Fundamentals of immunology for Blood

bankers
Blood Banking
Lec. 2
3rd Grade – Spring Semester 2021-2022

Goran Noori Saleh

MSc. At HMU(goran.nori@tiu.edu.iq)
13/02/2022
Importance of immunology in
Blood banking
• In order to make a selection of the compatible
donor it is essential to understand the
immunological characteristics of the blood in so far
as they apply to this area
• The study of immunologic reactions involving
all components of blood Deals with
antigens, antibodies and antigen-antibody
reaction
• Some aspects of basic immunology needs to
revised here before undertaking the study of blood
groups.
 Some terms :
• Immunoglobulin: Antibody formed as a result of immune
stimulus (exposure to foreign antigen).
• Naturally occurring: Antibody formed without prior
exposure to foreign antigen
• Autoantibody: Antibody formed to one's own antigens
(abnormal condition)
• Alloantibody: (unexpected, irregular, atypical): Antibody
formed to foreign antigens, but within the same
species. Stimulated by transfusion or pregnancy
• Antigens - These are substances of high molecular
weight, mostly protein but also carbohydrates and lipids
which when injected in the blood lead to the production
of antibodies. These react specifically with the
corresponding antigens.
• Allogenic antigens Non-self antigens

• Autologous antigens Self antigens

• Agglutinogen - Any antigen which is demonstrated by
aggutination reaction with the corresponding antibody.
• Antibody - It is a gamma globulin (immunoglobulin Ig)
produced in response to the administration of an
antigen and reacts specifically in vitro and vivo with that
• Immunization - The process by which a person or an animal develop
antibodies against a foreign antigen introduced in the body
deliberately or accidentally.
• Agglutinin: Antibody capable of causing agglutination when reacting
with corresponding antigen
• Isoagglutinin Name commonly given to blood group antibodies anti-
A and anti-B
• Saline agglutinin : Antibody capable of causing direct agglutination
of antigens suspended in a saline medium without requiring any
enhancement techniques.
• Hemolysin: Antibody capable of causing hemolysis when reacting
with corresponding antigen
• Cold antibody (Cold agglutinin) : Antibody whose optimal
temperature of reactivity is less than 30 C
• Warm antibody: Antibody whose optimal temperature of reactivity is
greater than 35 C
Clinical significance of IgG and
IgM Antibodies
- IgG will frequently cause in vivo hemolysis due to
antibody coating the RBC
- IgM generally does not cause in vivo hemolysis.
The most important of these exceptions are ABO
antibodies.
- Clinical of red cell antibodies in blood bank
depend on whether they can cause in vivo
hemolysis, which in turn will cause transfusion
reactions or hemolytic disease of the
newborn.
How many binding sites does IgM have?
10 binding sites IgM
What is the optimum temperature of reactivity for IgM?
4 C (may react at any temperature below 30 C)
Which Immunoglobulin can cross the placenta?
IgG

Where is IgG found in the largest concentration of all immunoglobulins?

In the plasma / serum

How many binding sites does IgG have?

2 binding sites

Non-RBC immune antibody.

Antibody that is present without any evidence of exposure
to foreign red cell antigen (Anti-A, anti-N, etc)
Important types of diseases in blood bank
• Immunodeficiency
• Hypersensitivity
• Monoclonal or polyclonal Gammopathies
• Autoimmune Diseases
• Hemolytic Disease of the Newborn

What makes a good antigen?

• Complexity and Foreignness
1) bigger is better
2)protein then carbohydrate then fat (most complex like
protein is best)
3) similarity to self (least similar is best)
• What is immunohematology?
• The study of human blood groups. The tests usually
being performed in the hospital blood bank.

Factors that affect agglutination

• Temperature
• pH
• Incubation time
• Ionic strength
Haptens

• small molecules that are too small to stimulate an

immune response

• may become antigenic when bound to larger carrier

molecules

• React with antibodies

• when it is combined with a larger carrier molecule,
usually a serum protein, it and its carrier together
form a conjugate that can stimulate an immune
response
• Epitopes single antigenic
determinants; functionally,
parts of the antigen that
combine with the antibody
• Fab regionbinds to
antigen
• Fc region responsible for
biological activity, the stem
• Opsonin A substance
(antibody or complement
protein) that binds to an
antigen and enhances
phagocytosis
• Adsorption - when red cells are mixed with antibodies to
their group there is rapid coating of the red cells by the
antibody which is then followed by agglutination. The
phenomenon of coating by the antibody is called
absorption
• Elution : This is the process of removing the adsorbed
antibodies from the red cells surface. It is used to get the
antibody in pure form and find out its specificity.
• Sensitization - some of the antibodies e.g. Rh antibodies,
fail to cause agglutiantion in saline medium but these
would be absorbed on the red cells. The phenomenon of
absorption without agglutination is called sensitization.
These sensitized cells are recognized by the coomb's test.
• Prozoneexcess antibody causing a false-
negative reaction
• Postzoneexcess antigen causing a false negative
 HLAs
• - Found on leukocytes and tissue cells
- HLA antibodies are produced as a result of transfusion
or pregnancy
- Antibodies have been associated with refractoriness and
transfusion reactions
- HLA testing is used to assess risk factors for disease
susceptibility
- Matching for organs and HPC transplants
Patients may become sensitized to HLAs by the
following exposures...
• 1. Pregnancy
2. Blood transfusions
3. Previous transplant
Antibodies to platelets may
cause..
• 1. Neonatal alloimmune thrombocytopenia (NAIT):
destructions of newborn platelets by maternal
antibody
• 2. Posttransfusion purpura (PTP): destruction of
platelets after transfusion
Factors contributing to
immunogenicity
• Properties of the antigen:
1.Chemical composition and complexity of the
antigen
2. Degree of foreignness
3. Size
4. Dosage and antigen density
5. Route of administration
 Fundamentals of Immunology for Blood
•Bankers
The immune system (IS) is
complicated, tightly
controlled, and includes
tissues, organs, cells, and
biological mediators that
coordinate to defend a host
organism against invasion by
a foreign substance or
abnormal cells of self-origin.
• Immunity refers to the
process by which a host
organism protects itself from
attacks by external and
internal agents.
 • The immune system interacts
with other host systems and
maintains the host
equilibrium.
• The two major roles for the IS
are:
• Protection from pathogens and
foreign substances
• Removal of abnormal and
damaged host cells

