible to which type of infection?
Pneumococcal / Streptococcus pneumoniae because it’s encapsulated
Opsonin and PAMP mediated phagocytosis by neutrophils is an important part of the innate immune response.
What could reduce the levels of phagocytosis?
Reduced spleen function
- hyposplenic/ asplenic patients
Less neutrophils
- chempotherapy
- phenytoin (anti-convulsant)
- leukaemia and lymphoma
Reduced neutrophil function
- Chronic granulomatous disease (no respiratory burst)
- Chediak- Higashi syndrome (no phagolysosome)
