Immunology 3

Question 1

Two major mechanisms of communication in immune system?

Answer 1

Direct contact - RECEPTOR : LIGAND interactions

Indirect contact - production and secretion of CYTOKINES

Question 2

Mechanism of direct contact?

Answer 2

Recteptor : ligand:

Receptor on immune cell recognises ligand on the surface of a pathogen/tissue cell/another immune cell

Question 3

Example of direct contact?

Answer 3

Between TLR4 and LPS

Toll-Like Receptor 4 detects lipopolysaccharide on gram -ve bacteria and activates innate immune system

Question 4

Mechanism of indirect contact?

Answer 4

Injured tissue cells and activated immune cells (both innate and adaptive) can produce and secrete CYTOKINES

Question 5

How do the cytokines in indirect contact function?

Answer 5

Will signal cells at local and distant sites

Can act on cells that produced them in autocrine signalling to cause changes

Question 6

Examples of cytokines?

Answer 6

IL-2, IL-10, IL-1, IL-6 (Interleukin)
IFNγ (Interferon γ)
TNFα (Tumour Necrosis Factor α)

Question 7

How do pathogens activate the innate immune system?

Answer 7

Innate immune cells must recognise and respond to pathogens

Macrophages, Mast cells, NK cells, Neutrophils

Question 8

What are the steps in activating the innate immune system?

Answer 8

Recognition phase
Activation phase
Effector phase

Question 9

Mechanism of recognition phase?

Answer 9

Pathogens express “signature” molecules not found on human cells: Pathogen Associated Molecular Patterns (PAMPs) - common to many different pathogens

Innate immune cells express specific receptors for PAMPS: Pattern Recognition Receptors (PRRs) - found intra and extracellularly thus, detect intra and extracellular pathogens

Question 10

Examples of PRRs on immune cells and the corresponding PAMPS on pathogens

Answer 10

Toll-like receptor 4 (TLR4) detects LPS on Gram -ve bacteria

Dectin 1 detects β-glucans of fungi

NOD2 detects Muramyl dipeptide of M. tuberculosis

TLR7 detects ssRNA in viruses

Question 11

What do the activation and effector phases cause?

Answer 11

Acute inflammation and pathogen killing

Question 12

How is tissue homeostasis regulated in the skin?

Answer 12

Induction of apoptosis

Specific recognition and removal of dying cells by phagocytes, like macrophages

Question 13

How are apoptotic cells cleared by tissue-resident macrophages?

Answer 13

Apoptotic cells release CYTOKINE-LIKE signals to attract and activate macrophages

Macrophages recognise specific signals expressed on surface of apoptotic cells

Phagocytosis occurs

Macrophages secrete anti-inflammatory cytokines (like IL-10)

Question 14

How does phagocytosis occur?

Answer 14

Receptor bind to ligands on apoptotic cells, forming phagocytic cup

Cup extends around target and pinches off, forming phagolysosome

Lysomesome fuses to form phagolysosome - contents degraded

Debris released into ECF

Question 15

What happens when physical barriers are breached by pathogens?

Answer 15

Wounded/infection skin tissue

PAMPs on pathogens are recognised by macrophages, mast cells and NK cells

Question 16

What do macrophages do as part of the early innate immune response?

Answer 16

Kill pathogens

Produce pro-inflammatory mediators

Question 17

What is the innate immune response of macrophages?

Answer 17

Phagocytosis

Production of toxic reactive oxygen and nitrogen species (oxygen dependent killing)

Question 18

How is the killing ability of macrophages enhanced?

Answer 18

By cytokines, like IFNγ - produced by NK cells and some T cells

Act on macrophages to:
Increase production of toxic O2 and N species
Increase microbicidal activity - destroys microbes
Boost antigen presentation capability

Question 19

What do mast cells do as part of the early innate immune response?

Answer 19

Produce pro-inflammatory mediatiors

Question 20

What is the innate immune response of mast cells?

Answer 20

Reside in tissue and protect mucosal surfaces, to protect against parasites

Degranulation - release of pre-formed pro-inflammatory mediators

Gene expression - produce new pro-inflammatory mediators

Question 21

What do NK cells do as part of the early innate immune response?

Answer 21

Kill infected tissue cells

Produce pro-inflammatory mediators

Question 22

What is the function of NK cells?

Answer 22

Specifically kill virally infected cell ad abnormal cancer cells

Produce pro-inflammatory mediators

Question 23

What are the systemic effects of cytokine release?

Answer 23

Neutrophil production
Acute Phase Response
Fever

Question 24

Function of acute phase response?

Answer 24

Change in plasma conc. of specific proteins in response to inflammation

Question 25

How does acute phase response occur?

Answer 25

Driven by cytokines produced during localised inflammatory responses
Changes are due to altered protein synthesis in liver (due to action of cytokines)

Some Acute Phase Proteins (APPs) increase; others decrease

Time course of all acute phase proteins are not the same

Question 26

Major functions of some acute phase proteins?

Answer 26

CRP (C reactive protein), SAP (serum amyloid protein) and complement proteins - prevent infection spread and act as diagnostic markers

Fibrinogen - would healing and coagulation

CRP, proteinase inhibitors - prevent systemic inflammation

Question 27

Function of C reactive protein?

Answer 27

Major acute phase protein in humans; acts as marker for inflammation (below 10mg/l is normal; inflammation increases in severity as value increase above 10)

Enhances phagocytosis - it OPSONIZES bacteria making phagocytes more able to recognise them

Complement system activation

Question 28

Structure of C reactive protein?

Answer 28

Pentraxin - 5 identical sub-units