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Flashcards in Innate Immunity Deck (42):

What are the essential functions of the innate immune system?

To sense and detect the presence of a pathogen - initially kickstart the immune response

To initiate a rapid response to pathogen, immediately after infection, allows control of the infection at a manageable phase until the adaptive response can determine and initiate a specific response

To eliminate damaged/infected cells and stimulate tissue repair

To alert and direct an appropriate adaptive immune response


What are the key features of the innate immune system?

Distinguishes between danger and homeostasis

Preformed (constitutive - ready to act) or rapidly formed components

Response begins within minutes

Low specificity: the same molecules and cells respond to a range of pathogens

Use pattern recognition receptors on their surface to detect molecules unique to pathogens

Reliant on germline genes that are the same regardless of the pathogen; do not undergo modification to enhance responses

No memory; responds the same at each infection with the same magnitude and same type of response.


What are pathogen-associated molecular patterns (PAMPs)?

- The body initially detects the presence of pathogens by
recognising molecules that are present on pathogens but not on
human cells
- These molecules are termed pathogen-associated molecular patterns
(PAMPs)- not present on human cells so once detected by the body's
innate cells, they know there's an infection, causing an innate response
- Good targets because they differ from molecules found in humans
- They are conserved among classes of microorganisms allowing for
broad recognition, so the same response cells are initiated - no
specificity is required
- They have an essential role in the function of the microbe so do not
undergo rapid evolution, hence the conservation


What are examples of PAMPs?

- Lipopolysaccharide (LPS) – Cell wall of G -ve bacteria

- Peptidoglycan – abundant on G +ve bacterial cell walls

- Lipoteichoic acids – found in G +ve bacterial cell walls

- Mannose-rich glycans – Short carbohydrate chains that terminate
with mannose sugar residues

- Flagellin – Found in bacterial flagella

- CpG – Unmethylated cytosine-guanine dinucleotides found in bacterial
and viral genomes, in bacteria these are unmethylated (unlike in
mammalian cells, where they are masked to prevent an autoimmune

- Single-stranded and double-stranded viral RNA


What are pattern recognition receptors (PRR)?

Human cells recognise PAMPs using a range of pattern recognition receptors

PRRs are:
- highly conserved between all mammals, almost identical between
humans so we will all react the same to an infection
– have broad specificity
– recognise conserved components of pathogens, eg PAMPs

PPRs are on the surface of cells which are likely to come into immediate contact with pathogens, for example epithelial cells

Main forms of PRRs are:
– membrane-bound signallers or endocyclic if pathogens enter cells
– soluble cytoplasmic
– phagocytic/scavenging so only send a signals to the phospholipid
membrane to initiate phagocytosis
– secreted and therefore bind to pathogens in the blood stream, many
bind to one pathogen to make it more obvious to innate response cells
in blood.


What are Toll-like receptors (TLR)?

Toll-like receptors are the best characterised form of PRR,
around 10-11 in humans

Highly conserved; also found in plants and invertebrates

Usually function as homodimers or heterodimers require two (same) molecules or two (different) molecules to bind in order to function.

All are membrane-bound, but their cellular location reflects the PAMPs
that they detect:
– TLRs that recognise extracellular ligands are found on the cell surface
– TLRs that recognise intracellular ligands e.g. Viral RNA that gets
expressed in our cells, are found on endosomes


Where are TLRs distributed on different cell types?

Predominately on innate immune cells that are present in tissues waiting to respond or are recruited into tissues then activated.

Some are on the epithelial surface but not the luminal surface as this is where the microbiome is.


What is the general conserved structure of TLRs?

Generally all have a very similar structure, the extracellular part is made up of a leucine-rich repeating structure that points towards the pathogen and has a complementary PAMP binding site. Then the TLR also has a a transmembrane system that holds the TLR in, then finallly and intramembrane system that contains the Toll-IL-1 receptor (TIR) signal transduction domain.


How do TLRs initiate intracellular signalling?

TLR domains recruit adaptor proteins (eg. Myd88)

The IRAK kinase is activated by autophosphorylation, which then recruits TRAF6. This then activates the kinase TAK1 which moves downstream and activates the IKK complex

IκB normally inhibits NF-κB; it is phosphorylated to release NF-κB. NF-κB translocates to the nucleus to initiate gene transcription

Inflammatory cytokines made that initiates other parts of the immune system:
– IFNα, IFNβ
– IL-1β, IL-6, IL-8 (CXCL8), TNFα

Extra cellular receptors converge on certain pathways giving a lot of cross pathways effects, which means no matter which protein is initiated it causes the same response


What are known defects in TLRs?

