Week 1: Innate Immunity and Inflammatory Response

Question 1

Why do we have innate defenses?

Answer 1

Innate Immunity may prevent pathogen establishment
Innate Immunity may limit pathogen multiplication
Innate Immunity provides protection from early death during the expansion phase of acquired immune response
Innate Immunity helps to instruct the nature of the aquired immune response generated after infection

Question 2

What is the complement cascade?

Answer 2

It is a chain reaction of a series of proteins which are enzyme components that is triggered by a pathogen which results in self amplication and results in a large immune response.

Question 3

What are the 3 pathways for the complement cascade?

Answer 3

Classical Pathway - antigen : antibody pathway
MB-Lectin Pathway - Mannose-binding lectin binds mannose on pathogen surfaces
Alternative Pathway - pathogen surfaces

Question 4

What pathway do most complement cascade reactions take?

Answer 4

Alternative Pathway

Question 5

What enzyme does the complement cascade mainly rely on?

Answer 5

C3 convertase

Question 6

What are complement regulatory proteins?

Answer 6

Self defense proteins to make sure no immune response against body’s own cells

Question 7

What do mast cells generate?

Answer 7

C5 and c3a bind to receptors on mast cells which degranulate and release chemotactic factors(attracts cells to site of infection) and vascular permeability mediators ( allows cells to move from lumen of vessel to tissue)

Question 8

How is the membrane attack complex formed in the formation of the complement?

Answer 8

c5b binds c6 and c7 and the c5b67 complex binds to the membrane by c7.
C8 binds to the complex and inserts to the membrane
c9 molecules bind to the complex and polymerize to form around 1-16 molecules of c9 to form a pore in the membrane to form a drill-like structure.

Question 9

How are pathogens opsonized in the complement system?

Answer 9

Pathogens are opsonized by c3b protein which is then attached onto by the phagocytic receptors.

Question 10

What are the stages of the acute inflammatory response?

Answer 10

Question 11

What is the difference between receptors of innate cells (phagocytes) and adaptive immunity (lymphocyte)?

Answer 11

Innate vs Adaptive

Rapid response(hours) vs slow response(days to weeks)

fixed vs variable

constant vs improving

Question 12

Answer 12

Learn this/keep in mind

Question 13

Receptors on phagocytes are coupled to x?

Answer 13

x=function

Question 14

What happens when a pathogen binds on to a receptor on a macrophage?

Answer 14

This causes the release of cytokines and small lipid mediators of inflammation

Question 15

What are toll like receptors on phagocytes?

Answer 15

They each recognize different signatures produced by different pathogens to induce a specific response to that pathogen. It is a modular approach for linking receptors to function.

Question 16

What do fungi produce?

Answer 16

Mannan

Question 17

What do gram negative bacteria produce?

Answer 17

Lipopolysaccharide (LPS)

Question 18

What do viruses produce?

Answer 18

Double strand RNA

Question 19

What do protozoa produce?

Answer 19

Glycosylphosphatidylinositol (GPI)

Question 20

What does each toll like receptor correspond to ?

Answer 20

Question 21

What are the principle of phagocytosis?

Answer 21

PAMP is attached to pattern recognition receptors > pseudopodia forming a phagosome > granule fusion and killing > release of microbial products

Question 22

What is the respiratory burst?

Answer 22

The production of toxic oxygen radicals (superoxide and hydrogen peroxide) by the phagocytic cells which attacks the membrane of the pathogen and destroys them.

oxygen radicals may directly damage the microbial membranes and/or activate microbicidal enzymes found in granules.

This happens when the pathogen is engulfed in the phagocyte.

Question 23

What generates the respiratory burst?

Answer 23

The activation of NADPH oxidase

Question 24

What are the phagocytic frequencies in blood?

Answer 24

Question 25

Neutrophils(Polymorphonuclear neutrophils) are:

Answer 25

. rapid responders

Mobilized from Bone marrow

Found in depots in tissue sites

highly phagocytic

produce multiple cytokines

Question 26

What are neutrophil extracellular traps?

Answer 26

Activated neutrophils catch bacteria using NETs. This is when neutrophils extrude their DNA like a fishing net to trap the pathogens. NETs contain:

chromatid

granule proteins

enzymes to degrade pathogen virulence factors

Question 27

Blood monocytes can….

Answer 27

Give rise to tissue macrophages

Can differentiate into more long-lived macrophages which are more terminally differentiated.

have distinct characteristics depending on which tissue they migrate to

Relatively long-lived compared to neutrophils so can act as host cells of pathogens that override the macrophage.

Most macrophages arise from non haematopoietic stem precursors

Question 28

Kupffer cells (Resident liver macrophages) can have:

Answer 28

specific forms and functions in different tissues (inc.homeostasis)

transcription factors and epigenetic mechanisms associated with development

responses to environmental cues

Question 29

Dendritic cells are …..

Answer 29

phagocytic cells specialized for interacting with lymphocytes

can be sedentary or migratory

are activated during innate immunity

play an important role in initiating immune responses

Question 30

How do leukocytes egress from blood to the tissue?

Answer 30

Cytokines are produced my macrophages at site of infection

This causes dilation of local small blood vessels

leukocytes move to periphery of blood vessels as a result of increased expression of adhesion molecules

Monocytes bind adhesion molecules on vascular endothelium near sites of infection and monocyte receptor attaches to chemokine

The monocyte then migrates through the gap in the endothelial cells into the surrounding tissues

The monocyte then differentiates into a macrophage and migrates to site of infection.

Question 31

What are chemokines?

Answer 31

They are a further heterogenous and complex family of small molecular weight chemotactic cytokines known as chemokines. chemokines general function is to induce cell migration.

Question 32

What happens if the release of cytokines is dysregulated?

Answer 32

Leukocytes will move out of the endothelial cells of the blood vessels into multiple sites of tissues around the body and cause the body to go in shock.

Question 33

cytokines can be release where else apart from the blood?

Answer 33

synapses

Question 34

What can be used to reduce inflammation?

Answer 34

Corticosteroids can be used to block cytokine release which therefore reduces inflammation.

Question 35

How are receptors, phagocytes and cytokines linked?

Answer 35

A specific TLR is linked to a specific response by the phagocytic cell which is linked to a specific cytokine that is released to attract other leukocytes.

Question 36

Why are t natural killer cells called atypical?

Answer 36

Their receptors are more typical of innate cells rather than lymphocyte cells.