Innate Immune Cells Flashcards
What has the immune system evolved to do?
- to sculpt colonization to benefit the host
How do single-celled organisms fight microbes?
- by harnessing toxic peptides to thwart invading microbes
- this mechanism is still found in complex animals
How have multicellular organisms evolved their immune system to fight invaders?
- they devote specialized cells to engulf bacteria and viruses
- evolved from nutritive phagocytes in gutless animals
How have higher vertebrates evolved their immune system to fight invaders?
- the big bang of immunology
- evolved second form/ adaptive immunity where specialized WBC exquistely target a specific pathogen and maintain the body as an immune memory
What does immediate innate, early induced innate and adaptive immune response all have in common?
- they all have the same end goal to remove the infectious agent
What cells are in innate immunity?
- macrophage
- dendritic cell
- mast cell
- NK cell
- complement protein
- neutrophil, eosinophil, basophil (grouped together into granulocytes)
What cells are in adaptive immunity?
- B-cell
- T-cell
- antibodies
- CD4+ T cell
- CD8+ T cell
What cells are in both innate and adaptive immunity?
- y T cell
- NK cell
Where do pluripotent hematopoietic stem cells live?
- in the bone marrow
T/F: there are a lot of pluripotent hematopoitic stem cells
- False
- there’s a small number in the body, but they’re self-renewing, so any amount is good because they can regenerate
What do pluripotenet hematopoietic stem cells respond to?
- stromal cells, cytokines, colony stimulating factors (CSF)
What are the lineage development and cell diferentiation of pluripotent hematopoietic stem cells mediated by?
- coordinated and regulated expression of transcription factors
What’s the cellular lifespan of red blood cells?
120 days
What’s the lifespan of T-cells?
30 years
What’s the lifespan of neutrophils?
1-2 days
T/F: normally hematopoiesis is steady state but can increase 10-20 fold in hemorrhage or infection
- True
What are the 5 colony stimulating factors?
- IL-3 (used to be multi-CSF)
- Macrophage-CSF (M-CSF)
- Granulocyte-CSF (G-CSF
- Granulocyte-macrophage- CSF (GM-CSF)
- Erythropoietin (EPO)
T/F: the environment cannot affect the innate immune system
False, it can affect the regulation of different cells
Can cells going through different stages of differentiation able to give rise to all blood cell types?
- no, they can still make multiple cell types but are no longer able to differentiate into all types of blood cells
What are the intermediate stages referred to as?
- common progenitor cells
T/F: pluripotent hematopoietic stem cells do not directly differentiate into immune cells
True, they have to pass through different stages of differentiation
What’s the dependent lineage from transcription factor GATA-1?
- erythroid
What’s the dependent lineage from transcription factor GATA-2?
- erythroid
- myeloid
- lymphoid
What’s the dependent lineage from transcription factor PU-1?
- erythroid (maturation)
- myeloid (late stages)
- lymphoid
What’s the dependent lineage from transcription factor Bmi-1?
- all lineages
What’s the dependent lineage from transcription factor Ikaros?
- lymphoid
The transition between various stages of differentiation is driven by what?
- exposure to cytokines, including CSFs
What does the activity of the transcription factor induce?
- all developmental changes involved in cell differentiation
T/F: neutophils, basophils, lymphocytes and eosinophils look very similar
False, they look very different
What’s the activated function of macrophages?
- phagocytosis and activation of bactericidal mechanisms
- antigen presentation
What’s the activated function of dendritic cells?
- antigen uptake in peripheral sites
- anitgen presentation
What’s the activated function of neutrophils?
- phagocytosis and activation of bactericidal mechanisms
What’s the activated function of eosinophils?
- killing of antibody-coated parasites
What’s the activated function of basophils?
- promotion of allergic responses and augmentation of anti-parasitic immunity
What’s the activated function of mast cells?
- release of granuoles containing histamine and active agents
T/F: monocytes can give rise to phagocytes
- true
Where are monocytes present?
- in the blood where they traffic to various tissues
When does the monocyte differentiate? What does it Differentiate into?
- once it enters a tissue the monocyte differentiates into a macrophage
- named according to tissue
Is monocyte differentiation specific?
- it’s very organ specific so it can fight off invaders
How much do monocytes account for in every organ in the body?
- 10-15%
What is the name of the macrophage/monocyte that captures and kills pathogens through phagocytosis?
- mononuclear phagocytes
What is the name of the macrophage/monocyte that processes and presents pathogen molecules to the T-cells?
