Innate immunity and the inflammatory process

Question 1

Timeline of innate imminology (immediate 0-4)

Answer 1

infection
recognition by perfomed, non specific effectiors
removal of infectious agent

Question 2

Early induced response (early 4-96)

Answer 2

infection
recognition of microbial -associated molecular patterns
Inflammation recruitment and activation of effector cells
removal of infectious agent

Question 3

Adaptive immune response (late>96 hours)

Answer 3

Infection
Transport of antigen to lymphoid organs 
Recognition by naive B and T cells
Clonal expansion and differentiation to effector cells
Removal of infectious agent

Question 4

Non-immunological barriers to infection Skin
Mechanical
Chemical
Microbiological

Answer 4

Mechanical
Epithelial cells joined by tight junctions
Longitudinal flow of air or fluid

Chemical
Fatty acids
Antibacterial Peptides

Microbiological
Normal Flora

Question 5

Non-immunological barriers to infection Gut
Mechanical
Chemical
Microbiological

Answer 5

Mechanical
Epithelial cells joined by tight junctions
Longitudinal flow of air or fluid

Chemical
Low pH
Enzymes (pepsin)
Antibacterial Peptides

Microbiological
Normal Flora

Question 6

Non-immunological barriers to infection lungs
Mechanical
Chemical

Answer 6

Mechanical
Epithelial cells joined by tight junctions
Movement of mucus by cilia

Chemical
Antibacterial Peptides

Question 7

Non-immunological barriers to infection eyes/nose
Mechanical
Chemical

Answer 7

Mechanical
Epithelial cells joined by tight junctions
Chemical
Salivary enzymes and lysozymes

Question 8

describe the classical pathway

Answer 8

Antigen antibody complexes (pathogen surfaces)
C1q C1r C1s C4 C2
C3 convertase
C3a C5a
Peptide mediators of inflammation, phagocyte recruitment

Question 9

describe the MB-Lectin pathway

Answer 9

Mannose-binding lectin binds mannose on pathogen surfaces
MBL MASP-1 MASP2 C4 C2
C3 convertase
C3b
Binds to complement receptors on phagocytes
Opsonization of pathogens
Removal of immune complexes

Question 10

describe the alternative pathway

Answer 10

Pathogen surfaces
C3 B D
C3 convertase
C3b
Terminal complement components C5b C6 C7 C8 C9
Membrane-attack complex, lysis of certain pathogens and cells

Question 11

describe the membrane attack complex

Answer 11

C5b binds to C6 and C7
C5b67 complex binds to membrance via C7
C8 binds to the complex and inserts into the cell membrane
C9 molecules bind to the complex and polymerize
1-16 molecules of C9 bind to form a pore in the membrane

Question 12

desribe the recognition mechaisms of innate immunity

Answer 12

Rapid response aka hours
Fixed
Limitted no. of specialities
Constant druing response

Question 13

desribe the recognition mechaisms of adaptive immunity

Answer 13

slow response so weeks and days
variable
numerous highly selective speciatlies
improve during response

Question 14

tow constants between adaptive and innate immunity

Answer 14

common effector mechanisms for the destruction of pathogens

Question 15

Innate immunity receptor characteristics

Answer 15

specificity inherited in the genome
expressed by all cells of a particular type eg macropgages
triggers immediate response
recognizes broad classes of pathogen
interacts with a range of molecular structures of a given type

Question 16

adaptive immunity receptor characteristic

Answer 16

encoded in multiple gene segments
requires gene rearrangement
clonal distribution
able to discriminate between even closely related molecular structures

Question 17

what initiates the release of cytokines and small lipids mediators of inflammation

Answer 17

bacteria binding to macrophage receptors

Question 18

what does the macrophage have on its surface

Answer 18

receptors for many bacterial constituents

Question 19

how do Pattern recoginition receptors PPR identifies the class of pathogen ?

