NMD2024

DAVAO MEDICAL SCHOOL FOUNDATION

PLASMA PROTEINS & IMMUNOGLOBULINS
COLLEEN ONGKINGCO-LUMANLAN, MD

BLOOD FUNCTIONS - Hb-Hp complex has high MW (155kDa). Thus,

- mostly carried out by plasma and its constituents cannot pass through the glomerulus (<70kDa)
1. Respiration - Hp prevents loss of Hb into the kidney
2. Nutrition o Conserve valuable iron in the body
3. Excretion - Low levels are found in hemolytic anemia
4. Acid-Base Balance - Hp half-life is 5 days; Hb-Hp complex is 90 min
5. Water Balance - Levels of Hp falls rapidly in situations where Hb
is constantly being released from RBC
PLASMA PROTEINS 3. Transferrin
- the STARLING equation is an equation that - Transports IRON around the body
illustrates the role of hydrostatic and oncotic o Iron is important because it is present in
forces in the movement of fluid across capillary Hgb, Mgb, and Cytochromes
membranes. o Iron is tightly regulated because there is
no physiologic pathway for excretion
from the body

- β1 -globulin glycoprotein

- transports Fe (2 moles Fe/1 mole Tf) into the

circulation where Fe is needed
- Tfr1 and Tfr2
o Receptors that bind iron to facilitate
endocytosis
- Lysosomes
o Acid medium dissociated Fe from
protein and leaves via DMT1 to enter
cytoplasm
- Enterocytes
o Iron in ferric state is reduced to ferrous
state by ferrireductase on the surface
PLASMA PROTEINS GENERAL CHARACTERISTICS of proximal duodenum
1. Mostly synthesized in the liver except for gamma - Divalent Metal Transporter (DMT1)
globulins (bound on membrane-bound o Transfer of iron from apical surface of
polyribosomes) enterocytes into their interiors
2. Mostly are glycoproteins except for albumin - Hepcidin
3. Many exhibit polymorphism o Important Role: down regulate
4. Each plasma protein has a characteristic half-life intestinal absorption of iron from
in the circulation intestine, placental transfer, and release
5. Acute Phase Proteins from macrophages
- Ferritin
PLASMA PROTEINS o Once inside the enterocytes, Fe is
1. Albumin stored as ferritin or transferred across
- Major (60%) protein of human plasma basolateral membrane into the plasmsa
- 40% of albumin in plasma and 60% in EC - Ferroportin
space o Carries Fe across basolateral
- Low MW and High conc. ~75-80% of osmotic membrane
pressure - Haphaestin
- Important Function o Has ferroxidase activity which releases
o Bind various ligands Fe from cells
 FFA, Calcium, Steroid o Ferrous to Ferric for transport across
Hormone, Bilirubin plasma by transferrin
o Transport copper and various drugs 4. Ferritin
2. Haptoglobin - Another protein important in the metabolism of
- Plasma glycoprotein that binds iron
extracorpuscular Hb (Hb-Hp Complex) - Stores Fe for future use
- 10% of Hgb degraded each day becoming - High Fe Levels – ferritin is synthesized
extracorpuscular - Low Fe Levels – ferritin not synthesized
 NMD2024
DAVAO MEDICAL SCHOOL FOUNDATION
PLASMA PROTEINS & IMMUNOGLOBULINS
COLLEEN ONGKINGCO-LUMANLAN, MD

