Inner compartment + blood + Immunphysiology Flashcards
1
Q
what are the major 3 subcompartments of the EC space ?
A
- intravascular
- interstitial
- transcellular
2
Q
what is the concentration for plasma water within the intravascular compartment ?
A
45 ml/bwkg
3
Q
what is the concentration of blood cells within the intravascular compartment ?
A
35 ml/bwkg
4
Q
what is the concentration of soft tissues within the interstitium compartment ?
A
120-150 ml/bwkg
5
Q
what is the concentration of fibrous connective tissues within the interstitium compartment ?
A
45 ml/bwkg
6
Q
what is the concentration of transcellular compartment ?
A
15ml/bwkg
7
Q
how do you quantify volume ?
A
by steward dilution principle
8
Q
How can we assess density by TBW?
A
weigh the mass (m)
quantify volume (V)
calculate density (m/V)
9
Q
LBM has a constant water content of
A
73 %
10
Q
fat has a constant water content of
A
10 %
11
Q
what the TOBEC measures ?
A
the fat content of the body with high precision.
12
Q
what fast distribution of the EC space using Stewart-principle can show us ?
A
volume of the soft tissues
13
Q
what the slow distribution of the EC space using Stewart-principle can show us ?
A
volume of the soft and fibrous tissues
14
Q
what the late distribution of the EC space using Stewart-principle can show us ?
A
volume of the bone tissue.
15
Q
what forces move water ?
A
osmotic and hydrostatic
16
Q
How long does it take to equalize the osmolality of the EC and IC compratments ?
A
few minutes
17
Q
What are the symptoms of isoosmotic hypovolemia ?
A
hemorrage, burn, vomiting, diarrhoea
18
Q
What are the symptoms of hyperosmotic hypovolemia ?
A
hydropenia:
decreased intake,
increased loss
increased evaporation
diabetes insipidus
19
Q
What are the symptoms of hypoosmotic hypovolemia ?
A
decreasing salt intake
primary salt loss
intensive sweating
salt loss through the kidneys
hypoadrenocorticalismus
20
Q
What are the symptoms of isoosmotic hypervolemia ?
A
oedema
overdosed physiological saline (per os or parenterally)
21
Q
What are the symptoms of hyperosmotic hypervolemia ?
A
hyperosmotic fliod intake (per os or parenterally)
22
Q
What are the symptoms of hypoosmotic hypervolemia ?
A
exaggerated water uptake.
Water retention in the kidney (ADH overproduction)
23
Q
How long does it take to form isoosmosis between IC and EC ?
A
half an hour
24
Q
How long does it take to restore isovolemia between IC and EC ?
A
couple of days
25
in P = r x C x R x T , what does the r mean ?
reflection coefficient
26
when membrane completely reflects a particle and it cannot get inside at all, what will be the value of reflection coefficient ?
1
27
what is the osmotic pressure for anelecctrolites of 1 mol dissolved substence in 1 liter ?
2.27 kPa
28
what is the unit which is used for measuring the body fluids ?
mmol/l
29
what is the unit which is used for measuring the osmotic pressure ?
kPa
30
what is the fpd of blood plasma?
- 0.56° C
31
what is the osmolality of fpd ?
300 mosmol/kg
32
What is oncotic pressure?
The pressure exerted specifically by protein and colloid in a compartment.
33
give 3 examples of anelectrolites components of the blood plasma and their concentrations
1. Glucose -
mammals: 5 mmol/l
Ru: 3 mmol/l
Birds: 10 mmol/l
2. Urea - 3-10 mmol/l
3. NPN (non-protein nitrogen) - 15-25 mmol/l
34
How can we quantify plasma proteins ?
with kjeldahl method
35
what is the concentration of amino acid in the plasma ?
5 mmol/l
36
what is the concentration of createnin in the plasma ?
50-200 μmol/l
37
what 2 independent proteins can be separated by paper-electrophoresis ?
albumin and fibrinogen
38
what size of molecules can get separated by ultracentrifuging ?
macromolecules
39
how does Ion exchange chromatography work ?
separates proteins on the basis of their charge
40
how protein mixture gets separated in Gel-filtration ?
by means of polysaccharide beads (dextran).
The protein with small molecular weight can get into the granules.
41
how does affinity chromatography work ?
one covalently binds a specific antibody formerly produced against the protein to the granules of the solid phase.
This protein will be selected from mixture by "recognizing system", while the other proteins are washed away in short time.
42
how does immune electrophoresis work ?
Antibody distributed in a gel poured on a sheet of glass develops precipitation arcs with the antigen in the electric field.
43
how does HPLC work ?
divides proteins in a solide phase column under high pressure perfusion.
44
what is the concentration of albumin in the blood plasma ?
45 g/l
45
what is the concentration of alpha-1 globulin in the blood plasma ?
4 g/l
46
what is the concentration of alpha-2 globulin in the blood plasma ?
6 g/l
47
what is the concentration of beta globulin in the blood plasma ?
8 g/l
48
what is the concentration of fibrinogen in the blood plasma ?
3-6 g/l
49
what is the concentration of gamma globulin in the blood plasma ?
15 g/l
50
what are the main functions of plasma proteins ?
1. Maintaining the oncoting pressure.
2. Transport funtions of albumins, globulins and lipoproteins.
3. Blood sedimentation.
4. Buffer action.
5. Blood clotting.
6. Immunity - immunoglobulins, complement proteins and signal proteins and peptides.
7. Enzymes in the plasma.
8. General protein metabolism - 25% plasmapheresis.
51
which protein in the plasma is responsible for most of the maintanace of oncotic pressure ?
albumin
52
what materials can albumin bind to and transport ?
- fatty acids
- bilirubin
- hormones
- vitamins
- metal ions (calcium, weakly: copper and zinc)
53
what materials can globulin bind to and transport ?
- transferrin: iron
- haptoglobin: hem
- transcortin: corticoids
- TBG (thyroxin binding globulin): thyroxin
- transcobalamin: B12-vitamin
- lipoproteins: see later
- wide variety of transport proteins
54
what VLDL stands for ?
Very Low Density Lipoprotein
55
what IDL stands for ?
Intermediate Density Lipoprotein
56
what LDL stands for ?
Low Density Lipoprotein
57
what HDL stands for ?
High Density Lipoprotein
58
what happens if erythrocyte sedimentation rate is high ?
there is more chance that inflammation present in the body.
Originally the cells have great negative charge because of the
albumin, so they repulse each other very much and sediment slowly. BUT After the globulins bind the total charge will decrease, there will be less repulse among the red blood cells so the sedimentation will get faster.
59
Plasma proteins are responsible for \_\_% of buffer capacity of the blood.
7
60
Plasma proteins are responsible for \_\_% of buffer capacity of the plasma.
15
61
hemoglobin is responsible for \_\_% of buffer capacity of the blood.
35
62
All coagulation factors are plasma proteins execpt \_\_\_\_\_\_\_\_
calcium ion (coagulation factor IV)
63
plasma proteins are the precursors of
anticoagulation and fibrinolysis
64
Immunoglobulins are part of ________ immunity
specific
65
Complement proteins are part of _________ immunity
non-speacific
66
10 g/l decrease means ___ kg decrease on the total protein content of the body
1
67
All the proteins synthesized in the liver, except :
1. gamma globulins: plasma cells.
2. HDL and VLDL: intestinal epithelium.
3. ic enzymes: from heart, liver, etc.
68
in which organ most of the proteins are synthesized ?
liver
69
what will hypo-and hyperproteinemia cause to the body ?
starving, kidney disease
70
what will dysproteinemia cause to the body ?
ratio changes,
e.g. :albumin/globulin
71
what will paraproteinemia cause to the body ?
pathological proteins appear, e.g. tumor Bence-Jones proteins
72
Define proteinemia
a lack of some of the fractions
| (genetic, e.g. fibrinogen)
73
What two important factors determine the formation of the ISF ?
transport through the capillary wall and forces determining transport
74
what can pass through the capillary wall without restriction ?
Water, electrolites and anelectrolites with small molecular weight.
75
which material movement is restricted in the capillary wall ?
Protein.
| (only a small amount of it can get through to the ISF mainly by pynocytosis and exocytosis)
76
If the protein transport into ISF is slow, why the protein concentration of the ISF is still high ?
while great part of the fluid moving out of the
capillary gets back to the capillary, so called Gibbs-Donnan effect, the proteins cannot get back.
