BB LEC PRELIMS Flashcards
In 1492, a physician bled three young boys and have an ill ________________ drink the blood.
Pope Innocent VIII
He used a quill of a goose attached to a bladder to demonstrate that the intravenous injections of substances into animals had systemic
effects.
Architect Sir Christopher Wren
was the first to perform ABO typing and began compatibility testing. He also suggested
the inheritance of ABO types.
Dr. Richard Weil
discovered the ABO blood group
Dr. Karl Landsteiner
Sodium Citrate was discovered in ____
1914
First Blood donor service was established by
Percy Oliver
Antibody screen was officially regarded as part of routine testing in ______
1950s
Main stars of Immunology are
Lymphocytes
First line of defense
- Unbroken Skin
- Mucus membrane
- Sebum from Sebaceous glands
- Lactic acid in sweat
- Earwax
- Excretion of Solids and Liquids (feces/urine)
- Acidity of Stomach, Intestines, and Vagina
- Cilia in respiratory tract
- Tears (With IgA)
- Saliva
Non-specific, No exposure required, No
memory
Natural Immunity
Specific, can Recognize, can Remember, can Respond
Adaptive Immunity
Benefit of Adaptive Immunity
Acquire Immunologic Memory
Recognized as a foreign body; Can be a Protein, Carbohydrate, or Lipid
Antigen
antigens of the host; no reaction in normal circumstances
Autoantigens
antigen of the others
Alloantigens
antigens from other species
Heteroantigens
part of the Antigen that reacts with Antibody
epitope
Responsible for the specificity of the antigen
epitope
“Partial antigen”
Non-immunogenic alone (it needs a carrier)
Haptens
responsible for the molecular weight of the antigen (usually over 10,000 Daltons)
carrier
Formerly “Human Leukocyte Antigen” encoded from the gene found in short arm of Chromosome 6
Major Histocompatibility Complex
Can cause an immune response if transplanted
Major Histocompatibility Complex
Brings antigen to cell surface for recognition by T-cells
Major Histocompatibility Complex
2 classes of Major Histocompatibility Complex
Class I
Class II
- High levels on nucleated cells including lymphocytes
- Low levels in the liver, Neural, Muscle, and Sperm cells
- Recognized by Cytotoxic T-cells (CD8+)
- HLA-A, HLA-B, HLA-C, HLA-E
CLASS I
- More Restricted
- Found on B-cells, Macrophage, Dendritic Cells (APC)
- Process extracellularly derived antigen
- Recognized by T-Helper cells (CD4+)
- HLA-DP, HLA-DQ, HLA-DR
CLASS II
Molecules that bind to Antigen and is very specific
Antibodies
Y-shaped with 4 protein chains (2 Identical light chains and 2 heavy chains
connected by disulfide bonds)
Antibodies
Upper regions with Antigen binding sites - “N-terminal”
Variable regions
Lower portion of the “Y” arm
Constant regions
Stem of the monomer, binds complement or cells
FC regions
Located between CH1 and CH2 (binds complement C1q)
- Connects 2 FAB regions and FC portion
Hinge region
Flexible due to high numbers of Proline
Hinge region
Protein with around 440 amino acids and a MW of 40-50K daltons
Heavy chains
Constant region of H chains is unique and gives the antibody its name
Heavy chains
Genes that code for H chains are in _________
Chromosome 14
With the Kappa and Lambda chains
Light chains
Kappa is with ____ amino acids
214
Lambda is with ____ amino acids
213
Largest antibody with molecular weight of
900 000 Daltons
Immunoglobulin M
A Pentamer named after it heavy chain “µ heavy chain”
IgM
First antibody made by infants
IgM
IgM reacts best in what temperature
at Room Temperature and/or Cold temperature
First Antibody produced during infection,
Last to leave
IgM
With a Delta Heavy chain, and has a molecular weight of 180 000 Daltons
Immunoglobulin D
Second type of IG to appear
IgD
Heat and acid labile, and is susceptible to proteolysis
IgD
Monomer found on B-cell surface, Blood, and Lymph
IgD
IgA is found in serum as a __________
Monomer
IgA is found in secretions as a _______
Dimer
Antibody that protects mucosal surfaces,
“Major secretory IG” (Tears, Saliva, Milk)
IgA
2 Types of IgA
IgA1
IgA2
Molecular weight of IgA
160 000 - 400 000 daltons
Major serum Immunoglobulin
Immunoglobulin G
Binds FC receptors, Activates complement, neutralizes toxins, and enhances phagocytosis.