- antigen presenting cells (APC)
- they present pathogen to cells in the adaptive immune system (like TOLLs) so T cells can activate and know how to attack
T/F: monocytes/macrophzges are 1st class of phagocytes
True
What’s the difference between monocytes and macrophages physically?
- macrophages have more lysosomes, phagosomes and pseudopodia (things sticking out)
What are the 5 changes that occur in a monocyte when it differentiates into a macrophage?
- enlarges 5-10x
- increases intracellular organelles
- increases phagocytic ability
- increased amount of hydrolytic enzymes
- begin to secrete a variety of soluble factors
T/F: macrophages serve the same functions in different tissues
False, macrophages serve different functions in different tissues
What are the 4 things macrophages do?
- detect pathogens (PRRs)
- clear infection (phagocytosis)
- activate adaptive immune system (MHC-T cells)
- shape/direct adaptive immune response (cytokines)
What are the receptors on macrophages?
- LPS receptor CD14
- Toll-like receptors (TLR)
- Fc receptors
- mannose receptor
- complement receptors
- IFNg receptor
- Chemokine receptors
How do macrophages clear infections through direct clearance?
- phagocytosis of pathogen, killing it
How do macrophages clear infections through enhanced inflammatory response?
- contain/isolate pathogen
- secrete cytokines
raise body temperature - recruit additional cells (neutrophils)
What are the 2 methods macrophages use to clear infections?
- direct clearance
- enhance inflammatory response
Where are dendritic cells located?
- skin
Do dendritic cells move?
- no they’re stationary
What do dendritic cells look like?
- unusually shaped phagocytic cells with long, spindly membrance processes
What do dendrtic cells (DC) express high levels of?
- MHCII
Why do DC express high levels of MHCII?
- DC are antigen presenting cells (like macrophages) and these high levels allow the cell-surface molecule to present the pathogens to the CD4+ T-cells
T/F: DC are most important cell type for the activation of naive T-cells
True
Where do dendritic cells develop?
- there are many different types of DC so different areas
- subset from lymphoid lineage
- subset from myeloid lineage
What are non-lymphoid dendritic cells called?
- depends on where it is in the body
- skin - Langerhans
- other organs - interstitial dendritic cells
What happens if a dendritic cell encounters a pathogen?
- after it picks it up in the tissue the DC will change its morphology in the blood and lymph to be veiled
- moves to lymph node
What do lymphoid dendritic cells called?
- depends on here it is in the body
- interdigitating DCs in T-cell rich organ sites
- follicular DCs in B-cell rich lymphoid organ site
How do Langerhans cells drain into the lymph node?
1) antigen uptake by Langerhans cells in the skin
2) Langerhans cells leave the skin and enter the lymphatic system
How do dendritic cells drain into the lymph node?
1) mature dendritic cells enter the lymph node from infected tissues and can transfer some antigens to resident dendritic cells
2) B7-positive dendritic cells stimulate naive T cells
How many functions do dendritic cells serve?
- one, they just want to pick up pathogens and take them to the lymph node
What are a couple physical features of neutrophils?
- lots of granules, have a primary and secondary granule
- odd shaped nucleus, like a U
What’s a metaphor for neutrophils?
- they’re like the front line horsemen of the innnate immune system
How long do neutrophils live for?
- relatively short-lived
- about 1-2 days and die naturally
- if they fight something then only hours
:’’(
Where do neutrophils live?
- in the blood
Where are neutrophils recruited from?
- from the blood vessels into the infected tissues
T/F: neutrophils are voracious phagocytes
- true
- they eat and digest invaders
What does polymorphonucelar cells (PMNs)?
- multiobed nucleus
- always refers to neutrophils
Are neutrophils granulocytes?
- yes
- they contain a lot of pre-synthesized effector molecules that are stored in granules
What happens during neutrophil extravasation?
1) endothelial activation
2) tethering and rolling
3) firm adhesion
4) tranmigration and chemotaxis
- goes from round to pancake shape
What are the 5 effector mechanisms used by neutrophils?
- phagocytosis
- degranulation
- oxidative burst
- cytokines
- NETs
Define phagocytosis
- eat the infecting pathogen
Define degranulation
- dump cytotoxic granular contents on the target
Define oxidative burst
- generation of reactive oxygen species (ROS) and reactive nitrogen species (NOS) that can be used to make hydrogen peroxide and hypochloric acid which is toxic to bacteria
Define cytokines
- inflammation, activation of other cells
Define NETs
- Neutrophil Extracellular Traps
- cell pokes out its own DNA to capture and contain bacteria
What are the thress types of granules in neutrophils?
