Lecture 3: Outline of Innate Immunity Flashcards
_________ immunity is present at birth.
Innate
Mention the components of innate immunity.
Mention the mechanical and chemical barriers of the body.
Mention antimicrobial proteins produced by epithelial cells and phagocytes.
- Lysozyme: a hydrolase that catalyses the hydrolysis of linkages in peptidoglycan and digests bacterial cell wall
- Defensins: disrupt and lyse the bacterial cell membrane directly
Describe the complement system.
Complement system involves >30 soluble proteins that can recognise features of microbial surfaces and mark them for destruction by coating them with C3b. These proteins are activated sequentially in a cascade, through one of the three pathways.
All pathways lead to the cleavage of C3 to C3a and C3b, where C3b covalently bound to surface components of the pathogen. This results in:
- Inflammation: migration of phagocytosis to infection site
- Phagocytosis: opsonisation
- Lysis of pathogen
Mention the order at which the complement pathway is activated.
- Alternative
- Lectin
- Classical
Mention the effector cells involved in innate immunity.
Describe the features of the innate immune system.
- non-specific
- stranger (novel microbial structures)
- danger (changes in expression of self-proteins)
- rapid response
- no memory
Mention the major effector function of innate immune effector cells.
- phagocytosis
- cytokine secretion
- cytotixicity
Are all cells of the innate immune system comprised of the myeloid lineage?
No, the NK cell comes from the lymphoid lineage
Describe and mention the granulocytes.
They are characterised by secretory granules in their cytoplasm and are short-lived phagocytic cells (hours to days).
- Neutrophils
- Phagocytosis and activation of bactericidal mechanisms
- Eosinophils
- killing of antibody-coated parasites
- Basophils
- anti-parasitic immunity
Are NK cells granulocytes?
Even though they have granules, NK cells are not considered granulocytes because their granules are far less numerous than those found in true granulocytes. Furthermore, NK cells have a different lineage than granulocytes, arising from lymphoid rather than myeloid stem cells.
Describe neutrophils.
- Not found in tissue
- Most abundant leukocyte in blood
- Elevated frequency in response to infection (increased production in the bone marrow)
- Half-life: 8 hours
- Main immune cells to eliminate bacterial pathogen
Describe eosinophils.
- granules contain arginine-rich basic protein (orange in eosin stain)
- small numbers in blood, but majority in tissue
- associated with fighting parasitic infections
- Two effector functions:
- release highly toxic proteins + free radicals
- produce immunomodulators: leukotrienes, prostaglandins, cytokines to amplify inflammatory response
Describe basophils.
- similar to eosinophils
- low number in blood
- life span - 1-3 days
- associated with fighting parasitic infections
- recruitment to the site of IgE-mediated allergic reaction
- release of histamine and cytokine
Describe mast cells.
- Only located in tissues
- Strategically located: particularly in sites that contact the external environment
- Associated with fighting parasitic (helminth) infections
- Potent provider of histamine and cytokine release
- Three key functions:
- Recruit other cells to sites of infection
- Increase inflammation: increase lymph flow to local lymph node
- Mast cell products trigger muscular contractions - physical expulsion
Describe dendritic cells.
- found in tissues and lymphatic organs
- consists of different subset - functional specialisation
- very potent at sensing pathogens and other danger signals
- critical role in antigen capture and antigen presentation to T cells
- Influence polarization of T cells through cytokine and co-stimulatory molecules
Describe NK cells.
- derived from the same progenitor cell as lymphocytes
- activation is by detecting changes in the expression of self-protein
- has activating and inhibiting receptors
- secrete anti-viral cytokines
- can lyse cells directly via the release of cytolytic granules (perforin, granzymes)
- Important in anti-viral and anti-tumour responses
Describe monocytes/macrophages.
- Macrophages are tissue-resident forms of circulatory monocytes
- Relatively long-lived cells. phagocytic role
- Orchestrate immune response (recruitment of other cells)
- Scavenger cells (clearing dead cells and cell debris)
Explain the main phases of inflammation.
- Surface wound allows bacteria entry - activating resident effector cells (such as macrophages) to secrete cytokines
- Vasodilation and increased vascular permeability allow fluid, protein, and inflammatory cells to leave blood and enter the tissue
- Infected tissue become inflamed, causing redness, heat, swelling, and pain
Discuss the key characteristics of inflammation.
- Redness and Heat: due to vasodilation and an increase in blood flow
- Swelling: blood vessels become more permeable, fluid leaks into tissue - edema
- Pain: inflammatory cells migrate into tissue and release mediators that stimulate nerve endings
- Loss of function