77
what is the name of the capillary in the liver which is permeable for proteins ?
sinusoid
78
What is the only component which cannot pass the capillary wall BUT only by the help of specific carrier systems ?
colloids
79
What are fenestrated capillaries?
have pores that span the endothelial cells and allow larger molecules to pass
80
name different ways of transport through the membrane, from Intravascular space to the Intrerstitial space
1. Through fenestration.
2. Through interendothelial ways.
3. In atrancellular way.
4. By endocytosis, exocytosis, pynocytosis.
81
What determines the composition of the ISF ?
Diffusion, osmotic conditions, electric forces and hydrostatic forces.
82
What is the most important force to ensure transport of substances by which the most substances cross the capillary membrane without restriction ?
diffusion
83
what will happen if the movement of some component is restricted between two compartments
the concentration of the diffusible ions will be different in the two compartments.
84
what will happen if both, the freely diffusible electrolytes (KCl) and the non-diffusible proteinate anions are present in container which has dyalizing membrane ?
proteinate anions attract cations, thus the distribution of the diffusible ions will be unequal on the two sides of the membrane.
| (after the balance developed)
85
what is electroneutrality ?
the total amount of anions and cations have to be equal in certain compartments.
86
what are the forces that control the capillary/ISF balance ?
1. Osmotic pressure -continuously moves water into the plasma.
2. Hydrostatic pressure continuously move water out of the plasma.
87
on the arterial end of the capillary hydrostatic pressure os higher than the oncotic one, what is the result ?
filtration
88
On the venous end of the capillary oncotic pressure is higher than the hydrostatic one, what is the result ?
resorption
89
what is the most well known kind of ISF overproduction (isoosmotic hypervolemia)
odema
90
in the capillary/ISF boarder the ________ end difference is higher than the ________ end.
arterial, venous
91
what are the main causes of edema ?
1. Increased hydrostatic pressure = increased filtration.
2. decreased plasma proteins within the capillaries = decreased reabsorption.
3. increased capillary permeability.
4. Blockage of lymphatic drainage.
5. Increased blood pressure.
92
why protein is considered as the cells' "main problem" in the intracellular fluid ?
cells needs the protein.
Proteins do not have a considerable osmotic effect, but they have got charge and therefore they attract a lot of ions from the EC compartment and in this way
osmolarity inside the cells increases very much.
If the cell does not protect itself from the high pressure, such a high amount of water may flow into the cell that it ruptures the cell.
93
how the protozoa cell protects itself from the high pressure water flow inside the cell ?
water pump
94
how the plant cell protects itself from the high pressure water flow inside the cell ?
thick cell wall
95
how the mammalian cell protects itself from the high pressure water flow inside the cell ?
ion pump
96
what is blood primary function ?
transportation
97
what have the red blood cells specialized for ?
transportation of gases
98
what have the white blood cells specialized for ?
defense
99
where is the bivalent iron located at the red blood cell ?
hem-base
100
what is the main duty of the neutrophil granulocytes ?
phagocytosis, as part of the natural defense
101
what is the main duty of the basophil granulocytes ?
bind the IgE antibodies with their receptors and in case they meet the adequate antigen (pathogenic agent), they empty proteolytic enzymes in the interstitium (degranulation). This loosens the tissues, immune cells can get into the interstitium.
102
what is the main duty of the eosinophil granulocytes ?
act against the over-reaction of the basophils and partly are responsive to parazitosis.
103
what is the main duty of the thrombocytes ?
play a role in the defense reaction and in hemostasis.
104
what is the main duty of the B-lymphocytes ?
main cells of the humoral immunity.
105
what is the main duty of the T-lymphocytes ?
main cells of the cellular immunity.
106
What are the transport functions examples of the blood ?
- transport of blood gases
- transport of nutrients
- transport of metabolits
- information transport
- heat-transport
107
what is the total buffer capacity (%) of bicarbonate buffers in the blood ?
53
108
what is the total buffer capacity (%) of non-bicarbonate buffers in the blood ?
47
109
define haemostasis
coagulation, the body's normal physiological response for the prevention and stopping of bleeding/haemorrhage
110
what are the conditions of homeostasis ?
1. isovolemia (constant volume)
2. isotonia (constant osmotic pressure)
3. isoionia (constant ion-composition)
4. isohydria (constant pH)
111
what is the water proportion in blood (%) ?
90
112
what are the corpuscular elements in the blood ?
red blood cells, white blood cells, thrombocytes.
113
what is serum ?
plasma fluid after the blood cells and the clotting proteins have been removed - no fibrinogen present, only fibrin.
114
what is plasma ?
liquid portion of blood; contains fibrinogen, water, proteins, salts, nutrients, lipids, hormones, and vitamins.
115
define hematocrit
the ratio of the volume of corpuscular elements to the total volume of blood.
| (hematocrit shows us the velocity of the sedimentation of corpuscular elements)
116
Hematocrit avarage values (%)
40
117
dog Venous Ht-values
0.46
118
hen Venous Ht-value
0.32
119
What is sedimentation?
process of allowing particles in suspension in water to settle out of the suspension under the effect of gravity.
120
Blood cell sedimentation of horse
60-70 mm/hour
121
Blood cell sedimentation of dog
5-10 mm/hour
122
Blood cell sedimentation of swine
1-14 mm/hour
123
Blood cell sedimentation of hen
1-4 mm/hour
124
Blood cell sedimentation of cattle
0-2 mm/hour
125
Blood cell sedimentation of human
3-10 mm/hour
126
Blood pH range
7.35-7.45 (slightly alkaline)
127
what is the flexible range of blood pH for a short time period ?
pH 7.1 (minimum) - pH 7.6 (maximum)
128
the pH of the venous vessels is _______ than the pH of the arterial vessels.
lower
129
denisty of plasma
1020 g/l
130
total density of blood
1050 g/l
131
denisty of blood cells
1090 g/l
132
total osmotic pressure
700 kPa
133
colloidosmotic (oncotic) pressure
2.7-4 kPa
134
osmolality
300 mmol/kg
135
blood volume
80 ml/bwt
136
plasma volume
45 ml/ttkg
137
blood cell volume
35 ml/ttkg
138
what substances help to determine the plasme space ?
- Evans blue
- 125-I or131-I.
-labeled: albumin,
globulin, fibrinogen.
139
what substances help to determine the blood cell volume?
- labeled red blood cells
| (32-P, 55-or 59-Cr, 51-Fe)
140
1,4,7 - ?
Normocythaemia :
1. Normocythaemic normovolaemia.
4. Normocythaemic hypovolaemia (Oligaemia) - blood loss, blood cells and plasma loss together.
7. Normocythaemic hypervolaemia - plethora, excess transfusion, permanent, exhausting physical work.
141
2,5,8 - ?
Polycythaemia:
2. Polycythaemic normovoloaemia - haemoconcentration, viscosity increases, increased load on heart (turbulence).
5. Polycythaemic hyopvoloaemia - anhydraemia: lack of water, thirst, end up with haemoconcentration.
8. Polycythaemic hypervolaemia.
142
3,6,9 - ?
Olygocythaemia:
3. Olygocythaemic normovoloaemia - haemodilution, blood gets diluted with concurrent normal volume.
6. Olygocythaemic hypovoloaemia.
9. Olygocythaemic hypervolaemia - hydraemia, intake of excess water, infusion(followed by haemodilution).
143
what are the factors that affect the blood volume ?
* amount of body fat.
* position of the body.
* muscle work.
* climate.
* nutrition.
* lack of oxygen.
* sympathetic activity.
* pregnancy.
* blood loss.
* changes in the total water supply.
144
the blood volume of new born
100 ml/bwt
145
the blood volume of an adult
80 ml/bwt
146
Red blood cells have no \_\_\_\_\_\_\_\_\_
mitochondria
147
red blood cells can make energy only by \_\_\_\_\_\_\_\_\_\_
anaerobic respiration
148
what is the avarage lifetime of a red blood cell ?
120 days
149
what is the lifetime of cattle, swine red blood cell ?
60 days
150
what is the lifetime of bird red blood cell ?
30 days
151
what is the hemoglobin amount in the blood ?
