Adobe Systems
Define footer – presentation title / department
1
Physiology of blood. Blood types.
Immune system.
Budínská Xenie

Adobe Systems
2
Final exame questions
̶76. Blood composition – values
̶77. Red blood cell. Haemolysis.
̶78. Haemoglobin and its derivatives
̶79. Suspension stability of RBC (sedimentation rate)
̶80. Mechanism of innate immunity
̶81. Acquired immunity
̶82. Blood groups antigens
̶83. Function of platelets
̶84. Hemocoagulation
̶85. Anticlotting mechanism
̶

Adobe Systems
3
Functions of the blood
̶homeostatic function
̶buffering
̶thermoregulation (transport of heat)
̶transport of substances
̶blood gases
̶nutrients
̶metabolites
̶vitamins
̶electrolytes
̶humoral control of organism (hormones)
̶defence of organism (immune functions)
̶blood clotting

Adobe Systems
4
Basic characteristics
̶Suspension character
̶6 - 8% total body mass
̶55% - fluid phase (plasma)
̶45% - formed phase (blood cells)
̶

Adobe Systems
5
Blood plasma. Inorganic substances
̶Na+ (137-147 mmol/l): osmotic pressure, volume, pH
̶Cl- (98-106 mmol/l): osmotic pressure, volume, pH
̶K+ (3,8-5,1 mmol/l): muscle aktivity
̶Ca2+ (2,1-2,7mmol/l): nerve excitability, muscle aktivity, blood clotting, membrane permeability,
bone mineralization
̶P (0,65-1,62 mmol/l): pH regulation, bone mineralisation
̶Mg2+ (0,75-1,25 mmol/l): enzyme activity, nerve excitability
̶HCO3- (25-34 mmol/l): CO2 transport, pH maintenance
̶Fe (16-25 μmol/l): part of haemoglobin - gas transport
̶I (275-630 nmol/l): thyroid hormone production

Adobe Systems
6
Blood plasma. Organic substances.
̶Plasma proteins 60-80 g/l
̶Albumins (40-48 g/l): oncotic pressure, transport of ions, fatty acids, hormones
̶Globulins (18-30 g/l)
α-globulins: transport of hormones, metals, vitamins
β- globulins: heme binding, vit. B12, iron, cholesterol transport
γ- globulins: antibodies, specific immunity
̶Fibrinogen (3 g/l): blood clotting
̶Lipids (4-10 g/l)
̶Glucose (4-5,5 mmol/l)
̶Nitrogen substances (0,2-0,4 g/l): urea, bilirubin, amino acids
̶Hormones, vitamins, enzymes, drugs

Adobe Systems
7
Formed blood elements

Adobe Systems
8
Haematopoiesis

Adobe Systems
9
Erythropoiesis
̶Erythropoietin - formation in the kidneys
̶acts on sensitive determinate progenitor cells in the bone marrow
̶stimulates nucleic acid synthesis
̶activates genes required for haemoglobin synthesis
̶increases Fe intake
̶Substances needed for erythrocyte production
̶amino acids: the protein part of haemoglobin
̶iron: binding of oxygen to haemoglobin and myoglobin
̶vitamin B12: essential for DNA synthesis
̶Folic acid: essential for DNA synthesis

Adobe Systems
10
Extinction of red blood cells
̶Spleen: phagocytosis of old and damaged erythrocytes
̶Hemoglobin=globin+hem
̶Globin – amino acids
̶Hem=CO2+Fe+biliverdin
̶Fe – synthesis of additional hemoglobin
̶

Adobe Systems
11
Red blood cell
̶biconcave disc - the shape increases the surface by 30%
̶shape is ensured by the protein spectrin
̶shape plasticity important for penetration through narrow capillaries

Adobe Systems
12
Functions of the RBC
̶Transport of respiratory gases
̶Buffering system
̶Maintaining blood viscosity

