Session 2

Question 1

How might patients vary?

Answer 1

Age - Elderly and very young are more susceptible to infection.
Gender - e.g. women are more likely to get UTIs.
Physiological state - e.g.. if pregnant there are lots of different hormones etc.
Pathological state - People with comorbidities are more likely to get infections.
Social factors - smoking and alcohol make patients more susceptible.
Time
Calendar time - More infections during winter.
Relative time - incubation period

Place
Current - living conditions
Recent - travel?

Question 2

What questions might you ask to determine exposure?

Answer 2

What were you doing? 
Where were you doing it?
When did you do it?
Who were you doing it with?
Were animals involved?

Question 3

What are the possible mechanisms of infection?

Answer 3

Contiguous (direct) Spread e.g hand to hand contact
Inoculation - e.g surgeons knife
Haematogenous - blood borne
Ingestion - e.g. food poisoning.
Inhalation - breathing in pathogens e.g. TB
Vector e.g. Malaria
Vertical transmission

Question 4

What strategy do we take towards an infection.

Answer 4

Take a history, perform an examination and investigations to make a diagnosis. Then treat it. also ensure infection prevention making sure the infection doesn’t spread.

Question 5

What’s the difference between specific and supportive treatment?

Answer 5

Specific is dealing with the infection directly e.g. antimicrobials.
Supportive is things like BP management, ventilator etc, essentially manage symptoms and keep patient well.

Question 6

How might we carry out treatment for an infection.

Answer 6

surgical intervention into an infection is called source control. Examples include draining of an abscess, debridement (removing dead tissue) and dead space removal (remove space or packing a space left from removal of tissue or abscess so that further infection doesn’t fill the space).

Question 7

What is infectivity?

Answer 7

Ability of a pathogen to establish itself in or on the host.

Question 8

What factors are important in determining whether a host becomes infected?

Answer 8

Infectivity, virulence factors and the hosts immunity.

Question 9

What is the immune system?

Answer 9

Cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)
Spleen is the largest lymphoid organ.

Question 10

What is an infectious disease?

Answer 10

Infectious disease = When the pathogen succeeds in evading and/or overwhelming the host’s immune defences

Question 11

What are the roles of the immune system?

Answer 11

• Pathogen recognition = Cell surface and soluble receptors
• Regulating itself = Minimum damage to host (resolution)
• Containing/eliminating the infection = Killing and clearance mechanisms
• Remembering pathogens = Preventing the disease from recurring

Question 12

What is the difference between innate immunity and adaptive immunity?

Answer 12

Innate immunity provides immediate protection 
• Fast (within seconds) 
• Lack of specificity
• Lack of memory 
• No change in intensity

Adaptive immunity provides long lasting protection
• Slow (days) 
• Specificity 
• Immunologic memory 
• Changes in intensity

Question 13

What are the first lines of defence in innate immunity?

Answer 13

Factors that prevent entry and limit growth of pathogens:
Physical barriers
Physiological  barriers
Chemical barriers
Biological barriers

Question 14

What are the physical barriers in innate immunity?

Answer 14

• Skin (surface area 1-2 m2) 
• Mucous membranes 
o Mouth 
o Respiratory tract 
o GI tract 
o Urinary tract 
• Bronchial cilia

Question 15

What are the physiological barriers in the innate immune system?

Answer 15

Physiological barriers
• Diarrhoea 
o Food poisoning
• Vomiting
 o Food poisoning 
o Hepatitis 
o Meningitis
• Coughing 
o Pneumonia
• Sneezing 
o Sinusitis

These attempt to remove the pathogen.

Question 16

What are the chemical barriers in innate immunity?

Answer 16

Chemical barriers 
• Low pH 
o Skin (5.5) 
o Stomach (1-3) 
o Vagina (4.4)
• Antimicrobial molecules
 o IgA (Tears, saliva, mucous membrane ) 
o Lysozyme (sebum, perspiration, urine) 
o Mucus (Mucous membranes) 
o Beta-defensins (epithelium) 
o Gastric acid + pepsin

Question 17

What are the biological barriers of innate immunity?