• The two major

branches of the IS
are:
• Innate, or natural—
the nonspecific
primitive IS
• Acquired, or
adaptive—the
specific, evolved IS
 • The two major arms of the acquired IS are:
• Humoral, mediated by B cells and antibody production
• Cellular, mediated by T cells and lymphokines
• The basic
mechanisms used
by the IS are:
• Recognition of
self and nonself
organisms, cells,
and tissues
• Removal of
unwanted
organisms, cells,
and tissues
(self or nonself)
• Repair of
damaged host
tissues
• The acquired IS demonstrates diversity and uniqueness:
• Individual B and T cells have vast arrays of unique membrane
molecules that can have configurations to match nearly any
antigen in the environment.
• Each individual lymphocyte has one unique receptor per cell
that
recognizes one epitope(part of an antigen molecule to which an antibody attaches itself).
• Antibodies and T-cell receptors recognize and react only with
the
antigen that matches and fits their specific configuration.
• Selected T and B cells can remain dormant and later respond more
carefully upon second exposure of a previously recognized
antigen.

• The acquired IS demonstrates tolerance this indicates

that immune responses against the host are either removed
or down regulated.
• There are three types of
lymphocytes: T cells, B cells,
and. NK cells (rejection of
both tumours and virally
infected cells)
• T cells (or lymphocytes) have
the T-cell receptor, which is
usually associated with the
CD3 complex, and T cells
require antigen presenting
cells to respond to antigens.
• There are two well-
characterized subpopulations
of T cells distinguished by CD
markers—T helper (TH,
CD4- positive) and T
cytotoxic (Tc, CD8-positive)
lymphocytes.
• CD8+ T cells (cytotoxic T cells) are cells of the
immune system that contribute to the body's
adaptive immune response. These immune cells are
characterized by a CD8 protein on their cell surface
that allow them to recognize, bind and kill cells
infected by intracellular bacteria, intracellular
viruses and cancer cells
• CD4+ T (helper cells) They are called helper cells
because one of their main roles is to send signals to
other types of immune cells, including CD8 killer
cells, which then destroy the infectious particle.
• TH lymphocytes have CD4 markers on their cell membranes,
provide B-cell help to stimulate the immune response, release
lymphokines when stimulated, and recognize antigens in
association with MHC class II molecules.
• TC lymphocytes have the CD8 marker on their membranes and can eliminate
specific target cells without the help of antibody (cytotoxicity).
• B lymphocytes make up about 5% to 15% of circulating lymphocytes and are
characterized by their membrane-bound antibodies (or immunoglobulins)
• Membrane-bound antibodies are manufactured
by B cells and inserted into their cell membranes,
where they act as antigen receptors.
• Stimulated B cells differentiate into plasma cells to
secrete humoral immunoglobulin; B cells receive
T-cell help for antibody production and for
immunologic memory; a single B cell clone
manufactures Ig of a single specificity for a specific
antigen for its entire cell lifetime.
• The primary, or original, immune response occurs
after the first exposure to an antigen.
• The secondary, or anamnestic, immune response
happens after a second exposure with the same
specific antigen.
• Complement consists of a large group of different
enzymatic proteins (convertases/esterases) that
circulate in an inactive proenzyme form. Once
the cascade is started, they activate each other in
a sequence to form products that are involved in
optimizing phagocytosis and cell lysis.
• Complement can be
activated through three
pathways:
•The classical pathway is
initiated by antigen-antibody
complexes and requires C1q
for activation to proceed.
•The alternative pathway is
activated by certain
macromolecules on the cell
walls of bacteria, fungi,
parasites, and tumor cells and
requires C3b, serum factors
B, D, properdin, and initiating
factor. Q/Which can activate complement? IgG or
•The lectin pathway is IgM?
activated by binding of
Both can! but IgG will only do it if conditions
mannose-binding lectin to are OPTIMAL. IgM is an incredibly good
microbes. activator.
• All three pathways meet at a
common point in the
cascade and result in the
formation of the membrane
attack complex to remove
unwanted cells.
• There are five classes (or
isotypes) of
immunoglobulins, all of
which have a basic four-
chain protein structure Antibody molecules are isotypic
consisting of two identical (based on heavy chain
light chains and two subtype), allotypic (based on
identical heavy chains. one heavy chain mutation), or
Disulfide (covalent) bonds idiotypic (based on
link each light chain to a hypervariable and variable
heavy chain and link the two regions of light and heavy
heavy chains to each other.
chains) and are reflected in the