2. Innate Immunity Flashcards
How is the innate immune system activated?
Tissue injury
Microbes breeching a barrier
Name 3 receptors that initiate the innate immune response
Toll-like receptors
RIG-1 type
NOD-like receptor
Name a receptor that can induce phagocytosis
Dectin-1
Describe the process of phagocytosis
Microbes bind to receptors on neutrophils and macrophages
Engulfed into phagosome
Phagosome fuses with the lysosome
What substances are used to kill microbes in phagocytosis?
NO
Reactive Oxygen Species
Lysosomal proteases
What is chronic granulomatous disease?
X-linked disease
Defect in NADPH oxidase results in dysfunctional phagocytosis
What does chronic granulomatous disease result in?
Frequent bacterial and fungal infections
Formation of granulomas
How is chronic granulomatous disease diagnosed?
DHR assay
What is the function of NADPH oxidase?
Produces reactive oxygen species
What mediators do macrophages release when they detect a microbe?
IL-1
TNF
IL-8
What result does the release of IL-1 and TNF have?
Causes endothelial cells to express selectin which results in rolling adhesion
What result does the release of IL-8 have?
Stimulates integrin on leukocyte, causes tight adhesion
Acts as a chemoattractant to guide leukocytes to the site of the infection
What are the functions of cytokines?
- Danger signal causing WBCs to be drawn out of the blood towards the site of damage
- Autocrine and paracrine to increase cytokine production
- Causes endothelial cells to increase adhesion molecules
- Increase permeability
- Causes fever
- Acute phase protein production by liver
What cells release chemokines?
Damaged and immune cells
What are the functions of chemokines?
Chemoattractant
Increase expression of adhesion molecules on immune cells
What are the classes of lipids involved in innate immunity?
Prostaglandins
Leukotrienes
PAF
What cells produce prostaglandins?
Endothelial cells
What are the functions of prostaglandins and leukotrienes?
Vasodilators and constrictors
What cells produce leukotrienes?
Immune cells
What cells produce PAF?
Endothelial and immune cells
What is the function of PAF?
Increase permeability
What processes lead to the resolution of acute inflammation?
Short life of neutrophils and inflammatory mediators
Macrophages become anti-inflammatory
Inhibitory cytokines limit inflammation
Growth factors act on fibroblasts to increase repair
Production of anti-inflammatory lipoxins, resolving and protectins
Name 2 inhibitory cytokines
IL-10
TGF-b
Name a growth factor which acts on fibroblasts
FGF
What cells are antigen presenters
Dendritic cells
Macrophages
B cell
What cells express MHC-II?
APCs
Where does MHC-II start?
ER
Transported to the endoscope after phagocytosis
Combines with antigen peptides and moves to the cell surface
What type of T cell interacts with MHC-II?
CD4+
What cells express MHC-I?
All nucleated cells
What type of T cells interact with MHC-I?
CD8+
What type of antigens is MHC-I used for?
Self-peptides
Cancer
Viruses
Intracellular bacteria
What type of antigens is MHC-II used for?
Extracellular pathogens
What factor can cause a NK cell to increase killing?
A reduction in MHC-I levels
What do NK cells use to kill cells?
Granzyme
Perforin
Where are the genes for the MHC found?
Chromosome 8
What are the variable MHC genes for class 1?
HLA-A, B or C
What are the variable MHC genes for class 2?
HLA-DP, DQ or DR
What are the functions of the complement system?
- c3a and c5a promote inflammation
- c3b promotes opsonisation and phagocytosis
- c6-9 form the membrane attack complex
What are the 3 complement pathways?
Classic
Alternative
Lectin
How does the complement cascade promote inflammation?
Chemoattractants for neutrophils and monocytes
Stimulate release of inflammatory mediators
Increase vasodilation and permeability
How does the complement cascade increase opsonisation and phagocytosis?
c3b deposited on surface of microbes
Recognised by Complement Receptor of phagocytes
Which bacteria is MAC especially effective in?
Neisseria
What does a c3 deficiency result in?
Frequent pyogenic infections
More severe in adults
What does a C2-4 deficiency result in?
Autoimmune diseases eg. SLE
What does a C5-9 deficiency result in?
Recurrent neisseria infections
What does a c1 inhibitor deficiency result in?
inability to switch off inflammation
Heriditary angioedema
