Transfusion

What is the concerns when transfusing blood?

Death, blood borne diseases, sterility of equipment and blood product, oxygen carrying capacity, and clotting

Who is credited with the first description of how to perform a blood transfusion?

Andrea Libavius (1615)

Who published the theory of circulation in 1628?

William Harvey

What did William Harvey's theory remove?

A major obstacle in the progress of blood transfusion

Who performed a questionable successful transfusion of lamb's blood to a human in 1667?

Jean Denis

Who is credited with describing the first recorded transfusion reaction?

Jean Denis

What were the symptoms of the first recorded transfusion reaction?

Pain in kidneys, increased pulse, black urine, nausea, and death

What was the legal consequence of the first transfusion reaction?

French and British passed legislation prohibiting further blood transfusions

Who successfully completed the first human-to-human blood transfusion in 1818?

James Blundell

How many transfusions did James Blundell perform and how many were successful?

Performed 10 transfusions, successful in 4

What were the two early methods used to prevent blood from clotting?

Defibration (removal of fibrin) and addition of chemicals

They prevented clotting but were highly toxic

What did scientists discover in 1914/15 prevents coagulation and is non-toxic?

Small amounts of citrate

What was added to citrate to improve RBC survival?

Dextrose

What is ACD and what is the RBC survival time?

Acid citrate dextrose and 21 days

Who discovered the A, B, AB, and O blood groups?

Karl Landsteiner - 1901

How many associates did Karl Landsteiner mix blood with?

5

What is the most important discovery to date in transfusion science?

Discovery of the ABO blood group system

What prize did Karl Landsteiner win and when?

1930 Nobel Prize in Medicine

How many blood group antigens have been added since 1951?

Approximately 300

What does an immune response to transfusion or pregnancy involve?

Foreign antigen enters host

What rushes to the site of a foreign antigen and partially digests it?

Macrophages

What happens to the antigen after partial digestion?

It is tagged with RNA to become a super antigen

What is the super antigen presented to?

Immunocompetent T or B cells

What is blast transformation?

Cells divide forming a clone of cells

What does a B cell clone produce?

Plasma cells that secrete antibody

What does a T cell clone produce?

Te or Tk cells that produce cytotoxins

What does humoral immunity produce?

Antibodies - B cells

What does cellular immunity produce?

Cytotoxins - T cells

What are memory cells?

Small lymphocytes that exist in peripheral circulation for long periods

What do memory cells retain?

Information about the antigen that caused their production

What happens upon second exposure to the same antigen?

Memory cells quickly undergo blast transformation, become mature (HI) or Te (CMI) cells

What is the first exposure to foreign antigen called?

Primary response

When may a primary response begin?

Approximately 10-14 days (may take several weeks to months)

What class of antibody is mostly produced in the primary response?

IgM

What class of antibody is produced at low levels during the primary response?

IgG

What happens to low antibody levels in the primary response?

May fall below detectable levels

What is produced in the primary response that sensitizes the individual?

Memory cells

What is the secondary response?

2nd exposure to same antigen in a sensitized individual

What class of antibody is primarily produced in the secondary response?

IgG (some IgM)

How does the secondary response compare to the primary response?

Rapid, higher antibody levels, and remains higher for longer

What is the anamnestic response?

When a primary response occurred but was not detected

What is the secondary response excellent for?

Protection against disease

What is the first phase of the primary response?

Lag phase (antibody levels low, not detectable)

What is the second phase of the primary response?

Log phase (antibody produced logarithmically)

IgM antibody rises first followed by IgG

What is the third phase of the primary response?

Plateau phase (antibody production remains stable)

What is the fourth phase of the primary response?

Decline phase (antibody is catabolized and levels decrease)

What type of response occurs upon subsequent exposure to the same foreign antigen?

A secondary or anamnestic response.

Describe the secondary response phases

There is a shorter lag phase, a longer plateau, higher antibody levels, and a longer decline phase.

What is the primary antibody class produced in a secondary (anamnestic) response?

IgG antibodies.

What is active immunization?

When antibodies are stimulated by direct contact with antigen

What are immune antibodies also called?

Atypical antibodies

When does active immunization occur?

In pregnancy and transfusion

What clinical problems can atypical antibodies cause?

Hemolytic Disease of the Newborn (HDN) or Hemolytic Transfusion Reaction (HTR)

What happens if the wrong ABO group is tranfused?