Adobe Systems
13
Haemoglobin
̶Red pigment transporting oxygen.
̶Protein, 64 450, 4 subunits.
̶Hem – derivative of porphyrine containing iron, conjugated with polypeptides (globin)
̶Types of hemoglobin:
̶Embryonic haemoglobin (t2e2, a2e2)
̶Fetal haemoglobin: Hb F, b2g2
̶Adult haemoglobin: Hb A, a2b2
̶Hemoglobin derivative:
̶oxyhaemoglobin - O2
̶carbaminohaemoglobin – CO2
̶methaemoglobin – Fe3+ in hem
̶carboxyhaemoglobin – CO

Adobe Systems
14
Hemolysis
̶Breakdown of RBC due to disintegration of its membrane – hemoglobin and intracellular fluid are
spilt into the solution
̶Physical (mechanical damage):
̶shaking, ultrasound, extreme temperature changes, UV radiation
̶Osmotic (hypotonic solution)
̶Chemical
̶strong acids and bases, fat solvents, surfactants (detergents)
̶Toxic
̶bacterial toxins, poisons (plant, snake, insect, spider), parasites
̶Immunological
̶transfusion of incompatible blood
Malaria
(Plasmodium spp.)

Adobe Systems
15
Suspension stability of blood
̶Helmholtz electrical double-layer:
̶negative charge on the membrane of RBC (sialic acid)
̶1st layer: positively charged ions (primarily Na+)
̶2nd layer: negatively charged ions (Cl-)
̶RBCs repel each other => suspension stability
̶Sedimentation rate indirectly corresponds to suspension stability of blood
̶Fahraeus-Westergren (FW) – direct method
̶A glass tube in vertical position
̶Measured after 1 hour (2 hours)
̶Wintrobe
̶100 mm long, thin glass tube in oblique position (45°)
̶Measured after 15 minutes
̶
RBC - -
+
-

Adobe Systems
16
Sedimentation rate
̶Men: 2-8 mm/h
̶Women: 7-12 mm/h
̶Newborns: 2 mm/h
̶Infants: 4-8 mm/h
̶
Effect on ESR
↑ value
↓ value
Erythrocytes
Number of RBCs
decelerates
accelerates
Size of RBCs
accelerates
decelerates
Plasma
Albumin
decelerates
accelerates
Imunoglobulins
accelerates
decelerates
Fibrinogen
accelerates
decelerates
Lipids
accelerates
decelerates

Adobe Systems
17
Blood groups
̶ is a classification of blood, based on the presence and absence of antigenic substances on the
surface of red blood cells
̶antigens (depending on the blood group system):
̶proteins
̶carbohydrates
̶glycoproteins
̶glycolipids
̶some of these antigens are also present on the surface of other types of cells of various tissues

Adobe Systems
18
AB0 system
̶Antigens on the surface of RBCs (agglutinogens): A, B
̶Antibodies in the blood (agglutinins): anti-A, anti-B (IgM)
̶Immunization against A and B happens during the first months of life (these antigens are also in
the diet) – agglutinins are then in the blood for the rest of the life
̶

Adobe Systems
19
Rh factor
̶Antigens D, d (also C,c, E, e, which are weaker) are only on RBCs
̶The strongest one is an antigen D – if present → Rh+ blood group
̶In recessive homozygotes (dd) → blood group Rh- (17% in Europe, <1% elsewhere)
̶in Rh- blood, antibodies (anti-D, IgG) develop only after immunization
̶The first reaction is weaker, the next encounter with Rh+ blood will trigger a stronger immune
response → hemolysis
̶
I. Rh- + Rh+ => N
II. Rh- + Rh+ => hemolysis
Rh+
Rh+
Rh+
Anti-D
(IgG)
Anti-D

Adobe Systems
20
Blood groups

Adobe Systems
21
Haematopoiesis

Adobe Systems
22
Innate immune system
̶already in place
̶rapid response
̶non-specific pattern response
̶functions:
̶physical barriers
̶leukocyte recruitment (inflammation)
̶antiviral defenses
̶Parts:
̶physical/chemical barriers
̶phagocytes (neutrophils, macrophages, dendritic cells, mast cells, NKCs)
̶complement
̶