Myd88 and IRAK4 deficiencies are autosomal recessive:
- Sufferers are susceptible to invasive bacterial infections from
Streptococcus pneumoniae, Staphylococcus aureus and Pseudomonas

NEMO deficiencies are X-linked (affect males more than females):
- Associated with skin disease and severe bacterial infections
- Can be detected with the CD62L shedding assay via flow cytometry
- Most people who die from Legionnaire’s disease have a mutation in
TLR5 – unable to recognise flagella of Legionella pneumophila


What are Nod-like receptors (NLRs)?

NOD-like receptors are soluble intracellular (cytoplasmic) PRRs - soluble within the plasma of cells

Contain nucleotide-binding oligomerisation domain (NOD) and leucine-rich repeats at the C-terminus

Essentially seek out intracellular pathogens

4 sub-families:
– NLRB (involved in IL-1 family production)
– NLRC (detect bacterial peptidoglycans)
– NLRP (activate caspase-1 to cleave pro-IL1 into an active secreted


What is the structure of NLRs?

Contain leucine rich repeats like TLRs that are good for recognising pathogens.

NAT domains are activated and become open allowing complexes to form. Don't activate in isolation but in these complexes they cross each and initiate each other.

Some NLRs have similar signalling roles to TLRs others are associated with formation of the inflammasome
- NFκB induces expression of IL-1β and IL-18 in a pro-(inactive) form
- The inflammasome activates caspases
- Caspases cleave IL-1β and IL-18


What are C-type lectins?

Scavenging and phagocytic, don't really signal

C-type lectins recognise carbohydrate structures on pathogens

Examples include:
– Dectin-1; binds β glucans
– Mannose receptor (DEC205 or CD206); binds mannosylated ligands,
those bound to a mannose sugar

Often act as phagocytic receptors which once bound to their target they clump around the cell to act as a signal for phagocyte cells; they endocytose the ligand they bind for degradation


What are examples of secreted PRRs?

C-reactive protein (CRP) is released in the acute phase response - wider system response in the innate immune system
CRP has roles in:
– Opsonisation - coating of a pathogen to make it more visible
– Complement activation - both this and above then lead to...
– Phagocytosis

Mannose-binding lectin (MBL) :
– Key role in the Lectin pathway of complement


What is phagocytosis?

Phagocytosis is the key mechanism used to remove free microorganisms in the tissues and in blood

Phagocytic cells: Macrophages, Neutrophils, Dendritic cells, Eosinophils, and B-lymphocytes

Unenhanced attachment - activation of TOL like and NOD like receptors; the recognition of PAMPs by endocytic PRRs on the surface of the phagocytes

Opsonisation (making pathogen more visible to immune system); the attachment of microbes to phagocytes using IgG, the complement proteins C3b and C4b (bind to surface of pathogen due to it's an ionic structure, if the phagocyte then has a C3b receptor it will then engulf it), and secreted acute phase proteins such as MBL and CRP.

Polymerisation and then depolymerisation of actin filaments sends out cell membrane extensions (pseudopodia - reach actin filaments around and then build a plasma membrane around it) out to surround and engulf the microbe (or necrotic cells / tissue debris)

This endocytic vesicle is called a phagosome.


What occurs during phagosome maturation?

An electron pump brings protons (H+) into the phagosome; this lowers the pH within the phagosome from 7.4 to 4.5 so that the acid hydrolases are activated in order to break down cellular proteins.

Phagosomes contain membranous sacs called lysosomes that contain various digestive enzymes, microbicidal chemicals, and toxic oxygen radicals.

The lysosomes fuse with the phagosomes to produce a phagolysosome so molecules are released to increase degradation.

Microorganisms are killed and digested by lysosomal enzymes


Which cells are activated by PRRs?

Tissue macrophages act as sentinels for initial detection of danger for pathogens via expression of PRRs

Cytokines and chemokines secreted affect endothelial cells lining nearby blood capillaries


What are the vascular effects of pattern recognition?

