B&L Unit 1 Flashcards

(331 cards)

1
Q

What is the equation for hematocrit?

A

length of RBC layer/ (RBVs + buffy coat + plasma)

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2
Q

The biconcave disc shape of RBCs increases surface area to volume ratio by _________% compared to a sphere

A

40

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3
Q

RBCs are _________% wider than capillaries

A

25

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4
Q

Hematopoiesis is the formation of _________

A

Blood cellular components

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5
Q

Erythropoiesis is the formation of _________

A

RBCs

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6
Q

Hemolysis is _________

A

Rupturing of RBCs and release of their contents

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7
Q

Hemostasis is _________

A

Stopping of bleeding

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8
Q

1 _________ can make _________ platelets

A

Megakaryocyte 5000

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9
Q

Acute leukemia cells are _________ compared to chronic leukemia cells

A

Immature

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10
Q

_________ proteins on the cell surface are expressed by cells of the innate immune system to identify pathogen-associated molecular patterns

A

Pattern-recognition receptor (PRR)

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11
Q

Pattern-recognition receptor proteins on the cell surface are expressed by cells of the _________

A

Innate immune system

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12
Q

_________ are foreign molecular structures on pathogens (bacterial cell wall protein, bacterial dsRNA) that are recognized by PRRs in the innate immune system

A

Pathogen-associated molecular pattern (PAMP)

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13
Q

_________ of the innate immune system recognize _________ of pathogens

A

PRRs PAMPs

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14
Q

Toll-like receptors are a type of _________

A

Pattern-recognition receptor

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15
Q

A PAMP-stimulated cell releases _________ and _________

A

cytokines chemokines

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16
Q

Chemokines are _________ to phagocytotic WBCs

A

chemotactic

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17
Q

Cytokines are secreted by what type of cell?

A

Immune cells

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18
Q

Cytokines can be classified as _________, _________, or _________ (types of macromolecules)