120-180 g/l
152
how many grams Hb for 1g RBC ?
0.35 g Hb
153
?
**MCHC** (Hb/Ht)
Mean Corpuscular Hemoglobin Concentration.
- Approximately: 5 mmol/l.
154
?
MCH (Hb/RBC)
Mean Corpuscular Hemoglobin.
- Approximately: 0.45 pc/l.
155
?
MCV (Ht/RBC)
Mean Corpuscular Volume
- Approximately: 80-100 pc/l.
156
what is Hemolysis?
leakage or disruption of the blood cells (mainly red blood cells).
157
how can RBC adapt to change easily ?
**Their special membrane characteristics, which has spectrin-protein-molecules on the internal side that provides flexible feature.**
These "molecular springs" are fixed forming a net on the internal side of the cell by ankyrine, actin and smaller connective molecules.
Red blood cells are resistant to the quite significant changes of the osmotic circumstances = osmotic resistance.
(Slight changes in the osmolality do not cause
permanent damage, only changing of the shape)
158
what slightly hyperosmotic environment will cause the red blood cell ?
change in shape - smaller size
| (osmotic resistance)
159
what slightly hypoosmotic environment will cause the red blood cell ?
change in shape - larger size.
| (osmotic resistance)
160
what is the minimal concentration for osmotic resistance ?
70-120 mmol/l NaCl.
| (Haemolysis just starts)
161
what is the maximal concentration for osmotic resistance ?
50-90 mmol/l NaCl
| (All the cells haemolyse)
162
how haemolysis of RBC can be caused ?
primary injury of the RBCs membrane
163
**?**
**Spectrin**
164
**?**
**ankyrine**
165
**?**
**actin-bridge**
166
What is hemoglobin?
the pigment (protein) coloring the red blood cells that plays main role in the transport of the blood gases and the forming of the blood's buffer capacity
167
How many sub units does hemoglobin have?
4
168
What is hemoglobin level in the blood ?
120-180 g/l blood
169
what is hem ?
non-protein part of the hemoglobin.
Consist of ferro-protoporphyrine.
In the porphyrine base iron has only four co-ordination sites.
The two other valences involved are bound to the imidazole ring of the protein (histidine) under and over the porphyrine base.
Only the bivalent iron (ferro) atom can bind the oxygen reversibly.
170
what is globin ?
protein part of hemoglobin, which its sterical structure of globin mainly determines the characteristics of the oxygen binding.
Allows allosteric stimulation, and it is able to bind a new oxygen even stronger after accepting the former one.
171
only the bivalent ____ atom can bind the oxygen reversibly
iron (ferro) Fe2+
172
What causes sickle cell anemia?
single amino acid change in the beta chain of hemoglobin - in the 6th position there is glutamine instead of alanine
173
why Hb-F has smaller affinity to the 2,3-DPG than the Hb-A ?
Amino acid sequence difference.
174
What are the chains of an adult animal Hb-A ?
2 alpha + 2 beta chain
175
What are the chains of a foetal periodl Hb-F ?
2 alpha + 2 gamma chain
176
hoy many oxygen molecules can 1 hem bind to ?
**1**
177
What is carbaminohemoglobin?
hemoglobin bound to carbon dioxide, which is responsible for about 20 % of the compete CO2 blood-transport.
178
Hemoglobin has affinty to
* **carbon monoxide** reversibly (with about 200 times bigger affinity than to oxygen),
* **OH** and **Cl radicals**.
* Can go through methaemoglobin (hemiglobin) forming during **nitrate or nitrite** intoxication.
179
what are the 2 most important buffer-bases in the blood ?
The Hb- anion and HCO3-
180
what is the acid/base pair that ensures the buffer action in hemoglobin ?
HHb/Hb-
181
**35%** of the buffer capacity of the blood is provided by \_\_\_\_\_\_\_\_\_\_\_
hemoglobin
182
What is the RBC lifespan in the blood circulation?
120 days
183
what happens to normal RBC, after 120 days in the circulation ?
become sphaerocytes
184
which organs filter the sphaerocytes?
spleen and liver
185
1,2,3,4,5 ?
**1.** Normal RBC-s age after 120 days in the
circulation - they become
sphaerocytes.
**2.** The spleen and the liver filter the sphaerocytes:
1% of the RBC-supply undergoes hemolysis daily.
**3.** _released_:
- hemoglobin
- RBC debris
**4.** The hemoglobin partly gets into the blood: haptoglobin binds it.
In case haptoglobin is saturated: hemoglobinaemia followed by hemoglobinuria.
The free plasma hem binds to hemopexin.
**5.** Large part of the hemoglobin is degraded inside the phagocytes.
186
when phagocyte eats hemoglobin, that transforms the globin and HEM to \_\_\_\_\_\_\_\_\_\_\_
**globin →** amino acid.
**HEM →** Fe2+ and protoporfirin-IX which furthermore changes to bilirubin.
187
During the degradation of the hemoglobin phagocytes convert the HEM part to \_\_\_\_\_\_\_\_\_\_
bilirubin
188
Bilirubin 1 consists of
albumin and Bilirubin which bind in the circulation
189
**1,2,3,4,5,6,7,8,9,10,11,12,13,14 ?**
**1.** Br-I
(+80% glucoronic acid,
+20% sulphate)
**2.** Br-II "direct billirubin"
**3.** Bile
**4.** Br-II enters interstitial lumen (then changes)
**5.** Br-I
**6.** UBG - urobilinogen (15%)
**7.** stercobilinogen (gets oxidized)
**8.** stercobilin - as feaces (85%)
**9.** other products - as feaces
**10.** vena portae by vv. hemorrhoidales
**11.** hepatocyte (becomes after to Br-I again)
**12.** systemic circulation (1%)
**13.** kidney
**14.** UBG - as urin
190
Describe the degradation of the hemoglobin
Bilirubin dissociates from the albumin and it is taken up by the hepatocytes. A major proportion of bilirubin is conjugated with glucuronic acid, while the rest with other molecules. This is called the conjugated bilirubin, or direct bilirubin, or bilirubin-II
* Bilirubin is excreted to the bile and ends up in the gut where it is first deconjugated by bacteria, then further degradation products produced. The most important degradation products are stercobilinogen, stercobilin(which makes the feces brown), and urobilinogen (UBG). Most of the UBG is absorbed in the gut entering the portal circulation and finally ending up in the liver. The UBG is converted back to bilirubin. A small part of UBG is absorbed by the vv hemorriodhales, entering the systemic circulation and excreted by the kidney.
* The whole degradation process has clinical relevance. The origin of the icterus can be diagnosed measuring degradation products.
191
what are the most important products in hemoglobin degradation ?
* stercobilinogen,
* stercobilin (makes the feces brown)
* urobilinogen (UBG)
192
**1,2,3,4,5,6,7 ?**
**1.** promyelocyte
**2.** normoblast
**3.** macroblast
**4.** haemocytoblast
**5.** acidophyl myelocyte
**6.** erythrocyte
**7.** giant cell
193
what extra organ in mice produces blood cells ?
spleen
194
what type of primordial cells during the embyonic life does not roam to the bone marrow ?
**T-progenitor cell**
| (that settles in the thymus and is responsible for T-lymphocyte production during adult life)
195
what are the factors affecting RBC Synthesis ?
* Oxygen supply
* Kidney status
* Age
196
What are WBC's active in?
Phagocytosis (neutrophils and monocytes), and antibody formation (lymphcytes).
197
where do white blood cells develop ?
* bone marrow
* thymus (only lymphocytes)
198
Leukocytosis can be caused by \_\_\_\_\_\_\_
bacterial, viral and parasitic infections, and also by inflammatory processes.
199
Leukopenia can be caused by \_\_\_\_\_\_\_\_\_
radioactive radiation, mushroom-toxins or some medications
200
White blood cell average absolute number
5-15 × 109 pcs/l
201
what species have neutrophylic type of white blood cell ?
horses, carnivores, (human)
202
what species have lymphocytic type of white blood cell ?
ruminants, swine, birds
203
what is the size of neutrophyls ?
10-14 μm
204
what is the size of eosinophyls ?
12-14 μm
205
what is the size of basophyls ?
8-10 μm
206
what is the size of lymphocytes ?