Immunoglobulin G
A monomer with Gamma Heavy chain
IgG
Main antibody in secondary response
IgG
IgG reacts best in what temperature
Body temperature
Can travel to the placenta and protect newborns
IgG
A monomer with an extra domain, molecular
weight is 190 000 Daltons
Immunoglobulin E
Plasma cells that produces IgE is usually on the ______
Lungs and Skin
IgE is bound to _______ and ________
Mast Cells and Basophils
Binds to FC receptors of Eosinophils for the
Major basic Protein
IgE
Antibody for allergy (Type 1hypersensitivity), and parasitic infections
IgE
Polypeptide products of activated cells
Cytokines
Controls cellular response and regulates the immune system (innate and adaptive response)
Cytokines
Cytokines binds to ______
target cell receptors
Polypeptide products of activated cells
Cytokines
Enumerate the five Cytokines
- Interleukins
- Interferons
- Stem Cell Factors
- Tumor Necrosis Factors
- Chemokines
Non-specific proteins
Complement
Completes the process of Antibody-Antigen complex
Complement
Most of the complement are synthesized in the ____
Liver
Complement reacts at pH: ___ and at Temp of ______
pH: 7.2 - 7.4
Temp: 30-37C
3 known pathways of complement
- Classical pathway
- Alternative pathway
- Lectin pathway
What the effects of Complement
- Chemotaxis
- Lysis of Cells
- Mediators
- Opsonization
- Increase Vascular Permeability
Participate in the process of cellular immunity
T-lymphocytes
Participate in the process of humoral immunity
B-lymphocytes
Natural cytotoxicity against cancer cells and virus infected cells
NK-lymphocytes
Lives as immature “Thymocytes” in the
Thymus
T-cells
60-80% of Circulating lymphocytes
T-cells
Thymocytes then matures as ______ and actively proliferates by the help of _______
Double negative Thymocytes; Interleukin 7
Double negative Thymocytes matures to ______________ (CD4+ and CD8+
cells)
Double Positive Thymocytes
T-helper cells is also known as
“Inducer cells” , “CD4+ cells”
Recognize antigen with MHC-II (found on surface of APC)
T-helper cells
due to expression of IL-12 by dendritic cells
Th1
development regulated by Interleukin 4
Th2
regulate activity of Th1 and Th2
T regulatory cells
For cell mediated immunity
Th1
For antibody mediated immunity; Helps B-cells produce antibodies
Th2
From IL10 responsive naive T-cells; CD25
T regulatory cells
“CD8 cells”
Cytotoxic T-cells
Destroys target cells
Cytotoxic T-cells
Kills cancer cells and destroys transplanted tissue
Cytotoxic T-cells
Cytotoxic T-cells produced _________ and targets cells by lysing the target cells
Perforin
Shuts down the immune response; Controls/Inhibit antibody production
T-suppressor cells
Markers of T-suppressor cells
CD2, CD3, and CD8 markers
Develops in the bone marrow
B-cells
B-cells matures to ________ to produce antibodies
Plasma cells
MHC class of B-cells
class II
Other names for Natural Killer Cells
“Third population”
“Kiss of death”
“Null cells”
“Granular lymphocytes”
Small population of Lymphocytes that does not express markers for T-cells or B-cells
Natural Killer Cells
Non-specific; Usually kills virally infected cells and Cancer cells
Natural Killer Cells
Branch of Biology that deals with molecular structures of cells
Molecular Biology
linear polymers composed of bases, sugars, and phosphate
Nucleic acids
a unique content of genetic information
Genome
sites in the genome that vary among different
individuals
Genetic polymorphism
carriers of genetic information; Thread-like material of the nucleus
Chromosomes
position of the genes in a chromosome
“Loci”
synthesis of RNA from a DNA template
Transcription
Transcription is mediated by _______________
DNA dependent RNA polymerase or “RNA polymerase”
Catalyze formation of phosphodiester bonds that links the nucleotides together to form a linear chain
RNA polymerase
an RNA with an equal length to the DNA
“Primary Transcript” or “Pre-RNA”
genes with intervening sequences
Split genes
long sequence of genes that are removed during RNA processing
Introns
short sequence that consist of functional genes
Exons
removal of introns from the newly synthesized RNA
RNA splicing
Mature RNA are translated to its respective amino acid to form proteins. This method is called _______
Translation
Number of blood group system and blood antigens
33; 300 respectively
Blood groups that are composed of antigens made up of glycoproteins or glycolipids
ABO, P, Lewis, H, I, and MNS
T or F. The remaining blood group systems has antigens that are indirect consequences of amino acid variation in the protein sequence.