A

Proteins Peptides Glycoproteins

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19
Q

Ig_________ is passed mother to fetus

A

G

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20
Q

IgG is a _________-mer

A

di

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21
Q

Ig_________ and _________ activate complement

A

G M

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22
Q

_________ is the first antibody to appear after exposure to a new antigen

A

IgM

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23
Q

Ig_________ is expressed on B cell membranes as their antigen receptor

A

D

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24
Q

Ig_________ is secretory

A

A

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25
Ig\_\_\_\_\_\_\_\_\_ attaches to mast cells and makes them release prostaglandins, leukotrienes, cytokines, and release granules
E
26
Ig\_\_\_\_\_\_\_\_\_ is involved in parasite resistance
E
27
Type I immunopathology is also known as \_\_\_\_\_\_\_\_\_
Immediate hypersensitivity (like allergies)
28
Immediate hypersensitivity is also known as \_\_\_\_\_\_\_\_\_
Type I immunopathology
29
Type II immunopathology is also known as \_\_\_\_\_\_\_\_\_
Autoimmunity
30
Autoimmunity is also known as \_\_\_\_\_\_\_\_\_
Type II immunopathology
31
Type III immunopathology is when antibodies are made against \_\_\_\_\_\_\_\_\_
Soluble antigens
32
Type IV immunopathology is \_\_\_\_\_\_\_\_\_-mediated
T-cell
33
The Wright-GIemsa stain stains _________ components in cells
Acidic
34
Eosin stains _________ components a _________ color
Basic Orange-red (hemoglobin and some granules)
35
Methylene blue will stain _________ components a _________ color
Acidic Purple-blue (DNA, RNA, basophil granules, cytoplasm of mature lymphocytes and monocytes)
36
3 white blood cell blood measurements we care about
WBC count WBC differential Absolute count = total and differential
37
\_\_\_\_\_\_\_\_\_ is the most common WBC in children up to 8
Lymphocyte
38
\_\_\_\_\_\_\_\_\_ become macrophages once they enter tissues
Monocytes
39
\_\_\_\_\_\_\_\_\_ and _________ are the granulocytes involved in allergies
Eosinophils (mediate) Basophils (central role)
40
\_\_\_\_\_\_\_\_\_ are the granulocytes that deal with bacterial infections
Neutrophils
41
\_\_\_\_\_\_\_\_\_ are immature RBCs (before they lose RNA and ribosomes and stuff)
Reticulocytes
42
The range for the platelet count is \_\_\_\_\_\_\_\_\_
150,000 - 400,000/uL
43
What is the difference between plasma and serum?
Serum is the clear part of the blood after clotting. Plasma is unclotted.
44
In the fetal stage, blood cells are produced by the _________ and \_\_\_\_\_\_\_\_\_
Liver Spleen
45
Myeloid means \_\_\_\_\_\_\_\_\_
Bone marrow
46
The pluripotent cells of the bone marrow are _________ and the multipotent cells are the \_\_\_\_\_\_\_\_\_
CFU-LM (LM = lymphoid/myeloid) CFU-GEMM (GEMM = granulocyte/erythroid/monocyte/megakaryocyte)
47
\_\_\_\_\_\_\_\_\_% of nucleated cells in bone marrow are stem cells/progenitors and \_\_\_\_\_\_\_\_\_% of these are pluripotetent
1 1
48
7 hematopoietic growth factors (HGFs)
Erythropoietin (Epo) -\> erythropoeisis Thrombopoietin -\> megakaryopoiesis Interleukin-3 (IL3) -\> eosiophils Interleukin-5 (IL5) -\> basophils Granulocyte colony-stimulating factor (G-CSF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Macrophage colony-stimulating factor (M-CSF)
49
What type of macromolecule are hematopoeietic growth factors?
Glycoproteins
50
5 types of cells that produce hematopoeietic growth factors
Activated T and B-lymphocytes Macrophages Fibroblasts Endothelial cells
51
The last neutrophilic precursor with the ability to divide is the \_\_\_\_\_\_\_\_\_
Myelocyte
52
M:E ratio and normal stuff
Myeloid : erythroid ratio from bone marrow biopsy. Should be about 3:1.
53
What is allostery?
When one hemoglobin binds to oxygen, there is a change in configuration that increases binding affinity.
54
What is positive cooperativity?
Substrate binding increases binding affinity for addtional substrate
55
Hemoglobin is _________ in the taut state and _________ in the relaxed state
Deoxygenated Oxygenated
56
The Bohr effect is when a low pH _________ oxygen affinity for hemoglobin and a high pH _________ oxygen affinity and curve shifts to the \_\_\_\_\_\_\_\_\_
Decreases -\> unloading b/c more CO2 Increases Right
57
Higher temperatures _________ oxygen affinity for hemoglobin and lower temperatures _________ oxygen affinity and the curve shifts to the \_\_\_\_\_\_\_\_\_
Decreases b/c exercise raises temps Increases Right
58
Hemoglobin is a \_\_\_\_\_\_\_\_\_-mer and myoglobin is a \_\_\_\_\_\_\_\_\_-mer
tetra mono
59
Alpha hemoglobin genes are on chromosome _________ and there are _________ copies from each parent. Beta hemoglobin genes are on chromosome _________ and there are _________ copies from each parent
16 2 11 1
60
The fetal hemaglobin tetramer is \_\_\_\_\_\_\_\_\_
a2y2
61
Hemaglobin F binds _________ poorly
2,3-BPG
62
The _________ effect is increased in fetal hemaglobin
Bohr
63
Methemoglobin forms when \_\_\_\_\_\_\_\_\_
iron is reduced from its 2+ state to its 3+ state, which doesn't bind oxygen Curve shifts left
64
In methoglobinemia, the patient looks _________ , arterial O2 pressure is _________ , blood is _________ color, and _________ with O2 exposure
Cyanotic Normal Red/chocolate/brown/blue Doesn't change
65
\_\_\_\_\_\_\_\_\_ can be givin via IV to reduce methemoglobin via the _________ pathway