7-20 μm
207
what is the size of monocytes ?
**15-25 μm**
208
What are the granular leukocytes?
Neutrophils, Eosinophils, Basophils
209
what are the granules of the neutrophil composed of, and what's their function ?
lysosomes that contain the enzymes (lysosyme, myeloperoxidase, superoxide-dismutase, acidic and alkalic phosphatase, nuclease, protease, etc.)
• 80% of the granules is formed by small, neutrophil granules.
• 20% by bigger, asurophil granules.
• Thier role includes perishing and digesting the particles as bacteria, funghi, viruses phagocytated by the cell.
210
which cells are the most important element in the cellular immunity ?
neutrophil granulocytes
211
what is the function of neutrophils ?
**phagocytosis**.
• they don't need a previous meeting with the foreign body for its recognition and elimination, display their effect immediately.
212
what is the life time of neutrophil granulocyte ?
* in circulation: 6-7 hours
* in tissue: 2-3 days
213
where are most of the neutrophil granulocyte found ?
**mostly in the bone marrow, spleen.**
When needed - leukocytosis.
**Few can be found at the circulation
(part adhere to the inner wall of vessels)**
214
where adhesion of white blood cell can be found ?
wall of the capillaries.
(for instance, neutrophil granulocytes can be seen inside of a venule)
215
what an increased number of stab (young) neutrophil granulocytes can indicate ?
infection
216
what an increased number of the polysegmented (mature) neutrophil granulocytes can indicate ?
**granulocytopenia**
(a decrease of peripheral blood granulocytes below lower limit of normal range)
217
what are the Developmental stages of neutrophil granulocytes ?
* **Stab** form (small stick shaped nucleus)
* **Jugend** form (bean shaped nucleus)
* **matured** neutrophil (nucleus with 3-5 segments)
* **over-matured** neutrophil (nucleus
with 5-10 segments)
218
how is the movement of neutrophil granulocytes operated ?
**based on the building up and dissociation of actin chains.**
As a result of the actin polymerisation actin fibers are continuously formed in the cell.
Tightly united actin-bundles gives the bases for migration by the phylopodiums.
This bundle is constantly built on the end closer to the plasma membrane and constantly degraded on the end of the actin chain closer to the nucleus.
219
describe diapedesis (emigration)
**leukocytes squeeze between two capillary endothelial cells into tissue space.**
There are **3 steps**-
* *1.** stretched phylopodium adheres in between two capillary endothelial cells (its selectin recognizes the receptors on this pole of the endothel)
* *2.** motion with the actin-filament: the neutrophil granulocyte (gr.) intrudes in between the two endothelial cells.
* *3.** Enter the interstitial space.
220
which process is demonstrated in the picture ?
endocytosis
221
What is phagocytosis?
uptake of cells and cell-debris
222
describe the endocytosis of the low density lipoprotein
The external part of the LDL-receptor binds an LDL, affected by this, the internal clathrin binding site activates and a clathrin coated pit is formed, that finally ends up with endocytosis and forming of a clathrin coated vesicule
223
What is clathrin?
a complex consisting of three small and three bigger peptides, that is inherited conservatively during evolution
224
**1,2,3,4,5,6,7 - ?**
**1.** ligand
**2.** lysosome
**3.** surface receptor
**4.** cellular membrane
**5.** nucleus
**6.** actin "cortex"
**7.** foreign body (e.g. bacterium)
225
describe the steps of phagocytosis
actin directed border forming.
* ligand binding and actin dependent forming of pseudopodia
* internalisation by the help of actin and other fusogenic proteins
* actin-binding and synthesisof fusogenic proteins
* phagosomesynthesis
* phago-lysosome synthesis
* digestion and residual bodysynthesis
* oxidative "burst" and digestion
226
The last step of phagocytosis is the killing of the pathogenic agent with the help of \_\_\_\_\_\_\_\_\_\_\_
**"respiratory burst"**
* First enzymatic step: NADPH-oxidase.
* Second enzymatic step:SOD.
* Third enzymatic step:MPO (myeloperoxidase).
227
What is opsonization?
**complement factors "flag" the microorganism for phagocytosis.**
They can bind foreign antigens similarly to immunglobulines, then they bind with the neutrophilgranulocytes and significantly stimulate phagocytosis.
228
* **name of the process ?**
* **1,2,3,4 -?**
**opsonization**
**1.** C3b receptor
**2.** C3b complement
**3.** Antigen (e.g. baterial membrane)
**4.** Neutrophil granulocyte
229
* **name of the process ?**
* **1,2,3,4 -?**
**Immune adherence**
**1.** Fc receptor
**2.** antibody (IgG)
* *3.** Antigen
(e. g. bacterial membrane)
**4.** Neutrophil granulocyte.
230
describe the immune adherence process
the specific immunglobulin (e.g. IgG) binds the antigen (e.g. bacterium).
Because of this specific binding, the Fc part of the antibody binds this complex to the Fc receptor of the neutrophil cell. _Results_: increased phagocytosis.
The cell expresses the Fc receptors on the surface again, making additional phagocytosis possible.
231
which white blood cell are the rarest ?
basophil granulocytes
232
What to basophil granules contain?
* histamine
* serotonin
* heparin besides
* _some more enzyme_s: myeloperoxidase, protease, hyaluronidase - specific, etc.)
233
what is the Basophil granulocyte's main function ?
to loosen the tissues where the antigens are present so the other defense elements (cells and molecules) can more easily get to the place of the infection
234
Describe the degranulation process
The basophil granulocytes bind the ready IgE type antibodies on their surface.
Then ,when an antigen binds to the IgE, the basophil cell quickly releases its enzyme-supply to the environment:
degranulation occurs.
The released enzymes loosen the environment and give space to additional immune processes.
235
what extreme degranulation might cause ?
pathological damage in the organism's own tissues like allergy.
236
237
how does the specific way of granulation work ?
There is a big amount of receptor proteins on surface of the basophil granulocytes that can bind the Fc part of the
IgE-type immunglobulins (Fc-receptor).
The IgE (that was produced earlier against another antigen) can still bind to the above mentioned receptor if the IgE did not bound the antigen yet (on the basis of this feature we call the IgE antibody cytophilic.
The basophil cell "equipped" with IgE roams in the interstice.
In case of meeting an antigen, it binds it. The binding itself evokes the vacation of the basophil cell granules (degranulation). The released materials loosen the tissues. The tissue infected by the antigens becomes accessible for the other cells of the immune apparatus. Extreme basophil activity (allergy) can cause pathological tissue destruction.
238
what materials are released during degranulation ?
* histamine
* heparin
* hyaluronidase
239
how does the non-specific way of granulation work ?
**right after the invasion of the antigen degranulation is stimulated by the C3a and C3b complement factors. The receptor specific for these factors is expressed to the surface of the cell again and again**, so called **natural immunity**: these are the complement factors of the plasma.
* Additional products of the degranulation are the heparin (prevents coagulation therefore accelerates the process of the antibodies getting into the interstitium) and the slow-reacting factor of anaphylaxis (SRS-A).
* This latter causes long lasting inflammation
240
241
what is the role of heparin releasing from the basophil granolocyte in the nonspecific way of immune response ?
Heparin helps by preventing coagulation
242
what is the function of the eosinophil granulocytes ?
Antiallergic cells.
The mast cells and the basophil granulocytes produce the substances responsible for allergic reactions (for example histamine), the eosinophil granulocytes play a main role in regulation of the inactivation and enzymatic break-down (histaminase) of these substances, their proportion in the blood increases during allergic processes (eosinophilia)
243
What is eosinophilia?
**higher than normal level of eosinophils**. Eosinophils are a type of disease-fighting white blood cell. This condition most often indicates a parasitic infection, an allergic reaction or cancer.
244
describe the eosinophil granulocyte granules
• Granules: all red
-(in horses cover also the nucleus)
• Enzymes
- histaminase
- aril-sulphatase
- myeloperoxidase
- acidic and alcalic phosphatase
- nuclease
245
what is the lifetime of eosinophil granulocyte ?
* incirculation: 3-8 hours
* in tissues: 3-5 days
246
what are chemotaxis ?
