Proliferation of Blood Physiology

nathan

RBC prolif.

Reticulocyte Count:Inc:•Bleeding compensation•Haemolytic anaemia•Haemolytic disease of newbornDec•Fe def anaemia•Pernicious anaemia•Aplastic anaemia•Radiation therapy•Marrow failure – inf/ca

SCA•Autosomal rec.•Mutation of Hb gene•Carriers res. To malaria•Life exp 40s

HDN•(maternal IgG fetus rbc)•Death from HF•Intrauterine transfusion – early induction if app.

Microcytic, hypochromic an.

Megaloblastic an.

Platelet prolif

IL-6,11 TPO

ET•1 of 4 myeloprolif disorders•More sensative to growth factors•JAK2 •Plt count >600 for 2+ mnths•Rx – interferon

ITP•Autoimmune attack of platelets•Rx with steroids

X1000 plt countNormal range 150-450

<20 transfusion20-50 monitoring50+ ok, conservative monitoring

Myeloprolif disorders (often assoc with JAK2 mutation)•ET – inc platelets•Myelofibrosis – fibrotic BM - pancytopaenia•Polycythaemia vera – inc RBC•CML – inc myeloid progenitors and products

Myeloid prolif.

1, myeloblast; 2, promyelocyte; 3, megakaryocyte; 4, neutrophil myelocyte; 5, young neutrophil metamyelocyte; 6, "band" neutrophil metamyelocyte; 7, polymorphonuclear neutrophil; 8, eosinophil myelocyte; 9, eosinophil metamyelocyte; 10, polymorphonuclear eosinophil; 11, basophil myelocyte; 12, polymorphonuclear basophil; 13-16, stages of monocyte formation.

myeloblast

Neutrophil eosinophil basophil monocyte – .......................................... macrophage in tissues

Occurs in red bone marrow (red vs yellow; foetus vs adult)

•Myeloblasts•Myeloblastic leukaemia

•Failure of haemopoeisis•Continual prolif of myeloblasts w/o diff.•Pancytopaenia and hypoplasia BM

•Neutropaenia•Febrile vs afebrile

•Severely predisposed to infection•Common post-chemo•Dec production, inc destruction•Aplastic anaemia, cancers, VitB12,folate def•Autoimmune, chemo

Neutrophils and Macrophages Physiology

• Invading viruses and bacetria are mainly destroyed by these.

• Nuetrophils are mature cells that can attack bacteria in blood

• Macrophages enter blood as monocytes (ineffective), mature in tissue (5x); can fight bacteria in tissues.

• WBC enter tissue spaces by diapedesis– Squishing through smaller than cell size whole in cappilaries.

• WBC are attracted to areas by chemotaxis.– Bact or viral toxins– Biproducts of degen. Inflam. Tissue– Complement– Biproducts of clotting

Neutrophils and Macrophages Physiology

• How do they kill – phagocytosis then intracellular destruction– Rough cell surface– Dead +foreign tissues lack protect, protein coat– a/b + c complex attracts eating cells to the right plc

• Neutrophil vs Macrophage phagocytosis– Netrophil – pseudopodia, around and fuse to create a chamber,

invaginates into cyto, vesicle. Can handle 3-20 bac.– Macrophage - >100 bac; engulf larger particles (RBC, protozoa),

can survive way longer• Destruction

– Vesicles of lysosymes and other enzymes/bacteriocydes fuse with evil vesciles for a deadly combination.

Inflammation – what do the neutrys and monoys do?