Methylene blue NADPH-dependent
66
Deoxyhemoglobin absorbs at _________ nm and oxyhemoglobin absorbs at _________ mm
660 940
67
\_\_\_\_\_\_\_\_\_ form the buffy coat
Leukocytes
68
Dendritic cells connect the _________ and _________ immune responses
Innate Adaptive
69
The neutropil has _________ granules, the eosinophil has _________ granules, an the basophil has _________ granules (color)
colorless - neutral red - eosin blue - basic
70
The central lymphoid organs are the _________ and \_\_\_\_\_\_\_\_\_
Bone marrow Thymus
71
The peripheral lymphoid organs are the _________ , _________ , and \_\_\_\_\_\_\_\_\_
Lymph nodes Spleen Peyer's patch
72
Lymphocytes interact with endothelial cells lining certain _________ in peripheral lymphoid tissues that are _________ (shape)
Postcapillary venules High and cuboidal
73
What is an immunogen?
An antigen in a form that can give rise to an immune response (can immunize)
74
What is a tolerogen?
An antigen delivered in a form/route that doesn't result in an immune response and prevents an immune response
75
Normal reticuolocyte count range
0.4-1.7% of RBCs
76
Absolute reticulocyte count equation
% of reticulocytes \* red cell count
77
REcognition/attachment Engulfment and Reticulocyte index equation
RI = reticulocyte count \* (patient Hb/normal Hb) \* stress factor Reticulocytes are pushed out of the one marrow before they are fully matured if the bone marrow is stressed
78
Anemia stress factors for the reticulocyte equation
1.5 - mild anemia 2.0 - moderate anemia 2.5 - severe anemia
79
Iron enters the duodenum through the transporter \_\_\_\_\_\_\_\_\_
DMT1
80
Low hepcidin means _________ iron absorption,
increased
81
3 nutritional deficiencies that can cause anemia
Iron Vitamin B12 Folate
82
Hormone deficiency that can cause anemia
Erythropoietin
83
2 types of anemia due to bone marrow damage
Aplastic anemia - blood cells aren't being made Leukemia - crowding out of normal blood-making cells by cancer cells
84
Bite RBCs are a histological indicator of _________ deficiency
G6PD
85
Alpha thalassemia is a lack of _________ hemoglobin chains
alpha
86
Signs of hemolysis (4)
Increased bilirubin Increased lactic dehydrogenase Decreased haptoglobin Hemosiderin in urine
87
The Leubering-Rapaport pathway in RBCs generates \_\_\_\_\_\_\_\_\_
2,3 DPG
88
2 types of anemia due to marrow damage
Aplastic anemia Leukemia
89
How does chronic inflammation cause anemia? (3)
Pro-inflammatory cytokines make cells resistant to erythropoietin Less erythropoietin production Iron is sequestered (since bacteria like to use it)
90
What does the spleen check for in RBCs?
Cytoskeleton abnormalities
91
The G6PD mutation causes problems in what RBC pathway?
The one that gets reduces oxygen radicals
92
7 components of the complete blood panel
Hemaglobin Hematocrit Red blood cell count Mean corpuscular volume White blood cell count Platelet count Mean platelet volume
93
How to calculate hematocrit by the RBC histogram
RBC volume (AUC) / total volume OR RBC count \*MCV (mean corpuscular volume)
94
Axes of the RBC and platelet histogram
size vs. count
95
Reticulocytes are retained in the bone marrow for about _________ days
3
96
Reticulocytes circulate in peripheral blood for _________ days before they become mature RBCs
1
97
What is the difference between a manual differential and an automated differential? What does the manual one add?
Slide vs. flow Morphology
98
What does the neutrophil nucleus look like on a stained slide?
Clumped chromatin in 2-5 lobes
99
What does a lymphocyte nucleus look like on a stained slide?
Most of cell Round Dense chromatin
100
What does the monocyte nucleus look like on a stained slide?
Irregular, lobed
101
What does the monocyte cytoplasm look like on a stained slide?
Often has vacuoles
102
What does an eosinophil nucleus look like on a stained slide?
Bi-lobed
103
What does a basophil nucleus look like on a stained slide?
Obscured by coarse purple-black granules
104
\_\_\_\_\_\_\_\_\_ are found on the skin and are helical and make holes in undesireable bacteria
Cathelicidins
105
\_\_\_\_\_\_\_\_\_ is downstream in the TLR pathway and turns on pro-inflammatory genes
NF-KB
106
If the body can't kill a pathogen, it \_\_\_\_\_\_\_\_\_
Walls it off
107
What 4 things happen in acute inflammation?
Vasodilation Leaky EC junctions Stretching of nerve fibers WBCs
108
What do dendritic cells do when they encounter a pathogen?
Eat it and present parts of it in the lymph node
109
Reticulocytes normally are _________ in response to anemia
Increased
110
What's the difference between signs and symptoms?
Symptoms are subjective and what the patient tells you Signs are objectives and what you see in the patient
111
What is claudication?
Extremity pain due to lack of oxygen
112
What is dyspnea?
Difficulty breathing
113
What is dysuria?
Painful urination
114
Iron is more soluble at _________ pH
Low
115
\_\_\_\_\_\_\_\_\_ binds to iron in the stomach and brings it to the duodenum
Gastroferrin
116
The presence of protein and amino acids _________ iron absorption
Decreases
117
How does vitamin C affect iron absorption?
It keeps it in the right valence state for absorption
118
The presence of phytates and oxalates _________ iron absorption
Decreases
119
What are the storage proteins for iron?
Ferritin Hemosiderin
120
What does ferritin do?
Stores iron intracellularly
121
What is the transport protein for iron?
Transferrin
122
What does transferrin do?
Binds iron in the plasma
123
How does iron get into RBCs?
