Session 2 ILOs - Infection Model and Innate Immunity

Question 1

Understand and describe a model of infection

Answer 1

The infection model acts as a scaffold to outline all aspects of an infection:
It shows how a patient interacts with an infection.
- The pathogen that causes it
- The symptoms the patient may present with
- The way in which the patient acquired the infection
- Why/how the pathogen causes the symptoms
- The management of the patient
- Likely prognosis/outcome for the patient

Question 2

Describe the human microbiome

Answer 2

The human microbiome is the total number and diversity of microbes found in and on the human body

Question 3

Identify microbes commonly found on the skin and other body sites

Answer 3

Skin:
(gram +ve cocci)
- Staphylococcus aureus
- Staphylococcus epidermidis
- Streptococcus species
(gram +ve bacilli)
- Corynebacterium species
- Propionibacterium acnes

Mouth:
- Streptococcus mutans (gram +ve cocci)

GI tract:
- Escherichia coli or E.Coli (gram -ve rods)

Upper respiratory tract:
- Streptococcus pneumonia (gram +ve cocci)

Vagina:

• Candida albicans (yeast)
• Corynebacterium species (gram +ve bacilli)

Question 4

Describe how microbes, normally present as commensals (part of the microbiome) can cause disease / infections in certain situations and give examples

Answer 4

If microbes can breach the innate barrier, e.g. skin or the mucosal membranes, then they can become infections where they can damage host tissue

Example:
- Bacteria normally present on the skin that breach the skin barrier either through cracked skin or cuts, can enter into the dermis and subcutaneous tissue leading to cellulitis

Example:
- Commensal Fungi (yeast) in the vagina e.g. candida albicans is kept in check by lactobacillus aureus. However if the level of lactobacillus aureus is reduced e.g. through antibiotics, then the candida albicans can grow leading to thrush

Question 5

Describe the different innate barriers to infection, including physical, physiological, chemical and biological and how they work to prevent microbe ingress

Answer 5

(Physical)
Skin:
- Tight junctions between keratinocytes prevent the ingress of microbes/pathogens present on the skin

Mucous membranes:
- Mucus produced by these membranes help to trap microbes

(Physiological)
Diarrhoea/vomitting:
- From food poisoning, aims to get the microbe out of the body

(Chemical)
Tears, saliva etc:
- Contains IgA (antimicrobial molecule) which binds to the microbe and prevents it from binding to the mucosal membrane

Low PH

• Stomach, skin, vagina
• Very low pH environment that is hostile to microorganisms

(Biological)
Normal flora
- Present at strategic locations to entry, (ie GI tract, vagina, skin) however not present in internal organs or tissues (this is pathogen if there is!)
- Synthesise vitamins (K,B12 and other B vitamins)
- Produce antimicrobial chemicals
- Compete with pathogens for attachment sites and resources

• These innate barriers work together to trigger the second line of defence
• The second line of defence causes inflammation and contains and clears the infection

Question 6

Describe how pathogens are recognised by cells of the innate immune system

Answer 6

Epithelial and endothelial cells express pathogen recognition receptors (PRRs).

Phagocytes will have PRRs on their cell surface that recognise and bind to pathogen-associated molecular patterns (PAMPs) on microorganisms so they can destroy them.

Question 7

Name and describe important opsonins

Answer 7

• These are essential for clearing encapsulated bacteria from the body, which can only be cleared by opsonins as they are poorly immunogenic
• Also bind to microbial surfaces and for enhanced attachment of phagocytes to microbes
• Also cause clumping together of microbes to make it easier for the phagocytes to destroy them all in one.

Complement proteins:

• C3b
• C4b

Antibodies

• IgG
• IgM

Acute phase proteins:

• C-reactive protein (CRP)
• Mannose-binding lectin (MBL)

Question 8

Describe the second line of defence, including the role of phagocytes and chemicals (complement and cytokines)

Answer 8

Phagocytes:

• Neutrophils, monocytes and macrophages bind to, ingest and destroy pathogens via oxygen dependant (respiratory burst) or oxygen independent pathways
• With the help of opsonins which enhance their phagocytic ability

Complement:

• These are a system of plasma proteins that collaborate to protect against bacterial infection which is activated by antigen-antibody binding or binding with cell wall components when there is an invasion.

The products of complement activation:

1) C3a and C5a:
Recruitment of phagocytes

2) C3b:
Opsonisation of pathogens

3) C5-C9:
Killing of pathogens via Membrane Attack Complex

• Cytokines: TNFa, IL-1, IL-6 ( these are cytokines produced by the macrophages at the site of infection to stimulate systemically that we need help. This stimulates the local inflammatory actions)

Cytokines causes:
1) Vascular changes - vasodilation and vascular permeability to increase chemoattraction - allowing more neutrophils and monocytes to get to the site of infection

2) Also act on hypothalamus to induce fever as very few organisms will grow when the temperature is up
3) Act on the liver to stimulate acute phase response
4) This results in redness, heat, swelling and pain, which is known as acute inflammation, which will allow you to contain the infection

Question 9

Describe how a clinical evaluation of the innate immune response helps to identify the presence of infection, and in particular that of acute inflammation and acute infection. As examples describe the role and evaluation of neutrophils and C-reactive protein.

Answer 9

Role and evaluation of neutrophils:

• First responder phagocyte
• Essential part of Innate immune system
• Circulate blood stream migrate to areas of inflammation by chemotaxis and phagocytose invading microbes and destroy them by by releasing reactive oxygen species.

Role and evaluation of C-reactive protein:

• Activates complement
• Recognises self and foreign molecules based on pattern recognition
• Binds to Fc receptors leading to generation of pro-inflammatory cytokines
• Acts as an opsonin for pathogens OR binds to microorganisms to make them more susceptible to phagocytosis

Question 10

Recognize the different interventions that affect integrity of the innate barriers and Understand the risk of infection associated with these interventions

Answer 10

CONTINUE LATER Physical barriers:
- Once they become damaged (e.g. scrape or cut) it allows pathogen freely into tissue ie commensal bacteria on skin

Physiologial barriers:

• Physiological responses often have side effects
• Coughing excessively can cause chronic damage or inflammation of the airways and may trigger or make asthmatic episodes worse
• Vomiting and diarrhoea lead to loss of fluid and electrolytes (e.g. potassium/ sodium) which can cause dehydration and electrolyte imbalance

For patients with intractable or severe diarrhoea and/or vomiting e.g. with cholera, supplements containing electrolytes and fluids need to be given to prevent dehydration and electrolyte imbalance which in extreme cases can be fatal. Thus, innate immune responses can cause severe complications. Some diseases and infections can also intentionally turn these physiological mechanisms on to try and weaken the body to make it more susceptible to infection.