• Inflammation – clinical signs, tissue changes– Vasodilation, inc permeability, clotting, mig of N and M, swelling

• Walling off process – prevents spread of toxins through lymphatics and tissue spaces

1. MACROPHAGE INVASION!!!!! (immediate)– Eat as much bad stuff as quickly as possible

2. NEUTROPHIL INVASION!!!! (1-2hrs) (neutrophilia)– Margination – cap. Endo. Altered so N’s stick– Diapedesis– Chemotaxis

3. More macrophages - takes ages cos BM +blood supplies are depleted

4. Inc production of G + M in BM

Eosinophils

• 2%• Insignificant• Role in chemotaxis and phagocytosis

• Eosinophilia in parasitic infections• Cant eat them but attach to parasites

and release toxins to kill them– Hydrolytic enzymes– Reactive O2– Major basic protein

• Accumulate in areas of allergic reactions

Neutrophil eosinophil basophil monocyte

Basophils/Mast Cells

• Release histamine during inflammation• Allergies – caused by IgE• The Ig attaches to these cells, and when the

antigen (allergen) comes to bind to IgE, it explodes the basophils/mast cells that release:– Histamine, bradykinin, serotonin, heparin, slow-

reacting substance of anaphylaxis, lysosymes– Responsible for most of allergic manifestations

Lymphocytic prolif.Prolif – thymus gland processes T-cell, liver B-cellfound in lymph tissue; spleen; thymus; tonsils; nodular tissue

lymphoblast

NK cell CD16

B – cell CD20

Plasma cell

T - cell

T-helper CD4

T-cytotoxic CD8Plasma cells make Ig’s

Bmemory cells

Lymphocytic mechanism of action descr. G+H Ch 34 pp439-450

Innate immunityNon-specific destruction of non-self materials•Phagocytosis•Gastric acid secretions•Skin•Blood compounds, C, NK cells (recognise and destroy foreign cells, tumour cells and inf. Cells.)Acquired/Adaptive•A/bs/bcell/humoral imm.•Tcell (cell-mediat.) imm.•Specifically targeted to antigens

Tsurpress.

What do lymphocytes do• Millions of diff. antigen specific t and b cells live in he

lymphoid tissue, when activated it clones itself; with a view to creating lots of ab’s or antigen-spec. Circ. T cells.

• B Activation – antigen is eaten by macrophage which presents it to b-cells; when it finds the right a/b ; also the t’s see the antigen and make helper t’s b cell. lymphoblastsplasmablasts– Plasma cells make their specific activating Ig– As well as making the plasmablasts, duplicate b cells are

created (memory cells) which circulate around the body in the lymph as to allow for secondary (more effective if reexposed) response. [immunisation]

antibodies• Variable portion

– – specific to antigen• Constant –

– proprties of ab, like C binding capacity.• Classes M G A D E

– M – high in primary response, lots of binding sites but few in number– G-bivalent - 75%– E – allergies

• What do a/bs do?– Directly attack evil things

• Agglutination• Precipitation – molecular complex becomes too large to be eff.• Neutrilisation – cover off virulent surface areas of toxin/pathogen• lysis

– Get complement to do the dirty work (classic pathway)• Next slide

A/bs activate C1. Opsonization and phagocytosis – makes the

phagocytes more attracted >100x2. Lysis3. Agglutination – changes invading cell surface

so they bind to eachother4. Neutrilization of viruses 5. Chemotaxis – phagocytes6. Activate mast cells and basophils7. inflammation

T-cells• Activation is similar to b cells but instead of producing ab’s they

produce more t cells, and memory t cells which can circulate in blood and lymph for mths/yrs.

• T-cells, unlike B, only recognise antigens when presented on MHC protein on APC (dendritic) in lymph.– MHC1- Tc; MHC2- Th

• Helpers – form lymphokines-act on BM and imm. Cells (Ils, interferon, GMCSF)– Of vital importance, nearly no acq. Imm. Without them. Destroyed by

HIV– Stimulates growth of Tc and Ts cells.– Stimulate B-cell diff– Activates macrophage sys.– Feedback on themselves

Tcells• Cytotoxic – after binding to evil cell, release hole-

forming proteins (perforins), cause fluid to rush into cell pop. Also, Tc cells can release toxins into cells. They can pull away from evil cells before they die (leaving them to die) and go kill other ones. They can last for months killing evil cells.– Especially lethal to virally inf. Cells; also roles in killing

cancer cells and other non-self• TSurpressor. – surpress Tc and Th. Proposed that these

cells prevent excessive destruction of self by Tc cells. Also maybe a role in immune tolerance.

• Immunisations and allergies.