Transferrin enters through clathrin-coated pits pH changes and iron affinity decreases Iron goes out into the cell via the DMT transporter
124
Hepcidin increases accumulation of \_\_\_\_\_\_\_\_\_
Ferritin
125
What 3 things cause hepcidin levels to increase?
Inflammation Infection Iron overload
126
How do we measure ferritin levels?
The intracellular amount is proportional to the tiny amount in plasma
127
Increased iron absorption can be due to a mutant _________ gene
HFE
128
What happens in HLA-H mutation?
Increased iron absorption in the duodenal crypt
129
What is hemochromatosis?
Iron overload from excessive gut absorption. Genetic.
130
What is the treatment for hemochromatosis?
Bloodletting
131
What is hemosiderosis?
Iron overload from excessive accumulation of hemosiderin
132
What is the treatment for hemosiderosis?
Iron chelation
133
Hemoglobin levels are measured by \_\_\_\_\_\_\_\_\_
Spectometry
134
RBC and platelet levels are measured by \_\_\_\_\_\_\_\_\_
Aperture impedance Or flow
135
The largest blood cells are \_\_\_\_\_\_\_\_\_
Monocytes
136
In aqueous solutions, iron forms \_\_\_\_\_\_\_\_\_
Insoluble hydroxides
137
What 3 things does the innate immune system recognize?
PAMPS DAMPS Absence of certain normal cell surface molecules
138
T cells secrete short-range mediators called \_\_\_\_\_\_\_\_\_
Lymphokines
139
What do type 1 helper T cells, Th1 do?
Recognize antigens, make lymphokines that attract macrophages
140
What do Th17 helper T cells do?
Create focused inflammation
141
What do type 2 helper T cells, Th2 do?
Stimulate macrophages to become alternatively activated Wall off pathogens
142
What do follicular helper T cells, Tfh do?
Activate B cells
143
What do Tregs do?
Make lymphokines to supress other T cells, keeping immune response in check
144
What do cytotoxic/killer T cells do?
Destroy things with foreign or abnormal antigens on surface
145
Myoglobin has a _________ partial pressure for oxygen than hemoglobin
Lower, so that it holds onto oxygen very tightly until oxygen concentration is very low
146
2 components of the heme prosthetic group
Ptoporphyrin ring + bound iron
147
Fetal hemoglobins have a _________ oxygen affinity than hemoglobin A
higher
148
What are Heinz bodies?
Precipitated denatured hemoglobin
149
\_\_\_\_\_\_\_\_\_ is found in people with high-affinity hemoglobin variants
Erythrocytosis (elevated RBC count)
150
3 signs of methemoglobinemia
Cyanosis Arterial partial pressure of oxygen is normal Oxygen exposure does not change blood color
151
What is the treatment for acquired methemoglobinemia?
Removal of inciting drug/chemical IV methylene blue to act as an electron receptor o reduce methemoblobin via the NADPH-dependent pathway
152
What is the treatment for carbon monoxide poisoning?
100% oxygen and/or hyperbaric chamber
153
\_\_\_\_\_\_\_\_\_ antibody is attached to mast cells
IgE
154
IgE stimulates the mast cells to make \_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_, and release _________ when it encounters an antigen
Prostaglandins Leukotrienes Cytokines Granules
155
In the embryonic stage, blood cells are produced by the \_\_\_\_\_\_\_\_\_
Yolk sac
156
How does blood flow work in the bone marrow?
Arteries -\> capillary-venous sinuses -\> central vein -\> systemic circulation Only mature blood cells are allowed to get into the sinuses
157
Does the reticulocyte have a nucleus?
No
158
Cellularity estimate equation for % of bone marrow occupied by hematopoietic cells
100-age Very approximate
159
Where in the lymph node to arterioles/veins enter/exit?
Hilum
160
Where does lymph go one it reaches the lymph node?
Afferent lymph channel -\> subscapular sinus -\> efferent lymph channel
161
In the lymph node, lymphocytes are arranged in \_\_\_\_\_\_\_\_\_
Follicles
162
Areas of dividing cells in lymph node follicles are \_\_\_\_\_\_\_\_\_
Germinal centers
163
2 tissue types in the spleen
Red pulp ~ lymph node medulla, filters White pulp
164
Peyer patches contain _________ cells unique to it
mucosal M cells
165
The part of the antigen that fits into the receptor is the \_\_\_\_\_\_\_\_\_
Antigenic determinant / epitope
166
How are sideroblastic anemias formed?
They are congenital/aquired
167
How does chronic infection/inflammation result in anemia?
IL1 reduces iron mobilizaiton, EPO production INF-y inhibits proliferation of erythroid precursors
168
How does lead poisoning lead to anemia?
Inhibits synthesis of protoporphyrin and enzyme that ligates iron to porphyrin ring
169
What types of anemia or normochromic and normocytic?
Thyroid Adrenal insufficiency Renal insufficiency Infection/inflammation/malignancy (sometimes microcytic or hypochromic though)
170
How is vitamin B12 absorbed?
Released from food in acidic stomach IF binds B12 released in terminal ilium and bound to TcII (transcobalamin binding protein II) Liver
171
B12 and folate are required for synthesis of \_\_\_\_\_\_\_\_\_
Methionine from homocysteine
172
What enzyme reduces iron?
Cytochrome B reductase
173
Which form of iron binds oxygen?
2+ (ferrous) 3+ (ferric) does not bind
174
4 causes of hemoglobin-related cyanosis
Too much Deoxyhemoglobin Methemoglobin Sulphemoglobinemia Or acquired from drugs
175
Is a blast forming unit committed to a lineage?
Yes
176
Can myeloid and lymphoid stem cells self-renew?
No Multipotent hematopoietic stem cells can though!
177
What does the pro-prefix in hematopoieisis mean?
The first committed cell in that lineage
178
What are the 4 things erythropoietin does?
