LA 1 Immunology and Genetics for TS

Question 1

Antigen

Answer 1

A foreign molecule that binds specifically to an antibody or a T-cell receptor.

Question 2

Antibodies

Answer 2

Immunoglobulins (glycoproteins) secreted by plasma cells (activated B lymphs) that recognize a particular epitope on an antigen and facilitate clearance of that antigen.

Question 3

Alloantibody

Answer 3

Antibody to “other” antigens - foreign antigens (most common type of Abs).

Question 4

Autoantibody

Answer 4

Antibody to “self” antigens.

Question 5

RBC alloantibodies are produced in response to:

Answer 5

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

Question 6

Non-red cell stimulated antibodies

Answer 6

Antibodies produced in response to “naturally occurring antigens” without an exposure to other person’s RBCs.

Question 7

Immunoglobulin

Answer 7

Antibody; glycoprotein secreted by plasma cells that binds to specific epitopes on antigenic substances.

Question 8

Sensitization

Answer 8

Binding of antibody or complement components to a red cell.

Question 9

Agglutination

Answer 9

Visible clumping of particulate antigens (on RBCs) caused by interaction with a specific antibody

Question 10

Extravascular hemolysis

Answer 10

Red cell destruction by phagocytes residing in the liver and spleen usually facilitated by IgG opsonization.

Question 11

Intravascular hemolysis

Answer 11

Red cell lyses occurring within the blood vessels usually by IgM activation of complement.

Question 12

In vivo

Answer 12

Referring to a reaction within the body.

Question 13

In vitro

Answer 13

Reaction in an artificial environment, such as in a test tube, microplate, or column.

Question 14

Lattice formation

Answer 14

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.

Question 15

Red cell antigens

Answer 15

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.

Question 16

Visible signs of Ag-Ab complex formation in vitro

Answer 16

1) agglutination (most often)

2) hemolysis (rarely)

Question 17

Stages of agglutination

Answer 17

1) sensitization - cannot be visualized; Abs bind to Ags on RBCs
2) lattice formation - leads to visible clumping of RBCs

Question 18

Factors that influence sensitization

Answer 18

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

Question 19

Factors that influence lattice formation

Answer 19

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

Question 20

Antigen-antibody reactions in vivo

Answer 20

1) sensitization of RBCs with antibodies

2) complement activation by Ag-Ab complex

Question 21

Sensitization of RBCs with antibodies

Answer 21

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

Question 22

Complement activation by Ag-Ab complex

Answer 22

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

Question 23

Zeta potential

Answer 23

Force that keeps RBCs apart from each other (repulsion) due to negative charges on RBC membranes

Question 24

2 main types of immunoglobulins in Transfusion Medicine

Answer 24

IgG (80%) and IgM (5-10%)

Question 25

IgG

Answer 25

Gamma heavy chains; 1 basic unit; can cross the placenta; sometimes activate complement

Question 26

IgM

Answer 26

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

Question 27

Significance of hemolysis in in vitro blood bank tests

Answer 27

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.

Question 28

Locus

Answer 28

Location of a specific gene on a specific chromosome

Question 29

Alleles

Answer 29

Alternate forms of a gene at a given locus

Question 30

Codominant expression

Answer 30

Equal expression of two alleles. Most blood group genes are codominant. Recessive and dominant expressions are uncommon.

Question 31

Amorph

Answer 31

“Silent” gene which doesn’t produce a detectable trait (antigen).

Question 32

Phenotype

Answer 32

Physical expression of inherited traits.

Question 33

Genotype

Answer 33

Actual genetic makeup inherited from parents; determined by family studies or molecular typing.

Question 34

Homozygous

Answer 34

“double dose” of an allele; identical genes received from each parent

Question 35

Heterozygous

Answer 35

“single dose” of each allele; different genes received from each parent

Question 36

Recessive expression

Answer 36

Trait expressed only when inherited from both parents

Question 37

Dominant expression

Answer 37

Gene product expressed over another gene.