Lecture 1: Outline of the Innate Immune System

Question 1

What are the general features of innate immunity?

Answer 1

barrier tissues, chemical defences, soluble factors and effector cells

Question 2

What are some examples of barrier tissues?

Answer 2

skin, mucosa, respiratory epithelia, intestine

Question 3

What are some examples of chemical defences?

Answer 3

antimicrobial peptides (e.g. defensins) and antimicrobial enzymes (e.g. lysozyme)

Question 4

What are some examples of soluble factors?

Answer 4

complement proteins (e.g. C3b deposition)

Question 5

What are some examples of effector cells?

Answer 5

granulocytes (neutrophils, eosinophils, basophils), monocytes/macrophages, dendritic cells, NK cells

Question 6

What do epithelial surfaces of the body provide? What do epithelial cells (and phagocytes) produce?

Answer 6

the first barrier against infection

several kinds of antimicrobial proteins

Question 7

What must an infectious against overcome in order to establish a focus of infection?

Answer 7

innate host defences

Question 8

How does skin aid in the innate immune response?

Answer 8

mechanical: longitudinal flow of air or fluid
chemical: fatty acids, β-defensins, lamellar bodies, cathelicidin
microbiological: normal microbiota

Question 9

How does the gut aid in the innate immune response?

Answer 9

mechanical: longitudinal flow of air or fluid
chemical: low pH, enzymes (pepsin), ɑ-defensins (cryptdins), RegIII (lecticidins), cathelicidin
microbiological: normal microbiota

Question 10

How do the lungs aid in the innate immune response?

Answer 10

mechanical: movement of mucus by cilia
chemical: pulmonary surfactant, ɑ-defensins, cathelicidin
microbiological: normal microbiota

Question 11

How do the eyes/nose/oral cavity aid in the innate immune response?

Answer 11

mechanical: tears, nasal cilia
chemical: enzymes in tears and saliva (lysozyme), histatins, β-defensins
microbiological: normal microbiota

Question 12

What is lysozyme?

Answer 12

a hydrolase that catalyses the hydrolysis of linkages in peptidoglycan and digests bacterial cell wall

Question 13

What do defensins do?

Answer 13

disrupt and lyse the bacterial cell membrane directly

Question 14

What is complement made up of and what does it recognise?

Answer 14

> 30 soluble proteins in the blood that can recognise features of microbial surfaces and mark them for destruction by coating them with C3b

Question 15

What are outcomes of the complement system?

Answer 15

migration of phagocytes to site of infection
opsonization and phagocytosis of microorganisms
lysis of pathogens

Question 16

How are proteins in the complement system activated?

Answer 16

they are activated sequentially in a cascade and activation can occur through three different pathways

Question 17

Where do all three pathways of the complement system converge?

Answer 17

at the activation of ‘C3’

Question 18

What are the three different pathways of the complement system?

Answer 18

the alternative pathway, the lectin pathway and the classical pathway

Question 19

What are main characteristics of the innate immunity?

Answer 19

non-specific (molecular patterns), rapid response (minutes-hours), no memory

Question 20

How does the immune system distinguish between stranger and danger?

Answer 20

stranger = novel microbial structures
danger = changes in the expression of self proteins

Question 21

What are the major effector functions of innate immunity?

Answer 21

phagocytosis, cytokine secretion and cytotoxicity

Question 22

What is the outcome of the innate immune response?

Answer 22

either resolution of infection or persistence of the pathogens -> adaptive immune response

Question 23

Which lineage comprises most of the cells of the innate immune system?

Answer 23

the myeloid lineage

Question 24

What are granulocytes characterised by?

Why are these cells also known as polymorphonuclear?

Answer 24

secretory granules in their cytoplasm and short-lived (hours to days)
because they have a multi-lobed nucleus

Question 25

What do neutrophils carry out and what do they activate? When is their frequency elevated?

Answer 25

phagocytosis and activation of bactericidal mechanisms | elevated frequency in response to infection (increased production in the bone marrow)

Question 26

What are eosinophils essential for? Where is the majority of eosinophils in the body? What is their effector function?

Answer 26

essential for killing parasites | majority in the tissues and generally have effect through degranulation into the local environment

Question 27

What is the role of basophils?

Answer 27

help drive the innate immune response with some role in anti-parasitic immunity -> low numbers in blood and are recruited to site of IgE-mediated allergic reactions

Question 28

What do eosinophil granules contain?

Answer 28

arginine-rich basic protein

Question 29

What are the effector functions of eosinophils? (hint: What do they release?)

Answer 29

secrete leukotrienes, prostaglandins, cytokines to amplify inflammatory response release highly toxic proteins + free radicals to damage parasite's plasma membrane

Question 30

How do basophils stimulate inflammation? (hint: What do they release?)

Answer 30

they tend to accumulate in damage tissues + release histamine, heparin and cytokines

Question 31

Where are mast cells located?

Answer 31

only seen in tissues and are strategically located everywhere: particularly in sites that contact the external environment

Question 32

What are the three key functions of mast cells?

Answer 32

1. recruiting other cells to sites of infections 2. increase inflammation = increase lymph flow to local lymph node 3. mast cell products trigger muscular contractions - physical expulsion

Question 33

Where are dendritic cells found? What is their role?

Answer 33

in tissues and lymphatic organs critical role in antigen capture and antigen presentation to T cells + influence polarisation of T cells through cytokines and co-stimulatory molecules

Question 34

What are NK cells derived from? How are they activated?

Answer 34

the same progenitor cells as lymphocytes | activation is by detecting changes in the expression of self protein

Question 35

What is the role of NK cells?

Answer 35

important in antiviral and antitumor responses -> can lyse cells directly via the release of cytotoxic granules and secrete antiviral cytokines

Question 36

What is the role of monocytes/macrophages?

Answer 36

orchestrate immune responses (recruitment of other cells) and clear dead cells and cell debris

Question 37

What is the difference between monocytes and macrophages?

Answer 37

macrophages are tissue-resident forms of circulatory monocytes

Question 38

What does an inflammatory response lead to?

Answer 38

⬆ vascular diameter and blood flow + blood vessels become more permeable and fluid leaks into tissue + inflammatory cells migrate into tissue and release mediators that stimulate nerve endings

Question 39

What is an inflammatory response caused by?

Answer 39

chemokines and cytokines