Activates stem cells Encourages mitosis and maturation Increases Hemoglobin B levels Reticiulocyte release
179
What is a feature of immature blood progenitor cells?
They are large and their nuclei are round
180
What are the 3 things thrombopoietin does?
Helps differentiate, mature, release platelets
181
The 2 ways neutrophils kill things
Phagocytosis Degranulation
182
Why do granulocytes have weird looking nuclei?
They can fit through small spaces
183
Eosinophils fight \_\_\_\_\_\_\_\_\_
Parasites
184
What is in the cortex and paracortex of the lymph node?
Cortex - B cells Paracortex - T cells
185
What is a lymph node germinal center? When does it occur?
A bunch of dividing cells that happens when an immune response occurs
186
\_\_\_\_\_\_\_\_\_ and _________ are factors that reduce iron mobiliaation and erythropoietin production
TNF IL1
187
\_\_\_\_\_\_\_\_\_ and _________ are factors that inhibit erythroid proliferation
INF-B (interferon beta) INF-Y (interferon gamma)
188
Endocrine causes of anemia result in \_\_\_\_\_\_\_\_\_
Reduced reticulocyte count and index
189
Under what anemic conditions do you transfuse?
Only when cardiovascular decompensation risk is present
190
Where are iron, vitamin B12, and folate absorbed in the GI tract?
Iron - duodenum Folate - jejunum B12 - terminal ilium
191
What helps us absorb vitamin B12?
Intrinsic factor
192
What enzyme stores vitamin B12 in the plasma?
Transcobalmin II (TcII)
193
5 major categories of vitamin B12 deficiency
Autoimmune disease Intrinsic factor deficiency Malabsorption Defective transport/storage Metabolic defect
194
6 major categories of folate deficiency
Dietary insufficiency Malabsorption Drugs and toxins Inborn errors of folate metabolism Increased demands Increased loss/metabolism
195
Sickle cell is a mutation in the _________ globin chain
Beta
196
What is poikilocytosis?
Variation in shep of RBCs
197
What is aplastic crisis in sickle cell disease?
When the bone marrow can't rapidly produce RBCs (since in sickle cell it always has to) Characteristic finding is low reticulocyte count
198
What happens to the spleen in sickle cell disease?
Lots of sickle RBCs become trapped in microcirculation Autoinfarction -\> destruction by age 5 Lots of infections
199
What happens to the lungs in sickle cell disease?
Increased vascular resistance -\> pulmonary arterial hypertension
200
How can you incrase expression of fetal hemoglobin?
Aministration of hydroxyurea Reduces anemia, pain crises, mortality Not sufficient evidence to show it helps the chronic complications
201
When do you transfuse people with sickle cell disease?
Acute worsening or acute end-organ injury
202
Domains of the light chain
1 variable, VL 1 constant, CL
203
Domains of the heavy chain
1 variable, VH 3-4 constant, CH1, CH2, etc
204
IgM forms a \_\_\_\_\_\_\_\_\_-mer
penta
205
Chain structure of IgG
2 light, 2 gamma
206
Chain structure of IgD
2 light, 2 delta Extra long hinge
207
Chain structure of IgE
2 light, 2 epsilon Extra constant domain
208
Chain structure of IgM
2 light, 2 mu w/ extra CHu4 domain Pentamer closed by J chain
209
Chain structure of IgA
2 light, 2 alpha Joined by J chain Wrapped by secretory component
210
When antibody types switch, the _________ chain changes, but the _________ does not
Heavy Light
211
2 types of light chains
kappa lambda
212
What is an antibody allotype?
Antibody chain alleles
213
What is an antibody idiotype?
A persons unique set of complementarity determining region You consider other people's idiotype antigenic
214
What is a lattice/immune complex?
A complex of antigens and antibodies (since antibodies can bind multiple epitopes, we get a growing network)
215
What is immune complex precipitation?
When the ratios of antigen to antibody are optimal, the complex get large and falls out of solution Agglutination is when this is cell-sized
216
Why is IgM good at activating complement?
You need two adjacent Fcs to start the complement cascade and IgM has five adjacent
217
The complement cascade activates \_\_\_\_\_\_\_\_\_
C3
218
The classical complement pathway is activated by \_\_\_\_\_\_\_\_\_
IgG or IgM complexes with antigens
219
Which antibody type is most resistant to enzymatic digestion?
IgA, with secretory component
220
What is the main complement inhibitor?
C1 esterase inhibitor
221
The alternative complement pathway is activated by \_\_\_\_\_\_\_\_\_
Bacterial cell wall components. It doesn't need an antibody - handy!
222
The lectin complement pathway is mediated by \_\_\_\_\_\_\_\_\_
Mannose-binding protein, a lectin
223
What are lectins?
Proteins that bind carbohydrates
224
4 actions of the complement pathway
Lysis Opsonization Chemotaxis Anaphylatoxis
225
What levels of hemoglobin A are needed for disease?
1/2 levels - some symptoms 1/4 levels - disease 0 levels - incompatible with life
226
Why is hydrops fetalis more common in asians than africans?
Asians are usualy have 0 alpha hemoglobins on a chromosome (--/aa) and Africans usually have 1 (-a/-a)
227
What are RBCs like in thelassemia?
Low MCV and low hemoglobin concentration
228
What do pyrogens do?
Casue hypothalamus to produce prostaglandins that results in increased body temperature Exogenous pyrogens cause leukocytes to release endogenous pytogens
229
What are 3 acute phase reaction proteins we should know about?
C-reactive protein Serum amyloid D Fibrinogen
230
3 cell types that have histamine
Mast cells Basophils Platelets
231
What does serotonin do to blood vessels?
Vasoconstriction to aid in clotting
