B&L Unit 1 Flashcards
What is the equation for hematocrit?
length of RBC layer/ (RBVs + buffy coat + plasma)
The biconcave disc shape of RBCs increases surface area to volume ratio by _________% compared to a sphere
40
RBCs are _________% wider than capillaries
25
Hematopoiesis is the formation of _________
Blood cellular components
Erythropoiesis is the formation of _________
RBCs
Hemolysis is _________
Rupturing of RBCs and release of their contents
Hemostasis is _________
Stopping of bleeding
1 _________ can make _________ platelets
Megakaryocyte 5000
Acute leukemia cells are _________ compared to chronic leukemia cells
Immature
_________ proteins on the cell surface are expressed by cells of the innate immune system to identify pathogen-associated molecular patterns
Pattern-recognition receptor (PRR)
Pattern-recognition receptor proteins on the cell surface are expressed by cells of the _________
Innate immune system
_________ are foreign molecular structures on pathogens (bacterial cell wall protein, bacterial dsRNA) that are recognized by PRRs in the innate immune system
Pathogen-associated molecular pattern (PAMP)
_________ of the innate immune system recognize _________ of pathogens
PRRs PAMPs
Toll-like receptors are a type of _________
Pattern-recognition receptor
A PAMP-stimulated cell releases _________ and _________
cytokines chemokines
Chemokines are _________ to phagocytotic WBCs
chemotactic
Cytokines are secreted by what type of cell?
Immune cells
Cytokines can be classified as _________, _________, or _________ (types of macromolecules)
Proteins Peptides Glycoproteins
Ig_________ is passed mother to fetus
G
IgG is a _________-mer
di
Ig_________ and _________ activate complement
G M
_________ is the first antibody to appear after exposure to a new antigen
IgM
Ig_________ is expressed on B cell membranes as their antigen receptor
D
Ig_________ is secretory
A
Ig_________ attaches to mast cells and makes them release prostaglandins, leukotrienes, cytokines, and release granules
E
Ig_________ is involved in parasite resistance
E
Type I immunopathology is also known as _________
Immediate hypersensitivity (like allergies)
Immediate hypersensitivity is also known as _________
Type I immunopathology
Type II immunopathology is also known as _________
Autoimmunity
Autoimmunity is also known as _________
Type II immunopathology
Type III immunopathology is when antibodies are made against _________
Soluble antigens
Type IV immunopathology is _________-mediated
T-cell
The Wright-GIemsa stain stains _________ components in cells
Acidic
Eosin stains _________ components a _________ color
Basic Orange-red (hemoglobin and some granules)
Methylene blue will stain _________ components a _________ color
Acidic Purple-blue (DNA, RNA, basophil granules, cytoplasm of mature lymphocytes and monocytes)
3 white blood cell blood measurements we care about
WBC count WBC differential Absolute count = total and differential
_________ is the most common WBC in children up to 8
Lymphocyte
_________ become macrophages once they enter tissues
Monocytes
_________ and _________ are the granulocytes involved in allergies
Eosinophils (mediate) Basophils (central role)
_________ are the granulocytes that deal with bacterial infections
Neutrophils
_________ are immature RBCs (before they lose RNA and ribosomes and stuff)
Reticulocytes
The range for the platelet count is _________
150,000 - 400,000/uL
What is the difference between plasma and serum?
Serum is the clear part of the blood after clotting. Plasma is unclotted.
In the fetal stage, blood cells are produced by the _________ and _________
Liver Spleen
Myeloid means _________
Bone marrow
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)
_________% of nucleated cells in bone marrow are stem cells/progenitors and _________% of these are pluripotetent
1 1
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)
What type of macromolecule are hematopoeietic growth factors?
Glycoproteins
5 types of cells that produce hematopoeietic growth factors
Activated T and B-lymphocytes Macrophages Fibroblasts Endothelial cells
The last neutrophilic precursor with the ability to divide is the _________
Myelocyte
M:E ratio and normal stuff
Myeloid : erythroid ratio from bone marrow biopsy. Should be about 3:1.
What is allostery?
When one hemoglobin binds to oxygen, there is a change in configuration that increases binding affinity.
What is positive cooperativity?
