Lecture 1: Outline of the Innate Immune System Flashcards
What are the general features of innate immunity?
barrier tissues, chemical defences, soluble factors and effector cells
What are some examples of barrier tissues?
skin, mucosa, respiratory epithelia, intestine
What are some examples of chemical defences?
antimicrobial peptides (e.g. defensins) and antimicrobial enzymes (e.g. lysozyme)
What are some examples of soluble factors?
complement proteins (e.g. C3b deposition)
What are some examples of effector cells?
granulocytes (neutrophils, eosinophils, basophils), monocytes/macrophages, dendritic cells, NK cells
What do epithelial surfaces of the body provide? What do epithelial cells (and phagocytes) produce?
the first barrier against infection
several kinds of antimicrobial proteins
What must an infectious against overcome in order to establish a focus of infection?
innate host defences
How does skin aid in the innate immune response?
mechanical: longitudinal flow of air or fluid
chemical: fatty acids, β-defensins, lamellar bodies, cathelicidin
microbiological: normal microbiota
How does the gut aid in the innate immune response?
mechanical: longitudinal flow of air or fluid
chemical: low pH, enzymes (pepsin), ɑ-defensins (cryptdins), RegIII (lecticidins), cathelicidin
microbiological: normal microbiota
How do the lungs aid in the innate immune response?
mechanical: movement of mucus by cilia
chemical: pulmonary surfactant, ɑ-defensins, cathelicidin
microbiological: normal microbiota
How do the eyes/nose/oral cavity aid in the innate immune response?
mechanical: tears, nasal cilia
chemical: enzymes in tears and saliva (lysozyme), histatins, β-defensins
microbiological: normal microbiota
What is lysozyme?
a hydrolase that catalyses the hydrolysis of linkages in peptidoglycan and digests bacterial cell wall
What do defensins do?
disrupt and lyse the bacterial cell membrane directly
What is complement made up of and what does it recognise?
> 30 soluble proteins in the blood that can recognise features of microbial surfaces and mark them for destruction by coating them with C3b
What are outcomes of the complement system?
migration of phagocytes to site of infection
opsonization and phagocytosis of microorganisms
lysis of pathogens
How are proteins in the complement system activated?
they are activated sequentially in a cascade and activation can occur through three different pathways
Where do all three pathways of the complement system converge?
at the activation of ‘C3’
What are the three different pathways of the complement system?
the alternative pathway, the lectin pathway and the classical pathway
What are main characteristics of the innate immunity?
non-specific (molecular patterns), rapid response (minutes-hours), no memory
How does the immune system distinguish between stranger and danger?
stranger = novel microbial structures danger = changes in the expression of self proteins
What are the major effector functions of innate immunity?
phagocytosis, cytokine secretion and cytotoxicity
What is the outcome of the innate immune response?
either resolution of infection or persistence of the pathogens -> adaptive immune response
Which lineage comprises most of the cells of the innate immune system?
the myeloid lineage
What are granulocytes characterised by?
Why are these cells also known as polymorphonuclear?
secretory granules in their cytoplasm and short-lived (hours to days)
because they have a multi-lobed nucleus
What do neutrophils carry out and what do they activate? When is their frequency elevated?
phagocytosis and activation of bactericidal mechanisms
elevated frequency in response to infection (increased production in the bone marrow)
What are eosinophils essential for? Where is the majority of eosinophils in the body? What is their effector function?
essential for killing parasites
majority in the tissues and generally have effect through degranulation into the local environment
What is the role of basophils?
help drive the innate immune response with some role in anti-parasitic immunity -> low numbers in blood and are recruited to site of IgE-mediated allergic reactions
What do eosinophil granules contain?
arginine-rich basic protein
What are the effector functions of eosinophils? (hint: What do they release?)
secrete leukotrienes, prostaglandins, cytokines to amplify inflammatory response
release highly toxic proteins + free radicals to damage parasite’s plasma membrane
How do basophils stimulate inflammation? (hint: What do they release?)
they tend to accumulate in damage tissues + release histamine, heparin and cytokines
Where are mast cells located?
only seen in tissues and are strategically located everywhere: particularly in sites that contact the external environment
What are the three key functions of mast cells?
- recruiting other cells to sites of infections
- increase inflammation = increase lymph flow to local lymph node
- mast cell products trigger muscular contractions - physical expulsion
Where are dendritic cells found? What is their role?
in tissues and lymphatic organs
critical role in antigen capture and antigen presentation to T cells + influence polarisation of T cells through cytokines and co-stimulatory molecules
What are NK cells derived from? How are they activated?
the same progenitor cells as lymphocytes
activation is by detecting changes in the expression of self protein
What is the role of NK cells?
important in antiviral and antitumor responses -> can lyse cells directly via the release of cytotoxic granules and secrete antiviral cytokines
What is the role of monocytes/macrophages?
orchestrate immune responses (recruitment of other cells) and clear dead cells and cell debris
What is the difference between monocytes and macrophages?
macrophages are tissue-resident forms of circulatory monocytes
What does an inflammatory response lead to?
⬆ vascular diameter and blood flow + blood vessels become more permeable and fluid leaks into tissue + inflammatory cells migrate into tissue and release mediators that stimulate nerve endings
What is an inflammatory response caused by?
chemokines and cytokines
