Plasma Chon
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Transcript of Plasma Chon
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PLASMA PROTEINS AND
IMMUNOGLOBULINS
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OUTLINE
PLASMA
ALBUMIN
HAPTOGLOBULIN TRANSFERRIN
FERRITIN
CERULOPLASMIN
IMMUNOGLOBULINS
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PLASMA PROTEINS & IMMUNOGLOBULINS
PLASMA
consists of water, electrolytes, metabolites, nutrients,proteins, hormones
total CHON in plasma: 7-7.5 g/dL
most common method of analyzing plasma CHON:electrophoresis
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STARLING FORCES
ARTERIAL END:
BHP- 37mmHg
IFHP-1 mmHg
BOP- 25 mmHg
VENOUS END:
BHP- 17mmHg
IFHP-1 mmHg
BOP- 25 mmHg
37
125
11
9
25 1
17
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PLASMA CHONs.
are mostly synthesized in the liver
generally synthesized on membrane-bound
polyribosomes are mostly glycoproteins
many exhibit polymorphism
each has a characteristic half-life in the circulation
levels may increase during acute inflammatorystates or secondary to certain types of tissuedamage
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ALBUMIN
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Albumin is the major CHON in plasma
60% of plasma CHON
produced in the liver
comprises about half of the blood serum protein
synthesized in the liver as preproalbumin whichhas an N-terminal peptide that is removed beforethe nascent protein is released from RER
proalbumin cleaved in the Golgi vesicles toproduce the secreted albumin
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Functions of Albumin
Maintains oncotic pressure Transports thyroid hormones Transports other hormones, particularly fat
soluble ones Transports fatty acids to the liver Transports unconjugated bilirubin Transports many drugs and serum albumin levels
can affect the half-life of drugs Competitively binds calcium Buffers pH
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Haptoglobin
abbreviated as Hp in blood plasma: binds free Hb released from
erythrocytes with high affinity and therebyinhibits its oxidative activity
haptoglobin-hemoglobin complex removed by thereticuloendothelial system
Clinical use used to screen for and monitor intravascular hemolytic anemia
In intravascular hemolysis: free hemoglobin released intocirculation haptoglobin binds the Hbdecline in Hp levels
in extravascular hemolysis: the RES phagocytoses the erythrocytesand hemoglobin is not released into circulation normalhaptoglobin levels
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Haptoglobin
FUNCTIONS
-bind free plasma hemoglobin which allows
degradative enzymes to gain access to thehemoglobin
-prevents loss of iron through the kidneys
-protects the kidneys from damage by hemoglobin
-acute phase reactant: levels increased ininflammatory state
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Transferrin
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Transferrin
blood plasma protein for iron delivery
glycoprotein that binds iron very tightly butreversibly
iron bound to transferrin is less than 0.1% (4 mg) ofthe total body iron, it is the most important ironpool, with the highest rate of turnover (25 mg/24 h)
has a molecular weight of ~76 kD
contains 2 specific high-affinity Fe(III) binding sites
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Transferrin
main source is the liver
main role: deliver iron from absorption centres in theduodenum to all tissues
decreases in inflammationCLINICAL SIGNIFICANCE:
increased in patients with iron deficiency anemia
decreased in iron overload diseases and proteinmalnutrition
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FERRITIN
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FERRITIN
globular protein complex consisting of 24 proteinsubunits
primaryintracellular iron-storage protein in bothprokaryotes and eukaryotes
keeps iron in a soluble and non-toxic form
Ferritin that is not combined with iron is called
apoferritin
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FERRITIN
serves to transport iron to areas that it is required presence of iron itself is a major trigger for the productionof ferritin
apoferritin binds to free ferrous iron and stores it in theferric state
as ferritin accumulates within cells of the RES, proteinaggregates are formed as hemosiderin
CLINICAL SIGNIFICANCE under steady state conditions, serum ferritin level
correlates with total body iron stores
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Ceruloplasmin
Blue in color due to high copper content
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Ceruloplasmin
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Kayser-Fleisherring
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PLASMA IMMUNOGLOBULINS
2 major components
1. B lymphocytes