Cytokines secreted by macrophages and other local cells that express PRRs induce changes in endothelial cell walls of blood capillaries, loosens the contact between the endothelial cells

This allows infiltration of inflammatory cells (neutrophils and monocytes) and plasma proteins to the site of infection this leads to responses such as inflammation

Vascular changes lead to characteristic signs of inflammation:
– Vasodilation (increased vascular diameter)
– Tumor (swelling; due to increased vascular permeability)
– Calor (heat)
– Rubor (redness)
– Dolor (pain)


What are the aims of inflammation?

Soon after initial damage and pathogen encounter, neutrophils (main phagocytic cells) are recruited to the infection site, followed by monocytes

Activated tissue macrophages (resident, and differentiated monocytes) and damaged tissue cells continue to release cytokines and chemokines that perpetuate the inflammatory response - keep immune response going until adaptive response can occur

Purpose of inflammation:
– Deliver effector molecules and cells to the infection site (plasma leaks
into tissue; contains antibodies, complement, antimicrobial peptides,
– Produce barriers that prevent spread of infection (eg. activate
fibrinogen that make fibrin clots that prevent spread of infection to new
– Promote repair


How does diapedesis of neutrophils occur?

Rather than free flow, the neutrophil circulates in peripheral blood by rolling in contact with the endothelial cells through to the site of inflammation.

They circulate until pass chemoattractants (TNFα, IL-1β) released by macrophages at site of inflammation signal to them, this slows the rolling down in the capillaries, allowing the neutrophil to be activated.


Slowing occurs because the endothelium is induced to express selectins: expression of P- E and L- selectins allows rolling then tethering of neutrophils via Sialyl Lewis X

If it finds cells that have been activated through the innate response adhesion occurs, where integrins (eg VLA4, LFA-1) are upregulated on the neutrophils and bind to VCAM1 and ICAM1 on endothelium.

TNFα increases vascular permeability and allows diapedesis, or movement of neutrophils across the endothelium (where there are gaps between endothelial cells the neutrophils will squeeze through into the damaged tissue)

Neutrophils move towards the site of infection in response to chemokines and complement components such as C5a and C3a.


What is the role of neutrophils?

Chemotaxis – Phagocytosis – Chemokines – Killing – Digestion

Responds to chemotactic factors released from damaged tissue

Rolls and attaches to the endothelial cell wall:
- protein and carbohydrate interactions allow them to exit the capillary at
the correct site close to infection (selectins/integrins and their ligands)

Become activated by chemotactic factors (eg. CXCL8)

Tightly adheres through the integrin family of proteins

Migrates across the endothelial cell wall

Phagocytose microorganisms so that they are contained within a vesicle or phagosome

Releases granule products and reduced oxygen species
(eg. hydrogen peroxide and superoxide) to kill organisms


How do neutrophils undergo a respiratory burst?

A respiratory burst is a so specialised intracellular killing mechanism.

Neutrophils contain cytoplasmic granules which fuse to the phagosome, (giving a species slightly different to phagolysosme as the granule contents are different)

Signalling induces assembly of membrane-associated NADPH-oxidase:
- 6 diff subunits; one subunit transfers an electron to O2 forming superoxide anions (O2–) in lumen of phagolysosome
- This is converted to H2O2 by superoxide dismutase
- Other chemicals are also produced via conversion of H2O2 (hydroxyl
radical, hypochlorite and hypobromite)
- This disrupts the molecular structures on the surface of the pathogens

This NADPH oxidase reaction results in transient oxygen consumption by the cell = RESPIRATORY BURST


How do neutrophil defects lead to poor bacterial clearance?

Defects in structural components of neutrophils are characterised by persistent chronic infections that are autoimmune disorders, leading to repeated bacterial infections.

Defects can occur in:
- Adhesion to endothelium (No rolling / diapedesis)
- Neutrophil chemotaxis (Can’t get to site of infection)
- Phagocytosis (Can’t engulf bacteria)
- Killing of bacteria (Can’t release granule contents)


What common diseases are associated with neutrophil defects?