Substrate binding increases binding affinity for addtional substrate
Hemoglobin is _________ in the taut state and _________ in the relaxed state
Deoxygenated Oxygenated
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
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
Hemoglobin is a _________-mer and myoglobin is a _________-mer
tetra mono
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
The fetal hemaglobin tetramer is _________
a2y2
Hemaglobin F binds _________ poorly
2,3-BPG
The _________ effect is increased in fetal hemaglobin
Bohr
Methemoglobin forms when _________
iron is reduced from its 2+ state to its 3+ state, which doesn’t bind oxygen Curve shifts left
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
_________ can be givin via IV to reduce methemoglobin via the _________ pathway
Methylene blue NADPH-dependent
Deoxyhemoglobin absorbs at _________ nm and oxyhemoglobin absorbs at _________ mm
660 940
_________ form the buffy coat
Leukocytes
Dendritic cells connect the _________ and _________ immune responses
Innate Adaptive
The neutropil has _________ granules, the eosinophil has _________ granules, an the basophil has _________ granules (color)
colorless - neutral red - eosin blue - basic
The central lymphoid organs are the _________ and _________
Bone marrow Thymus
The peripheral lymphoid organs are the _________ , _________ , and _________
Lymph nodes Spleen Peyer’s patch
Lymphocytes interact with endothelial cells lining certain _________ in peripheral lymphoid tissues that are _________ (shape)
Postcapillary venules High and cuboidal
What is an immunogen?
An antigen in a form that can give rise to an immune response (can immunize)
What is a tolerogen?
An antigen delivered in a form/route that doesn’t result in an immune response and prevents an immune response
Normal reticuolocyte count range
0.4-1.7% of RBCs
Absolute reticulocyte count equation
% of reticulocytes * red cell count
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
Anemia stress factors for the reticulocyte equation
1.5 - mild anemia 2.0 - moderate anemia 2.5 - severe anemia
Iron enters the duodenum through the transporter _________
DMT1
Low hepcidin means _________ iron absorption,
increased
3 nutritional deficiencies that can cause anemia
Iron Vitamin B12 Folate
Hormone deficiency that can cause anemia
Erythropoietin
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
Bite RBCs are a histological indicator of _________ deficiency
G6PD
Alpha thalassemia is a lack of _________ hemoglobin chains
alpha
Signs of hemolysis (4)
Increased bilirubin
Increased lactic dehydrogenase
Decreased haptoglobin
Hemosiderin in urine
The Leubering-Rapaport pathway in RBCs generates _________
2,3 DPG
2 types of anemia due to marrow damage
Aplastic anemia Leukemia
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)
What does the spleen check for in RBCs?
Cytoskeleton abnormalities
The G6PD mutation causes problems in what RBC pathway?
The one that gets reduces oxygen radicals
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
How to calculate hematocrit by the RBC histogram
RBC volume (AUC) / total volume OR RBC count *MCV (mean corpuscular volume)
Axes of the RBC and platelet histogram
size vs. count
Reticulocytes are retained in the bone marrow for about _________ days
3
Reticulocytes circulate in peripheral blood for _________ days before they become mature RBCs
1
What is the difference between a manual differential and an automated differential? What does the manual one add?
Slide vs. flow Morphology
What does the neutrophil nucleus look like on a stained slide?
Clumped chromatin in 2-5 lobes
What does a lymphocyte nucleus look like on a stained slide?
Most of cell Round Dense chromatin
What does the monocyte nucleus look like on a stained slide?
Irregular, lobed
What does the monocyte cytoplasm look like on a stained slide?
Often has vacuoles
What does an eosinophil nucleus look like on a stained slide?
Bi-lobed
What does a basophil nucleus look like on a stained slide?
Obscured by coarse purple-black granules
_________ are found on the skin and are helical and make holes in undesireable bacteria
Cathelicidins
_________ is downstream in the TLR pathway and turns on pro-inflammatory genes
NF-KB
If the body can’t kill a pathogen, it _________
Walls it off
What 4 things happen in acute inflammation?
Vasodilation Leaky EC junctions Stretching of nerve fibers WBCs
What do dendritic cells do when they encounter a pathogen?
Eat it and present parts of it in the lymph node
Reticulocytes normally are _________ in response to anemia
Increased
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
What is claudication?
Extremity pain due to lack of oxygen
What is dyspnea?
Difficulty breathing
What is dysuria?
Painful urination
Iron is more soluble at _________ pH
Low
_________ binds to iron in the stomach and brings it to the duodenum
Gastroferrin
The presence of protein and amino acids _________ iron absorption
Decreases
How does vitamin C affect iron absorption?
