IMED4111 - Introduction to Immunology - Thurs Week 7 Flashcards
What is the innate immune response?
> RAPID response to infection
Relatively non-specific
> responds the same way each time a foreign substance is encountered
orientates the adaptive immune system
maintains tissue integrity and repair
What does the innate immune response consist of?
Physical barriers (skin, mucosal membranes, saliva, mucous)
- Soluble proteins (complement, acute phase proteins - interleukins IL1, IL6, IL8, TNF-alpha, anti-microbial peptides)
- Cellular components (neutrophils, macrophages, NK cells)
- Cytokines (IFN-gamma, TNF-alpha) - cell-cell communication
What is the acute phase response?
> immediate inflammatory response which is INITIATED by the recognition of pathogen (innate immunity)
release of acute phase proteins in response to inflammatory stimuli
What are the 4 STEPS of the acute phase response?
STEP 1 - Innate immunity senses non-self (conserved structures)
STEP 2 - cytokines produced
STEP 3 - acute phase reactants produced locally and by the LIVER
STEP 4 - measures to localise spread of infection and enhance systemic resistance to infection - RESPONDERS COME TO SITE OF INFECTION
What are pattern recognition receptors (PRRs)?
Pattern recognition receptors are a way that the innate immunity recognises non-self
- they recognise, altered, oxidsed, damaged cells
What are Pathogen Associated Molecular Patterns (PAMPs)?
Pathogen associated molecular patterns (PAMPs) are conserved elements on pathogens (usually on-human cells) that Pattern recognition receptors (PRRs) recognise
> PAMPs include Lipopolysaccharide (LPS), Flagellin, dsRNA, unmethylated CpG DNA
What are Damage/Danger Associated Molecular Patterns (DAMPs)?
These are molecules that are normally sequestered within cells but are released as a result of tissue damage.
> e.g. tumour DNA, hsp, uric acid, heparin sulfate
What are two main types of Pattern Recognition Receptors (PRRs)?
Toll-like Receptors (TLR) and Nod-like Receptors (NLR)
What are Toll-Like Receptors (TLR)?
They are the most important Pattern Recognition Receptors (PRRs).
> highly conserved
recognise a range of PATHOGEN-ASSOCIATED molecules from bacteria and viruses
Where are Toll-Like Receptors (TLRs) located?
Toll-like Receptors (TLRs) are located:
> cell surface
walls of intracellular vesicles (PARTICULARLY in dendritic cells and macrophages)
What do Toll-Like Receptors (TLRs) activate?
> NFkB, AP-1
to induce pro-inflam cytokines & chemotactic factors
> Interferon Regulatory Factor (IRF) to induce antiviral type I interferons (IFN alpha and IFN beta)
What are NOD-like receptors (NLRs)?
Intracellular PROTEINS and a type of Pattern Recognition Receptors (PRRs), and are expressed in the cytoplasm of cells that are regularly exposed to bacteria
> GUT epithelial cells
dendritic cells
macrophages
What is NOD2?
NOD2 is a protein of the NOD-like Receptor (NLR) family.
NOD2 proteins recognise intracellular MDP (muramyl dipeptide), which is a peptidoglycan constituent of both Gram positive and Gram negative bacteria.
> activating the NF-κB protein and other pro-inflammatory genes
Where is NOD2 strongly expressed?
Paneth cells (epithelium of small intestine)
- regulate potent antimicrobial peptides
What is an example of a disease associated with NOD2 loss of function?
Crohn’s disease
> type of Inflammatory Bowel Disease (IBD)
> Chronic inflammatory disorder, in which the body’s immune system attacks the gastrointestinal tract possibly directed at microbial antigens - NOT AUTOIMMUNE THO
> loss of antimicrobial activity results in heightened T-cell mediated inflammation
What are NALPs?
NALPs is a subfamily of NOD-like Receptors (NLRs)
NALP3 is best characterised (also known as cryopyrin or NLRP3) and has a pyrin domain
What is NALP3?
> Best characterised NOD-like Receptor (NLR) from the NALP subfamily
also known as Cryopyrin or NLRP3
> has a pyrin domain
expressed primarily in macrophages as a component of the inflammasome
What is the inflammasome?
> Multi-protein complex (3 components)
> It is expressed in myeloid cells and is a component of the innate immune system
> promotes maturation of the inflammatory cytokines IL-1β & IL-18
What activates the inflammasome?
Urate Crystals
Causes Gout
What disease are associated with mutations in NALP3?
Inappropriate increased activation of the inflammasome
Two types of HEREDITARY periodic fever syndromes
> Muckel-Wells
> Familial Cold inflammatory Syndrome
What is C reactive Protein (CRP) and what does it do?
> pro-inflammatory acute phase protein
important opsonin
> binds to bacterial structures, damaged cell membranes, apoptotic cells and microorganisms
protection against gram negative bacteria strep. pneumoniae by mopping up dead cells
Where is C Reactive Protein (CRP) produced and how?
> Produced by the Liver
production is influenced by IL-6
short half life (19h)
CRP levels rise rapidly
What is C Reactive Protein useful for?
BEST MARKER FOR ACUTE PHASE RESPONSE
> organic disease screening
monitoring responses
diagnosis of infection in immunosuppressed patients
risk factor for CVD
BUT does not rise in Systemic Lupus Erythematosus (SLE), Sjogrens or UC
SO look for a cause in these patients if they have a raised CRP
What is Systemic Lupus Erythematosus (SLE)?
Systemic lupus erythematosus is a systemic autoimmune disease -
- body’s immune system mistakenly attacks healthy tissue.
