Infection - Innate Immunity

Question 1

What is the difference between infectivity and virulence?

Answer 1

Infectivity is the capacity of a pathogen to establish itself within a host. Virulence is the capacity of a microbe to damage the host

Question 2

Define immune system

Answer 2

Cells and organs that contribute to immune defences against infectious and non-infectious conditions

Question 3

Define infectious disease

Answer 3

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

Question 4

What are the four main roles of the immune system?

Answer 4

• pathogen recognition
• containing/eliminating the infection
• regulating itself
• remembering pathogens

Question 5

Describe some key differences between innate and adaptive immunity

Answer 5

Innate immunity:

• fast (seconds)
• lack of specificity and memory
• no change in intensity

Adaptive immunity:

• slow (days)
• specific
• has immunologic memory
• changes in intensity

Question 6

What are ‘barriers’ in immunity?

Answer 6

Factors that prevent entry and limit growth of pathogens

Question 7

Give some examples of physical barriers in innate immunity

Answer 7

• skin
• mucous membranes (mouth, respiratory tract, GI tract, urinary tract)
• bronchial cilia

Question 8

Give some examples of physiological barriers in the innate immune system

Answer 8

• diarrhoea
• vomiting
• coughing
• sneezing

Question 9

Give some examples of chemical barriers in the innate immune system

Answer 9

• low pH (skin is 5.5, stomach is 1-3, vagina is 4.4)

- antimicrobial molecules

Question 10

Give some examples of antimicrobial molecules that form part of the innate immune system

Answer 10

• IgA (tears, saliva, mucous membrane)
• lysozyme (sebum, perspiration, urine)
• mucus (mucous membranes)
• beta-defensins (epithelium)
• gastric acid and pepsin

Question 11

What are ‘biological barriers’?

Answer 11

Non-pathogenic normal flora found in strategic locations, eg. nasopharynx, mouth/throat, skin, GI tract, vagina. They are not found within internal organs/tissues

Question 12

Give some benefits of the body having ‘normal flora’ (non-pathogenic microbes)

Answer 12

• compete with pathogens for attachment sites and resources
• produce antimicrobial chemicals
• synthesise vitamins (K, B12, other B vitamins)

Question 13

Give some examples of normal flora that inhabit the skin

Answer 13

• staphylococcus aureus
• staphylococcus epidermidis
• streptococcus pyogenes
• Candida albicans
• clostridium perfringens

Question 14

Give some examples of normal flora that inhabit the nasopharynx

Answer 14

• streptococcus pneumoniae
• neisseria meningitidis
• haemophilus species

Question 15

How could normal flora be displaced from its normal location to a sterile location?

Answer 15

• breaching skin integrity (skin loss, surgery, injected drugs, IV lines)
• faecal-oral route (foodborne infection)
• fecal-perineal-urethral route (UTI infection)
• poor dental hygiene/dental work

Question 16

Which groups of patients are seen as high risk for infections from normal flora?

Answer 16

Patients who are/have:

• asplenic/hyposplenic
• damaged or prosthetic valves
• previous infective endocarditis

Question 17

Give some examples of conditions that may cause a host to become immunocompromised, allowing overgrowth of normal flora

Answer 17

• diabetes
• AIDS
• malignant diseases
• chemotherapy

Question 18

What is thrush caused by?

Answer 18

Vaginal yeast infection (candida albicans) that can occur when normal flora is depleted by antibiotics

Question 19

What are macrophages?

Answer 19

Phagocytes which are present in all organs. They ingest and destroy microbes via phagocytosis, and present microbial antigens to T cells (part of adaptive immunity). They produce cytokines/chemokines

Question 20

What are monocytes?

Answer 20

Phagocytes which are present in the blood. They are recruited at the infection site where they differentiate into macrophages

Question 21

What are neutrophils?

Answer 21

Phagocytes which make up 60% of blood leukocytes. They are increased during infection, when they are recruited by chemokines. They ingest and destroy pyogenic bacteria

Question 22

What is the function of basophils/mast cells?

Answer 22

Early actors of inflammation (vasomodulation) which are important in allergic responses

Question 23

What are eosinophils used for?

Answer 23

Defence against multi-cellular parasites (worms)

Question 24

What are natural killer cells for?

Answer 24

They kill all abnormal host cells (either infected with virus or malignant)

Question 25

What are dendritic cells for?

Answer 25

Present microbial antigens to T cells (in acquired/adaptive immunity)

Question 26

How does the phagocyte recognise the pathogen to be consumed?

Answer 26

Pathogen will have microbial structures (pathogen-associated molecular patterns or 'PAMPs') and phagocyte has pathogen recognition receptors

Question 27

What is opsonisation of microbes?

Answer 27

Coating proteins called opsonins bind to the microbial surfaces, leading to enhanced attachment of phagocytes

Question 28

Give some examples of opsonins

Answer 28

- complement proteins (C3b, C4b) - antibodies (IgG, IgM) - acute phase proteins (C-reactive protein and mannose-binding lectin) These are all essential in clearing encapsulated bacteria

Question 29

What are the two phagocyte intracellular killing mechanisms?

Answer 29

- oxygen dependent pathway | - oxygen independent pathway

Question 30

What is the oxygen-dependent killing pathway?

Answer 30

Reactive oxygen-containing molecules are produced by the phagocyte which are anti-microbial

Question 31

What are the different methods of oxygen-independent destruction of pathogens?

Answer 31

- production of lysozymes which break down bacterial cell wall - production of lactoferrins which are present in neutrophil granules and remove the essential iron from bacteria - electrically charged cationic proteins damage the bacterium's membrane - proteolytic/hydrolytic enzymes digest the proteins of destroyed bacteria

Question 32

What is the difference between the alternative pathway and the MBL pathway of complement activation?

Answer 32

- alternative pathway is initiated by cell surface microbial constituents (endotoxins on E.coli) - MBL pathway is initiated when MBL binds to mannose containing residues of proteins found on many microbes

Question 33

What are complement proteins C3a and C5a responsible for?

Answer 33

Recruitment of phagocytes

Question 34

What are complement proteins C3b-C4b responsible for?

Answer 34

Opsonisation of pathogens

Question 35

What are complement proteins C5-C9 responsible for?

Answer 35

Killing of pathogens, membrane attack complex

Question 36

What are the antimicrobial actions of macrophage-derived TNF-alpha (and where do they take place)?

Answer 36

- liver (CRP and MBL activate complement/opsonisation) - bone marrow (neutrophil mobilisation) - inflammatory actions (vasodilation, vascular permeability, adhesion molecules lead to attraction of neutrophils) - hypothalamus (increased body temperature)

Question 37

What three things can lead to reduced phagocytosis?

Answer 37

- decreased spleen function (asplenic/hypersplenic patients) - decreased neutrophil number (chemotherapy, certain drugs, leukaemia and lymphoma) - decreased neutrophil function (chronic granulomatous disease, Chediak-Higashi syndrome)