Disorder: Leucocyte Adhesion Deficiency Type II
Phase: rolling
Molecular defect:
- Sialyl Lewis X carbohydrate epitope
- SLC35C1

Disorder: Leucocyte Adhesion Deficiency Type I
Phase: adhesion
Molecular defect:
- Deficiency in CD18, the β2 integrin subunit, preventing expression of
LFA-1 (cannot heterodimerise with CD11)

Disorder: Chronic Granulomatous Disease
Phase: oxidative burst
Molecular defect:
- NAPDH Oxidase Subunit; Cannot produce ROS
- Extended lifespan and granuloma formation
- Gp91phox, p67phox, p47phox, p22phox

Disorder: Myeloperoxidase Disease
Phase: oxidative burst
Molecular defect:
- Cannot produce hypochlorous acid (HOCl)
- Usually clinically silent

Disorder: Chediak-Higashi Syndrome
Phase: Granule Release
Molecular defect:
- Large granule size and failure to release contents
- LYST ; Lysosomal trafficking regulator gene


How is Chronic Granulomatous Disease diagnosed?

This is characterised by a defect in NADP oxidase so ROS aren't produced

Tends to affect boys because it is x-linked, so often also check mother to see if she is a carrier.

Diagnosed by dihydrorhodamine (DHR) assay; detected via flow cytometry: Assesses the formation of red fluorescence rhodamine product in presence of reactive oxygen species


What are neutrophil extracellular traps (NETs)?

Way neutrophils die after infection, spitting out a NET of DNA Fibres that prevent recurring infection in the area, by catching other pathogens, extracellular bacteris that haven't been engulfed:

- Neutrophils undergo the process of NETosis – the formation of
NETs under influence of various triggers (e.g. cytokines, fungi,
viruses, bacteria).

- This is a suicide mechanism to ensure effective pathogen killing
after their death.

- NETs are an extracellular network of DNA fibres studded with
nuclear (eg. histones) and granule proteins (e.g. MPO, elastase)
that can trap and/or neutralise pathogens.

- NETs can expand up to 15 times the size of the originating cell to
increases the range for effective capture of pathogens.

- Can lead to autoimmune diseases if NETS are not cleared correctly


What is neutrophilia?

Abnormally high numbers of neutrophils.

1. Acute shift from marginating to circulating pool: Increase is
measured in WBC, not total WBC
- causes: Steroid treatment, Exercise, Epinephrine, Hypoxia,
Seizures, Other stress

2. Chronic Stimulation: Excess cytokines stimulate proliferative pool
- causes: Infection, Down's Syndrome, Pregnancy/Eclampsia,
Chemotherapy recovery, Myeloproliferative disorders, Marrow


What is neutropenia?

Abnormally low numbers of neutrophils.

1. Decreased production in the bone marrow, causes include:
- Medication: Antibiotics, Chemotherapeutics (low numbers can due to
them being used up attacking rapidly proliferating cells)
- Myelofibrosis, causes fibrotic accumulations in bone marrow
reducing space for neutrophil production

2. Increased destruction in peripheral circulation, causes include:
- Autoimmune diseases: Rheumatoid Arthritis, SLE

3. Acute Shift from Circulating to Marginating Pool (e.g.trying to get out
of blood stream into tissues, this is highly indicative of sepsis)
- Severe infection / Endotoxin release
- Haemodialysis (dialysis causes surfaces of capillaries to become
sticky, so it's not actually less cells, just less detectable)
- Cardiopulmonary bypass

If the patient visit is prompted by a FEVER and absolute neutrophil count is low → TREAT PROMPTLY FOR INFECTION


What are the principle features of complement?

Key component of innate immune system
enhances adaptive immune responses

1. Attraction and activation of phagocytes for microbial killing
2. Clearance of immune complexes and apoptotic cells
3. Triggers and amplifies inflammatory reactions
4. Performs direct microbial killing by cell lysis


What is complement?

Over 50 preformed soluble plasma proteins (approximately 10% of plasma proteins) and membrane-bound proteins

Identified in late 1800’s as a heat labile component of serum with bactericidal activity, so can be inactivated by heat

Shown to opsonise microorganisms and enhance (complement) antibody-mediated responses

Evolutionarily ancient – predates the development of adaptive immunity as homologous proteins are found in some invertebrates (e.g. starfish)


How is complement activated?