It keeps it in the right valence state for absorption
The presence of phytates and oxalates _________ iron absorption
Decreases
What are the storage proteins for iron?
Ferritin Hemosiderin
What does ferritin do?
Stores iron intracellularly
What is the transport protein for iron?
Transferrin
What does transferrin do?
Binds iron in the plasma
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
Hepcidin increases accumulation of _________
Ferritin
What 3 things cause hepcidin levels to increase?
Inflammation
Infection
Iron overload
How do we measure ferritin levels?
The intracellular amount is proportional to the tiny amount in plasma
Increased iron absorption can be due to a mutant _________ gene
HFE
What happens in HLA-H mutation?
Increased iron absorption in the duodenal crypt
What is hemochromatosis?
Iron overload from excessive gut absorption. Genetic.
What is the treatment for hemochromatosis?
Bloodletting
What is hemosiderosis?
Iron overload from excessive accumulation of hemosiderin
What is the treatment for hemosiderosis?
Iron chelation
Hemoglobin levels are measured by _________
Spectometry
RBC and platelet levels are measured by _________
Aperture impedance Or flow
The largest blood cells are _________
Monocytes
In aqueous solutions, iron forms _________
Insoluble hydroxides
What 3 things does the innate immune system recognize?
PAMPS DAMPS Absence of certain normal cell surface molecules
T cells secrete short-range mediators called _________
Lymphokines
What do type 1 helper T cells, Th1 do?
Recognize antigens, make lymphokines that attract macrophages
What do Th17 helper T cells do?
Create focused inflammation
What do type 2 helper T cells, Th2 do?
Stimulate macrophages to become alternatively activated Wall off pathogens
What do follicular helper T cells, Tfh do?
Activate B cells
What do Tregs do?
Make lymphokines to supress other T cells, keeping immune response in check
What do cytotoxic/killer T cells do?
Destroy things with foreign or abnormal antigens on surface
Myoglobin has a _________ partial pressure for oxygen than hemoglobin
Lower, so that it holds onto oxygen very tightly until oxygen concentration is very low
2 components of the heme prosthetic group
Ptoporphyrin ring + bound iron
Fetal hemoglobins have a _________ oxygen affinity than hemoglobin A
higher
What are Heinz bodies?
Precipitated denatured hemoglobin
_________ is found in people with high-affinity hemoglobin variants
Erythrocytosis (elevated RBC count)
3 signs of methemoglobinemia
Cyanosis Arterial partial pressure of oxygen is normal Oxygen exposure does not change blood color
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
What is the treatment for carbon monoxide poisoning?
100% oxygen and/or hyperbaric chamber
_________ antibody is attached to mast cells
IgE
IgE stimulates the mast cells to make _________, _________, _________, and release _________ when it encounters an antigen
Prostaglandins Leukotrienes Cytokines Granules
In the embryonic stage, blood cells are produced by the _________
Yolk sac
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
Does the reticulocyte have a nucleus?
No
Cellularity estimate equation for % of bone marrow occupied by hematopoietic cells
100-age Very approximate
Where in the lymph node to arterioles/veins enter/exit?
Hilum
Where does lymph go one it reaches the lymph node?
Afferent lymph channel -> subscapular sinus -> efferent lymph channel
In the lymph node, lymphocytes are arranged in _________
Follicles
Areas of dividing cells in lymph node follicles are _________
Germinal centers
2 tissue types in the spleen
Red pulp ~ lymph node medulla, filters White pulp
Peyer patches contain _________ cells unique to it
mucosal M cells
The part of the antigen that fits into the receptor is the _________
Antigenic determinant / epitope
How are sideroblastic anemias formed?
They are congenital/aquired
How does chronic infection/inflammation result in anemia?
IL1 reduces iron mobilizaiton, EPO production INF-y inhibits proliferation of erythroid precursors
How does lead poisoning lead to anemia?
Inhibits synthesis of protoporphyrin and enzyme that ligates iron to porphyrin ring
What types of anemia or normochromic and normocytic?
Thyroid Adrenal insufficiency Renal insufficiency Infection/inflammation/malignancy (sometimes microcytic or hypochromic though)
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
B12 and folate are required for synthesis of _________
Methionine from homocysteine
What enzyme reduces iron?
Cytochrome B reductase
Which form of iron binds oxygen?