o TfR is synthesized to promote uptake of

Fe from transferrin o Wilson’s Disease
5. Ceruloplasmin  Genetic disease
 Copper cannot be
- α2-globulin, blue color due to high copper excreted from the bile and
content accumulates in the liver,
brain, kidney, and RBC
- carries 90% of copper present in the plasma  Copper Toxicosis:
(albumin carrier the 10%)  Increase in level of
copper in liver
- 1 mole of ceruloplasmin binds 6 atoms of cells inhibit
copper very tightly coupling to
apoceruloplasmin
- Albumin donates copper more readily = LOW CERULO-
PLASMIN in
plasma
COPPER  Hemolytic Anemia,
 Essential trace elements Chronic Liver Disease,
 Metal cofactors for a variety of enzymes: Neurologic Symptoms
o Cytochrome C Oxidase  Frequent c
 Cellular respiration  Variety of mutations in a
o Ceruloplasmin gene coding copper-
 Iron hemostasis binding P-type ATPase
o Tyrosinase (ATP7B protein)
 Melanin formation  Rx:
o Various Enzymes d  Diet low in copper
 Neurotransmitter  Penicillamine
production (chelates copper,
o Lysyl Oxidase give for a lifetime)
 Connective tissue 6. α1-antiproteinase
synthesis - formerly, α1-antitrypsin
o Superoxide Dismutase - principal serine protease inhibitor of human
 Protect against oxidants plasma
 Excess: - inhibits trypsin, ELASTASE, and certain
o “problem”; oxidizes proteins, proteases
lipids, bind to nucleic acids and - deficiency may have a role in certain cases of
enhance free radical production EMPHYSEMA
 Carried by ALBUMIN to liver and leaves - Decrease in this protein with increase PMNs of
the liver through CERULOPLASMIN WBC during pneumonia
 Disease Association: o Individual cannot countercheck the
o Menke’s Disease proteolytic damage to the lung by
 “kinky” or “steely” hair proteases such as ELASTASE
disease - Smoking
 X-linked disorder of copper o Oxidizes methionine (residue of protein)
metabolism, only males to methionine sulfoxide thus
affected inactivated
 Involves nervous system,  Cannot neutralize proteases
connective tissue,  Accelerates development of
vasculature emphysema
 Fatal in infancy 7. α2-macroglobulin
 Mutation in the gene - large plasma glycoprotein
ATP7A for a copper- - 8-10% of total plasma protein
binding P-type ATPase: - 10% zinc is transported by α2-macroglobulin
direct efflux of copper from - Synthesized in monocytes, hepatocytes, and
cells astrocytes
- Major member of plasma proteins that include
complement proteins C3 and C4
- Binds many proteinases
 NMD2024
DAVAO MEDICAL SCHOOL FOUNDATION
PLASMA PROTEINS & IMMUNOGLOBULINS
COLLEEN ONGKINGCO-LUMANLAN, MD

- Important panproteinase inhibitor

- Binds many cytokines (PDGF, TGF β, etc) and
targets them towards particular tissues
AMYLOIDOSIS
o Accumulation of various insoluble
fibrillar proteins between cells of tissues
o May be due to increased production or
accumulation of mutated forms
o Now generally classified as:
 AX
 A – amyloidosis
 X – protein in the Fibrils
o General approach to treatment:
 Prevent production of precursor
protein
 Stabilize structures of precursor
protein
 Destabilize amyloid fibrils so
that they can re-convert to their
normal conformations

PLASMA IMMUNOGLOBULINS

Immune System
- B lymphocytes – mainly derived from bone
marrow cells of higher animals
- T lymphocytes – are of thymic origin, involved
in cell-mediated immunologic processes
- Innate immune system – defends against
infection in a non-specific manner
Plasma Immunoglobulins
- Synthesized mainly in the plasma cells
- Specialized cells of the B cell lineage
- Synthesize and secrete immunoglobulins into
plasma in response to exposure to a variety of
antigens
- 2 identical Light Chains
o Half of light chain toward the carboxyl
end is the CONSTANT region
o amino terminal half is the VARIABLE
region
- 2 identical Heavy Chains
o 1 quarter of the heavy region toward the
amino terminal is the variable region
o 3 quarters are referred to as the
constant region
Functional Regions:
- Action of enzyme papain produces:
o 2 antigen binding fragment (Fab)
 Binds 2 molecules of antigen
o 1 crystallizable fragment (Fc)
 Responsible for functions of Ig
other than direct binding of
antigen
General Characteristics
- All light chains are either Kappa or Lambda
o Never a mixture
- 5 types of Heavy Chain determine the class of
Immunoglobulin
o CH regions designated as G, A, M, E, D
- No 2 variable regions are identical
- Constant regions determine the class-specific
effector functions
- Both light and heavy chains are products of
multiple genes
- Antibody diversity depends on gene
rearrangements
- Class switching occurs during immune
responses:
o Ab of IgM normally precede molecules
of the IgG class
- Over and under production of Ig may result in
disease state
- Hybridomas provide long-term source of highly
monoclonal antibodies
 NMD2024
DAVAO MEDICAL SCHOOL FOUNDATION
PLASMA PROTEINS & IMMUNOGLOBULINS
COLLEEN ONGKINGCO-LUMANLAN, MD

- Immunoglobulins play a key role in the defense

mechanism of the body

SUMMARY

- Plasma contains many proteins with a variety of

functions

- Albumin, not glycosylated, is the major protein

and principal determinant of intravascular
osmotic pressure

- Haptoglobin binds extra-corpuscular Hb

- Transferrin binds iron, transporting it to sites

where it is required

- Ceruloplasmin contains substantial amounts of

copper, but albumin appears to be more
important with regards to its transport

- α1-antitrypsinisthemajorserineprotease inhibitor
of plasma, particularly the elastase of
neutrophils

- α2-Macroglobulinisthemajorplasmaprotein that
neutralizes many proteases