Innate immunity

Question 1

what is innate immunity?

Answer 1

the first line of defence

Question 2

when is the innate immune system activated?

Answer 2

breach of physical barriers that can lead to infection

Question 3

what are the two responses?

Answer 3

first (instant)and second (hours later)

Question 4

what are the different defences triggered by the barriers?

Answer 4

Question 5

what is complement

Answer 5

complement is a collection of soluble and membrane-bound proteins. (aka the first line of defence

Question 6

where is complement made?

Answer 6

liver constitutively (no stimulus required) in a zymogen form (pro-enzyme (inactive form))

Question 7

where can complement be found

Answer 7

blood, lymph, extracellular fluids

Question 8

how is complement activated?

Answer 8

complement is activated through a cascade of enzymatic reactions that occur due to infection

Question 9

what is the most important complement protein and why ?

Answer 9

C3 Without it people are more prone to infections

Question 10

describe the key complement event

Answer 10

C3 is cleaved into two parts C3a which moves to activate other cells and C3B (larger) tags bacterium for destruction

Question 11

what are the three activation pathways?

Answer 11

Question 12

describe the alternative pathway of complement activation

Answer 12

iC3 levels increase in the vicinity of a pathogen
A hydrolysis event takes place and causes the recruitment of protein B which then recruits protein D
protein D can cleave B into Ba and Bb
Bb binds to C3b forming thus producing C3 convertase (iC3Bb)(soluble)
causing the cleavage of C3 to C3a, which recruits more proteins to continue the cycle and Cb, which covalently binds and tags pathogens.

Question 13

describe how complement activation is tightly regulated with the use of properdin

Answer 13

properdin is a plasma protein that maintains C3bBb by preventing cleavage thus extending the life of C3 convertase
- postive regulator

Question 14

describe how complement activation is tightly regulated with the use of factor H&I

Answer 14

Question 15

describe how complement activation is tightly regulated with the use of DAF and MCP (self defence)

Answer 15

Question 16

describe phagocytosis as a first line of defence in innate immunity

Answer 16

• Complement activation leads to deposition of C3b on the bacterial cell surface
• CR1 on macrophage binds C3b on bacterium
• endocytosis of the bacterium by macrophages
  -Macrophage membranes fuse, creating a phagosomethen lysosome fusesvwith phagosome forming a phagolysosome

Question 17

explain the effect phagocytosis has as a first line of defence to bacteria

Answer 17

-complement activation opsonisation and phagocytosis keep bacterial levels low at start of infection

Question 18

explain how complement activation can result in cell in lysis

Answer 18

C3b binds C3 convertase to (C3bBb) to make C3b2Bb
-> a C5 convertase

C5 convertase activity results in assembly of the membrane attack complex (MAC)

Question 19

explain how protectin (CD59) tightly regulates complement activation

Answer 19

on the cells of pathogens complement components C5-C( assemble a complex that perforates the cell membrane.

on human cells CD59 binds to the C5b678 complex and prevents recruitment of c9 to form the pore

Question 20

Complement activation induces inflammatory responses

Answer 20

Question 21

define inflammation

Answer 21

Complex, multifactorial response to infection, damage, trauma

Question 22

Is inflammation synonymous with INFECTION

Answer 22

no

Question 23

how is inflammation characterised

Answer 23

Calor (Heat)
Dolor (Pain)
Rubor (Redness)
Tumor (Swelling)

Question 24

describe acute inflammation

Answer 24

A local reaction where the Movement of proteins and cells from blood to tissue

Question 25

acute inflammation usually is predominant in what WBC type

Answer 25

neutrophils

Question 26

explain the Kinetics of acute inflammation

Answer 26

between 30 minutes and one hour after some trauma or infection exudate levels increase and comes down over two or three days. 6 to 8 hours after trauma neutrophils infiltrate and then disappear because they become apoptotic so apoptosis levels increasing and they're coming down. Apoptosis levels disappear because mononuclear cells like monocytes ( which become macrophages in the tissue) eat those apoptic cells and migrate away. early in the time frame of inflammation molecules like histamine and compliment a as time goes on, we get soluble factors such as prostaglandins and leukotrienes. Later on, we get cytokines like TNF alpha and interleukin 8 and interleukin 6. Lastly, some repair cytokinins like TGF beta.