2+ (ferrous) 3+ (ferric) does not bind
4 causes of hemoglobin-related cyanosis
Too much Deoxyhemoglobin Methemoglobin Sulphemoglobinemia Or acquired from drugs
Is a blast forming unit committed to a lineage?
Yes
Can myeloid and lymphoid stem cells self-renew?
No Multipotent hematopoietic stem cells can though!
What does the pro-prefix in hematopoieisis mean?
The first committed cell in that lineage
What are the 4 things erythropoietin does?
Activates stem cells Encourages mitosis and maturation Increases Hemoglobin B levels Reticiulocyte release
What is a feature of immature blood progenitor cells?
They are large and their nuclei are round
What are the 3 things thrombopoietin does?
Helps differentiate, mature, release platelets
The 2 ways neutrophils kill things
Phagocytosis Degranulation
Why do granulocytes have weird looking nuclei?
They can fit through small spaces
Eosinophils fight _________
Parasites
What is in the cortex and paracortex of the lymph node?
Cortex - B cells Paracortex - T cells
What is a lymph node germinal center? When does it occur?
A bunch of dividing cells that happens when an immune response occurs
_________ and _________ are factors that reduce iron mobiliaation and erythropoietin production
TNF IL1
_________ and _________ are factors that inhibit erythroid proliferation
INF-B (interferon beta) INF-Y (interferon gamma)
Endocrine causes of anemia result in _________
Reduced reticulocyte count and index
Under what anemic conditions do you transfuse?
Only when cardiovascular decompensation risk is present
Where are iron, vitamin B12, and folate absorbed in the GI tract?
Iron - duodenum Folate - jejunum B12 - terminal ilium
What helps us absorb vitamin B12?
Intrinsic factor
What enzyme stores vitamin B12 in the plasma?
Transcobalmin II (TcII)
5 major categories of vitamin B12 deficiency
Autoimmune disease Intrinsic factor deficiency Malabsorption Defective transport/storage Metabolic defect
6 major categories of folate deficiency
Dietary insufficiency Malabsorption Drugs and toxins Inborn errors of folate metabolism Increased demands Increased loss/metabolism
Sickle cell is a mutation in the _________ globin chain
Beta
What is poikilocytosis?
Variation in shep of RBCs
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
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
What happens to the lungs in sickle cell disease?
Increased vascular resistance -> pulmonary arterial hypertension
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
When do you transfuse people with sickle cell disease?
Acute worsening or acute end-organ injury
Domains of the light chain
1 variable, VL 1 constant, CL
Domains of the heavy chain
1 variable, VH 3-4 constant, CH1, CH2, etc
IgM forms a _________-mer
penta
Chain structure of IgG
2 light, 2 gamma
Chain structure of IgD
2 light, 2 delta Extra long hinge
Chain structure of IgE
2 light, 2 epsilon Extra constant domain
Chain structure of IgM
2 light, 2 mu w/ extra CHu4 domain Pentamer closed by J chain
Chain structure of IgA
2 light, 2 alpha Joined by J chain Wrapped by secretory component
When antibody types switch, the _________ chain changes, but the _________ does not
Heavy Light
2 types of light chains
kappa lambda
What is an antibody allotype?
Antibody chain alleles
What is an antibody idiotype?
A persons unique set of complementarity determining region You consider other people’s idiotype antigenic
What is a lattice/immune complex?
A complex of antigens and antibodies (since antibodies can bind multiple epitopes, we get a growing network)
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
Why is IgM good at activating complement?
You need two adjacent Fcs to start the complement cascade and IgM has five adjacent
The complement cascade activates _________
C3
The classical complement pathway is activated by _________
IgG or IgM complexes with antigens
Which antibody type is most resistant to enzymatic digestion?
IgA, with secretory component
What is the main complement inhibitor?
C1 esterase inhibitor
The alternative complement pathway is activated by _________
Bacterial cell wall components. It doesn’t need an antibody - handy!
The lectin complement pathway is mediated by _________
Mannose-binding protein, a lectin
What are lectins?
Proteins that bind carbohydrates
4 actions of the complement pathway
Lysis Opsonization Chemotaxis Anaphylatoxis
What levels of hemoglobin A are needed for disease?
1/2 levels - some symptoms 1/4 levels - disease 0 levels - incompatible with life
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)
What are RBCs like in thelassemia?
Low MCV and low hemoglobin concentration
What do pyrogens do?
