Studied by 3 peopleWhat are the 5 functions of blood?
transportation, regulation, restriction, defence, stabilization/
Hematocrit
percent of total blood volume occupied by packed (centrifuged) red blood cells normal hematocrit = 37-54%
what are the percentages of different proteins in the blood
60% albumins, 35% globulins, 4% fibrinogen
where are most plasma proteins made
liver
role of albumins in blood plasma
colloid osmotic pressure and carriers for hormones
role of globulins in blood plasma
alpha and beta = clotting factors, enzymes, carriers gamma = antibodies
role of fibrinogen in blood plasma
cleaved to form fibrin in blood clotting
granulocytes
neutrophils, eosinophils, basophils
phagocytes
neutrophils and monocytes
how many RBC's are in the blood
5 million RBC/microL of the blood
How many RBCs are made per second?
2-3 million
how long is the lifespan of a red blood cell
120 days
what is the production of red blood cells called
erythropoiesis
Eryhtropoietin
hormone secreted by the kidneys that stimulates red blood cell formation --> produced in response to low oxygen (stabilizes HIF1alpha) and activates erythropoetin gene
what does the process of erythropoiesis require
iron, vit B12, folate
Do mature RBCs have a nucleus?
no, there is no need for new transcription and they undergo anaerobic metabolism
what is the process of making blood cells called
hematopoiesis
what are the percentages of erythrocytes and leukocytes in the bone marrow?
25% developing erythrocytes and 75% developing leukocytes (b/c higher turnover)
what regulates hematopoiesis
cytokines: colony stimulating factor (from endothelial cells and WBCs) and interleukins (from WBCs)
what is the effect of cytokines on hematopoiesis
survival, proliferation and differentiation of different cell type s
Where does hematopoiesis occur in adults?
bone marrow: pelvis, spine, ribs, cranium, proximal end long bones
Where does hematopoiesis occur in embryos?
yolk sac, liver, spleen, bone marrow
What can ulcerative colitis lead to?
contributing to the low production of erythrocytes as it may contribute to low levels of folate absorption
what is the process of RBC removal
90% are engulfed by macrophages and then broken into their amino acids --> the heme groups are converted to biliverdin and then to billirubin which goes to the liver to then either go to the kidneys to be converted to bilirubin derived products for excretion in the urine or to the small/large intestine for excretion -the Fe2+ is either transported in circulation by transferrin or stored in liver as ferritin
Jaundice
yellowing of the skin and the whites of the eyes caused by an accumulation of bile pigment (bilirubin) in the blood --> caused by: high turnover of RBCs, liver disease (can't process it), and bile duct obstruction (pushed back into liver)
causes of low production of RBCs
-destruction of stem cells via drugs and radiation (aplastic anemia) -inadequate nutrients: iron, folic acid, vit B12 (nutritional, pernicious anemia) -low erythropoietin (renal anemia/kidney failure)
causes of high removal of RBCs
-Hemolytic: genetic (defects in proteins), parasitic infections, drugs (antibiotics and anti-seizure drugs), autoimmune reactions -Hemorrhagic: excessive blood loss
Polycythemia
hematocrit is too high (>54%) therefore theres too high of a production of RBC while same removal levels -causes high blood viscosity -result from: mainly abnormal erythrocyte precursors (ie. cancerous) as well as low O2 delivery to tissues
Functions of the immune system
-destroys pathogens, detects and kills abnormal cells, removes debris from body
types of pathogens
parasitic worms, fungi, protozoa, bacteria, viruses
what are the two types of defence against pathogens
Innate immunity = rapid, non-specific
acquired immunity = slower, specific
General Components of the Immune system
tonsils, lymph nodes, spleen, GALT, bone marrow, lymphatic vessels, thymus
Roles of the lymphatics