Question 27

what is chronic inflammation

Answer 27

Prolonged and Non-resolving inflammation that leads to loss of function that leads to further disease e.g. Rheumatoid arthritis

Question 28

describe how Cells of innate immunity recognise pathogens

Answer 28

recognise via pattern recognistion receptors such as manose R scavener r and glucan r which are all lectins and recognise carbs on microbacteria surface (aka pathogen associated molecular patterns) which leads tomphagocytosis

Question 29

what are Toll-like receptors (TLR)

Answer 29

Family of signalling receptors Expressed by different cell types Recognise different pathogens Tailor innate immune responses to WHAT and WHERE

Question 30

explain how Toll-like receptors (TLR) sense infection

Answer 30

TLR signalling switches on cytokine production ->-Informs adaptive immunity

Question 31

how do Pathogens induce cytokine release

Answer 31

Question 32

characteristics of neutrophils

Answer 32

Neutrophils- most abundant white blood cell Huge bone marrow reserve of mature neutrophils Products of inflammation attract neutrophils to sites of infection Neutrophils are adapted for working without oxygen They will die hours after entry to infected tissue- forming pus (MYELOPEROXIDASE

Question 33

how neutraphils get out of blood

Answer 33

the infection causes local endothelia to upregulate adhesion molecules which allow neutrophils to stick via a low affinity interaction so that blood flow allows neutrophils to roll down into the vessel wall. until another firm adhision can occur cells migrate through gsaps in endothelium cells into tissue where receptors detect chemokine to cells migrae up chemokine to site of infection

Question 34

what do mast cells do

Answer 34

Release of vasoactive amines e.g. histamine Release of cytokines e.g. TNF-a Recruits °Ab(antibodies) °Complement °Fluid (exudate) (helps AntigenPresenting Cells drain into lymph) °Cells

Question 35

where are mast cells located

Answer 35

Resident in tissues & sub mucosae

Question 36

what activates mast cells

Answer 36

C3a and C5a activate mast cells → anaphylatoxins

Question 37

neutrophils eating pathogens

Answer 37

Question 38

how do pathogens die by oxygen-independent mechanism

Answer 38

Lysozyme, defensins, and elastase are all found in azurophilic granules enzymes and NADPH oxidase components are found in specific granules This alters pH in the phagosome to activate proteases (high pH) and acid hydrolases (low pH)

Question 39

how do pathogens die by oxygen-dependent mechanism

Answer 39

This alters pH in the phagosome to activate proteases (high pH) and acid hydrolases (low pH) This alters pH in the phagosome to activate proteases (high pH) and acid hydrolases (low pH)

Question 40

what is Chronic granulomatous disease (CGD)

Answer 40

Mutations in genes for NADPH oxidase No respiratory burst No pH change in phagosome No damage to pathogens Infections are not cleared and remain in localised nodules - granulomas

Question 41

the effects of Inflammatory cytokines on the body

Answer 41

They are pyrogens - raise temperature Reduce bacterial & virus growth Enhance adaptive immunity They stimulate the production of acute phase proteins C-reactive protein (CRP) and Mannose-binding lectin (MBL)->(2nd response of innate immunity)

Question 42

how does Acute phase proteins enhance innate immunity

Answer 42

CRP binds to bacterial and fungal cell walls MBL binds to mannose-containing carbohydrates Both are opsonins (enhance phagocytosis) Synthesis increases 1000-fold in the acute phase response

Question 44

Innate Defence to viruses: the interferon response

Answer 44

Question 45

characteristics of natural killer cells

Answer 45

NK cells are the killers of innate immunity Large granular lymphocytes NK are lymphocyte cells of innate immunity – kill and make cytokines Activity increases 20-100 times on exposure to the interferons NK provide an early response to virus infection – until cytotoxic T cells are ready People with no NK cells – persistent viral infections despite normal adaptive immune responses

Question 46

NK express inhibitory and activating receptors

Answer 46

NK are partly-activated so need to be tightly controlled Several cell surface receptors that recognise alterations in cell surface proteins Infection, malignancy and trauma can all cause changes in the surface characteristics of cells NK can detect these changes

Question 47

how do NK Cells work

Answer 47

NK use their receptors to distinguish healthy and sick cells