16 - innate defences against infection

Question 1

what is innate immunity?

Answer 1

• simple recognition systems
• limited capacity
• there before infection starts
• no memory

Question 2

innate defence mechanisms

Answer 2

• barriers
• cellular defences
• molecular defences

Question 3

physical barriers to infection

Answer 3

skin
• fatty acids
• commensals (humoral factors)

mucus membranes 
• mucus - helps to clear infectious agent 
• cilia - clearing 
• commensals 
• low pH

Question 4

chemical barriers to infection

Answer 4

lysozyme in tears

acid in stomach (pH 2)

Question 5

antibacterial enzymes

Answer 5

lysozyme - digests the peptidoglycan layer to degrade the bacteria

secretory phospholipase A2

tears, saliva and phagocytes

Question 6

what do antimicrobial peptides (AMPs) do?

Answer 6

make holes and break down the membranes

Question 7

recognition by the innate system

Answer 7

need to discriminate between self and non-self

effective in combatting many pathogens

see problems when you have deficiencies of a component of immunity

Question 8

what are pattern recognition receptors (PRRs)

Answer 8

allow identification of pathogens

recognise simple molecules and regular patterns

located on host cells
• macrophages
• neutrophils
• dendritic cells

Question 9

examples of PPRs

Answer 9

toll-like receptors (TLRs)

NOD-like receptors

RIG-I-like helicases

Question 10

what are toll-like receptors (TLRs)?

Answer 10

• membrane surface receptors
• evolutionary conserved
• 10 identified in humans
• each has its own repertoire of PAMPs - lock and key

Question 11

what are NOD-like receptors?

Answer 11

• intracellular receptors

* nucleotide-binding oligomerisation domain

Question 12

what are PAMPs?

Answer 12

pathogen-associated molecular patterns

• mannose-rich oligosaccharides
• peptidoglycans
• lipopolysaccharides
• unmethylated CpG DNA

Question 13

what is blood made up of?

Answer 13

• RBCs
• WBCs
• plasma
• platelets

Question 14

what is haematopoiesis?

Answer 14

the formation of blood cellular compartments

all cellular blood compartments are derived from haematopoietic stem cells

Question 15

what are leucocytes?

Answer 15

white blood cells

produced from pluripotent haematopoietic stem cells in the bone marrow

Question 16

what are the types of leucocytes?

Answer 16

lymphocytes (B, T and NK)

monocytes (tissue macrophages)

granulocytes

tissue mast cells

Question 17

what are the 3 types of granulocytes?

Answer 17

neutrophils

eosinophils

basophils

Question 18

neutrophils

Answer 18

most common WBC in blood

multi lobed nucleus

Question 19

eosinophils

Answer 19

involved in allergic reactions and can attack multicellular parasites such as worms

Question 20

basophils

Answer 20

involved in allergic reactions

able to release histamine, which helps trigger inflammation, and heparin, which prevents blood from clotting

Question 21

cellular defences

Answer 21

phagocytosis - neutrophils and macrophages

extracellular killing

inflammation is the goal

Question 22

what happens if we have a problem with are phagocytes?

Answer 22

• bacterial infections
• fungal infections
• recurrent infections

Question 23

what is phagocytosis?

Answer 23

ingestion and killing of microorganisms by specialised cells

main phagocytic cells:
• neutrophils
• mononuclear phagocytes

Question 24

neutrophils in phagocytosis

Answer 24

• first line of defence
• short lived cells - days
• polymorphonuclear (PMN) cell
• abundant in sites of acute inflammation

Question 25

mononuclear phagocytes

Answer 25

• more sophisticated
• longer lived cells - months
• blood monocytes, Kuppfer cells, alveolar macrophages
• monocyte –> macrophage

Question 26

process of phagocytosis

Answer 26

1. recognition
2. internalisation - phagosome
3. fusion - phagolysosome
4. killing
5. digested products released

Question 27

what allows recognition to initiate phagocytosis?

Answer 27

common bacterial components (mannose, LPS)

complement (C3b)

antibody (Fc)

Question 28

phagocytic killing mechanisms

Answer 28

• acidification
• toxic oxygen products
• toxic nitrogen oxides
• antimicrobial peptides
• enzymes
• competitors

Question 29

oxygen dependent killing

Answer 29

1. hexose monophosphate shunt generates NADPH
2. NADPH oxidase generates reactive oxygen intermediates
3. reactive oxygen intermediates are bacteriostatic or bacteriocidal

Question 30

additional functions of macrophages

Answer 30

can be activated by bacterial products or cytokines

secrete soluble factors - cytokines

present antigen to lymphocytes

Question 31

extracellular killing is active against…

Answer 31

• organisms too large for phagocytosis

* infected cells

Question 32

cells involved in extracellular killing are…

Answer 32

eosinophils - killing of antibody-coated parasites

NK cells - release lytic granules that kill some virus-infected cells and attack some tumour cells

Question 33

NK cells

Answer 33

activated by IFN-alpha/beta and IL12
• interferon and interleukin

can produce IFN-gamma - helps to control infections

contain viral infections whilst adaptive/specific responses kick in

Question 34

what are cytokines?

Answer 34

low molecular weight proteins secreted by cells that stimulate or inhibit the activity, proliferation or differentiation of other cells

includes the subgroups: 
• interferons 
• interleukins 
• lymphokines 
• chemokines

link the innate and adaptive responses

Question 35

general properties of cytokines

Answer 35

• secretion is a brief, self-limited event
• action is often pleiotrophic and redundant
• influence the synthesis and actions of other cytokines
• action may be local and systemic
• imitate their actions by binding to specific membrane receptors on target cells

Question 36

what is the cellular response to most cytokines?

Answer 36

changes in gene expression in target cells, resulting in the expression of new functions and sometimes proliferation of the target cell

Question 37

3 major categories of cytokines

Answer 37

mediators and regulators of innate immunity

mediators and regulators of adaptive immunity

stimulators of haematopoiesis

Question 38

cytokines - mediators and regulators of innate immunity

Answer 38

produced mainly by mononuclear phagocytes in response to infectious agent

Question 39

cytokines - mediators and regulators of adaptive immunity

Answer 39

produced mainly by T lymphocytes in response to specific recognition of foreign antigens

Question 40

cytokines - stimulators of haematopoiesis

Answer 40

produced by bone marrow stromal cells, leukocytes and other cells

stimulate the growth and differentiation of immature leukocytes

Question 41

important cytokines

Answer 41

• IL2
• IL1
• TNF alpha
• interferons

Question 42

2 distinct groups of chemokines

Answer 42

CXC

CC

Question 43

effects of cytokines secreted by macrophages

Answer 43

inflammation

fever

acute phase response - involves liver

act on lymphocytes - influence function

Question 44

what does inflammation do?

Answer 44

brings cells and molecules from blood into site of infection

• increases blood supply - via vasodilation
• increases vascular permeability - leaky
• increases expression of adhesion molecules

Question 45

what does inflammation trigger?

Answer 45

• macrophage derived cytokines
• complement
• mast cells - histamine release
• T-cell derived cytokines

Question 46

what is endotoxic shock?

Answer 46

excessive cytokine release in gram-negative bacterial infection

widespread effects of cytokines on vascular epithelium
• circulatory shock
• disseminated intravascular coagulation (DIC)