return excess tissue fluid to blood
transport pathogens + dendritic cells to lymph nodes
transport fat from digestive system to blood
role of lymph nodes and spleen
both contain mature immune cells fro response -nodes = to minor the lymph --> the lymphatics are draining into the lymph nodes -spleen = monitors blood
types of immune cells
lymphocytes (B, T, NK), macrophages, dendritic cells, mast cells ,neutrophils, eosinophils, basophils
Parts of the innate immune response
physical barriers, 2) phagocytes, 3) natural Killer (NK) cells, 4) Antimicrobial proteins, 5) Inflammation, 6) Fever
Physical barriers
epithelium blocks entry (first line), glandular secretions (mucous, enzymes) trap, stomach acidity destroys, mechanical removal (tears, coughing, GI motility) removes
phagotcytes
at the epithelium, there are cell adhesion molecules when infected (for neutrophils) --> chemotaxins attract cell, cells undergoes diapedesis (moves in), then phagocytosis
two ways for phagocytosis
toll like receptors bind pathogen
sapsule around pathogen --> antibodies bind the capsule (specific) and the phagocyte has antibody/Fc receptor to bind and engulf
What types of cells are antigen-presenting cells (ACP)
macrophages and dendritic cells -fuse phagosome with lysosome and present antigen (class II MHC + antigen)
Natural Killer cells
in the lack of expression of MHC class I receptors (binds NK inhibitory receptor) on infected cells, NK produce interferons and granule release to cause pores to form in target cell to kill
antimicrobial proteins
-interferons: alpha and beta = prevent replication, gamma = activate macrophages -complement proteins: 25 plasma prot, destroy target membranes, stimulate inflammation, attract phagocytes, enhance phagocytosis
Three pathways of complement activation
alternative, lectin, classical -all three end up activating the membrane attack complex (C5-9)
Inflammation
localized response to injury --> swelling, redness, heat, pain Roles = slow spread of pathogens, mobilize defences, sets stage for repair -Kinin cascade leads to formation of bradykinin = vasodilator and stimulates pain receptors -mast cells release histamine and heparin for dilation of vessels and attraction of neutrophils
Fever
Body temp > 32.7˚C caused by pyrogens (bacterial components, interleukin-1 from activated macrophages) which change set point in hypothalamus --> causes increases metabolic activity of host and inhibits some pathogens
Features of Acquired Immunity
specificity, versatility, memory, tolerance
Specificity
activated by and responds to specific antigen -B and T cells have receptors that recognize specific shapes
Versatility
ready to confront any antigen at anytime -different B and T cells have diff receptors
memory
"remembers" any antigen it has encountered -some activated B and T cells are long lasting
tolerance
responds to foreign substances but ignores normal tissues -B and T cells with receptors that recognize self are deleted or not activated
B vs T cell receptors
B = immunoglobulin like receptors (bind extracellular antigens) T = receptors that bind both viral antgen and MHC
Clonal selection
selecting for the cell that has that specific kind of receptor
Clonal expansion
the cell that is recognized becomes activated and you get a lot more of the same kind of cell
Clonal memory
long lived cell and continue to reproduce (can be activated if the body recognizes the antigen again)
Primary vs Secondary Immune Response
1˚ = lag for the activation of the antibodies produced 2˚ = antibody concentration increases straight b/c antibodies are already in system
where do T and B lymphocytes originate
Bone Marrow
where do T cells undergo selection
in the thymus
where do B cells undergo selection
in the bone marrow
every human has between 10^7 and 10^9 different shaped ...
Fabs
the light chain of the antibodies is the .....
light chains
memory
"remembers" any antigen it has encountered
How are B cells activated ?