False. *antigens that are direct
Single nucleotide polymorphisms
- Gene deletion
- insertion
- intergenic recombination
- substitution
- translocation; and
- duplication
Shape of RBC membrane to allow a close to maximum surface to volume ratio and optimal gaseous exchange.
biconcave shape
Functions of RBC Membrane
- Deformability
- Osmotic Balance
- Support for Antigens
- Gas Exchange
Controls the active transport of Na+ and K+ in the cell
Na+ K+ pump
Intracelluar ratio of Na and K
1:12
Extracellular ratio of Na and K
25:1
Percentage of Proteins, Lipids, and Carbohydrates in the RBC membrane.
Proteins: 50%
Lipids: 40%
Carbohydrates: 10%
Proteins found in the outer surface to the entire membrane including the inner cytoplasmic side that support the CHO defined blood group antigens
Integral protein (Transmembranous)
Produced by Component A and Glycophorin A which gives the RBC a negative charge for Zeta potential.
Sialic acid
Other integral proteins
Glycophorin B
Glycophorin C
Anion-Exchange-Channel Proteins
A type of protein that forms the cytoskeleton and is found in the cytoplasmic surface of the membrane.
Peripheral Protein (Skeletal)
For normal RBC membrane
Spectrin and Actin
How many amino acids does each alpha and beta spectrin have that forms a helix shape sheath?
106
Spectrin and actin are fixed into the membrane by the protein called …
Ankyrin
Ca2+ ATPase is for calcium flow and is controlled by
Calmodulin
Other peripheral proteins
Ankyrin
Protein 4.1
Adducin
Dematin
Tropomyosin
Tropomodulin
The distribution of lipids depends on these enzymes
Flippases, Floppases, Scramblases
Major constituents of the external surface of lipids.
Phosphatidylcholine
Sphingomyelin
Major constituents of the internal surface of lipids
Phosphatidlyserine
Phosphatidylethanolamine
Phosphatidylinositol
Lipids in esterified form which confers tensil strength to the lipid bilayer and is very hydrophobic that is why it is placed parallel to the acyl tails of the phospholipids.
cholesterol
Formed by carbohydrates and lipids which protects RBC from impact with other RBCs or vessel walls.
glycocalyx
Discovered ABO group
Dr. Karl Landsteiner
Most important blood group in transfusion practice
ABO
Individuals have < answer > in their serum against the < answer > absent from their RBCs.
antibodies; antigens
ABO inheritance follows
simple mendelian genetics
ABO is inherited via
codominant expression
Location of ABO genes and number of exons
Chromosome 9, 7 exons
Group O gene is considered an < answer > and is an autosomal recessive trait with the inheritance of two O genes that are nonfunctional
amorph
Q1: Formation of ABH antigens depends on these three genes from three seperate loci;
Q2: these genese code for the production of …
ABO, Hh, Se
Glycosyltransferase
Formation of ABH antigens develops…
2nd month of fetal life and will stay forever
Precursor substance for the formation of ABH antigens
Paragloboside/Glycan
What type of precursors are RBC ABO antigens contstructed?
Type 2
H gene is at
Chromosome 19
Is the H gene inherited dependently or independently from ABO genes?
independently
ABO gene spans about
18 to 20 kb
These exons encode for the catalytic domain of the ABO glycosyltransferases.
