T1 L2: Innate immune defences & inflammation 1 Flashcards
What is innate immunity?
The first line of defence against infection which is present from birth and is passed down genetically
It occurs within minutes of pathogen recognition
What are some receptor characteristics of innate immunity?
- Specificity is inherited
- It expressed by all cells of a particular type
- It triggers an immediate response
- It recognises a broad class of pathogens
- Interacts with a range of molecular structures of a given type
- Able to discriminate between closely related molecular structures
What are some characteristics of adaptive immunity?
- Encoded in multiple gene segments
- Requires gene rearrangement
- Clonal distribution
- Able to discriminate between closely related molecular structures
What is trained immunity?
Innate immune memory
Cells respond differently the second time because of epigenetic and metabolic reprogramming
It lasts for weeks of months because the training occurs in haemopoietic stem cells of bone marrow
What are some physical innate barriers to infection?
Skin
Respiratory tract
GI tract
What are some soluble innate barriers to infection?
Complement
Defensins
Collectins
What are some induced innate barriers to infection?
- Innate immune cells
- Pattern recognition receptors (PPR’s)
- Interferons
What is the function of lysozymes?
They disrupt bacterial cell walls by acting on peptidoglycans
Found in blood and tears
What is the function of antimicrobial peptides?
They kill pathogens by disrupting microbial membranes
Found pretty much everywhere
Which molecules bind to pathogens and target them for phagocytosis and to activate compliment?
Collectins, ficolins, and pentraxins
They act as opsonins by activating the complement pathway.
Where are lysozymes secreted?
By phagocytes and Paneth cells from the small intestine
Describe the process by which lysozymes disrupt the cell wall
They cleave the bonds between alternating sugars that make up peptidoglycan. Then phospholipase A2 comes and disrupts the phospholipids underneath
Which type of bacteria have exposed peptidoglycan layers?
Gram-positive bacteria
What are histatins?
A type of antimicrobial peptide
They are produced by the oral cavity and are active against pathogenic fungi like candida albicans
What are Cathelicidins?
A type of antimicrobial peptide
Humans only have LL-37 which has broad spectrum activity against both gram-negative and gram-positive bacteria
What are defencins?
They are amphipathic peptides that insert themselves into the cell membrane and create a pore
They have two classes: alpha and beta
What are the 3 main types of antimicrobial peptides?
Histatins, Cathelicidins, and Defensins
What are some characteristics of antimicrobial peptides?
- They are secreted by neutrophils, epithelial cells, and Paneth cells in the crypts of the intestine
- Kill bacteria in minutes
- Attack fungi and viruses and kill them by inhibiting DNA and RNA synthesis
What does amphipathic mean?
Hydrophilic on one side and hydrophobic on the other
How do collectins work?
They have globular lectin-like heads that bind to bacterial cell surface sugars
Sialic acid hides mannose antigens on host cells
How do Ficolins work?
They have a fibrinogen-like domain that recognises acylated compounds (COCH3) such as bacterial cell wall monosaccharides
How do Pentraxins work?
They are multimeric proteins in the plasma that bind to Fc gamma receptors to opsonise the pathogen
Eg. C-reactive protein (CRP). It binds to phosphocholine on bacterial surfaces. It’s used as a marker for inflammation
What are the 3 pathways to complement?
Classical, lectin, and alternative pathway
Describe the classical pathway of complement
Antigen-antibody complexes form of the pathogen surface. Molecules like C1q, C1r, C1s, C4, and C2 are created
C2 and C4 come together to cleave C3 causing amplification
Describe the lectin pathway of complement
Mannose-binding lectin or ficolin binds to carbohydrates on pathogen surfaces and molecules like MBL/ficolin, MASP-2, C4, and C2 are released
C2 and C4 then cleave C3 to cause amplification
Describe the alternative pathway of complement
Activated by pathogen surfaces to release molecules like C3, B, and D
Activated by C3 in the blood which can spontaneously become C3a and C3b but is very unstable
C3bBb hydrolyses C3 creating more C3b which amplifies the signal
How do all 3 complement pathway converge?
The products of each pathway are converted into C3
In what form do complement components circulate in the blood?
As pro- innactive forms
Which compound initiates the classical pathway of complement?
Activation of C1 when it binds to the Fc region
It’s made up of 3 proteins: C1q, C1s, and C1r
Why is IgM the most effective at activating complement?
Because complement is triggered by binding to Fc regions and IgM has 5
At least 2 are needed
What is the function of properdin?
It extends the half-life of C3bBb from 5 min to 30 min by protecting it from proteases
This allows more amplification of the alternative pathway
What is a membrane attack complex (MAC)?
It’s a ring of C9 molecules created once C5 is cleaved. It’s the end product of complement.
It creates a pore when it inserts itself into a cell membrane
Human cells have proteins that prevent MAC formation
What is hereditary angioedema?
A C1 inhibitor deficiency that causes the classical complement cascade to be easily activated
It can be treated with C1 inhibitor injections
What does a mannose-binding lectin (MBL) deficiency cause?
Serious pyogenic infections in neonates and children
What does pyogenic mean?
A pus-producing infection
What does a C3 deficiency cause?
The most severe complement deficiency leading to successive severe infections
What does a C8 deficiency cause?
These patients are prone to infections with Neisseria meningitis
What does a C4 deficiency cause?
90% of these people go on to develop the autoimmune disease systemic lupus erythematosus (SLE)
What is systemic lupus erythematosus (SLE)?
The person have lots of autoantibodies that cause excessive inflammation
It’s caused by a C4 deficiency because that means less C3b is cleaved
What is the function of C3b?
Opsonisation
It binds to immune complexes and then CR1 on erythrocytes which transport them to phagocytes in the liver and spleen.
Phagocytes recognise them via their Fc receptors and engulf them