Casue hypothalamus to produce prostaglandins that results in increased body temperature Exogenous pyrogens cause leukocytes to release endogenous pytogens
What are 3 acute phase reaction proteins we should know about?
C-reactive protein
Serum amyloid D
Fibrinogen
3 cell types that have histamine
Mast cells Basophils Platelets
What does serotonin do to blood vessels?
Vasoconstriction to aid in clotting
Which blood cell types have serotonin?
Platelets
2 arachadonic acid pathways for inflammation
Cyclooxenase -> prostaglandins, thromboxanes Lipoxygenase -> leukotrienes, lipoxins
Lipoxins antagonize ______
Leukotrienes
What is a quantitative vs. qualitative hemoglobin disorder?
Quantitative is decrased/imbalanced production of normal globin chains Qualitative is production of abnormal globin chains
4 downstream consequences of ineffective erythropoiesis in thalassemia
Anemia
Bone marrow expansion
Extramedullary hematopoiesis
Increased intestinal iron absorption
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.
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
Peripheral blood smear in thalassemia (3 abnormal findings)
Hypochromia Target cells Microcytosis
4 types of thalassemia syndromes
alpha-thalassemia
beta-thalaseemia
Sickle beta-thalassemia
Hb E syndromes
What effect does iron deficiency have on red blood cell numbers, mean corpuscular volume, and red cell distribution width
Decreased
Increased
Increased
With what other comorbidity is it difficult to diagnose beta-thalassemia
Iron deficiency. It makes the hemoglobin ratios look normal.
Is RBC sicklin reversible?
Yes, at first
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
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
What is sickle solubility testing?
Detects hemoglobin precipitates by looking at cloudiness of a hemoglobin extract of blood
What are the 3 antibody fragments?
Fc binds antibody receptors (Fab)2 is both Fab regions stuck together Fab binds antigens
What is the secondary structure of the immunoglobulin fold?
Antiparallel beta sheet wiht disulfide bond holding it together
What is antibody valence?
Number of antigens an antibody can bind
____________ is the most common antibody in the blood
IgG
The epitope is the part of the antigen that interacts with the ____________ region of the antibody and is a ____________ shape
Complementarity-determining Flat
What is antibody cross-reactivity?
When antibodies bind to different antigens
IgG plasma half-life is ____________
26 days
Which antibody can pass to the fetus?
IgG
How many J chains are there per antibody complex?
Just one
How is the IgM pentamer held together
4 disulfide bonds, 1 J chain
What is IgM’s single 2 weaknesses?
Will make blood too viscous Has a hard time getting out of the blood
Classical pathway C steps
1 4 2 3 5 6 7 8 9
How is C1q activated in complement?
It binds 2 adjacent Fc ends of bound antibodies
What are the 4 consequences of complement?
Lysis
Opsoniation - eating of pathogen
Chemotaxis
Anaphylatoxis - release of histamine from mast cells
What complement components make up the membrane attack complex?
6,7,8,9
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
Can a newborn make IgG?
No! It starts at 3-6 months
What cells express CD4 and what cells express CD8?
Helper T - CD4 Killer T - CD8
__________ secrete, IL__________ , which recruits neutrophils and monocytes
Th17 CD4+ T cells 17
IL17 recruits __________ and __________
Neutrophils Monocytes
__________ secrete, which __________ activates classical pathway macrophages
Th1 CD4+ T lymphocytes IFN-gamma
__________ secrete __________, __________, and __________, which activates alternative pathway macrophages and eosinophils
Th2 CD4+ T lymphocytes IL4, IL5, IL13
Mast cells express Ig__________
E
2 phases of B cell activation
- Binding of antigen to B cell receptors (membrane-bound versions of the antibody it will eventually secrete)
- If the binding is strong enough, activation takes place
What is the genetic process by which we get such large B cell diversity?
VJD recombination
What is somatic hypermutation?
B cell clones are hypermutable so daughter cells make slightly different antibodies.
What is affinity maturation?
Selection of best antigen-fitting B cell mutants after antigenic stimulation allows an incresae of affinity during an immune response
What part of the antibody switches in class switching?
Heavy chain class (never light chain class)
5 reasons B cells are so diverse
- 2-chain receptors - heavy and light
- Recombination of germ-line segments - V, D, and J combinations
- K or Gamme light changes
- N region diversity - random nucleotides are added or subtracted at VD and DJ hoins
- Somatic hypermutation
What is hemolysis?
An abnormal decrease in red cell survival or increase in turnover
What are two mechanisms for red cell destruction?
