Transcript MORPHOLOGIE DES HEMATIES Normales et Pathologiques

Blood group serology
The Nature of Blood
 The
term blood refers to a highly
complex mixture of cells, enzymes,
proteins, and inorganic substances.
 The
fluid portion of blood is called
plasma. It is composed primarily of w
 ater and accounts for 55% of blood
content.
Blood Solids:
 Suspended in the plasma are these solid (cells)
materials:
 Red blood cells or erythrocytes
 White blood cells or leukocytes
 Platelets
Serum
 The liquid that separates from the blood when a
clot is formed. Blood clots when fibrin (a protein)
traps and enmeshes the red blood cells.
Blood serology includes the study of:
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Red Blood Cells Antigens.
White Blood Cells Antigens.
Platelet Antigens.
Antibodies in the serum.
Compatibility studies for
transfusion purposes.
Antigen:
A substance, foreign to the body that stimulates the
production of antibodies by the immune system.
 Were originally defined as, non-self molecules which
bound specifically to antibodies.
 Antigens which induce adaptive immunity are called
immunogens.
 All immunogens are antigens, and are usually called
antigens unless their ability to induce an immune
response is being changed.
 Some antigens, called haptens, are not immunogenic
unless they are covalently linked to immunogenic
carriers (usually proteins).
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Hapten: Small foreign molecule that is not antigenic.
Must be coupled to a carrier molecule to be antigenic.
Once antibodies are formed they will recognize
hapten.
The antigen bound by a unique antibody in a specific
part which is called an epitope. Most proteins have
several epitopes that are recognized by different B
cells and induce a polyclonal antibody response.
 Most are proteins or large polysaccharides from a
foreign organism.
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 Microbes:
Capsules, cell walls, toxins, viral
capsids, flagella, etc.
 Non-microbes: Pollen, egg white, red blood
cell surface molecules, serum proteins, and
surface molecules from transplanted tissue.
 Lipids and nucleic acids are only antigenic
when combined with proteins or
polysaccharides.
 Molecular weight of 10,000 or higher.
Epitope:
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Small part of an antigen that interacts with an
antibody.
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Any given antigen may have several epitopes.
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Each epitope is recognized by a different
antibody.
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There are two types of immune response:
 Negative Ag response:
Once Ag in the body, there is no response either
humeral or cellular immunity " non responsive''.
e.g. if a patient accepted a given kidney.
 Positive Ag
response.
Antibody
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A protein (immunoglobulin) produced by a B-cell
that binds to a specific foreign antigen in the
blood or body fluids.
This leads to attack by the immune system.
Belong to a group of serum proteins called
immunoglobulins (Igs).
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Proteins that recognize and bind to a
particular antigen with very high specificity.
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Made in response to exposure to the antigen.
One virus or microbe may have several
antigenic determinant sites, to which
different antibodies may bind.
 Each antibody has at least two identical
sites that bind antigen: Antigen binding
sites.
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Types of Ab:
Allo Abs:
Produced when the Ag is from the same species, e.g.
from human to human.
 Auto Ab:
Ag is a self Ag; stimulate production of Auto-Ab.
e.g. immune haemolytic anaemias.
 Hetero Ab:
Ag from a different species, e.g. from a camel to
human
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Brief Introduction to Antibody Structure
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The Ab takes a flexible Y-shaped molecule; it consists
of four polypeptides chains linked by disulphide
bonds:
 2 identical light chains "L" which is called kappa.
 2 identical heavy chains "H" which is called
lambda.
Variable Regions: Two sections at the end of Y’s
arms. Contain the antigen binding sites (Fab).
Identical on the same antibody, but vary from one
antibody to another.
Constant Regions: Stem of monomer and lower parts
of Y arms.
Fc region: Stem of monomer only. Important because
they can bind to complement or cells.
Heavy chains have five different
isotypes which divide the Igs into
five different classes, each with
different effector functions (in
humans IgG1-4, IgA1-2, IgD,
IgM, IgE).
Ab classes:
Antibodies are grouped into one of five immunoglobulin
classes:
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1- IgA (IgA1-2): alpha
Structure: Dimer
Percentage serum antibodies: 10-15%
Location: Secretions (tears, saliva, intestine, milk), blood and lymph.
Half-life in serum: 6 days
Complement Fixation: No
Placental Transfer: No
Known Functions: Localized protection of mucosal surfaces.
Provides immunity to infant digestive tract. Called as secretory IgA
(sIgA).
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IgG (IgG1-4): Gamma.
The most common serum antibody. It can pass from
mother to fetus during pregnancy, and diffuse across
mucosal surfaces, the molecular weight is 160.000 D.
IgG is also present in vaginal secretions, in higher
concentrations than sIgA.