-mainly bone marrow derived-synthesis of circulating humoral antibodies
called immunoglobulins
2. T lymphocytes
-thymic origin
-cell mediated immunologic processes
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GENERAL FUNCTIONS OF IMMUNOGLOBULINS
A. Antigen binding
Ig bind specifically to one or a few closely relatedantigens
primary function of antibodies and can result inprotection of the host
valency of antibody refers to the number ofantigenic determinants that an individual
antibody molecule can bind
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GENERAL FUNCTIONS OF IMMUNOGLOBULINS
B. Effector Functions
1. Fixation of complement results in lysis of cells and release of biologically active
molecules2. Binding to various cell types Ie. phagocytic cells, lymphocytes, platelets, mast cells,
and basophils
some immunoglobulins also bind to receptors onplacental trophoblasts, which results in transfer of theIg across the placentatransferred maternalantibodies provide immunity to the fetus and newborn
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BASIC STRUCTURE OF IMMUNOGLOBULINS
A. Heavy and Light Chains All Ig have a 4 chain
structure as their basic unit
composed of two identicallight chains (23kD) and twoidentical heavy chains (50-70kD)
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BASIC STRUCTURE OF IMMUNOGLOBULINS
B. Disulfide bonds1. Inter-chain disulfide bonds
heavy and light chains and the 2 heavy chains are heldtogether by inter-chain disulfide bonds and by non-covalent interactions
No. of inter-chain disulfide bonds varies amongdifferent immunoglobulin molecules
2. Intra-chain disulfide bonds Within each of the polypeptide chains there are also
intra-chain disulfide bonds.
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BASIC STRUCTURE OF IMMUNOGLOBULINS
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BASIC STRUCTURE OF IMMUNOGLOBULINS
C.Variable (V) and Constant (C)Regions
both the heavy and light chain couldbe divided into 2 regions based on
variability in the amino acidsequences. These are the:
1. Light Chain - VL (110 amino acids) andCL (110 amino acids)
2. Heavy Chain - VH (110 amino acids)and CH (330-440 amino acids)
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BASIC STRUCTURE OF IMMUNOGLOBULINS
D. Hinge Region region at which the arms of
the antibody molecule
forms a Y called the hinge region
because there is someflexibility in the molecule at
this point
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IMMUNOGLOBULIN FRAGMENTS:
STRUCTURE/FUNCTION RELATIONSHIPS
produced by proteolytic digestion
A. Fab antigen binding or Fab fragments
contained the antigen binding sites of theantibody each Fab fragment is monovalent whereas
the original molecule was divalent combining site of the antibody is created
by both VH and VL
different combinations of a VH and VLresult in antibodies that can bind adifferent antigenic determinants.
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IMMUNOGLOBULIN FRAGMENTS: STRUCTURE/FUNCTION
RELATIONSHIPS
B. Fc
Fc =easily crystallized
mediates effector functions Ig
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HUMAN IMMUNOGLOBULIN CLASSES
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HUMAN IMMUNOGLOBULIN CLASSES
Immunoglobulin classes-divided into 5 different classes, based on
differences in the amino acid sequences in the constantregion of the heavy chains All Ig within a given class will have very similar heavy chain
constant regions. These differences can be detected bysequence studies or more commonly by serological means(i.e. by the use of antibodies directed to these differences).
1. IgG - Gamma heavy chains
2. IgM - Mu heavy chains 3. IgA - Alpha heavy chains 4. IgD - Delta heavy chains 5. IgE - Epsilon heavy chains
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STRUCTURE AND SOME PROPERTIES OF IG CLASSES
A. IgG1. Structure
monomers subclasses differ in the number of disulfide bonds and length of
the hinge region
2. Propertiesmost versatile immunoglobulin because it is capable
of carrying out all of the functions of immunoglobulinmolecules.
a) IgG is the major Ig in serum - 75% of serum Ig is IgG b) IgG is the major Ig in extra vascular spaces c) Placental transfer
only class of Ig that crosses the placenta
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STRUCTURE AND SOME PROPERTIES OF IG CLASSES
B. IgM
Structure normally exists as a pentamer but it can also exist as a monomer the pentameric form all heavy chains are identical and all light
chains are identicalProperties a) 3rd most common serum Ig. b) 1st to be made by the fetus and 1st Ig to be made by a
virgin B cells when it is stimulated by antigen. c) good complement fixing Igvery efficient in leading to
the lysis of microorganisms. d) As a consequence of its structure, IgM is also a good
agglutinating Ig.
