LA 1 Immunology and Genetics for TS Flashcards
Antigen
A foreign molecule that binds specifically to an antibody or a T-cell receptor.
Antibodies
Immunoglobulins (glycoproteins) secreted by plasma cells (activated B lymphs) that recognize a particular epitope on an antigen and facilitate clearance of that antigen.
Alloantibody
Antibody to “other” antigens - foreign antigens (most common type of Abs).
Autoantibody
Antibody to “self” antigens.
RBC alloantibodies are produced in response to:
1) transfusion: patient is exposed to foreign antigens on transfused red blood cells
2) pregnancy: mother is exposed to foreign antigens on baby’s RBCs (antigens inherited from the father)
3) environmental factors: patient is exposed to environmental factors which mimic RBC antigens
Non-red cell stimulated antibodies
Antibodies produced in response to “naturally occurring antigens” without an exposure to other person’s RBCs.
Immunoglobulin
Antibody; glycoprotein secreted by plasma cells that binds to specific epitopes on antigenic substances.
Sensitization
Binding of antibody or complement components to a red cell.
Agglutination
Visible clumping of particulate antigens (on RBCs) caused by interaction with a specific antibody
Extravascular hemolysis
Red cell destruction by phagocytes residing in the liver and spleen usually facilitated by IgG opsonization.
Intravascular hemolysis
Red cell lyses occurring within the blood vessels usually by IgM activation of complement.
In vivo
Referring to a reaction within the body.
In vitro
Reaction in an artificial environment, such as in a test tube, microplate, or column.
Lattice formation
2nd stage of agglutination (after sensitization): combination of antibody and a multivalent antigen due to random collisions to form cross-links and result in visible agglutination.
Red cell antigens
Located on the RBCs: they are part of the cell membrane or protrude from the cell membrane. Ags removal destroys the integrity of the membrane and leads to hemolysis.
32 RBC blood group “systems”; more than 200 RBC antigens.
Visible signs of Ag-Ab complex formation in vitro
1) agglutination (most often)
2) hemolysis (rarely)
Stages of agglutination
1) sensitization - cannot be visualized; Abs bind to Ags on RBCs
2) lattice formation - leads to visible clumping of RBCs
Factors that influence sensitization
1) plasma to cell ratio: increased amount of plasma (i.e. increased amount of RBCs) increases the chance of sensitization
2) temperature of reaction: 37C for IgG; 20-24C for IgM
3) incubation time - need adequate time for reaction: 30-45 mins
4) pH: optimum for most reactions is 7.0
5) ionic strength: if ionic strength is lowered, Ag-Ab binding is enhanced since there is less competition for charged sited
Factors that influence lattice formation
1) distance between red cells: lower zeta-potetial enhances agglutination
2) concentration of Ag and Ab
3) centrifugation: forces RBCs closer - if RBCs are sensitized, it’s easier for them to agglutinate
Antigen-antibody reactions in vivo
1) sensitization of RBCs with antibodies
2) complement activation by Ag-Ab complex
Sensitization of RBCs with antibodies
Abs attach to Ags on RBCs. These “sensitized RBCs” are recognized as defective and removed by the spleen, etc. -> extravascular hemolysis - RBCs are broken down outside of blood vessels -> Anemia
Complement activation by Ag-Ab complex
Occurs in vivo - may or may not occur depending on which antibody is involved.
Complement cascade is activated by Ag/Ab complex:
- if activated only to C3 -> sensitization, extravascular hemolysis
- if activated to C9 (MAC) -> disruption of RBC membrane -> intravascular hemolysis - RBCs are destroyed inside the vessels -> Anemia + Clotting problems + Shock - could result in death
Zeta potential
Force that keeps RBCs apart from each other (repulsion) due to negative charges on RBC membranes
2 main types of immunoglobulins in Transfusion Medicine
IgG (80%) and IgM (5-10%)
IgG
Gamma heavy chains; 1 basic unit; can cross the placenta; sometimes activate complement
IgM
Mu heavy chains; 5 basic units held together with a J chain (joining chain); cannot cross the placenta (too large); more likely to activate complement
Significance of hemolysis in in vitro blood bank tests
Red cell hemolysis observed in the tube is also an indicator of the reactivity of an antigen and antibody in vitro.
If the complement system is activated by an immune complex, hemolysis of the red cells along with agglutination can occur. The final steps in the process of complement activation initiate the membrane attack complex, causing membrane damage. As a consequence of this damage, intracellular fluid is released to the reaction environment.
A hemolyzed patient sample is not acceptable for serologic testing in the blood bank because hemolysis is interpreted as a positive reaction.
Locus
Location of a specific gene on a specific chromosome
Alleles
Alternate forms of a gene at a given locus
Codominant expression
Equal expression of two alleles. Most blood group genes are codominant. Recessive and dominant expressions are uncommon.
Amorph
“Silent” gene which doesn’t produce a detectable trait (antigen).
Phenotype
Physical expression of inherited traits.
Genotype
Actual genetic makeup inherited from parents; determined by family studies or molecular typing.
Homozygous
“double dose” of an allele; identical genes received from each parent
Heterozygous
“single dose” of each allele; different genes received from each parent
Recessive expression
Trait expressed only when inherited from both parents
Dominant expression
Gene product expressed over another gene.
