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DD & BL Unit III / Final Exam > Immunology > Flashcards

Flashcards in Immunology Deck (71)
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1

How are monoclonal antibodies made?

Monoclonal antibodies derive from the progeny of a single B cell that has been fused with a multiple myeloma tumor cell; the resultant hybrid line can grow forever in culture and make a specific antibody

2

Humira

A fully human mAb to TNF-a shown to slow the progress of rheumatoid arthritis

3

-omab

Murine - monoclonal antibodies made from immunized mice

4

-ximab

Chimeric - mAbs genetically engineered at the DNA level to have mouse VL and VH domains (25%) but human C domains (75%)

With time, patients will still make human anti-cheric antibody (HACA)

5

-zumab

Humanized mAbs - only the CDRs of the V domains are from the mouse (2% foreign)

Still, with time, patients will make human anti-human antibody (HAHA)

6

-umab

Human - SCID mice are implanted with human bone marrow, thymus, and lymph node; immunization of the mouse with antigen now produces human antibodies

7

Herceptin

Humanized Ab to EGF receptor HER-2

Downregulates the receptor and sensitizes the cell to killing by ADCC

8

Naturak Killer (NK) Cells

Large granular lymphocytes (LGLs) which make up 5-10% of blood lymphocytic cells; they are part of the innate immune system with receptors against molecules that appear on the surface of stressed or dysregulated cells; they recognize these cells and send apoptotic signals

9

Antibody-dependent cell mediated cytotoxicity (ADCC)

NK cells have receptors for the Fc end of IgG; NK cells can recognize therapeutic mAb coating target cells and send apoptotic signals to that cell

10

Chimeric Antigen Receptor (CAR)

T cells can be removed from cancer patients and transformed using a lentivirus vector to express a chimeric antigen receptor (CAR); the CAR is usually comprised of the VL/VH fragment of an antibody with high specificity against tumor-related antigens, a transmembrane region, and an intracellular T-cell signaling molecule such as CD3

This transformed CTL can then bind a tumor target with high affinity and specificity and be triggered via its normal TCR pathway to become a fully cytotoxic cell

11

Blood group antigens

Glycolipids found on the surface of all body cells, including RBCs; comprised of a basic "H antigen" linked by a specific glucosyl transferase to variant terminal sugars; the 3 possible alleles of the glucosyl transferase enzyme confer antigenic specificity A, B, or O

12

Blood group substances

Glycoproteins found in the body fluids of people who have the Secretor (Se) phenotype (80%); these glycoproteins are antigenically similar to blood group antigens

13

Rh antigens

Rh antigens are proteins coded for at two loci, the most important of which is the D/d locus

D is dominant over "d" which is an amorph and does not make protein

Genotypes DD or Dd type as Rh+ and 85% of US whites have this phenotype; Rh- individuals do not make isohemagglutinins against Rh unless they are immunized by Rh+ cells

14

ABO Isohemagglutinins

IgM antibodies made against foreign ABO blood antigens; theey appear in the blood between 3 and 6 months of age

15

Bombay blood type

These individuals lack the transferase gene that puts the final sugar on the core ABO antigen polysaccharide; therefore, they do not express even the basic "H" antigen and all blood is foreign to them

In a lab not looking for this the individual will type as "O"

16

Crossmatch procedure

Plasma from the blood recipient is mixed with red cells from the donor; agglutination means that lots of high activity antibodies against the donor's RBCs exist in the recipient's serum

This test is further evaluated in a medium that neutralizes the repulsive charges of RBCs, providing a more sensitive test for agglutination

17

Direct Antiglobulin Test Procedure

Uses antibody against human Ig to detect human Ig on the surface of RBCs

Patient's RBCs are washed and antibody against human Ig is added; if the RBCs had some human Ig on them then the antiglobulin will cross-link the antibody-bound RBCs, leading to agglutination

Detects cells that were coated with antibody in vivo

18

Indirect antiglobulin test procedure

Uses antibody against human Ig to detect human Ig in plasma

Patient's serum is added to donor RBCs; the patient's antibody will bind the donor's RBCs but may not be enough to agglutinate; antiglobulin is added, which cross-links the donor's RBCs that have been bound by the patient's Ab

Detects antibody in the circulation

19

Heterophile antibodies

Antibodies that are directed against one antigen but also cross-react with a different antigen

20

Monospot test

Antibody test for EBV (Mononucleiosis)

Patients make a serum antibody to EBV viral antigen that happens to cross-react with sheep RBCs; therefore, agglutination of sheep RBCs with addition of the patient's serum is a positive screening test for EBV mononucleiosis

21

Hemolytic Disease of the Newborn - Complications

High levels of bilirubin released from lysed RBCs can cross the BBB and damage the basal ganglia, resulting in cerebral palsy or death

Jaundice

22

Hemolytic Disease of the Newborn - Mechanism

When an RhD- mom is pregnant with an RhD+ baby, any event (labor, abortion, miscarriage) that allows escape of RBCs from placental to maternal circulation can sensitize the mother to produce IgG against RhD

In a subsesquent pregnancy with an RhD- fetus these anti-RhD IgG can cross the placenta and gain access to fetal circulation where they opsonize fetal RBCs for destruction by the RE system, causing massive hemolysis

23

Rh-immune globulin (RhoGAM)

RhoGAM is IgG antibody to RhD; these antibodies combine with fetal red cells in maternal circulation, opsonizing them for destruction before they can immunize her against RhD

Should be administered at 28 weeks and also each time there is a chance of being immunized by RhD cells, including delivery, abortions, fetal manipulations, amniocentesis, etc.

24

ABO Hemolytic Disease of the Newborn

Rarely, some type O mothers can make IgG isohemagglutinins against the fetal ABO antigens; these IgG can cross the placenta and cause hemolytic disease of the wrong-type fetus

25

Serum protein electrophoresis

Serum is applied to an agar plate and voltage is applied across the plate causing proteins to separate by size; proteins can be stained and the results are given as a trace with the following peaks:

Albumin, alpha1, alpha2, B, and gamma

Immunoglobulins generally segregate into the gamma peak

26

Bence Jones Protein

Free Ig light chains seen in the urine of patients with multiple myeloma; diagnosed by protein electrophoresis

27

Single radial immunodiffusion

Gel containing rabbit anti-serum to human Ig is plated and human serum is added to a well in the middle of the plate

Ig within the patient's serum will precipitate out with the anti-Ig in the agar and the size of the precipitated ring gives information about how much Ig was present in the serum

This technique can be used to measure any multivalent antigen that can form a precipitate with the appropriate antibody, as long as you have the specific antiserum

28

Test for antinuclear antibodies

Patient serum is added to human cells grown on a slide and fixed with an agent that makes the cells' plasma membranes permeable to antibodies; fluorescent-labeled anti-human IgG is added and the pattern of fluorescences allows detection of antibodies attached to nuclear antigens

29

Test for immune complexes in the serum

Immune complexes in serum are insoluble in the cold; if a Type III process is suspected, a sample of patient serum is refrigerated and examined after 1-7 days for precipitate called mixed cryoglobulin

30

Passive agglutination

Ex: Rheumatoid factor (IgM anti-IgG) is detected by its ability to agglutinate latex beads that have been coated with IgG; this test is more sensitive due to the larger effective size of the antigen