232
Which blood cell types have serotonin?
Platelets
233
2 arachadonic acid pathways for inflammation
Cyclooxenase -\> prostaglandins, thromboxanes Lipoxygenase -\> leukotrienes, lipoxins
234
Lipoxins antagonize \_\_\_\_\_\_
Leukotrienes
235
What is a quantitative vs. qualitative hemoglobin disorder?
Quantitative is decrased/imbalanced production of normal globin chains Qualitative is production of abnormal globin chains
236
4 downstream consequences of ineffective erythropoiesis in thalassemia
Anemia Bone marrow expansion Extramedullary hematopoiesis Increased intestinal iron absorption
237
4 'levels' of alpha thalassemia
-1 = silent carrier -2 = Minor - trait state -3 = Intermedia - moderate anemia, needs transfusions sometimes -4 = Major - severe anemia, need transfusions like monthly. Hydrops fetalis.
238
Thalassemia effects on mean corpuscular volume, hemoglobin concentration, red cell distribution width, RBC count, reticulocyte count
Decreases MCV Decreases MCH, MCHC Uniform RBCs (normal distribution width) Increased RBC numbers Increased reticulocyte numbers
239
Peripheral blood smear in thalassemia (3 abnormal findings)
Hypochromia Target cells Microcytosis
240
4 types of thalassemia syndromes
alpha-thalassemia beta-thalaseemia Sickle beta-thalassemia Hb E syndromes
241
What effect does iron deficiency have on red blood cell numbers, mean corpuscular volume, and red cell distribution width
Decreased Increased Increased
242
With what other comorbidity is it difficult to diagnose beta-thalassemia
Iron deficiency. It makes the hemoglobin ratios look normal.
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Is RBC sicklin reversible?
Yes, at first
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What is acute chest syndrome in sickle cell disease?
A vicious cycle of hypoxia and sickling. Lungs can be fucked up and result in hypoxia due to infection, fat emolism, or pulmonary vasoocclusion
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What is sickle lung disease?
A common comlication of sickle cell anemia Progressive obliteration of pulmonary vasculature due to chronic inflammation and destruction Results in pulmonary hypertension, which results in R sided heart failure
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What is sickle solubility testing?
Detects hemoglobin precipitates by looking at cloudiness of a hemoglobin extract of blood
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What are the 3 antibody fragments?
Fc binds antibody receptors (Fab)2 is both Fab regions stuck together Fab binds antigens
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What is the secondary structure of the immunoglobulin fold?
Antiparallel beta sheet wiht disulfide bond holding it together
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What is antibody valence?
Number of antigens an antibody can bind
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\_\_\_\_\_\_\_\_\_\_\_\_ is the most common antibody in the blood
IgG
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The epitope is the part of the antigen that interacts with the ____________ region of the antibody and is a ____________ shape
Complementarity-determining Flat
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What is antibody cross-reactivity?
When antibodies bind to different antigens
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IgG plasma half-life is \_\_\_\_\_\_\_\_\_\_\_\_
26 days
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Which antibody can pass to the fetus?
IgG
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How many J chains are there per antibody complex?
Just one
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How is the IgM pentamer held together
4 disulfide bonds, 1 J chain
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What is IgM's single 2 weaknesses?
Will make blood too viscous Has a hard time getting out of the blood
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Classical pathway C steps
1 4 2 3 5 6 7 8 9
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How is C1q activated in complement?
It binds 2 adjacent Fc ends of bound antibodies
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What are the 4 consequences of complement?
Lysis Opsoniation - eating of pathogen Chemotaxis Anaphylatoxis - release of histamine from mast cells
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What complement components make up the membrane attack complex?
6,7,8,9
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What happens if an immature B cell is exposed to an antigen it likes?
Receptor editing If this fails, apoptosis triggered This is because the antigens in the bone marrow are likely to be of self
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Can a newborn make IgG?
No! It starts at 3-6 months
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What cells express CD4 and what cells express CD8?
Helper T - CD4 Killer T - CD8
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\_\_\_\_\_\_\_\_\_\_ secrete, IL\_\_\_\_\_\_\_\_\_\_ , which recruits neutrophils and monocytes
Th17 CD4+ T cells 17
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IL17 recruits __________ and \_\_\_\_\_\_\_\_\_\_
Neutrophils Monocytes
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\_\_\_\_\_\_\_\_\_\_ secrete, which __________ activates classical pathway macrophages
Th1 CD4+ T lymphocytes IFN-gamma
