Lecture 2: Innate Immunity and Complement Flashcards
What are the 2 main aims of innate immunity?
- Eliminate Pathogens
- Initiate adaptive immune response
What are examples of chemical barriers in the innate immune system?
- Low stomach pH
- Anti-microbial peptides in skin and in saliva
- Enzymes in secretions
What do defensins and cathelicidin do?
Disrupt bacterial membranes
What does lysozyme do?
Cleaves peptidoglycan in bacterial cell wall
What is phagocytosis?
Is the uptake of particulate materials (e.g. pathogens, dead cells) by a cell.
What are types of phagocytes?
Neutrophils
Macrophages
Dendritic cels
What are the functions of phagocytes in immunity?
- They kill pathogens and take up cell debris
- They detect pathogen-associated molecular patterns (PAMPs) and secrete cytokines
- They present pathogen-derived antigens on their surface (as antigen presenting cells) to activate B and T cells
What is a pattern recognition receptor?
Pattern recognition receptors (PRRs) are receptors on and in our cells that recognise pathogen-associated molecular patterns (PAMPs)
What are the 4 main families of PRRs?
- Toll-like receptors (TLRs)
- C-type lectin receptors (CLRs)
- Intracellular nucleic acid receptors
- Nucleotide oligomerization domain/leucine-rich repeat containing receptors (NLRs)
Which cells have intracellular PRRs?
Most
Which cells have extracellular PRRs?
- Macrophages
- Dendritic cells
- Natural killer cells
What are the 2 domains in toll like receptors?
Exterior and TIR
What is in the exterior domain of toll like receptors?
Leucine-rich repeats
What is the role of leucine-rich repeats in the toll-like receptor?
Ligand recognition
What is the role of the TIR domain in toll-like receptors?
Signalling
What are the two types of intracellular RNA receptors?
MDA5 and RIG-I
What does MDA5 detect?
Long double-stranded RNA
What does RIG-I detect?
Short dsRNA and RNA with a tri-phosphate at its 5’ end
PRR signalling activates transcription factors that then switch on many different genes, leading to the secretion of what?
Cytokines Interferons Chemokines Antimicrobial peptides Enzymes
What is the end response when PAMP of bacteria or tissue damage is detected?
Inflammation
What is the end response when PAMP of virus or intracellular bacteria is detected?
Interferon response
Name 4 anti-inflammatory cytokines?
IL-6
TNF-a
IL-1
IL-8
Name a pro-inflammatory cytokine
IL-10
What do natural killer inhibitory receptors detect?
Self molecules such as MHC.
What do natural killer activating receptors detect?
Altered self
What is the complement system?
A group of serum proteins in the blood that performs a critical defence against pathogens, especially extracellular bacteria
How many proteins are in the complement system?
About 35
Where are most complement proteins made?
The liver
What are the 7 functional categories of complement proteins?
Initiators Enzymes Opsonins Anaphylatoxins Membrane attack proteins Complement receptors Regulatory proteins
What do initiators do, in terms of complement protein function?
Bind pathogens components/ antibodies
What do enzymes do, in terms of complement protein function?
Convertases
What do opsonins do, in terms of complement protein function?
Promote phagocytosis
What do anaphylatoxins do, in terms of complement protein function?
Cause inflammation
What do membrane attack proteins do, in terms of complement protein function?
Lyse pathogens
What do complement receptors do, in terms of complement protein function?
These are on phagocytes or neutrophils
What do regulatory proteins do, in terms of complement protein function?
Limit complement activation
What are the three pathways of complement activation?
Classical
Lectin
Alternative
What is the classical pathway initiated by?
IgG and IgM
What is the lectin pathway initiated by?
Lectins that bind of carbohydrates on the surface of pathogens
What ate the 3 effector functions of complement?
Membrane attack complex to form pores in the pathogen membranes
Opsonins to promote phagocytosis
Anaphylatoxins to promote inflammation
A constant interplay between the innate and adaptive system is which cell?
Dendritic
Why do we need innate immunity?
Fast response against bacteria
Help initiate adaptive responses