Last two exons (exon 6 & 7)
Results from any mutation in an A or B transferase gene that causes loss of glycosyltransferase activity and nonfunctional enzyme
Group O phenotype
Most common Group O results from a single nucleotide ….
deletion
Carbohydrate structures of ABO antigens are composed of
glycoproteins and glycolipids
RBC membrane proteins carry over ____________________ A or B or H antigens mostly located on the major integral membrane protein, Band 3
2 x10^6
ABO Antigens can be found in/on …
- platelets
- Endothelial and epithelial cells of the lungs and gut
- Epithelial cells of the urinary and reproductive tracts
ABO indicidence:
Usually found in African Americans and Asians (11% in whites, 20% in blacks)
Group B
ABO incidence:
Most common in Asians (40 - 45% in whites, 50% in blacks)
Group A and O
Rarest ABO
AB
Basic antigenic material of ABO which is found in greatest concentrations on the RBCs of Group O individuals and least in A1B
H antigen
anti-H antiserum
Ulex europeus
Secretor genes
Se gene or FUT2 gene
SeSe and Sese genostypes secretes A, B, H antigens in …
saliva
sweat
urine
milk
tears
This allelle is an amorph
se
Inheritance of hh gene therefore no “H” subtance
Bombay phenotype
Bombay phenotype was first reported by
Dr. Bhende in 1952 in Bombay, India
Bombay phenotype is caused a mutation in this gene which produces a silenced gene.
FUT1 gene
Bombay phenotype fails to react with …
Anti A
Anti B; or
H
Bombay phenotype people produces the ff. autoantibodies
Anti A
Anti B
Anti H
Bombay blood group is rare and can only be found in
4 out of 1 million
Produced by Bombay phenotypes which is an IgM that react at 37 C
Anti H
Phenotypes where RBCs completely lack H antigens or have only small amounts of H antigen present
Para Bombay Phenotypes
In Para-Bombay phenotypes, RBCs express weak forms of A and B antigens which are only detected in this technique
elution technique
More common subgroup
A subgroups
Inheritance of A1 gene elicits production of high concentrations of ___________________ which then converts all H subtances to A1 antigen
3-N-acetylgalactosaminyl transferase
Due to polymorphims at the ABO locus
Subgroups
This subgroup results from a single-base substitution at nucleotide 1059
A2
Used to differentiate A subgroups
Dolichos biflorus
These subgroups demonstrate weak or no agglutination of red cells with anti-b reagents
B subgroups
ABO antibodies develops and peaks at…
Develops at 3-6 months after birth
Peaks at 5-10
ABO antibodies are mostly
IgM (some are IgG)
autoantibody
Anti H
Q1: Also known as cell group where patient’s rbcs are added to sources of commercial antisera to detect antigens on an individual’s RBCs
Q2: What specimen is used
forward grouping; Red cells
First ABO red cell typing reagents were derived from
pooled human plasma sources
B cells secrete antibodies that are specific for the multiple epitopes of the injected antigen. This contains multiple antibody specificities
polyclonal antibody reagents
creates an immortal clone that manufacturers antibodies of a defined specificity
Monoclonal antibody reagents
Also known as serum grouping or serum testing which detects ABO antibodies using known reagents RBCs
What are these reagent RBCs and from what specimen is it obtained
Reverse grouping
A1 and B cells
Patient serum
Classic methods for visualization of antigen-antibody reactions
Agglutination (observed with hemolysis)
If present in tube grading, this is noted and considered a positive reaction
hemolysis
Factors influencing antigen-antibody reactions
- Temperature (IgM: Below 22, IgG: 37)
- Type of antibody
- Centrifugation (Brings reactants closer together)
- Antigen-antibody ratio
- pH (6.5 - 7.5)
- Dosage effect
Technical Errors (CCC FI MM UW)
- Clerical errors/incorrect recording of results
- Cell suspension problems: Too heavy or too light
- Contaminated reagents
- Failure to add reagents
- Improper identification of Blood specimen, patient, slides, test tubes
- Mix up in samples
- Missed observation of hemolysis
- Uncalibrated centrifuge
- Warming during centrifugation
What are the 4 ABO discrepancies?
Group 1: Discrepancy that happens between forward and backward grouping due to weakly reacting or missing antibodies
Group 2: Discrepancies are due to weakly reacting or missing antigens
Group 3: Discrepancy due to Protein or Plasma
abnormalities
Group 4: Discrepancy due to unexpected antigen reaction or miscellaneous