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\_\_\_\_\_\_\_\_\_\_ secrete \_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_, and \_\_\_\_\_\_\_\_\_\_, which activates alternative pathway macrophages and eosinophils
Th2 CD4+ T lymphocytes IL4, IL5, IL13
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Mast cells express Ig\_\_\_\_\_\_\_\_\_\_
E
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2 phases of B cell activation
1. Binding of antigen to B cell receptors (membrane-bound versions of the antibody it will eventually secrete) 2. If the binding is strong enough, activation takes place
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What is the genetic process by which we get such large B cell diversity?
VJD recombination
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What is somatic hypermutation?
B cell clones are hypermutable so daughter cells make slightly different antibodies.
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What is affinity maturation?
Selection of best antigen-fitting B cell mutants after antigenic stimulation allows an incresae of affinity during an immune response
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What part of the antibody switches in class switching?
Heavy chain class (never light chain class)
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5 reasons B cells are so diverse
1. 2-chain receptors - heavy and light 2. Recombination of germ-line segments - V, D, and J combinations 3. K or Gamme light changes 4. N region diversity - random nucleotides are added or subtracted at VD and DJ hoins 5. Somatic hypermutation
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What is hemolysis?
An abnormal decrease in red cell survival or increase in turnover
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What are two mechanisms for red cell destruction?
Intravascular - turnover within the vascular space Extravascular - ingestion and clearance by macrophages
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What is a structural RBC cause of hemolysis?
Hereditary spherocytosis
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What are two enzyme disorders that causes hemolytic anemia?
1. G6PD deficiency - \> lack of oxidative protection - \> oxidant stress - \> early RBC death 2. Pyruvake Kinase deficiency - \> decreased ATP - \> increased 2,3-DPG
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2 categories of autoimmune hemolytic anemia
Cold and warm Refer to the temperature at which antibodies bind and activate complement Cold -\> intravascular hemolysis Warm -\> extravascular hemolysis
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Most red cell turnover occurs in the \_\_\_\_\_\_\_\_\_\_
Spleen
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What treatment is made for hereditary spherocytosis?
Splenectomy
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What type of inherited disorder is G6PD deficiency?
X-linked recessive
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Histological RBC changes in G6PD deficiency
Blister cells Teardrop cells Heinz bodies
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What are the stages of B cell maturation and the antibody production?
Pro-B makes mu Pre-B makes mu and L or K chain, producing cIgM Immature B makes cIgM and sIgM. The self-reactive check occurs here Mature B makes sIgM and sIgD
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When do babies make IgG? IgM?
IgG 3-6 months after birth IgM 3 months after fertilization
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How are old people's adaptive immune systems different than young people?
More memory cells Fewer naive cells So, less flexible and a larger stored library
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What does haptoglobin do?
Haptoglobin scavenges free hemoglobin in the blood
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How does paroxysmal nocturnal hematuria work?
An acquired defect in the myeloid stem cell gets rid of the anchoring protein GPI Then, MIRL and DAF, which turn off complement are not expressed on the cell surface In times of acidosis, ALL blood cells are in danger of dying from complement
291
How do you test for paroxysmal nocturnal hematuria?
Sucrose test - activates complement Acidify serum - activates complement Flow to look for presence of DAF (CD55)
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What are the two types of immune hemolytic anemia? What characterizes each?
Warm IgG-mediated Extravascular hemolysis Spleen eats Cold IgM-mediated Intravascular hemolysis Activates complement
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What test is used to diagnose warm autoimmune hemolytic anemia?
Coomb's test, either direct or indirect
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What is the difference between the direct and indirect Coomb's test?
Direct test confirms the presence of antibody-coated RBCs The indirect test confirms the presence of anti-RBC antibodies in serum
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How does microangiopathic hemolytic anemia work?
RBCs are sheared as they pass through circulation Causes: Microthrombi Prosthetic heart valces Aortic stenosis
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4 causes of microcytic anemia
Iron deficiency Chronic disease Sideroblastic anemia Thalassemia
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What are the causes of iron deficiency anemia in infants, children, adults, and old people?