**White blood cells migrate towards higher concentration of specific signals (chemicals).**
• Most important chemicals:
– products of tissue beakdown
– histamine
– complement factors
– broken polysaccharide capsule of bacteria
– chemotaxines produced by white blood cells:
• ECF-A (eosinophil chemotaxis factor for anaphylaxis)
– t-cells
– mast cells
– basophils
247
The eosinophil cell takes
up and breaks down both the ___________ and \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
histamine, SRS-A (slow reacting substance of anaphylaxis)
248
what are the most effective substances against parasites
"alkalic" proteins
249
250
what is the biggest white blood cell ?
monocyte
251
What is the role of monocytes during the antigen-eliminatory processes?
to "present" the antigen to the other cells of the immune system
252
Mononuclear phagocytes Lifetime
* in circulation: 10-40 hours
* in tissues: 2-3 month
253
what are the 2 constituents of the MS (macrophag system) of mononuclear phago ?
**1.** RES: reticulo endothelial system (Mecsnyikov)
**2.** RHS: reticulo histiocyticsystem
- task: antigen presentation, secretion
254
what do the mononuclear phagocytes granules contain ?
**• Enzymes:**
– proteases
– myeloperoxidase
– superoxid dismutase
– acidic and alcalic phosphatase
**• Secreted enzymes:**
– collagenase
– elastase
– angiotensine convertase
255
256
describe the antigen presentation
```
APC cells (eg. macrophages, or B-lymphocytes) manage to express the digested pieces of the phagocytosed antigen together with their own surface proteins (MHC, Main Histocompatibility Complex, II,) to the cell surface.
The adequate receptor of the helper T-lymphocyte (Th) recognizes the piece of the antigen and the MHC-complex. This initiates the immune system and finally leads to antibody production. This occurrence is called the antigen-presentation
```
257
If not only the MHC-I, but the MHC-I plus an antigen complex occurs on the surface of an infected somatic cell, what will happen ?
it will be recognized by the cytotoxic T-lymphocyte receptors and the infected cell will be destroyed
258
what materials do MPS cells secrete ?
**• loosening tissues with enzymes:**
– collagenase
– elastase
– angiotensine convertase
**• Stimulation of immune response:**
– interleukin-1
– interferon
– prostaglandins
259
what sizes of lymphocytes can be found in the blood circulation ?
only small (7-8 μm) and middle (10-12 μm)
260
what are the two groups of lymphocytes ?
(divided by their origin and function)
* The **T-lymphocytes** of a thymus origin are responsible for the cellular immunity.
* The **B-lymphocytes** of the Bursa Fabricii (in mammals instead: it is produced in bone marrow, embryonic liver and spleen) for the humoral immunity.
261
what is the lifetime of lymphocyte ?
from few hours to years
262
what is found on the membrane surface of the lymphocyte ?
- Immunoglobulin-like structures
- receptors
263
what happens to the number of lymphocytes at lymphopaenia ?
their number in the blood decreases
264
what happens to the number of lymphocytes at Lymphocytosis ?
their number in the blood increases
265
what is the type and function of lymphocyte when it has size of 7-8 μm ?
B-lymphocyte.
Its function is to turn to plasma cell and to produce immunoglobulins
266
what is the type and function of lymphocyte when it has size of 10-12 μm ?
T-lymphocyte.
Its function includes take part as cells of the cellular immune response; stimulation of the humoral immune response.
267
what is the type and function of lymphocyte when it has size of 15-20 μm ?
"0" cells
(NK cells)
It's function as lymphocyte-like cells; to kill cells which got infected by tumor or virus.
268
hematopoietic location
red bone marrow
269
what are the multipotent pre-colony-forming-cells ?
developed during the embryonic life are able to reproduce and develop in any direction (red blood cell production, white blood cell production)
270
what is the only one type of cells that during the embryonic life, does not migrate to the bone marrow ?
the T-progenitor cell, that settles in the thymus and is responsible for T-lymphocyte production during adult life
271
What is the role of CSF ?
secreted glycoproteins that bind to receptor proteins on the surfaces of hematopoietic-multipotent-primordial cell- stem cells.
272
Thrombocytes (platelets) size
* mammals: 1.5 -3.5 μm.
* birds: 8-10 μm, with nucleus, able to phagocyte
273
what is the number of Thrombocytes (platelets) in blood ?
2-8×1011 pc/l
274
what is the lifetime of Thrombocytes (platelets) ?
5-10 days
275
Where thrombocytes are found?
mainly in the circulation
276
what are the smallest blood cells ?
thrombocytes (platelets)
277
where are thrombocytes originated from ?
the polycaryocyte giant cells of the red marrow
278
279
**CP ?**
**P ?**
**CP.** Cytoplasmatic Processes.
**P.** Platelets
280
what are the blood groups ?
complex antigens (containing proteins, lipids and carbohydrates) appearing on the surface of the blood cells.
• Their appearance is ensured by a known genetic code.
281
The blood-type system is a group of antigens encoded on ______ locus
the same
282
how many groups are in human blood ?
15
283
when are antibodies produced ?
postnatally
284
why the blood transfusion means less trouble in animals than in humans ?
**1.** There are only few naturally produced antibodies against red blood cell antigens.
**2.** The antigens -against which antibodies can be found in other individuals -can be found not only on the red blood cells, but in the plasma too.
285
what happens to the antibody in case of transfusion ?
neutralized in the plasma already and its RBC-dissolving capacity diminishes
286
who was the American Physiologist that has found first the blood types (AB0) in 1930 ?
Karl Landsteiner
287
what are hemagglutinogens ?
compounds on the surface of the RBC-s forming the antigens.
Their appearance is determined by genes located on different chromosomes.
288
289
what are hemagglutinins?
any **of a group of antibodies that cause agglutination of the foreign red blood cells.**
These substances are found in plants, invertebrates, and certain microorganisms.
The result of these processes is that in the blood plasma of an individual many antibodies may occur that are directed against blood group antigens in another individual.
290
what are natural hemagglutinins ?
- antibodies are present without pervious immunization
- agglutinate the red blood cells of animals expressing the corresponding antigens
- as an example, human anti-A and anti-B isohemagglutinin (previously alpha and beta) agglutinate red blood cells with A an B antigens, respectively.
291
what are artificial hemagglutinins ?
**– antibodies form only after previous immunization.**
**– immunization can be:**
* _natural_(e.g.: Rh or certain animal blood types)
* _artificial_(e.g.: preparation of specific blood group reagents by immunization)
292
what are the isohemagglutinins ?
antibodies that agglutinates RBC-s of the same species
293
what are the 2 reactions between the RBCs and the plasma antibodies ?
**1. Agglutination**
**2. Hemolysis** (the disruption of RBC-s)
These reaction can occur together or alone.
294
what reaction is more typical in human blood: Agglutination or Hemolysis ?
Agglutination
295
what reaction is more typical in animal blood: Agglutination or Hemolysis ?
Hemolysis
296
297
exaplain biochemical polymorphism
many biochemical functions are carried out by structurally different, but functionally equivalent molecules.
Blood groups are one of these biochemical polymorphisms
298
cattle transferrin polymorphism
six types of serums separated on agarose gel, belonging to cows of different genotypes transferrin.
299
why the description of human blood group antigens is important ?
understanding the basic mechanisms and its importance in general orientation.
300
what are the two most important system in human blood group ?
AB0 and Rh
301
name some known human blood types
- AB0(+)
- Rh(+)
- MNSsrarely
- P no
- Lutheran(+)
- Kell(+)
- Duffy(+)
- Kidd(+)
(+: it can develop incompatibility)
302
The H-antigen encoded by the H-gene forms the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
AB0 blood system
303
If there are no additional groups synthesized (A or B), which group is the default group ?
0 group
304
why there are no antibodies that formed against all types of the AB0 blood system ?
it is present in all humans - the genotypes are HH, HA, AA, HB, BB, AB
305
which blood group does the **N-acetyl-galactose-amine transferase** enzyme form ?
**A blood group antigen**
306
which blood group does the 0-(zero)-gene form, if it is responsible to suppress the production of N-acetyl-galactose-amine transferase and of the N-acetyl-galactosyl transferase enzymes ?
0-group appears.
Accordingly no A or B blood group is formed.
307
which blood group does the **galactosyl-transferase enzyme** form ?
**B blood type antigen**
308
309
how can we determine the type of a red blood cell belonging to an unknown blood group ?
by agglutination reaction.