Not active in body all the time, activated in a stepwise process

Activated locally at sites of infection and trigger an amplification cascade

Most proteins in activation pathways are zymogens activated by proteolytic cleavage, which forms a major and minor fragment:

Major fragments generally have 2 purposes:
- Bind to cell surfaces or the upstream complex (enzyme that caused
the cleavage)
- Enzymatic cleavage of the next component

Minor fragments have secondary biological effects:
- Chemotaxis of leucocytes
- Anaphylatoxins


What is the classical pathway (activation pathway 1):

Initiated by antigen:antibody complex formation:

1. Antibody binds to foreign antigen and causes conformational
change, in the constant region that doesn't directly bind, in Fc

2. C1 complex (of C1r C1s and C1q) binds to the Fc regions of two
adjacent antibodies in the complex (IgM preferentially, and IgG)

3. This activates C1r; causing C1r to cleave C1s

4. The C1s group cleaves C4 into a C4a and C4b group. C4b goes on to
bind to the microbial cell surface

5. Simultaneously C1s also cleaves C2 into C2b and C2a

6. C2b binds to C4b; this C4b2b complex forms an enzyme known as
the C3 Convertase

(Note: Nomenclature change with
C2a and C2b in literature/textbooks)

7. This C3 convertase (C4b2b) cleaves C3 (C2b has the catalytic
activity and is localised by binding to C4b)
- C3a causes inflammation
- C3b causes opsonisation and cytolysis

8. The newly cleaved C3b binds to C4b2b; C4b2b3b forms an enzyme
known as the C5 Convertase


What is the lectin pathway (activation pathway 2):

Initiated by microbe cell surface carbohydrates:

1. Mannose-binding lectins (MBLs) bind to microbe-specific
carbohydrates, (like C1q), Mannose, GlcNAc, (like C1r and c1s)

2. MBLs bind to MBL-Associated Serine Proteases (MASPs)

3.MASPs cleave C4 and C2; produce C4b2b (C3 convertase)

4. Identical pathway to classical pathway then used to activate C3 and
produce C4b2b3b (C5 convertase)


What is the alternate pathway (Activation pathway 3)?

Initiated by microbial/damaged/artificial cell surfaces and spontaneous hydrolysis of C3:

1. Continuous and spontaneous hydrolysis of C3 leads to C3b binding to
foreign surfaces AND C3b produced from classical and lectin
pathways provides amplification effects

2. C3b binds to Factor B

3. While bounds to C3b, Factor B is cleaved by the protease Factor D; Bb
remains bound to C3b to form C3bBb (another form of C3

4. The C3bBb cleaves C3 (Bb has the catalytic activity and is
localised by binding to C3b)

5. C3b binds to C3bBb; C3bBb3b forms a C5 convertase


What is the Common terminal lytic pathway

1. Each activation pathway produces a C5 Convertase that
cleaves C5 into C5a and C5b

2. C5b binds to the microbial cell surface and binds to C6

3. C5b6 recruits C7, which drives the whole complex deeper into
the membrane

4. C5b67 binds to C8.

5. C5b678 recruits and polymerises C9 within the microbial cell surface
and forms pores in the membrane

6. This complex is known as the Membrane Attack Complex (MAC)

7. Solutes and large molecules flow freely through the pores, and water
enters the microbial cell disturbing the osmotic balance to cause
osmotic lysis


What are the effector functions of complement?

Direct cell osmotic lysis via the terminal lytic pathway:
- Creation of pores that breach the lipid bilayer of cell surfaces
- Kills gram-negative bacteria (such as the genus Neisseria)
- Sub-lytic quantities of MACs will disturb cellular functions

Chemotaxis of leucocytes and anaphylatoxic inflammation:
- C3a and C5a are bioactive fragments (chemotaxic proteins that are
released into capillaries that attract neutrophils), bind to specific cell
surface receptors on leucocyte populations
- This creates a chemotactic gradient at the site of complement
activation that motile leucocytes migrate up to
- Increase adhesion and release of proinflammatory enzymes and
cytokines by macrophages and neutrophils
- Activate mast cells and basophils to stimulate degranulation and
histamine release causing vascular permeability and smooth muscle

Opsonisation and Phagocytosis:
- Amplified production of C3b and C4b coats the microbial cell surface
- The complement receptor CR1 on phagocyte cell surfaces binds
to C3b and/or C4b
- This causes phagocytosis and destruction of the opsonised microbe

Clearance of immune complexes via solubilisation:
- Coating with C1 and C3/C4 fragments will mask antigens and prevent
the aggregation and precipitation of large immune complexes
- C3b opsonises foreign antigens to block further antibody binding and
disrupt large complexes
- CR1 on erythrocytes binds to C3b and transports the immune complex
to be internalised by splenic macrophages

The complement receptor CR2 forms part of the B-cell receptor (BCR) complex:
- If the antigen that binds to the BCR is also coated with fragments from
C3, these fragments will bind to CR2 and provide an additional signal to
the B-cell
- This increases potency of B-cell activation by 10-100 fold
- In the absence of CR2 activation, B-cell tolerance may occur
- In the lymphoid organs, C3-opsonised foreign particles bind to CR2 on
follicular dendritic cells
- This retains the antigen at the site of mature B-cell development into
memory B-cells and plasma cells


Why does complement need to be regulated?