Structure: Monomer
Percentage serum antibodies: 80%
Location: Blood, lymph, intestine
Half-life in serum: 23 days
Complement Fixation: Yes
Placental Transfer: Yes
Known Functions: Enhances phagocytosis, neutralizes
toxins and viruses, protects fetus and newborn.
IgM: Mew.
 Heavy molecular weight 1000.000.
 Structure: Pentamer Percentage serum antibodies:
5-10%
 Location: Blood, lymph, B cell surface (monomer)
 Half-life in serum: 5 days
 Complement Fixation: Yes
 Placental Transfer: No
 Known Functions: First antibodies produced during
an infection, before IgG. Effective against microbes
and agglutinating antigens.
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IgD: Delta
Structure: Monomer
Percentage serum antibodies: 0.2%
Location: B-cell surface, blood, and lymph
Half-life in serum: 3 days
Complement Fixation: No
Placental Transfer: No
Known Functions: In serum function is unknown.
On B cell surface, initiate immune response.
IgE: Epsilon.
 Structure: Monomer
 Percentage serum antibodies: 0.002%
 Location: Bound to mast cells and basophils
throughout body. Blood.
 Half-life in serum: 2 days
 Complement Fixation: No
 Placental Transfer: No
 Known Functions: Allergic reactions, possibly lysis
of worms.
Antigen-Antibody Reaction
The interaction between the Ag and its specific Ab
to form a complex is mediated by multiple
bonds between the ADS and the ABS. these
bonds include:
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Hydrogen bonding.
Electrostatic bonds.
Vander waals bonding.
Hydrophobic bonding.
-Hydrogen bonding results from formation of hydrogen
bridges between appropriate atoms.
- The electrostatic forces results from attraction between
oppositely charged groups.
- Vander Waals bonds generated by the interaction
between electron clouds.
- The Hydrophobic bonds may contribute to about half
of the total attractive forces between the Ag and Ab.
These bonds operate over a short distance; therefore the
ADS must closely approach to ABS before interaction
can occur.
Notes:
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The Ag-Ab reaction is enhanced in presence of
electrolytes.
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The Ag-Ab reactions are characterized by:
1) Being highly specific.
2) Depending in the non-covalent bonds; therefore
they are mostly reversible.
Consequences of Antigen-Antibody
Binding:
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Antigen-Antibody Complex: Formed when an antibody
binds to an antigen that it recognizes.
Affinity: A measure of binding strength.
1. Agglutination:
2. Opsonization:
3. Neutralization:
4. Antibody-dependent cell-mediated
cytotoxicity:
5. Complement Activation:
1. Agglutination:
Antibodies cause antigens (microbes) to
clump together.
 IgM is more effective that IgG.
 Hemagglutination: Agglutination of red
blood cells. Used to determine ABO
blood types and to detect influenza and
measles viruses.
2. Opsonization:
 Antigen (microbe) is covered with antibodies
that enhance its ingestion and lysis by
phagocytic cells.
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3. Neutralization:
 IgG inactivates viruses by binding to their surface and
neutralize toxins by blocking their active sites.
4. Antibody-dependent cell-mediated cytotoxicity:
 Used to destroy large organisms (e.g.: worms). Target
organism is coated with antibodies and bombarded with
chemicals from nonspecific immune cells.
5.Complement Activation:
 Both IgG and IgM trigger the complement system which
results in cell lysis and inflammation.
Erythroblastes acidophiles
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Description
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Hématies nucléées
Observation
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Moelle stimulée ou irritée
Hyperrégénération de la lignée
rouge après hémorragie ou
hémolyse
Dysérythropoièse
Infiltration maligne
Myélofibrose
Post splénectomie
Précipités d’Hémoglobine H
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Description
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Granules très nombreux de petite
taille visibles au au bleu de crésyl
Observation
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Hémoglobinose H
Syndrome myéloprolifératifs
dysérythopoièse
Corps de Heinz
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Description
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Observation
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Corpuscules de 0,3µm de diamètre
visibles après coloration spéciale par l
e bleu de crésyl brillant correspondant
à l’hémoglobine dénaturée
Hémolyse toxique
Hémolyse par des agents oxydants
chez les sujets déficients en glutathion
ou ayant une Hémoglobine instable
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ß Tthalassémie
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Post splénectomie
MGG d’après atlas hématologie F.G.H
Hayhoe editions Flammarion 1970
Parasites
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Plasmodium falciparum
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Plasmodium vivax
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Lames du service d’hématologie
de l’hôpital de Saint Denis (93)
2002
Plasmodium falciparum
Photos
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Microscopie Electronique
D’après l’ouvrage
« les Cellules du Sang »
M.BESSIS
Editions Masson 1972 avec leur autorisation
Microscopie optique
Viviane GUILLAUME
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Lames provenant pour la plupart du service d’ hématologie
CHU La Pitié Salpêtrière pendant la préparation du DERBH
et du CHU de Nancy avec l’aimable autorisation de Mr le DrVISANICA