**In case of incompatibility agglutination is seen**, that can be used for determination of the blood cells' antigen-type.
310
311
how is the first fetus able to survive the delivery if an Rh negative mother can be immunized by the blood cells of her own Rh positive foetus ?
because (No antibody can be found naturally in the serum against this RBC-antigen)
And yet no damage occurs because the foetal RBC usually gets into the mother's body only via micro-injuries during the delivery - which means it had no exposure to the mother's blood.
312
why at 2nd pregnancy erythroblastosis foetalis occurs followed by last stage of death ?
During second pregnancy the small amount of RBC entering the mother's sensitized immune system, stimulates the production of anti-Rh (IgG!!!) antibodies that (by getting back to the foetus after penetrating the placenta) dissolve the foetal red blood cells and a clinical pattern called erythroblastosis foetalis occurs causing yellow jaundice and in its last stage the death of the foetus (morbus hemolyticus neonatorum).
313
314
how does Rh-incompatibility happen ?
when an Rh negative recipient gets red blood cells from a Rh positive donor.
The Rh-negative recipient is immunized and the forming IgG antibody dissolves the red blood cells of the recipient.
315
which inappropriate blood transfusion can cause significant damage: the first or the second ?
second.
That time there is a significant anti-Rh antibody production
316
what human blood type is the most common for europids ?
type 0
317
what human blood type is the most common for negrid ?
type 0
318
what human blood type is the most common for mongoloid ?
type A
319
Which human blood type is the rarest on the planet ?
type AB
320
how the animal blood group systems significantly differ from those of the human ones ?
**1.** In most cases there are no naturally formed antibodies against the RBC-antigens of other individuals.
**2.** In many cases the blood type antigens appear in the plasma, too.
**3.** Most of the time the artificially formed antibody has an hemolysing and not an agglutinating character.
321
how to produce an antibody that only reacts with the C-blood type antigen when we have no specific antigen against the single C-group ?
- we immunize the animal no.2 with the no.1's washed red blood cells (A, B, C antigens)
- in animal no. 2 only anti-B and C is produced (polyvalent serum)
- washing it with B RBC-s: we remove anti-B
- The remaining is the monovalent anti-C serum
322
323
describe the twin hood in cattle
the monozygotic twins having the same sex (MZ, one sperm -one ovum). They are the most suitable for comparative examinations.
Unfortunately, twin births are quite rare (3%)
324
what is chimeras ?
**organisms with a mixture of genetically different cells.**
Dizygotes that the hemopoietic progenitor cell migrates from one fetus to the other before an immune response could occur against it and starts producing the red blood cells with the antigen structure similar to the original individual. This way, there would be red (and white) blood cells present in both twins with their own and the other one's antigen structure too. These individuals are called chimeras
325
What is freemartinism?
**male and female co-twins develop; antimullerian hormone from male is shared to female and causes mullerian ducts to regress in female leading to sterility.**
Besides the typical XX female chromosome, white blood cells in those females of freemartin chimer, XY type chromosomes can be detected as a sure proof of later sterility
326
explain the The pleiotropic effect
one quality affects more different qualities, they are inherited together.
327
what is the goal of the blood-transfusion ?
substitution of the lost RBC-s and assuring normal gas-transport.
328
how can Blood transfusion be applied in large animals?
**because of the lack of naturally occurring antibodies -theoretically blood can be transfused without consideration.**
In clinical practice (for example in a horse) we previously _transfuse a small proportion_ (2-300 ml) of the total blood amount to be transfused (2-3 l). _If there is no sign of incompatibility reaction, the whole amount will be transfused._
329
how can Blood transfusion be applied in small animals?
**because some antibodies may occur in case of certain blood types** –
_the three-drop-test must always be completed: the mixture of 1 drop of donor blood cells, 1 drop of recipient's plasma, 1 drop of physiological sodium-chloride solution._
## Footnote
**If there is no hemolysis or agglutination, the transfusion can be completed without the complete knowledge about the blood groups.**
330
can cat recieve blood donation from a dog donor ?
**yes, as a life-saving act –blood of a donor dog can be transfused.**
This is however not anymore used, since blood typing kits are available for small animals.
331
Dog blood can be given to dogs only by
completing cross reaction tests
332
Dog blood can be given to cats only in
case of emergency without testing
333
Cat blood can be given to cats only by
completing cross reaction tests
334
describe the hemolytic illnesses of the newborn in horses
**– Rh-like antigens
– problem formed only postnatally**
– epitheliochorial placenta
– immunglobulins absorbed from the colostrum
(first 36 hours)
**– symptoms:**
• hemolysis
• neonatal jaundice
**– solution:**
• giving the newborn into nursing
335
describe the hemolytic illnesses of the newborn in swines
**– Rh-like antigens, postnatal problem**
**– Su antigen might cause incompatibility**
– epitheliochorial placenta
– immunglobulins absorbed from the colostrum
**symptoms:**
• hemolysis
• neonatal jaundice
**solution:**
• giving the newborn into nursing
336
What is hemostasis?
Hemostasis is a complex defense reaction that prevents the loss of blood in case of internal (intrinsic) or external (extrinsic) vessel injury.
337
how does hemostasis work ?
The hemostasis starts with a vascular reaction later the aggregation of platelets (thrombocytes) forms the first mechanical barrier preventing any further blood loss (white thrombus). In the meantime the other hemostatic processes start (coagulation). During this the stronger, red blood cells containing red thrombus -kept together by the fibrin fibres -is forming. Together with the regeneration process of the endothelial tissue, the thrombus is eliminated. This is followed by complete healing.
338
how often do capillary injuries occur in a physiological environment ?
everyday, due to everyday mechanical activities.
339
how does the hemostasic system maintain balance between lack of coagulation and over-reaction ?
**the intrinsic way of the hemostasis is constantly working together with a self-inhibiting mechanism.**
This balance makes sure that the aggressive coagulation mechanism does not lead to pathological clot-formation. The lack of coagulation (hemophylia) or its over-reaction (thrombus/clot-formation) are frequent pathological processes.
340
what are the most common bleeding that the veterenarian meets ?
external bleedings or internal bleedings caused by injuries.
341
where do the physiological micro-injuries occur ?
in all tissues, constantly.
342
what is the importance of hemostasis ?
capability of immediate reparation of physiological bleedings.
343
344
what are the symptoms of hemostasis imbalance caused by decreased local healing ?
hemophilia, bleeding sickness
345
what are the symptoms of hemostasis imbalance caused by mechanistic pathologically increased clot forming ?
thrombosis, pathological clot forming
346
what are the symptoms of hemostasis imbalance caused by pathologically decreased clot removal ?
thrombosis, pathological clot forming
347
what are the symptoms of hemostasis imbalance caused by damaged local healing ?
haemophilia, bleeding sickness (rare form, infection)
348
what happens in the vascular reaction ?
| (hemostasis)
**vessel contraction.**
The vascular reaction occurs right after the injury of the vessel. It is an automatic process
– The direct consequence of the injury of the smooth muscle cells is that the membrane potentials of the injured cells will be different from that of the surrounding cells.
The potential-differences arising this way cause the contraction of the surrounding smooth muscle cells.
– The reflex contraction, caused by CNS-activation also occurs.
– These can be completed with the effects of the humoral vasoconstrictor substances released from the injured cells.
349
what is the function of the vascular reaction ?
| (hemostasis)
Mechanical defense as the first line of defense, and decrease the perfusion - so that thrombocytes can stick to the injured surface more easily.
Provides an optimal condition for the accumulation (aggregation) of platelet for several minutes
(the basis of further reactions)
350
how long does the vascular reaction last ?
(hemostasis)
6-10 minutes
351
Platelets (thrombocytes) do not attract to intact endothelial surfaces.
So how can they bind to the injured endothelial areas ?
**they bind with their specialized surface receptors to the negative charges of the injured endothelial areas** (so called adhesive glycoproteins).
We call this **primary aggregation.**
• Also, the protein produced by the endothelial cells and present in the plasma (the so called von Willebrand factor) is activated by the exposed sub-endothelial proteins (especially collagen). The activated von Willebrand factor connects the injured surface with the thrombocytes, so their aggregation increases.