Answer 17

• Normal flora 
• Non pathogenic microbes 
• Strategic locations 
o Nasopharynx 
o Mouth/Throat 
o Skin 
o GI tract 
o Vagina (lactobacillus spp) 
• Absent in internal organs/tissues 

Benefits
• Compete with pathogens for attachment sites and resources
• Produce antimicrobial chemicals
• Synthesize vitamins (K, B12, other B vitamins)
• Immune maturation

Question 18

Give examples of normal flora that inhabit the skin and nasopharynx

Answer 18

• The skin Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pyogenes
Candida albicans
Clostridium perfringens 

• The nasopharynx
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus species

Question 19

Where should normal flora never be found?

Answer 19

In internal organs/tissues

Question 20

How can normal flora cause clinical problems?

Answer 20

Normal flora is displaced from its normal location to sterile location 
• Breaching the skin integrity 
o Skin loss (burns) 
o Surgery 
o IV lines 
o Skin diseases 
o Injection drug users 
o Tattooing/body piercing
• Fecal-oral route 
o Foodborne infection
• Fecal-perineal-urethral route 
o Urinary tract infection (women)
• Poor dental hygiene/dental work 
o Dental extraction 
o Gingivitis 
o Brushing/Flossing 

Common cause of harmless bacteraemia

Question 21

What patients are at risk of serious infections?

Answer 21

o Asplenic (and hyposplenic) patients
o Patients with damaged or prosthetic valves
o Patients with previous infective endocarditis
o immunosuppressed / immunocompromised

Question 22

When might patients be immunocompromised?

Answer 22

o Diabetes
o AIDS
o Malignant diseases
o Chemotherapy (mucositis)

Question 23

What might allow normal flora to be depleted

Answer 23

Can be depleted by antibiotic therapy.
o Intestine -> severe colitis (Clostridium difficile)
o Vagina -> thrush (Candida albicans)

Question 24

What are the second lines of defence in the innate immunity?

Answer 24

Phagocytes and chemicals involved in inflammation.

Factors that will contain and clear the infection

Question 25

What are the two types of pathogen entering a site?

Answer 25

Endogenous, living on skin | Exogenous, not living on site.

Question 26

What are the main phagocytes and what are their functions? (innate immunity)

Answer 26

Macrophages  - Present in all organs  - Ingest and destroy microbes (Phagocytosis) - Present microbial antigens to T cells (adaptive immunity)  - Produce cytokines/chemokines Monocytes  - Present in the blood (5-7%)  - Recruited at infection site and differentiate into macrophages Neutrophils (pus)  - Present in the blood (60% of blood leukocytes)  - Increased during infection  - Recruited by chemokines to the site of infection  - Ingest and destroy pyogenic bacteria: Staph. aureus and Strep. pyogenes

Question 27

What are the other key cells of the innate immunity?

Answer 27

Basophils/ Mast cells - Early actors of inflammation (vasomodulation)  - Important in allergic responses Eosinophils  - Defence against multi-cellular parasites (worms) Natural Killer cells  - Kill all abnormal host cells (virus infected or malignant) Dendritic cells  - Present microbial antigens to T cells (acquired immunity)

Question 28

How are pathogens recognised?

Answer 28

Microbial structures: • Pathogen-associated molecular patterns (PAMPs): Carbohydrates, Lipids, Proteins, Nucleic acids Phagocytes: • Pathogen Recognition Receptors (PRRs): Toll Like Receptors Opsonisation of microbes: Coating proteins called opsonins that bind to the microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes

Question 29

Give some examples of opsonins and what are they crucial in clearing out?

Answer 29

Complement proteins • C3b • C4b Antibodies • IgG • IgM Acute phase proteins • C-reactive protein (CRP) • Mannose-binding lectin (MBL) Essential in clearing encapsulated bacteria: • Neisseria meningitidis • Streptococcus pneumoniae • Haemophilus influenzae b

Question 30

Explain the process of phagocytosis.

Answer 30

1. Chemotaxis and adherence of phagocyte to microbe. 2. Ingestion of microbe by phagocyte through endocytosis. 3. Formation of phagosome. 4. Fusion of phagosome with lysosome to form phagolysosome. 5. Digestion of ingested microbe by enzymes 6. Formation of residual body containing indigestible material. 7. Discharge of waste material.

Question 31

what are the phagocyte's intracellular killing mechanisms?

Answer 31

Oxygen-dependent pathway (respiratory burst)  Toxic O2 products for the pathogens: Hydrogen peroxide, Hydroxyl radical, Nitric oxide, Singlet oxygen, Hypohalite ``` Oxygen-independent pathways  Lysozyme  Lactoferrin or transferrin Cationic proteins(cathepsin)  Proteolytic and hydrolytic enzymes ```

Question 32

What is the complement pathway?

