Phagocytes

describe the characteristics and function of different innate immune cells, professional (primary) phagocytes = neutrophils, dendritic cells, macrophages. non-phagocytic cells = eosinophils, basophils, mast cells, natural killer cells

what group of immune cells is the innate immune system mostly governed by?

myeloid cells

what group of immune cells is the adaptive immune system mostly governed by?

lymphoid cells

which organisms have an adaptive immune system?

vertebrates

where do all blood cells originate from? (name of stem cell)

pluripotent hematopoietic stem cells

from which progenitor cells do megakaryocytes and erythroblasts originate from?

myeloid progenitor cells

what makes natural killer cells different from other lymphoid cells?

they do not express antigen-specific receptors

what are the 3 main roles of macrophages?

to patrol its native tissue for non-self material, phagocytose non-self material, release cyto/chemokines to activate other immune cells

give 2 molecules macrophages recognise to detect foreign material

PAMPs, opsonins (antibodies or complement proteins)

what are chemokines?

proteins that trigger chemotaxis in certain cells e.g. IL-8 stimulates neutrophil migration

give the two states macrophages can be polarised to

M1 and M2

what signals cause macrophages to enter M1 (pro-inflammatory) state?

interferon gamma, LPS

name 4 proteins M1 macrophages start expressing

CD40, CD80/86, TNF-alpha, iNOS

what is the role of CD40(R)?

recognises CD40L that is typically found on CD4 T cells which initiates Th1 cell response

name 2 proteins that favour the M2 state in macrophages

IL-4, IL-13

give 4 molecules M2 macrophages express

IL-10, TGF-beta, CD163, CD206

what is CD163?

scavenger receptor that helps minimise inflammation through increasing expression of anti-inflammatory cytokines

what is CD206?

mannitol receptor that encourages phagocytosis of most microbial antigens

how do dendritic cells sample their environment?

their membrane extensions allow for macropinocytosis (e.g. of soluble PAMPs)

why are dendritic cells important?

they are the most prevalent antigen presenting cells and activate the adaptive immune system

what is the difference between CD103^+/- dendritic cells?

CD103+ will move to the lymph nodes for antigen presentation, CD103- will stay in the tissue to keep inflammatory/T cell response in the primary site of infection

which innate immune cells are most abundant in the blood?

neutrophils

how do neutrophils operate?

they will respond to cytokines and chemokines by quickly moving to site of infection and phagocytosing the pathogen, then dying by apoptosis

name 3 examples of signals that attract neutrophils

C5a, IL-8, interferon gamma

how does chronic granulomatous disease (CGD) arise?

mutations in NOX genes lead to the expression of defective NADPH oxidase that is needed for oxidative bursts, preventing phagocytes from killing non-self material effectively

what is the main function of eosinophils?

kill large objects that cannot be phagocytosed normally, such as IgE-coated parasites, via release of granules

what is the known function of basophils?

allergy

name the 3 granulocytes

neutrophils, eosinophils, basophils

what do mast cells do?

release histamine granules upon IgE recognition, release various inflammatory mediators (e.g. chemokine CCL3 that attracts phagocytic immune cells)

which 3 cytokines released by mast cells promote eosinophil activation?

IL-3, IL-5, GM-CSF (granulocyte-macrophage colony-stimulating factor)

which cells play key roles in allergic reactions?

mast cells, eosinophils, basophils

which is the only lymphoid-derived cell that is involved in innate immunity?

natural killer cells

what do natural killer cells do?

patrol tissues and look for virally infected/cancerous cells. changes in MHC I expressed on these cells will be detected by the natural killer cell’s inhibitory receptor failing to bind to MHC I and produce an inhibitory signal for its activating receptor, triggering granule release

after physical defences are bypassed, which cell type responds to pathogens first?

macrophage

3 main functions of macrophages

release inflammatory signals, phagocytose pathogen, become an APC to activate adaptive responses

how do cytokines attract leukocytes to the site of infection?

they allow dilation of blood vessels to facilitate travel to the infection site, whilst also stimulating endothelial cells to express more adhesion proteins to encourage leukocytes to roll along the blood vessel wall to help their extravasation

what is extracellular trapping by neutrophils?

the release of genetic material and enzymes that traps pathogens, preventing them from continuing to infect the host