352
main characters of secondary activation in thrombocyte reaction
* the earlier introduced actin and microtubule system of the thrombocytes as well as their secrations activate the reaction.
* A huge number of filopodia are formed, with their help the platelets bind to each other and to the exposed collagen fibres: the white thrombus is formed.
* From the numerous factors responsible for secondary activation, the vascular endothel produces prostacyclines (PGI2) and nitrogen monoxyde (NO), which prevent the production of the factors responsible for aggregation (e.g. thromboxane A2
(TXA2).
353
In the presence of intima injury this inhibition is automatically turned off,
what stimulating factors can thrombocytes produce on their own then?
TXA2, serotonine, adenosine-diphosphates
(will stimulate other thrombocytes increasing the aggregation and the secretion of coagulation factors)
354
what happens in Primary activation of thrombocyte reaction ?
the platelet binds to the exposed collagen
355
what factor increases the primary activation ?
von Willebrand
356
when the thrombocytes bind together, what do they secrete ?
coagulation factors
357
what 2 compounds production stops during Thrombocyte reaction?
PGI2 and NO
358
what does Thrombocyte release ?
* 5-HT (serotonin)
* ADP
* PF-3
* TXA
* coagulation factors
359
Thrombocyte accumulation and aggregation lead to secreating \_\_\_\_\_\_\_\_\_\_\_\_\_
white thrombus
360
361
362
what is the most important enzyme of the cuagulation but at the same time of the anticoagulation too ?
thrombin
363
364
what are the factors which are found in extrisnic way of coagulation only ?
* factor III, thromboplastin, or thromokinase)
* VII (proconvertin)
* VIIa (convertin)
365
366
what causes hemophilia A ?
Factor VIII deficiency
367
what causes hemophilia B ?
Factor IX deficiency
368
what are the 3 mechanisms that stop the blood coagulation ?
**1. Anticoagulation:** the untouched endothelial cells bind the thrombin. The thrombin activates a plasma protein, the protein-C with the help of calcium. The active protein-C directly prevents the activation of the key enzymes of both the intrinsic and extrinsic activation complex (factors V and VIII)
**2. Fibrinolysis:** the thrombin stimulates the activation of an inactive plasma protease, the plasminogen. The forming plasmin is one of the most effective proteolytic enzyme that dissolves the fibrin-net. (The plasmin is so effective that its over-reaction could cause damage also to the surrounding tissues. The activating antiplasmin has an opposite effect.)
**3. Thrombolysis:** together with the loosening of the clot, the phagocytosis starting from the inside also decreases the size of the thrombus. The increasing perfusion plays a role in the demolition of the thrombus, too.
369
370
Coagulation factor I
**fibrinogen**
elementary substance of the stable fibrin net
371
Coagulation factor II
**Prothrombin**
central enzyme: clot forming and elimination
372
Coagulation factor III
**tissue factor (thromboplastin)**
initiator of the extrinsic way
373
Coagulation factor IV
**Calcium ion**
fixes and activated the member of the cascade
374
Coagulation factor V
**Proaccelerin**
a member of the central activator complex
375
Coagulation factor VII
**Proconvertin**
initiator of the extrinsic way
376
Coagulation factor VIII
**Antihaemophilic factor-A**
a member of the intrinsic activator complex
377
Coagulation factor IX
**Christmas factor** (antih.-B)
member of the intrinsic way
378
Coagulation factor X
**Stuart-Prower factor**
integrator of the intrinsic and extrinsic ways
379
Coagulation factor XI
**Plasma thromboplastin antecedent**
secondary initiator of the intrinsic way
380
Coagulation factor XII
**Hageman factor (contact factor)**
primary activator of the intrinsic way
381
Coagulation factor XIII
**Lóránd-Laki, fibrin stabilizing factor**
forms a fibrin-polymer from monomers
382
Kininogen
activator of factor XII and kallikrein
383
Kallikrein
activator of factor XII
384
Vitamin K function
The reduced vitamin K in the liver forms a coenzyme of the carboxylation of the glutamic acid.
Needed for proper function of clotting factors II, VII, IX, and X and proteins C and S (K is for Koagulation).
385
Dicumarol
competitive inhibitor of Vitamin K epoxide reductase used as an anticoagulant
386
what is antigen ?
a substance that evokes an immune response or tolerance. They are identified as non-self entities.
387
What is a hapten?
small molecular weight antigen , which can not induce immune reaction itself, but specifically recognized by immunoglobulins
388
What is the epitope?
The part of an antigen molecule to which an antibody attaches itself.
Antigen determinant, well circumscribed region of the antigen molecule that evokes immune response
389
What is a xenoantigen?
antigen that is found in more than one species
390
What is a alloantigen?
antigen, present in only some individuals of a species
391
What is an autoantigen?
Any of an organism's own antigens (self-antigens)
392
MHC
**Major Histocompatibility Complex.**
alloantigens on the cell surfaces, glucoproteins.
_Function_: binds peptide fragments and display them on the cell surface for recognition by the appropriate T cells.
393
PRR
**Pattern Recognition Receptors.**
these receptors are found on macrophages, dendritic cells, and they recognize the Pathogen-Associated Molecular Pattern (PAMP)
394
PAMP
**Pathogen Associated Molecular Pattern.**
(bacterial LPS, viral capsid, viral RNA, etc.),
induces activation of innate immunity.
395
396
397
where the blood cells are produced in embryo ?
yolk sac, later in the foetal liver and spleen
398
where the blood cells are produced at 4-5 months of gestation?
bone marrow gradually, becomes the principle site of all blood cells production
399
where the blood cells are produced after birth?
all blood cells are produced in the bone marrow
400
what is the progenitor cell of all blood cells which produced in the bone marrow ?
Hematopoietic stem cells
401
402
what cell type mature in the thymus ?
T cells
(which will go back into circulation when mature)
403
A lymph node consists of
• outer connective tissue capsule.
• trabeculae.
meshwork of reticular fibres.
* cortex
* medulla
• paracortex
(deep cortex)
404
what does the cortex of lymph nodes contain mostly ?
B-lymphocytes
405
what does the paracortex of lymph nodes contain mostly ?
* T-lymphoctyes
* dendritic cells
```
• HEV = High
Endothelial Venules (special post capillary venules)
```
406
what is the function of HEVs ?
enables lymphocytes to directly enter a lymph node from the blood by crossing through the HEV
407
what does the medulla of lymph nodes contain mostly ?
immunglobulin secreting plasma cells
408
where is the spleen located ?
**left side of the abdomen**
(left upper quadrant)
409
what is the function of red pulp ?
destroy old red blood cells
410
what 2 main tissues does the spleen contain ?
white pulp and red pulp.
411
what is the function of white pulp ?
**Immune function of the spleen.**
composed of lymphocytes and lymphoid nodules.
412
what does MALT stand for ?
Mucosa-Associated Lymphoid Tissue
413
what is MALT main function ?
protect mucosal surfaces: IgA production
414
what are the components of Components of MALT ?
• GALT
Gut-Associated Lymphoid Tissue
• BALT
Bronchus-Associated Lymphoid Tissue
• NALT
Nasal-Associated Lymphoid Tissue
• CALT
Conjunctival-Associated Lymphoid Tissue
415
Where are the Peyer's patches located?
mainly in the mucous membrane of **jejunum** and **ileum**.
• a component of **GALT**.
416
Waldeyer's ring
* composed of the pharyngeal, tubal, palatine, and lingual tonsils.
* first line defense in the respiratory infections.
417
vermiform appendix
worm-like projection of lymphatic tissue hanging off the cecum with no digestive function; may help to resist infection
418
what are the 2 components/types of the immune system ?
Natural (inborn, innate) and Acquired (specific, adaptive)
419
describe the natural (inborn, innate) immune system
* older evolutionary defense
* recognizes microbial components
* can react immediately
* it mediates the initial protection against invaders (first line of defense)
* has no memory
420
describe the acquired (specific, adaptive) immune system
* it requires innate immunity
* it is antigen specific response
* it reacts later, after the innate immune response (there is a latency period)
* it has immunological memory
421
which immune system acts as the first line of defense ?
Natural (inborn, innate) immune system
422
423
the machrophages in the liver are called
Kupffer cells
424
the machrophages in the connective tissu are called
histiocytes
425
the machrophages in the bone are called
osteoclasts
426
the machrophages in the brain are called
mikroglia
427
what are the functions of macrophages in the innate immune system?