Answer 19

by

recognising “pathogen associated molecular patterns” (PAMPs)

Question 20

principles of phagocytosis

Answer 20

attachment by pattern recognition receptors 
pseudopodia forming a phagosome
granule fusion and killing
release of microbial
granule fusion and killing
the release of microbial products

Question 21

during phagocytosis what do phagocytes switch on

Answer 21

potent antimicrobial

mechanisms

Question 22

when does the activation of NADPH oxidase happen and what is released

Answer 22

during the “Respiratory burst” and
releases toxic oxygen radicals
(superoxide and hydrogen peroxide)

Question 23

what is wrong with the Oxygen radicals

Answer 23

may directly damage
microbial membranes and / or activate
microbicidal enzymes found in granules

Question 24

role of phagosomes in innate immunity

Answer 24

pathogen killing
pathogen processing
pathogen presentation TLRS
Pathogen presentation to cytosolic sensors NODs/NALPs

Question 25

role of phagosomes in adaptive immunity

Answer 25

antigen dgredation antigen processing antigen presentation MHCII Antigen presentation via cytosol MHCI

Question 26

what are the Microbicidal mechanisms of phagocytes and the products

Answer 26

``` Acidification Toxic oxygen derived products Toxic nitrogen oxides Antimicrobial peptides Enzymes Competitors ```

Question 27

what proportion of leukocytes are Neutrophil

Answer 27

40-75

Question 28

what proportion of leukocytes are Eosinophil

Answer 28

1-6

Question 29

what proportion of leukocytes are Basophil

Answer 29

<1%

Question 30

what proportion of leukocytes are Monocyte

Answer 30

2-10

Question 31

what proportion of leukocytes are Lymphocyte

Answer 31

20-50

Question 32

what proportion of leukocytes are Dendritic cells

Answer 32

<1%

Question 33

how do activated neutrophils catch bacteria

Answer 33

“neutrophil extracellular traps” or NETs

Question 34

what does NET contain

Answer 34

chromatin and granule proteins (incl. enzymes to degrade | pathogen virulence factors)

Question 35

what do monocytes give rise to

Answer 35

tissue macrophages

Question 36

what do most macrophages arise from?

Answer 36

non-hematopoietic precursors!

Question 37

what are dendritic cells

Answer 37

a third type of phagocyte (related to monocytes / macrophages) but specialised for interacting with lymphocytes

Question 38

what do cytokines produced by macrophages cause and what happens to leukocytes as a result

Answer 38

dialiation of local small blood vessels | leukocytes then move to periphery of blood vessel as a result of increeased expression of adhesion molecules

Question 39

desribe the action of the monocyte

Answer 39

Monocyte binds adhesion molecules on vascular endothelium near sites of infection and gets chemokines signal the monocyte migates into surrouding tissue monocytes differentiates into a macrophage and migrates to the site of infection

Question 40

what are Cytokines and chemokines

Answer 40

The hormones of the immune system

Question 41

what do Cytokines and chemokines allow

Answer 41

communication between a variety of immune and non- immune cells

Question 42

names of Cytokines and chemokines

Answer 42

Mostly referred to as “interleukins” hence IL-1, IL-2, IL-3 etc, but some use “functional names” e.g “tumour necrosis factor” (TNF)

Question 43

what are chemokines

Answer 43

A further heterogeneous and complex family of small molecular weight chemotactic cytokines are known as “chemokines” (approx 30 also)

Question 44

Cytokines and chemokines regulation

Answer 44

• Mostly short acting “hormones” but can have systemic effects e.g. in shock • May be released in a polar fashion at “synapses” • Recognised on target cells by specific receptors (with some redundancy) • Receptor expression is highly regulated to control the targets and duration of response • Subsets of cytokines / chemokines may be selectively coregulated and help define cell subsets e.g Th1 and Th2 CD4+ lymphocytes

Question 45

Function of natural killer cells (an ‘innate’ lymphocyte

Answer 45

``` Involved in tumour surveillance Kill “altered self” targets Produce macrophage activating cytokines e.g. IFNg ```

Question 46

what is at the head of a cytokine cascade responsible for symptoms of rheumatoid arthritis

Answer 46

TNF

Question 47

TNF blockade may cause what

Answer 47

TB reactivation | - increased risk of secondary infection

Question 48

what do steroids affect

Answer 48

multiple aspects of immune | function, including cytokine release

Question 49

steroid affect on the immune system

Answer 49

steriod receptors are found in the cytoplasm complexed with a heat shock protein Hsp90 Steriods cross the cell membrane and bind to the steroid receptors complex releasing Hsp90 The steroid receptor complex can now cross the nuclear membrane In the nucleus, the steroid receptors bind to specific gene regulatory sequences and activate transcription

Question 50

two example steriods

Answer 50

cortisol | prednisone

Question 51

Corticosteroid therapy of physiological effects

Answer 51

decreased inflammation caused by cytokines decreased NO Decreased prostaglandins and leukotrienes Reduced emigration of leukocytes from vessels introduction of apoptosis in lymphocytes and eosinophils

Question 52

Corticosteroid therapy of effect on

Answer 52

increased endonucleases decreased adhesion molecules decreased NOS