PMI02-2003 Flashcards
What organisms have innate immunity?
Plants
Vertebrates and invertebrates
Fungi
What innate barriers are in place to prevent adherence?
Normal flora (commensals)
Local chemical factors
Phagocytes (esp in lungs)
What innate responses are triggered when the epithelium is breached?
Wound healing
AMPs
Phagocytes
Complement
What innate cells/substances are involved when there is local infection of tissues?
Complement
Cytokines and chemokines
Phagocytes
NK cells, macrophages
Dendritic cells
Where is mucosal epithelia found?
Lining externally exposed body cavities
What do most mucosal epithelia secrete and what is the importance of this?
Mucus
Harder for microbes to adhere and it helps to remove microbes/debris
What cells produce alpha-defensins?
Neutrophils
What cells produce beta-defensins?
Epithelial cells
Give examples of antibacterial peptides.
Defensins
S100As
Cathepsins
Cryptidins
Phospholipase A
Lactoferrin
Histatin
Lysozyme
What is lactoferrin?
Scavenger protein for iron
How large are antibacterial peptides and which cells usually produce them?
20-60 amino acids long
Secreted by epithelial cells naturally
What is the complement cascade?
Collection of proteins in serum and tissue fluid which detect microbes and generate responses
What are the three methods of activation of the complement cascade?
Classical pathway
Mannose-binding lectin pathway
Alternative pathway
Describe the classical pathway of complement activation.
- Non-specific or specific antibodies bind to antigen on pathogen surface
- C1 proteins associate and bind to antibody
- Activated C1s cleaves C4
- C4b binds to pathogen surface and associates with C1 proteins
- C4b binds C2 so C1s can cleave C2 = C4b2b complex formed
- C4b2b cleaves C3 many times. C3b may bind to C4b2b or directly to pathogen
What is required to initiate the classical pathway and how does it do this?
C1q
Interacts with bound antibody at the Fc portion (or less likely binds directly to pathogen)
What do lectins bind to?
Carbohydrates
What is mannose?
Major component of microbial cell walls, especially fungal
Which other activation pathway is the mannose-binding lectin pathway most similar to? How does it differ?
Classical pathway
But activated by mannose-binding lectin which has a similar role to C1s (C4 cleavage)
What initiates the alternative pathway?
Spontaneous cleavage of C3 (hydrolysis)
Describe the alternative pathway.
- C3 undergoes spontaneous hydrolysis to form C3(H20) which binds to factor B
- This binding allows factor D to cleave factor B to create C3b(H20)Bb complex
- C3b(H20)Bb cleaves C3
What do all three complement activation pathways result in the formation of?
C3b
What roles does C3b have?
C5 convertase –> MAC and anaphylatoxin formation
Binds directly to pathogen surface –> opsonisation
What are the three outcomes of the complement cascade?
Recruitment of inflammatory cells and increased vascular permeability
Opsonisation
MAC/killing of microbe
What are anaphylatoxins and what do they do?
“a” molecules following cleavage of complement proteins, trigger inflammation
Increase vascular permeability by acting on endothelial cells –> allows extravasation of immunoglobulin and more complement
Chemoattractant to macrophages, PMNs, leukocytes
What is opsonisation and why is it important?
Flagging microbes to aid phagocytosis
Many microbes have evolved coats/capsules (carbohydrate mainly) to evade phagocytosis/recognition
What complement molecules are involved in the membrane attack complex?
C5b
C6, C7, C8, C9
Describe the formation of the MAC.
- C5b associated with C6 and C7 = C5b67
- C5b67 binds membrane via C7
- C8 binds complex and inserts into cell membrane
- 1 - 16 C9 molecules bind to complex at C8 and polymerise to form a pore in the membrane
How big is a MAC?
~15nm high and 10nm in width
Which lymphoid cell is involved in innate immunity?
NK cell
What is the most common myeloid innate immune cell?
Neutrophil/polymorphonuclear leukocyte
What are PRRs?
Pathogen recognition receptors
Recognise pathogen-associated molecular patterns (PAMPs)
Give examples of PAMPs.
C/G-rich DNA
Double-stranded RNA
Oligosaccharides
Lipoproteins
Give three examples of PRRs.
Toll-like receptors
C-type lectin receptors
NOD-like receptors
What does recognition of a pathogen typically lead to?
Phagocytosis
Secretion of inflammatory mediators and cytokines
Which cell links the innate and adaptive immunity?
Dendritic cells
What is a cytokine?
Small glycoprotein (~17kDa)
Give examples of pro-inflammatory cytokines.
IL-1α
IL-1β
TNF-α
Interferon-γ
What are the functions of pro-inflammatory cytokines?
Induce many of the effects associated with inflammation, including:
Macrophage activation
Stimulate inflammatory mediator release
Activate adaptive immunity
Trigger pyrexia
Give examples of anti-inflammatory cytokines.
IL-4
TGF-β
What are the functions of anti-inflammatory cytokines?
Antagonistic to pro-inflammatory cytokines
Mediate adaptive humoral immunity response
What are growth factors and colony stimulating factors important for?
Immune cell development and increasing secretions
What cell changes are growth factors responsible for?
Cell growth
What cell changes are colony stimulating factors responsible for?
Differentiation
What are the functions of chemokines?
Attract/recruit immune cells to site of inflammation/infection
Which receptors do mucosal chemokines commonly act through?
CCR6 receptors
When are type 1 interferons produced and why?
Produced by all cells in response to viral infection to render surrounding cells non-permissive to infection (quiescence)
Also trigger inflammation for removal of infected cells