Antigen binds to specifci B cells
Antigen is internalized, digested and combined with MHC and then transported to the cell surface
and the specific helper T cells recognizes antigen and MHC becomes activated and secretes cytokines
activated B cell divides. some daughter cells becomes plasma cells and secrete antibodies, others become memory B cells
Antibodies protect us
Activates B lymphocytes
Acts as opsonins
Causes antigen clumping and inactivation of bacterial toxins
activates antibodies-dependent cellular activity
triggers mast cell degranulation (release histamine and heprin)
activates complements
how are antibodies classed
grouped into classes based on their F portion (all formed from B cells)
classes of antibodies
IgG, IgM, IgA, IgE, IgD
IgG
most common type of circulating antibody, transferred across the placenta from mother to baby (so baby has same antibodies)
IgM
first type of antibody to be secreted in response to a new antigen, good at causing antigen clumping and activating complement
IgA
crosses epithelial cells, protects epithelial surfaces and present in breast milk
IgE
fights parasites, eosinophils have receptors for the IgE, releases histamines
IgD
unknown role (less clear)
Types of humoral immunity
active vs passive
T cell activation
Cell binds to T lymphocyte (specific interaction)
signal transduction activates T lymphocyte
Helper T cells
-have CD4 to recognize the MHC -binds MHC class II and antigen -releases cytokines that suppress or activate other immune cells -activated T and B cells
Cytotoxic T cells
-have CD8 -bind MHC Class I and antigen -kill infected/cancerous cells -use perforin and granzymes to kill or by activating death receptor, Fas
MHC Class II
located on dendritic cells, macrophages and B cells, present exogenous antigen (some foreign), and activate helper T cells -antigen fragments (from lysosome) get bound to MHC II and then move to surface
activation of helper T cells
costimulation of the APC and inactive CD4 cell to activate and then split into active helper T and inactive memory
cytokines will stimulate ....
helper T cells, cytotoxic T cells and B cells
MHC Class I
located on all nucleated cells (so all but RBC) and present endogenous antigen (any protein made by the cell), activates cytotoxicT cells
activation of cytotoxic T cells
infected cell bind inactive cytotoxic T, cytokines from helper T (IL-2, interferon gamma) further activate -active Tc binds infected cell and1) releases lymphotoxin (disrupt cell metabolism), release cytokine (stim apoptosis), and release perforin (cell membrane)
advantages of the immune system
protective immunity and tumor immunity
disadvantages of the immune system
recurrent infection (deficient response), allergy (immune), rejection (immune), autoimmunity (immune), cancer (deficient)
Percentages of the ABO blood groups
A = 42% B = 9% AB = 3% O = 46%
percentages of Rh blood group in europeans
Rh+ = 85% Rh- = 15%
what type of antibodies does type A blood have
anti-B antibodies
what type of antibodies does type B blood have
anti-A antibodies
what type of antibodies does type O blood have
Anti-A and Anti-B
what is the universal recipient
AB
what is the universal donor
O
hemolytic disease of the newborn
RBC's are being destroyed -anemia, jaundice, enlarged liver and spleen, sever edema (clumping blocks capillaries)
how does hemolytic disease of the newborn develop
any rupture of the blood vessels between the placenta of the mother's blood and fetal blood -the mother (Rh-) mounts an immune response to the first Rh+ baby --> then for the second pregnancy, the mothers immune system has memory and targets the second Rh+ fetus
How can hemolytic disease of the newborn be prevented?
by injecting anti-D antigen antibodies into the Rh- mother during and following her pregnancy, which will bind and remove the fetal RBCs before immune response triggered, thus no memory of the D antigen
what is the half life of platelets
10 days
what is the role of thrombopoetin
increase platelet numbers -is a cytokine which stimulates the development of megakaryocytes and production of platelets
Phases of Hemostasis
Vascular Phse
Platelet Phase
Coagulation Phase
Vascualr phase
after injury, the blood vessels constrict due to neurogenic (neurons in surrounding area) and myogenic control (smooth muscle around vessels) --> reduces blood loss (short lived)
what is the vasocontriction prolonged by
serotonin, endothelin-1, and thromboxane A2
platelet phase
exposed collagen - binds and activates platelets (with adaptor vWf to bind both)
factors released from platelet (eg. ADP, PAF, serotonin, thromboxane A2)
factors attract more platelets
platelets aggregate and form plus
what does PAF stand for
platelet activating factor
differences between inactive vs active platelets
inactive = small, dislike fragments active = spiky, outer surface and adhere to each other
what prevents platelet adhesion with no injury
Prostacyclin (prostaglandin I2, PGI2) and NO are released from intact endothelium and prevent platelet adhesion and are vasodilators
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