Infants - breast feeding Children - diet Adults - peptic ulcer disease (M), menorrhagia or pregnancy (F) Old people - colon polyps/carcinoma (developed world), hookworm (developing world)
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What are the 4 stages of iron deficiency anemia?
1. Storage iron is depleted. Ferritin decreases, serum ferritin decreases, TIBC increases 2. Serum iron is depleted. Serum iron decreases, % iron saturation decreases 3. Normocytic anemia. RBC count decreased but they look normal 4. Microcytic, hypochromic anemia
299
What are the lab findings for iron deficiency anemia? RBC morphology Ferritin TIBC Serum iron % iron saturation Free erythrocyte protoporphyrin
Microcytic, hypochromic, increased RDW Decreased ferritin Increased TIBC Decreased serum iron Decreased % saturation Increased free erythrocyte protoporphyrin
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What are the lab findings for anemia due to chronic disease? RBC morphology Ferritin TIBC Serum iron % iron saturation Free erythrocyte protoporphyrin
Microcytic, though in the early phase, is normocytic Increased ferritin Decreased TIBC Decreased serum iron Decreased % saturaiton Increased free erythrocyte protoporphyrin
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What causes sideroblastic anemia?
Defective proroporphyrin synthesis -\> low heme From: Genetic Alcoholism Lead poisoning B6 deficiency
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What are the lab findings for sideroblastic anemia? RBC morphology Ferritin TIBC Serum iron % iron saturation
Microcytosis Increased ferritin Decreased TICB Increased serum iron Increased % iron saturation
303
What are the following hemoglobin's chain composition? HbA HbA2 HbF HbH Hb Barts
alpha2, beta2 alpha2, delta2 alpha2, gamma2 beta4 gamma4
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Causes of macrocytic anemia
Folate deficiency Vitamin B12 deficiency
305
What causes megaloblastic anemia's characteristic cells?
Can't produce appropriate DNA precursors so rapidly dividing cells become large because they can't divide
306
How do folate, vitamin B12, and homocysteine do their thing?
Folate enters the body and is methylated Vitamin B12 takes the methyl group so folate can do its DNA shit Homocystiene takes the methyl group and becomes methionine
307
What are the lab findings for folate deficienty? RBC morphology Neutrophil morphology Serum folate Serum homocysteine Methylmalonic acid
Macrocytic RBCs Hypersegmented neutrophils Decreased serum folate Increased serum homocysteine Normal methylmalonic acid
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What is pernicious anemia?
B12 deficiency from Intrinsic factor deficiency from Autoimmune destruction of parietal cells
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What are the lab findings for vitamin B12 deficiency? RBC morphology Neutrophil morphology Spinal cord morphology Serum B12 Serum homosysteine Serum methylmalonic acid
Macrocytic RBCs Hypersegmented neutrophils Subacute combined degeneration of spinal cord Decreased serum B12 Increased serum homocysteine Increased methylmalonic acid (destinguishes from folate deficiency)
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What are the lab findings for extravascular hemolysis? Spleen Bilirubin Gallstones Marrow
Splenomegaly Jaundice from unconjugated bilirubin Bilirubin gallstones Marrow hyperplasia
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What are the lab findings for intravascular hemolysis? Hemoglobin Urine Serum haptoglobin
Hemoglobinemia Hemoglobinuria, hemosiderinuria (b/c builds up in renal tubular cells) Decreased serum haptoglobin
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Where does clonal deletion of T and B cells occur?
Where they mature T cells - thymus B cells - bone marrow
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What does haptoglobin do?
Binds free hemoglobin
314
What does hepcidin do?
Decrease gut iron absorption Increase macrophage iron sequestration
315
What is MCHC?
Mean corpuscular hemoglobin concentration
316
How do you calculate mean corpuscular volume?
hematocrit / red blood cell count
317
How do you calculate mean corpuscular hemoglobin concentraiton? (equation)
Hemoglobin levels / hematocrit
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At which step do all complement pathways merge?
C3 convertase cleaving and activating C3
319
Which complement derivatives are chemotactic?
C3a C5a (but pick this one if given the option of both)
320
What makes up the membrane attack complex in complement?
C5b and C6-9
321
Which 2 complement factors cause mast cell degranulation?
C3a C5a
322
Which complement component acts as an opsonin for phagocytosis?
C3b
323
What is anaphylatoxis?
Part of complement Release of histamine from mast cells
324
IL-3 stimulates \_\_\_\_\_\_\_\_\_ IL-5 stimulates \_\_\_\_\_\_\_\_\_
Basophils Eosinophils
325
\_\_\_\_\_\_\_\_\_ stimulates basophils \_\_\_\_\_\_\_\_\_ stimulates eosinophils
IL-3 IL-5
326
What does lead poisoning inhibit?
Protoporphyrin formation
327
Where is ferroportin located?
On the basal surface of intestinal cells. Iron goes out of these cells into the blood
328
What is in the white pulp of the spleen?
Lymphocytes
329
What cells are in the sheath that surrounds teh central arteriole of the spleen?
T cells B cells are a little further out
330
Sickle cells is a _______ to _______ substitution
Glutamine Valine
331
CD\_\_\_\_\_\_\_ marks immature T cells
1