Answer 32

• 20 serum proteins • Most important C1-C9 • 2 activating pathways: o Alternative pathway Initiated by cell surface microbial constituents (endotoxins on E. Coli) o MBL pathway Initiated when MBL binds to mannose containing residues of proteins found on many microbes (Salmonella spp. Candida albicans) C3a and C5a: Recruitment of phagocytes C3b-C4b: Opsonisation of pathogens C5-C9: Killing of pathogens Membrane Attack complex

Question 33

What is the role of cytokines and chemokines?

Answer 33

* Chemoattraction * Phagocyte activation * Inflammation

Question 34

What are the anti-microbial actions of macrophage-derived cytokines such as TNFa/IL-1/IL-6

Answer 34

``` Systemic actions: • Liver (opsonins) CRP MBL (-> complement activation) • Bone marrow Neutrophil mobilization • Hypothalamus Increased body temperature ``` Local inflammatory actions: • Blood vessels Vasodilation Vascular permeability Expression of adhesion molecules -> attraction of neutrophils

Question 35

Give a summary of the innate immune response

Answer 35

1. Innate barrier breached: entrance and colonization of the pathogens. 2. Complement, mast cells and macrophages activation (PRR) Phagocytosis (opsonins) Cytokine/chemokine production 3. Vascular changes Vasodilation/Vascular permeability Chemoattraction Neutrophils Monocytes (TNF, IL-8) 4. Hypothalamus Fever Liver Acute phase response 5. Redness, heat, swelling and pain: local inflammation

Question 36

What can cause a decrease in phagocytosis?

Answer 36

• Decrease spleen function o Asplenic patients o Hyposplenic patients • Decrease neutrophil number (1.8 109/l) o Cancer chemotherapy o Certain drugs (phenytoin) o Leukaemia and lymphoma • Decrease neutrophil function o Chronic granulomatous disease (No respiratory burst) o Chediak-Higashi syndrome (no phagolysosomes formation)

Question 37

Explain the stages of the bacterial growth cycle

Answer 37

During lag phase, bacteria adapt themselves to growth conditions. It is the period where the individual bacteria are maturing and not yet able to divide. Because bacteria reproduce by binary fission the number of cells increases exponentially (log phase) with time depending on the species, the minimum doubling time can be as short as 10 minutes or as long as several days. An example of a rapidly growing bacterial species is Escherichia coli. Eventually, growth slows and ceases entirely (stationary phase) as nutrients are depleted, and toxic waste products accumulate. Most cells in a stationary phase are not dead, however. If they are diluted into fresh growth medium, exponential growth will resume after a lag phase. Cycle consists of lag phase, log phase, stationary phase and death phase.

Question 38

Describe surface growth of bacteria

Answer 38

If a single bacterial cell is placed on a solid nutrient agar surface, the progeny of this cell remain close to the site of deposition and eventually form a compact macroscopic mass of cells called a colony. or rapidly growing species, overnight incubation at 30°C to 37°C is sufficient to produce visible colonies, each containing millions of cells. The gross characteristics of colonies (for example, color, shape, adherence, smell, and surface texture) can be useful guides for identification of the species of bacterium. Some species do not form compact circular colonies because the cells are capable of movement and swarm over the agar surface, especially if the surface is moist. Other species, particularly the actinomycetes, grow as long filaments of cells (mycelial growth).

Question 39

What is CRP?

Answer 39

CRP is a protein, produced in the liver, that binds to phospholipids on the surface of bacteria. It then acts as an opsonin stimulating phagocytosis. CRP also activates the complement system and CRP production increases dramatically during inflammation through the actions of TNF and is a good indicator of inflammation. CRP is also increased during non-infectious diseases such as autoimmune disease rheumatoid arthritis. The increased production of CRP also increases plasma viscosity.

Question 40

What are neutrophils and what do they do?

Answer 40

Neutrophils are a type of white blood cell that helps heal damaged tissues and resolve infections. Neutrophil blood levels increase naturally in response to infections, injuries, and other types of stress. They may decrease in response to severe or chronic infections, drug treatments, and genetic conditions. The body produces neutrophils in the bone marrow, Unlike some other cells or blood components, neutrophils can travel through junctions in the cells that line blood vessel walls and enter into tissues directly.