Infection 4 - Innate Immunity (Part 1)

Question 1

What are the 2 main aspects of the immune response and the differences between them?

Answer 1

1) Innate immunity - immediate protection, fast, lack of specificity + memory. No change in intensity
2) Adaptive immunity - slow, specific, immunologic memory. Changes in intensity.

Question 2

What are the innate physical barriers that protect against infection?

Answer 2

• Skin - SA of 1-2M^2
• Mucous membranes - mouth, respiratory, GI + urinary tract
• Bronchial cilia in respiratory epithelium

Question 3

What are the innate physiological barriers that protect against infection?

Answer 3

• Diarrhoea
• Vomiting
• Coughing
• Sneezing
• All function to expel to pathogen out of the body.

Question 4

What are the innate chemical barriers that protect against infection?

Answer 4

• Low pH - skin (5.5), stomach (1-3), vagina (4.4)
• Antimicrobial molecules - e.g.: IgA in tears + saliva, lysozymes (sebum + urine), mucous (from membranes), gastric acid + pepsin.

Question 5

What are the innate biological barriers that protect against infection?

Answer 5

• Normal flora - i.e.: in nasopharynx, mouth, skin, GIT, vagina etc. Absent in sterile internal organs/tissues
• They compete with pathogens for attachment sites + resources, synthesise vitamins, produce antimicrobial chemicals etc.

Question 6

Give some examples of normal flora that inhabit the skin, the mouth/nasopharynx and the GIT

Answer 6

Skin = Staph Aureus + Staph Epidermis
Mouth = Streptococcus Pneumoniae + Neisseria Meningitidis 
GIT = E.Coli

Question 7

What are 3 pays in which normal flora can cause infection + clinical problems? - Give examples for each

Answer 7

1) Normal flora displaced to sterile locations - by breaching of skin integrity (surgery, I.V, burns, tattoos etc), fecal-oral route, fecal-perineal-urethral route (UTI’s in women) + poor dental hygiene
2) Host immuno-compromised and normal flora overgrows and becomes pathogenic - e.g.: in diabetes, AIDS, malignant diseases.
3) When normal flors in mucosal surfaces are depleted by antibiotics - e.g.: loss of lactobacilli in vagina leads to thrush.

Question 8

The second line of defence involves macrophages and cytokines/chemokines. How do macrophages recognise foreign pathogens?

Answer 8

• Macrophages recognise pathogen-associated molecular patterns (PAMP’s), and bind to them via pathogen recognition receptors (PRR’s) on the surface of the macrophage.
• PAMP’s include LPS’s (which bind to TLR4 PRR) and peptidoglycan (which bind to TLR2 PRR)

Question 9

What is the role of opsonin proteins + opsonisation?
Give 3 examples of opsonins.
What are opsonins essential for clearing?

Answer 9

• Opsonins bind and coat the protein to enhance the interaction between the microbe and macrophage, phagocytosis + clearance of microbe
• 1) Complement proteins (e.g.: C3b + C4b) 2) Antibodies (e.g.: IgG + IgM) 3) Acute phase proteins (e.g.: CRP + MBL).
• NB: Opsonins vital in clearing encapsulated bacteria such as neisseria meningitidis.

Question 10

Once the macrophage has engulfed the pathogen, what are the 2 ways the microbe can be destroyed?

Answer 10

1) Oxygen-dependent pathway (respiratory burst) - Toxic O2 products kill pathogens - e.g.: H2O2, hydroxyl radicals, NO etc.
2) Oxygen-independent pathways - e.g.: lysozymes, lactoferrin, cationic proteins, proteolytic/hydrolytic enzymes

Question 11

What are complement system proteins?

What are the 2 pathways in which complement proteins are activated?

Answer 11

• Circulate in blood as inactive precursors that are activated in a cascade fashion resulting in phagocyte activation + microbe digestion.

1) Alternative pathway - initiated by cell surface components (e.g.: endotoxins on E.coli)
2) MBL pathway - initiated when MBL binds to mannose containing residues of proteins found on microbes

Question 12

What are the roles of the following complement proteins:

• C3a + C5a
• C3b
• C5-C9

Answer 12

C3a/C5a = Recruitment of phagocytes
C3b = Opsonisation of pathogens
C5-9 = Killing of pathogens via membrane attack complex

Question 13

What is the role of macrophage-derived cytokines such as TNFa, IL1 + IL6?

Answer 13

• Cause liver to produce opsonins such as CRP + MBL
• Cause neutrophil mobilisation from bone marrow
• Cause hypothalamus to increase body temp
• Cause inflammatory actions, e.g.: vasodilation + permeability of blood vessels

Question 14

Therefore, give a 5 step summary of the innate immune response.

Answer 14

1) Innate barriers breached
2) Complement, mast cells + macrophage activation - leading to phagocytosis
3) Vascular changes + Chemoattraction - vasodilation and attraction of neutrophils/monocytes
4) Hypothalamus + Liver - temp increases + acute phase proteins released
5) Inflammation - leading to redness, heat, swelling + pain