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STRUCTURE AND SOME PROPERTIES OF IG CLASSES
C. IgA
1. Structure
Serum IgA is a monomer but IgA found insecretions is a dimer2. Properties a) IgA is the 2nd most common serum Ig.
b) IgA is the major class of Ig in secretions -tears, saliva, colostrum, mucusimportant inlocal (mucosal) immunity.
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STRUCTURE AND SOME PROPERTIES OF IG CLASSES
D. IgD
1. Structureexists only as a monomer.
2. Properties a) found in low levels in serum; its role in serum
uncertain
b) primarily found on B cell surfaces where itfunctions as a receptor for antigen
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STRUCTURE AND SOME PROPERTIES OF IG CLASSES
E. IgE
1. Structureexists as a monomer
2. Properties
a) IgE is the least common serum Ig since it bindsvery tightly to Fc receptors on basophils and mast
cells even before interacting with antigen. b) Involved in allergic reactions
c) plays a role in parasitic helminth diseases
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CLINICAL IMPLICATIONS OF HUMAN IMMUNOGLOBULIN CLASSES
IgG1. Increases in:
a) Chronic granulomatous infectionsb) Infections of all typesc) Hyperimmunizationd) Liver diseasee) Malnutrition (severe)f) Dysproteinemia
g) Disease associated withhypersensitivity granulomas,dermatologic disorders, and IgGmyelomah) Rheumatoid arthritis
2. Decreases in:
a) Agammaglobulinemia
b) Lymphoid aplasia
c) Selective IgG, IgAdeficiency
d) IgA myeloma
e) Bence Jones proteinemia
f) Chronic lymphoblastic
leukemia
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CLINICAL IMPLICATIONS OF HUMAN IG CLASSES
2. Decreases in:
a) Agammaglobulinemia
b) Lymphoproliferative disorders
(certain cases)c) Lymphoid aplasia
d) IgG and IgA myeloma
e) Dysgammaglobulinemia
f) Chronic lymphoblastic leukemia
IgM
1. Increases (in adults) in:
a) Waldenstrm's
macroglobulinemia
b) Trypanosomiasisc) Actinomycosis
d) Carrin's disease (bartonellosis)
e) Malaria
f) Infectious mononucleosis
g) Lupus erythematosush) Rheumatoid arthritis
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CLINICAL IMPLICATIONS OF HUMAN IMMUNOGLOBULIN CLASSES
IgA
1. Increases in:a) Wiskott-Aldrich syndrome
b) Cirrhosis of the liver (most cases)c) Certain stages of collagen andother autoimmune disorders such asrheumatoid arthritis and lupuserythematosusd) Chronic infections not based onimmunologic deficienciese) IgA myeloma
2. Decreases in:a) Hereditary ataxia telangiectasiab) Immunologic deficiency states (e.g.,dysgammaglobulinemia, congenitaland acquired agammaglobulinemia,and hypogammaglobulinemia)c) Malabsorption syndromesd) Lymphoid aplasia
e) IgG myelomaf) Acute lymphoblastic leukemiag) Chronic lymphoblastic leukemia
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CLINICAL IMPLICATIONS OF HUMAN IMMUNOGLOBULIN CLASSES
IgD 1. Increases in: a) Chronic infections
b) IgD myelomasIgE
1. Increases in: a) Atopic skin diseases such as eczema
b) Hay feverc) Asthmad) Anaphylactic shock
e) IgE-myeloma 2. Decreases in: a) Congenital agammaglobulinemia
b) Hypogammaglobulinemia due to faulty metabolism orsynthesis of immunoglobulins
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SUMMARY
Plasma contains many proteins with variety of function
Albumin is the major CHON and is the principaldeterminant of intravascular osmotic pressure
Haptoglobulin binds extracorpuscular hemoglobin
Transferrin binds iron, transporting it to sites where it isrequired
Ceruloplasmin binds copper
Immunoglobulins play a key role in the immune defense