Adobe Systems
23
Recognizing invaders
̶Pathogen-associated molecular patterns (PAMPs):
̶common molecular patterns typically found on pathogens (ex. Bacterial lipopolysaccharides,
mannose, viral nucleic acids)
̶Damage-associated molecular proteins (DAMPs):
̶common molecular patterns found on the surface of injured or dead host cells (ex. Heat shock
proteins)
̶Pattern recognition receptors:
̶receptors on cells of the immune system that recognize PAMPs and DAMPs
̶when the pattern recognition receptor binds a ligand (PAMP or DAMP) this triggers signal pathway
activation → transcription factors → gene expression of inflammatory and antiviral products →
recruitment/activation of immune cells

Adobe Systems
24
Complement cascade
̶system of proteins; part of the innate immune system
̶functions:
̶cell lysis (membrane attack complex – MAC)
̶opsonize
̶attract other immunological cells
̶complement activation pathways:
̶classical activation pathway
̶alternative activation pathway
̶lectin activation pathway

Adobe Systems
25
Complement activation pathways
̶classical (Ab dependent) complement activation pathway:
̶IgM/IgG brings together multiple C1 complexes
̶inhibitor falls off C1
̶C1 starts cascade that cleaves C3
̶alternative (Ab INdependent) complement activation pathway:
̶spontaneous cleavage of C3
̶lectin complement activation pathway:
̶mannose binding lectin (MBL) binds mannose on pathogen surface
̶activates MASP
̶MASP cleaves C3

Adobe Systems
26
Common pathway
C3 => C3a + C3b
C3b
opsonization
C3b + proteins
C5 => C5a + C5b
C3a
Chemoattractants:
-attraction
-activatation
macrophages
C5b + C6 – 9=>MAC
The membrane attack complex (MAC) is a complex of proteins typically formed on the surface of
pathogen cell. Assembly of the MAC leads to pores that disrupt the cell membrane of target cells,
leading to cell lysis and death.

Adobe Systems
27
Adaptive immune system
̶develops in response to pathogen (antigen)
̶specific (responds to Ag)
̶diverse (recognizes a lot of Ags)
̶immunological memory
̶humoral immunity:
̶targets extracellular pathogens in blood + mucosal secretions
̶B-cells → make Ab
̶cell-mediated immunity:
̶targets intracellular pathogens
̶T-cells (Cytotoxic T-cells (CD8+), Helper T-cells (CD4+)

Adobe Systems
28
Major histocompatibility complex
̶MHC I expressed on all nucleated cells
̶what's happening inside cell (endogenous peptides)
̶MHC class I recognized by CD8+ T cells
̶MHC II expressed on APCs
̶shows what's happening outside cell (exogenous peptides)
̶MHC II recognized by CD4+ T cells
̶

Adobe Systems
29
Immunoglobulin structure
̶2 identical heavy chains
̶2 identical light chains
̶constant region (Fc) remains the same among all antibodies in a class
̶Fab fragments (fragment antigen-binding region) are responsible for antigen recognition and
binding; form the "arms" of the Y;
̶The variable region (Fv) is the top part of the Fab fragment; this area varies between antibodies;
contains the paratope (antigen binding site)
̶
̶

Adobe Systems
30
̶IgM:
̶is the first antibody produced by activated naive B-cells
̶first response to early infection
̶can be attached to cell surface or secreted into blood & lymph
̶can activate classical complement pathway
̶IgG
̶is the most abundant ab in blood
̶can pass from parent to fetus via the placenta
̶tags antigens so phagocytes can eat them (opsonization)
̶capable of antibody-dependent cellular cytotoxicity
̶IgA:
̶is responsible for mucosal immunity
̶secreted in GI, respiratory, and genitourinary tracts and found in saliva, tears, & milk
̶ IgE:
̶provides helminth protection
̶is responsible for mast cell degranulation
̶IgD
̶co-expressed with IgM
̶least understood