Intravascular - turnover within the vascular space
Extravascular - ingestion and clearance by macrophages
What is a structural RBC cause of hemolysis?
Hereditary spherocytosis
What are two enzyme disorders that causes hemolytic anemia?
- G6PD deficiency
- > lack of oxidative protection
- > oxidant stress
- > early RBC death
- Pyruvake Kinase deficiency
- > decreased ATP
- > increased 2,3-DPG
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
Most red cell turnover occurs in the __________
Spleen
What treatment is made for hereditary spherocytosis?
Splenectomy
What type of inherited disorder is G6PD deficiency?
X-linked recessive
Histological RBC changes in G6PD deficiency
Blister cells
Teardrop cells
Heinz bodies
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
When do babies make IgG? IgM?
IgG 3-6 months after birth
IgM 3 months after fertilization
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
What does haptoglobin do?
Haptoglobin scavenges free hemoglobin in the blood
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
How do you test for paroxysmal nocturnal hematuria?
Sucrose test - activates complement
Acidify serum - activates complement
Flow to look for presence of DAF (CD55)
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
What test is used to diagnose warm autoimmune hemolytic anemia?
Coomb’s test, either direct or indirect
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
How does microangiopathic hemolytic anemia work?
RBCs are sheared as they pass through circulation
Causes:
Microthrombi
Prosthetic heart valces
Aortic stenosis
4 causes of microcytic anemia
Iron deficiency
Chronic disease
Sideroblastic anemia
Thalassemia
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)
What are the 4 stages of iron deficiency anemia?
- Storage iron is depleted. Ferritin decreases, serum ferritin decreases, TIBC increases
- Serum iron is depleted. Serum iron decreases, % iron saturation decreases
- Normocytic anemia. RBC count decreased but they look normal
- Microcytic, hypochromic anemia
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
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
What causes sideroblastic anemia?
Defective proroporphyrin synthesis -> low heme
From:
Genetic
Alcoholism
Lead poisoning
B6 deficiency
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
What are the following hemoglobin’s chain composition?
HbA
HbA2
HbF
HbH
Hb Barts
alpha2, beta2
alpha2, delta2
alpha2, gamma2
beta4
gamma4
Causes of macrocytic anemia
Folate deficiency
Vitamin B12 deficiency
What causes megaloblastic anemia’s characteristic cells?
Can’t produce appropriate DNA precursors so rapidly dividing cells become large because they can’t divide
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
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
What is pernicious anemia?
B12 deficiency from
Intrinsic factor deficiency from
Autoimmune destruction of parietal cells
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)
What are the lab findings for extravascular hemolysis?
Spleen
Bilirubin
Gallstones
Marrow
Splenomegaly
Jaundice from unconjugated bilirubin
Bilirubin gallstones
Marrow hyperplasia
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
Where does clonal deletion of T and B cells occur?
Where they mature
T cells - thymus
B cells - bone marrow
What does haptoglobin do?
Binds free hemoglobin
What does hepcidin do?
Decrease gut iron absorption
Increase macrophage iron sequestration
What is MCHC?
Mean corpuscular hemoglobin concentration
How do you calculate mean corpuscular volume?
hematocrit / red blood cell count
How do you calculate mean corpuscular hemoglobin concentraiton? (equation)
Hemoglobin levels / hematocrit
At which step do all complement pathways merge?
C3 convertase cleaving and activating C3
Which complement derivatives are chemotactic?
C3a
C5a (but pick this one if given the option of both)
What makes up the membrane attack complex in complement?
C5b and C6-9
Which 2 complement factors cause mast cell degranulation?
C3a
C5a
Which complement component acts as an opsonin for phagocytosis?
C3b
What is anaphylatoxis?
Part of complement
Release of histamine from mast cells
IL-3 stimulates _________
IL-5 stimulates _________
Basophils
Eosinophils
_________ stimulates basophils
_________ stimulates eosinophils
IL-3
IL-5
What does lead poisoning inhibit?
Protoporphyrin formation
Where is ferroportin located?
On the basal surface of intestinal cells. Iron goes out of these cells into the blood
What is in the white pulp of the spleen?
Lymphocytes
What cells are in the sheath that surrounds teh central arteriole of the spleen?
T cells
B cells are a little further out
Sickle cells is a _______ to _______ substitution
Glutamine
Valine
CD_______ marks immature T cells
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