- azurophilic (primary)
- specific (secondary)
- gelatinase (tertiary)
What makes granules a great risk for collateral damage?
- the granules in neutrophils can either fuse with the phagosome or it can be released into the extracellular environment (i think this is the dangerous part)
How long is the life span of neutrophils?
- once fully mature 1-2 days
What are the stages of formation for neutophils?
1) myeloblast
2) promyelocyte
3) myelocyte
4) metemyelocyte
5) band cell
6) PMN
How can a neutrophil suicide be useful?
- by killing themselves they release the contents of their nuclei and mitochondrial DNA
- the nucleic acid + bactericidal enzymes makes a lethal network outside the cell to trap and kill bacteria
What are some physical features of eosinophils?
- lots of granules
- contains large red-staining granules
What specific type of infection are eosinophils primarily used for?
- parasitic infections
- the number of eosinophils increase to 10-20% of blood leukocytes during a parasitic infection
How is the recognition of parasites enhanced?
- by the addition of an antibody to an eosinophil
What are some physical features of basophils?
- lots of large granules
- horse-shoe shaped nucleus
- lobed nucleus and heaily granulated cytoplasm
What reactions are basophils primarily used in?
- allergic responses
- antiparasitic immunity
T/F: basophils are phagocytes
- False
- they aren’t phagocytes
How do basophils attack invaders?
- they aren’t phagocytes so instead release large amount of pharamacologically active compunds from in their granules
What are basophils important mediators for?
- hypersensitivity
- allergic responses
What are some physical features of mast cells?
- normal nucleus
- large granules
What activates mast cells?
- IgE
- bacterial products
- parasites
What are mast cells coated with? How does this help them?
- IgE
- the cell can bind with up to 200 different IgE to its surface
What’s a granule content in mast cells?
- neurotransmitters that regulate blood vessel tone
What are mast cells known for?
- fighting infections
- ability to cause allergies
Where do mast cells differentiate?
- in the tissue
- phenotype varies on location
Where are mast cells located?
- at host-environment interfaces
- skin, lungs, gut
How involved are mast cells in immune responses?
- very involved
- they’re responsible for telling other cell types to make aware that something is happening and they need to help
T/F: natural killer cells are clonal
- False, they are not clonal
Are NK cells more responsive to bacterial or viral invaders?
- viral
- other cells are primarily bacterial
Do NK cells have markers for B or T-cells?
- no
Why are NK cells names natural killer cells?
- they can kill target cells without prior immunization
How are NK cells regulated?
- by a balance of activating and inhibiting receptors
How do NK cells recognize targets?
- they can recognize targets labeled with antibody
- known as antibody-dependent cellular cytotoxity (ADCC)
What is the negative feedback loop seen in NK cells?
- MHC class I on normal cells is recognized by inhibitory receptors that inhibit signals from activating receptors
- NK cell does not kill the normal cell
When would a NK cell kill another cell?
- altered or absent MHC class I cannot stimulate a negative signal, the NK cell is triggered by signals from activating receptors
- activated NK cell releases granule content, inducing apoptosis in the target cell
T/F: NK cells are readily potent helpers available to fight against virus
True
What is the endothelium?
- a single cell layer that forms continuous lining to contain the blood
What are 3 things the endothelium is important for?
- plays critical role in homeostasis
- it’s a barrier
- it’s responsive to many mediators
How does the endothelium help maintain homeostasis?
- helps maintain coagulation and vascular tone (aka blood pressure)`
How does the endothelium act as a barrier?
- it regulates the movement of both fluids and macromolecules and leukocytes
How is the endothelium responsive to mediators?
- can actively engage in recruitment of different cells
When the endothelial cells are activated what can they do?
- produce oxidants, lipid mediators, cytokines, NO
- promote coagulation and regulate vascular tone
- increase microvascular permeability
- express adhesion and activation molecule resulting in increased leukocytes recruitment
Where are platelets derived from?
- bone marrow
- megakaryocyte “bits”
Do platelets have a nucleus? Granules?
- no nucleus but lots of granules
What are 2 major responses platelets are responsible for for?
- homeostasis (critical)
- inflammation (participates)
Do platelets bind to neutrophils or can neutrophils adhere to platelets?
- both!
How deos removing platelets affect inflammation?
- it can reduce the inflammatory response
What do platelets help the body with?
- helps to shield the body from infections
- can enhance the effector function of other cells (NET production by neutrophils)
