White blood cells and phagocytosis

Explain the oxygen dependent process of digestion of the pathogen

activation of the phagocyte causes the production of nadph oxidase- o2 to superoxide ion 02- h20 + o2- -----> h202; oh arginine + o2 ---> NO + citruline via iNOS h202 + no---> peroxynitrite radicals the oxidising radicals produced are effective in killing bacteria but can also harm normal cells if released from the phagocyte

What cell presents an antigen to a t cell?

dendritic cell - phagocyte

Explain the stage of chemotaxis of a phagocyte

enters tissue follows gradient of chemoattractants to site - cytokines- IL8 released by damaged cells - bacterial components

Explain the oxygen independent digestion of the pathogen

lysosomes disgest the pathogen - lysozyme - proteolytic enzyme - defensins - lactoferrin - binds to iron and competes with bacteria for iron

Explain the phagocytosis of other dead tissue cells

must be able to detect between apoptic and viable cells - silent removal; no inflammation apoptic - different structure - eat me signals - attract phagocyte and stimulate engulfment viable cells - dont eat me signals - repells phagocyte - no engulfment the outcomes of engulfment of apoptic cells; - pro-healing cytokins are released by phagocyte - IL-10 cytokin - TGFb- promotes tissue healing - presents self antigens- allows for self tolerance, no stimulation of adaptive immunity

What are the granulocytes?

neutrophil- PMN most present in the blood stream 4-5 hours 4-5 days in tissue forms puss when dead part of acute inflammation Basophil blue with H and e 0.2-1% in blood degranulation releases histamine and serotonin- inflammatory mediatorys- hypersensitivity type 1- allergies Mast cell near blood vessels - not in circulation degranulation releases serotonin- hypersensitivity type 1 - parasites eosinophil 4% of wbc part of allergy and parasites inflammatory response - release eosinphilic cation protein bigger targets

What are the phagocytic cells?

neutrophil- highest amount of wbc in the blood - acute inflammation - 8-10 hours in the blood and 4-5 days in tissue monocyte proliferates into macrophage in the tissue - releases cytokines that mediate inflammation - TGFb; blood monocyte;caged nucleus and less granules; tissue macrophage; more granules 20-40 hours in blood dendritic cell- long to catch bacteria presents antigen to t cells - on skin- mucosa and tissues- like to respiratory system MHC---- TCR antigen recognition co- stimulation CD80/86----- CD28 cytokines released

Explain the process of englufment

pathogen is coated with opsonin allowing quick identification 1) phagocyte binds to pathogen 2) this stimulates changes to the actin in the cytoskeleton 3) pseudopods form around pathogen 4) vesicles from membrane of phagocyte surround the pathogen in a phagosome 5) lysosomes binds to form a phagolysosome 6) digestion and destruction of the pathogen digestion of pathogen depends on oxygen independent and dependent reactions

Explain the lymphoid lineage

stem cell multipotent progenitor cell-common committed precursor- NK+ T Pro B late precursor and mature form B and L are part of adaptive immunity

Explain the myeloid lineage

stem cells common multipotent progenitor cells- myeloid cell committed precursor late precursor mature form immature basophil- basophil immature eosinophil- eosinophil monoblast- monocyte myeloblast- neutrophil pre-dendritic cell- dendritic cell

What are the steps in phagocytosis?

- migration and accumulation 1) chemotaxis 2) identification and attachment 3) engulfment 4) digestion

Explain the stage of identification and attachment in phagocytosis

- must identify as foreign and not part of self PAMP- on pathogen needed for survival PRR bind to these - Toll-like receptors TLR on membrane > essential in innate immunity > conserved during evolution > stimulate the production of inflammatory cytokines > lipoteichoic acid on gp > liposacchardie on gn > bacterial dna sequences > single/ double rna strands of viruses > glucans in fungi - C type lectin - CTLR on dendritic cells - NOD like r - NLR in cytosil - RIG like helicase - RLR in cytosil - Scavenger receptors- on membrane and bind to various bacterial components

what is the role of phagocytes?

- part of innate immune system identify, engulf and destroy pathogens and apoptic dead cells - dendritic cells present antigens to t cells- linking innate and adaptive immunity; t cell releases cytokines to influence b cell to produce antibodies

How to pathogens sabotage phagocytosis?

1) prevent binding by being in a capsule- streptococcus pneumonae 2) block destruction - mycobacterim; prevents lysosome adhering - salmonella- resistant to ROS 3) prevent engulfment Yersinia 4) kill phagocyte- toxin damages cell wall- staphlococcus aureus

Explain the process of recognition and attachment part 2

Opsonization bacteria is coated with opsonin - complement - c3b c4b - immunoglobulin antibody phagocytes have receptors for opsonins allows quick and efficient regonition of pathogen aids phagocytosis

What are the effector cells of the innate immune system?

Phagocytes; neutrophils, macrophages, dendritic cells- all from myeloid lineage - bone marrow Other cells; mast cells, eosinophils, basophils - myeloid lineage - bone marrow - natural killer cells- from lymphoid lineage - bone marrow