Immediate antigen/antibody is transfused, hemolysis, activation of complement, and death

What is the main function of antibody?

the result of humural immunity - to combine with corresponding antigen

In transfusion, what does the patient's antibody combine with?

Transfused (donor) antigen

What happens when some antigen/antibody reactions activate all complement components?

Hemolysis of transfused cells occurs

What can hemolysis of transfused cells cause?

Decrease in blood pressure, shock, organ failure, and death

What type of reaction is usually related to ABO incompatibility?

Complement activation causing hemolysis

What is sensitization in antigen/antibody reactions?

Antibody attaches to red cell but complement is NOT activated

What happens to sensitized red cells?

Recognized as abnormal and removed by the R.E. system (Reticuloendothelial system) - macrophages in spleen

What happens when antigen/antibody reactions activate only some complement components?

Usually C1, C4, C2, C3 attach, then complement activation stops

What happens to red cells sensitized with complement components?

Do not hemolyze but are recognized as abnormal by R.E. system and removed

When is transfusion not beneficial to the patient?

When the results of humoral immunity decrease RBC survival in transfused cells. Therefore, transfusion has not been beneficial (may be harmful)

If a primary response occurs in a transfused patient, what remains circulating to potentially cause a secondary response?

Foreign antigens.

In a transfused patient who mounts a primary response, what is the theoretical consequence of remaining foreign antigens?

A secondary response and subsequent cell destruction.

Theoretically, what would all transfused individuals produce that would destroy transfused cells?

High levels of IgG antibodies.

What percentage of transfused individuals form blood group alloantibodies?

Less than 1%

In reality, what percentage of transfused individuals produce high levels of IgG antibodies and destroy transfused cells?

Less than 1%.

What percentage of transfused individuals form blood group alloantibodies?

Less than 1%.

Why do less than 1% of transfused individuals form blood group alloantibodies?

Because of variables.

What are RBC antigens in a suppressed immune systems?

Most RBC antigens are poor immunogens, and not all antigens are presented/processed at the same time

If there are only a few cells present each day insufficient antigens to stimulate alloantibody production

What happens when a primary/secondary response occurs while transfused cells are circulating?

Cell destruction

What is DHTR?

Delayed Hemolytic Transfusion Reaction

What is the basic structure of an immunoglobulin molecule called?

Monomer

How many chains of amino acids compose each monomer?

4 chains

How many heavy chains are in an immunoglobulin monomer?

2 identical long chains

How many light chains are in an immunoglobulin monomer?

2 identical short chains

What are the two types of light chains?

Kappa and lambda

What protein is capable of acting as an antibody?

Immunoglobulins

Define Antibody

a specific reactive immunoglobulin produced in response to a KNOWN antigen

What si the principle function of an antibody?

To bind corresponding antigens

However, secondary function may exhibit: compliment activation placental transfer

What can immunoglobulins (antibodies) function as when used to immunize a different species?

Antigens.

What is produced when immunoglobulins from one species are used to immunize a different species?

Anti-immunoglobulins (anti-antibodies).

What are the three specific antigenic determinants exhibited by anti-immunoglobulins?

Isotype, allotype, and idiotype.

What term describes the antigenic determinant of an immunoglobulin that is shared by all members of a species? Isotype.

What term describes the antigenic determinant of an immunoglobulin that differs between individuals of the same species? Allotype.

What term describes the antigenic determinant of an immunoglobulin that is unique to a specific antibody molecule? Idiotype.

What are the five classes of heavy chains?

Gamma, mu, alpha, delta, epsilon

What determines the class of an immunoglobulin?

The heavy chain

What holds the two halves of the monomer together?

Inter-chain disulphide bonds

What holds the lengths of chains together?

Intra-chain disulphide bonds

What are the folded areas of immunoglobulin chains called?

Domains or Homology regions

How many domains are in a heavy chain?

3 or 4 domains

How many amino acids are in a heavy chain?

Approximately 400 amino acids

How many domains are in a light chain?

2 domains

How many amino acids are in a light chain?

Approximately 200 amino acids

What does the constant region of an immunoglobulin determine?

The class of antibody

What are the constant regions of the heavy chain labeled?

CH1, CH2, CH3, and CH4

What is the constant region of the light chain labeled?

CL

What is the variable region concerned with?

Antigen binding and confers specificity to the antibody

What are the variable regions labeled?

VH on the heavy chain and VL on the light chain