* *A.** **Phagocytosis: internalisation and elimination (ingestion)
1. ** recognition of pathogen by receptor - PAMP+PRR or opsonisation of an antigen: binding of an antibody/complement factor to an antigen.
* *2.** endocytosis.
* *3.** phagolysosome.
* *4.** intracellular destruction of the structure.
**B.** **antigen presentation.**
**C.** **recognition of tumor cells, inflammation.**
428
How can the innate immune system recognizes the PAMP structures?
through receptors: Pattern Recognition Receptors (PRRs),
for instance: Toll Like Receptors (TLR)
429
what is the role of neutrophil granulocytes in the innate immune system ?
important in the defense against bacteria
430
what is the role of eosinophil granulocytes in the innate immune system ?
important in the defense against parasites play a role in allergic reactions
431
what is the role of basophil granulocytes in the innate immune system ?
inflammation
432
what content do mast cell release during degranulation in innate immune system ?
* **histamine** - local vascular dilatation, Permeability of vascular wall is increased.
* **chemotactic factors** - migration of granulocytes to the inflammatory site.
* **heparin** - bloodcoagulation.
* **TNFα (Tumour Necrosis Factor alpha)** - an inflammatory cytokine produced by macrophages/monocytes during acute inflammation.
433
what is the importance of dentritic cell in the immune system ?
Dendritic cells build a bridge between the adaptive and innate immune system.
These cells are APCs.
434
What are natural killer cells?
Lymphocytes, part of the innate immune system, that attack foreign cells, cancer cells, and normal cells infected with viruses, by exocytosis of granules that causes target cell lysis.
435
how can Natural Killer (NK) cells differentiate between an healthy cell and a tumor cell ?
healthy cell has a normal amount of MHC I, while tumor cell has a reduced number of MHC I
436
what are the main molecular components of the innate immune system ?
• proteins in the blood and tissue fluids, mainly inactive enzymes - 1 activated enzyme is able to activate more than 1 inactive enzyme (mainly produced by the liver)
437
What are the 3 pathways of the complement system?
• **alternative pathway:** previously unknown antigen appears in the body as a trigger (pathogens with fewer amount of sialic acid in their membrane).
- most of the Gram negative bacteria.
- a few Gram positive bacteria.
- Ig-antigen complexes.
- viruses, parasites, etc.
* **classic pathway:** an immuncomplex activate this pathway.
* **MBL (Mannose Binding Lectin)**-activated pathway.
438
what is an immuncomplex ?
a molecule formed from the binding of 1 antigen to multiple antibodies or 1 antibody to multiple antigens
439
440
what are the functions of the complement system ?
• **membrane attack complex**
_transmembrane channel_:
disrupts the cell membrane of target cells.
* **opsonization:** C3b fragments coat the pathogen → enhance phagocytosis.
* **facilitate inflammation**
- activation of mast cells and basophil granulocytes.
- chemotaxis (neutrophil granulocytes).
441
what is the the primary organ for B-lymphocyte development in mammals ?
bone marrow
| (and foetal liver)
442
what is the the primary organ for B-lymphocyte development in birds?
Bursa Fabricii
443
during maturation, the B-cells are transformed into
plasma cells
| (which takes part in the humoral immune response)
444
during B cells maturation, what happens at antigen-independent development phase ?
immunocompetent B cells expressing antigen-specific membrane **IgM** (and **IgD**) are generated in the bone marrow
445
during B cells maturation, what happens at antigen-dependent development phase ?
Antigen-induced activation of B cells leads to **plasma cells** or **memory cells** in the **secondary lymphoid** **organs**
446
when do T cell get matured ?
only after the cells react against antigens but they do not react against self antigens.
447
T cells recognize only
antigens that are displayed on cell surfaces with MHC
448
describe the T-lymphocytes maturation
**in Bone marrow**: as hematopoietic
stem cells **→** T-cell precursors **→** **in thymus**: T-cell precursors **→** mature Tlympocytes
449
what are the positive and negative selections in the thymus ?
selection in which **T cells** must go through **both**:
positive and negative selection in the thymus.
**Positive selection**: all cells surviving this step are able to recognize at least one of our own MHC molecules.
**Negative selection**: cells that have very strong and continuous binding, will be eliminated.
450
What types of T lymphocytes are there?
• **Cytotoxic T cells.**
detect antigens when they are presented on a cell surface together with MHC I → kill virally infected cells / kill tumor cells → similar to NK cells, however _they are not antigen specific_ (!)
• **T helper cells.**
cytokine production → activation, maturation of other immune cells
• **Regulatory T cells.**
suppression of both the adaptive and innate immune response.
451
MHC genes („Major Histocompatibility Complex") code proteins, which behave as antigens only during \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
incompatible organ transplantation
452
what is MHC main function ?
bind and present peptides derived from an exogenous/endogenous.
453
what are the types of MHC - name, localiztion and main function ?
**• MHC I**
**localization:**
present on the surface of each nucleated cells.
**main function:**
present peptides derived from endogenous protein antigens.
**• MHC II**
**localization:**
present on the surface of Antigen Presenting Cells
(macrophages, dendritic cells)
**main function:**
present peptides derived from exogenous protein antigens.
454
what is immunglobulin ?
```
An antibody (AB), also known as an immunoglobulin (Ig),
is a large Y-shape protein produced by plasma cells that is used by the immune system to identify and neutralize pathogens such as bacteria and viruses. The antibody recognizes a unique molecule of the harmful agent, called an antigen
```
455
what are the two functions of Immunglobulins?
* membrane-bound immunglobulins → **antigen recognition.**
* Immunglobulins secreted by plasma cells → **humoral immunity.**
456
457
458
Fab stands for
Fragment Antigen Binding site
459
Fc
responsible for effector function
(part of the antibody which can bind to the Fc receptor of Neutrophil granulocyte)
460
how many amino acids there are in the domains, that both heavy and light chains are consist of ?
110 amino acids
461
describe the isotypes of the Ig classes
* found in all individuals of a given species.
* Determined by constant regions.
* IgG, IgM, IgA, IgD, IgE
462
describe allotypes
an immunoglobulin variation that can be found among antibody classes.
• Determined Y hypervariable regions
463
describe idiotypes
changes within the same antibody class, in the same individual, dertermined at the variable region.
464
IgA
**mucosal immunity.**
[in tears, saliva, etc.]
* dimer
* a secretory component protect against enzimes.
465
IgM
the first antibodies to be produced in a humoral immune response are always IgM.
* remain in the circulation
* pentamer (5 monomers)
• in case of ABO incompatibility - the huge size of the molecules blocks the transplacental transfer of
IgM → IgG can transfer → Rh incompatibility
466
IgG
* In blood mainly this class
* Antibacterial, antiviral effect, Rh blood group system.
* Produced during the secondary immune response
* Opsonization (enhance phagocytosis)
* monomer transfer through the placenta (Rh incompatibility)
467
IgE
* allergy
* defense against parasites
468
how many different immunglobulins are produced in the body ?~ 10^9
~ 10^9
469
The body produces antibodies against \_\_\_\_\_\_\_\_\_\_\_\_
all possible antigens
470
gene encodine for each and every possible Ig in the genom is impossible in terms of space, what is the solution ?
gene rearrangament → the immunglobulin repertoire
uses only a limited number of genes
471
describe the gene rearrangament
Gene segments, which encode the variable domins, are located far away from each other.
* *1.** Double strand breaks in the DNA.
* *2.** addition/deletion of nucleotids at the ends.
* *3.** rearrangement (Genes locating far away from each other will be close to each other during recombination)
• The gene segments join each other randomly resulting in almost unlimited number of variable regions capable for recognizing millons of different possible antigens produced.
472
describe the mechanism of Cytotoxic T cells Cellulare immune response
Th (helper) cells → cytokine → Tc activation, proliferation → Tc recognize the antigen → exocytosis of Tc granules → apoptosis of the target cell
473
describe the humoral immune response
Mature B lymphocytes are developed: each of them are specific for 1 given epitope → contact with antigen → Activation, proliferation and differentation of B lymphocytes → Developing of plasma cells/memory cells → immunglobulins
474
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