Immunology Part 3 Flashcards
What is the local effects of
- NO
- Prostaglandins/leukotrienes
- histamines
?
Vasodilatation
Increased vascular permeability
Smooth muscle contraction
Pain
What are the local effects of pro-inflammatory cytokines?
Increased vascular permeability
Endothelial cell activation
What are the local effects of chemokines?
Leukocyte (neutrophil) recruitment and activation
Transendothelial migration:
What is found on the suface of neutrophils?
On surface of neutrophils
- Carbohydrates
- ligands for selectins
- integrins (LFA-1)
- receptor for ICAM-1
What does the neutrophil encounter as it rolls alon gthe endothelium?
Selectins
ICAM-1
`What happens to the neutrophil as it rolls alon the endothelium?
- weak binding ‘rolling’ to selectins
- strong binding to ICAM-1
- Stable adhesion and aggregation to ICAM-1
- Transendothelial migration
What happens to the neutrophil after transendothelial migration?
Chemotaxis to site of infection, attracted by chemokines
What is the result of increased vascular permeability in acute inflammation?
Tight junctions lost- gaps form between endothelial cells
What is the result of vasodilatation and increased blood flow in acute inflammation?
Loss of intravascular fluid and increased plasma viscocity slows flow allowing neutrophils to flow in the plasmatic zone; this is margination
This occurs only in venules…
What happens to endothelial cells at sites of acute inflammation?
Endothelial cellls become activated leading to expression of adhesion molecules
ICAM-1 and selectins
What is the process by which neutrophils squeeze between endothelial cells?
Diapedesis
What are some compounds that are chemotactic to neutrophils?
Bacterial products
Complement components
Cytokines: known as chemokines
What are the killing mechanisms of neutrophils?
Phagocytosis
Degranulation
NETs
How do neutrophils undergo phagocytosis?
Use PRRs to bind and phagocytose pathogens
What are the two distinct mechanisms by which neutrophils kill internalised pathogens?
- anti-microbial proteins and enzymes
- reactive oxygen species ROS
What is degranulation used for by neutrophils?
Killing of extracellular pathogens:
bacteria and fungi
May cause tissue damage and systemic inflammation
What do NETs do?
Immobilise pathogens
- prevent them from spreading
- facilitates their phagocytosis
What do neutrophils release to cause acute inflammtion?
TNFa
What are the three pathways of complement activation?
- classical pathway
- mannose binding lectin pathway
- alternative pathway
What does the activation of complement cause?
Activation of downstream complement proteins
leading to….
- pathogen killing
- pathogen opsonisation
- leukocyte recruitment and inflammation
- removal of immune complexes
Where does MBL pathway activate complement?
C3
How is the alternative pathway activated?
Spontaneous breakdown of C3 into C3a and C3b
What does the alternative pathway trigger?
Amplification loop whereby C3b triggers conversion of C3 to C3b
What does C3b result in?
Conversion of C5 to C5a and C5b
What does C5b do?
Bind to surface of pathogens
Assembles with C6, C7, C8 and C9 to form membrane attack complex
What is the role of MAC?
Inserts into target cell walls- making a funnel shaped hole
Causing osmotic cell lysis of pathogen
Define opsonisation?
coating of pathogens by humoral factors (opsonins) to facilitate phagocytosis
What are examples of opsonins?
- C3b
- C-reactive protein (CRP)
- IgG / IgM
Where are receptors for opsonins located?
Surface of phagocytes
What are C3a and C5a known as?
Anaphylatoxins
What is the tole of anaphylatoxins?
Promote inflammation BY;
- acting directly on blood vessels
- increasing permeability
- activating mast cells
- causing the release of pro-inflammatory mediators and chemokines
Describe the regulation of complement?
- Only cleaved Complement proteins are active
- Active Complement proteins have very short half-life
- Some Complement proteins are only produced during an Acute Phase Response
- Some Complement proteins do not bind to human cells
- Complement inhibitors and regulatory proteins limit activation of the system
What is a dendritic cell?
Professional antigen presenting cell