Maintain ability to combat infection

Uncontrolled activation can deplete complement proteins leaving the host compromised to infection

Prevention of damage to autologous host cells

Complement activation has the potential to cause severe damage not only to microbes but also to host cells and tissues

Strict regulation is needed to avoid unnecessary damage to self due to overt or mistargeted activation

Healthy host cells may be opsonised by C3b through the bystander effect in the local vicinity of complement activation

Inflammatory mediators stimulate non-specific inflammation

In the activation pathways many components are inherently unstable and decay unless they are stabilised by binding to cell surfaces, receptors or other complement proteins


What are examples of soluble regulators of complement (plasma proteins) and which pathway do they act on?

C1 inhibitor:
- classical (target C1r) and lectin pathways (target MASPs)
- causes dissociation

- classical and lectin (targets C4b in both)
- displaces C2b and acts as a cofactor for factor 1

Factor H:
- alternative pathway (targets C3b)
- displaces B.B. and a cts as a cofactor for factor 1

Factor I:
- classical, lectin and alternative pathways (targets C3b and C4b)
- acts as a serine protease to cleave C3b and C4b

- terminal pathway (targets C5b67)
- Blocks the hydrophobic membrane insertion site of soluble C5b67

S protein (victronectin):
- terminal pathway (targets C5b67)
- Blocks the hydrophobic membrane insertion site of soluble C5b67


What are examples of membrane-bound regulators of complement and which pathway do they act on?

Membrane Cofactor Protein (MCP; CD46):
- classical, lectin and alternative pathways (targets C3b and C4b)
- cofactor for Factor I, catalyses cleavage of C3b and C4b activating
breakdown of compliment proteins

Decay Accelerating Factor (DAF; CD55):
- classical, lectin and alternative (targets C4b2b and C3bBb)
- displaces C2b and Bb

Protectin; CD59:
- terminal (targets C7 and C8)
- Blocks binding of C9 to C5b678; prevents C9 polymerisation and
formation of the membrane attack complex on bystander host cells
blocks MAP complex from forming on host cell

CR1; CD35:
- classical, lectin and alternative (targets C3b)
- Acts as a cofactor for Factor I to catalyse cleavage of C3b


What are common deficiencies in complement pathway components?

C1 (q, r, s), C2 and C4 = No activation of classical pathway
- causes autoimmune diseases (SLE, RA)

MBLs and MASPs = No activation of lectin pathway through PRRs
- causes recurrent bacterial infections

Factor B and/or D = No C3b amplification through alternative pathway
- causes recurrent pyogenic bacterial infections
- requires prophylactic antibiotic therapy

C3 = No opsonisation or activation of terminal pathways
- causes recurrent pyogenic bacterial infections
- requires prophylactic antibiotic therapy

Factor H and/or I = Uncontrolled activation of alternative pathway
- causes

C3 = cannot form membrane attack complexes
- causes recurrent infections from G - ve bacteria


What is the acute phase response?

Systemic effects of infection; largely due to IL-6 inducing acute-phase protein production in hepatocytes in the liver

Can be used as a non-specific indicator of an inflammatory response,
where you are unsure what the inflammatory response was to

Different kinetics and levels of change amongst reactants
Indirectly assessed using the erythrocyte sedimentation rate (ESR) - the more proteins in your plasma the quicker your ESR

Assessment of acute phase reactants can be used to:
- monitor the progress of diagnosed disease activity
- Assess response to therapy in inflammatory diseases (eg. rheumatoid
arthritis, vasculitis)


Which acute phase reactants are commonly used to monitor infection?

C-reactive protein (CRP) is clinically used for direct and quantitative measurement of inflammation:
- Large incremental change and fast responding
- Secreted PRR that opsonises microbes
- Short half-life; useful for serial measurement

Procalcitonin is increasingly used as a specific biomarker for sepsis in bacterial infections