Blood and antibodies
Fox Chapter 15 (immune system)
also part of Chap 13 (for blood)
A figure from Chapter 20
Overview of blood cell types
plasma and hematocrit (formed elements), Buffy coat between
I. Plasma - (serum lacks fibrinogen) fluids, nutrients, O2, CO2, ions
proteins (synthesized in liver except gamma globulins)(clotting)
Erythrocytes 5-6 million/ml
Leucocytes 5-10 thousand/ml
Platelets 250,000-400,000/ml formed from megacaryocytes
(antibodies) ions, wastes, hormones
Platelets 250,000/ml from megacaryocytes
Clotting Platelet adhesion then fibrin (from fibrinogen)
activated Hageman factor
prothrombin -> thrombin
Hemophelia is famous disorder
Hemophelia (4 SLIDES)
Pix from Curtis and Barnes also Ritchie and Corola also Johnson et al textbooks
Nicholas II & Alexandra
- Alexis, Family
problem with AIDS for clotting factor
Red blood cells (corpuscles) (erythrocytes)
O2 transport, hemoglobin, anemia
last 120 days, made in marrow, recycled
iron recycling in liver is what makes feces dark (and skin yellow in jaundice
[hepatitis]) - bile pigments
There are non-specific responses to injury
White blood cells (leucocytes as in leukemia)
Polymorphonuclear granulocytes (phagocytosis, etc)
neutrophil (60-70%) phagocytosis
here is a picture
from our histology course of a neurtophil showing the complex nucleus
chemotaxis after 30-60 min
more synthesized especially in bacterial infection
reset thermostat (pyrogens)
eosinophil (1.5%) phagocytosis
allergic and parasitic inflamation
basophil (0.1%) histamine containing
like mast cells
Phagocytosis and review slides
Phagocytosis (cell eating), fusion of primary lysosome, formation of secondary
blood cells (SEM=
scanning electron micrograph))
white blood cell engulfing
bacterium (Light Micrograph) (Ritchie and Corola)
white blood cell engulfing
Pix from Jaret paper, June1986 National Geographic
macrophage - asbestos
fibrin LM (Ritchie
monocytes (5%) (as in mononucleosis) (phagocytosis)
late chemotaxis become macrophages
alveolar macrophages in lungs
Kupffer's cells in liver
Inflammation and phagocytosis
Triad redness, warmth, swelling
Histamine (from mast cells, platelets)
There are specific responses involving antibodies and other mechanisms
T-cells (80%) (thymus - near heart) cell
(transplant) cytotoxic, suppressor, helper (AIDS)
B-cells (20%) (bone marrow, actually bursa of Fabricius) (become plasma
This topic is fundamental and a bit confusing.
genotypes IA IA or IA i have phenotype A, A antigens, anti-B antibodies
genotypes IB IB or IB i have phenotype B, B antigens, anti-A antibodies
genotype IA IB has phenotype AB, A and B antigens, no antibodies
genotype ii has phenotype O, no antigens, antibodies to both A and B
O universal donor, AB universal recipient
There are already antibodies since blood group polysaccharides are like
those of bacteria even though there was no previous exposure to antigens.
IgM not cross placenta
- mother and + fetus problem if blood crosses over (during delivery)
problem is next time since IgG crosses placenta
treat mother with antibodies (passive immunity) then she will not mount
Active and passive immunity
When I was a kid, nearly everrybody got measles, mumps, and chicken pox.
We were presumably immune for life (active immunity). When we had the disease
was part of out health record.
Vaccines - active immunity (like disease)
memory cells of immune system
Edward Jenner 1796 "encowment"
Farmers were less likely to get smallpox because they got a related disease,
When I was a kid, you could not enroll in school without the scar
Smallpox is so completely eliminated that one issue is whether to get rid
of lab virus.
When I was a kid, there was (still) a polio epidemic.
A kid at a birthday party I went to got polio, so I went to the family doctor
for gamma globulin, passive immunity
(1954 Salk vaccine injected, soon Sabin vaccine in sugar cube)
lymph system and nodes
Humoral immunity - B cells
clones of plasma cells and memory cells derived from B cells for specific
Another version of this figure
(showing only erythrocytes)
Interesting continued development through life of monocytes, granulocytes
and lymphocytes from stem cells
note, the bone marrow which makes blood cells is mostly in the head and
ribs, the two most likely locations for X-rays which are dangerous
Antigen (virus or bacterial coat, usually not self)
Antigenic determinant (epitope 5-15 anino acids)
IgD on B cells, antigen receptors
2 long chains and 2 short chains, variable region at the end of all 4 makes
it specific for antigen
An amazing mechanism where the gene is rearranged accounts for diversity.
IgG most abundant, monomer, cross placenta
Antibodies cross placenta, also in mother's milk, and late weaning covers
until child's own antibodies are formed.
IgE allergy, bind to mast cells (histamine)
helper T cells express CD4
antigen presenting macrophage
MHC major histocompatability complex 20 genes 50 alleles each
Class II MHC only on macrophages (and B lymphocytes)
antigen presented by to B cell
cytotoxic (killer) T cells express CD8
Class I MHC - actually on lots of cells (including the infected cellsshown
[try to match MHC (tissue typing) for transplantation]
Interleukin-2 is released by helper T cells to cause killer and helper cells
In the biology department,
is our expert in immunology
and Profs Janowiak
are our experts in microbiology
Exam questions from 2004 - 2011 related to this lecture
Thrombin acts on fibrinogen. Answer either (1) What is the activated product
of fibrinogen? or (2) What is the function of that product?
fibrin, blood clotting
Monocytes. Answer either (1) After they migrate out of the blood stream
and further develop, what are they called? or (2) What do they do in this
new location and role?
Answer either (1) Why does flu still exist while smallpox has been nearly
eradicated worldwide? or (2) Why does polio still exist while smallpox has
been nearly eradicated worldwide?
flu mutates and has alternative hosts like birds and pigs, politics - some
people think vaccination is an evil western plot
Antibodies interact with antigens. Answer either (1) What part of the antibody
molecule binds to the antigen? or (2) What do we call the portion of an
antigen molecule to which the antibody binds?
the variable part at the tip of the Y-shaped tetramer, epitope or antigenic
In addition to destroying "microbes" through phagocytosis and
lysosomal degradation, how can a macrophage communicate to a helper T cell
about what antigens to "worry" about?
present antigen to helper T with MHC-2 and CD4
Why can I be reasonably certain that your MHC (major histocompatibility
complex) is different from mine?
20 genes, 50 alleles each = lots of variability
MHC II is on macrophages and B cells. Why is it useful that MHC I is expressed
in a wider variety of cells?
because a killer cell uses that to connect to any kind of cell that gets
infected to kill it
Why was there a new "selection pressure" against hemopheliacs
coltting factor, prepared from blood of multiple donors, might have HIV
A neutrophil arrives at the site of the injury. Answer either (1) What does
it do when it gets there? or (2) What do they call the process of its attraction
to move to tht site?
Why would blood cells be expected to agglutinate for a type B transfusion
into a type A recipient?
the Y shaped antibody molecule can hold two red blood cells together.
There are some interesting differences in ABO blood groups vs. Rh factor
antibodies. Answer either (1) Why would there be a bad reaction to the first
type A transfusion into a B recipient? or (2) Why would an Rh- mother only
have to worry (a lot!) about her further pregnancies after she has born
an Rh+ baby?
there is already antibody, the IgG crosses the placent
In 1796, Jenner exposed people to cowpox to give them immunity to smallpox.
What did Lady Montague do 3/4 of a century earlier to make people immune
she exposed them to smallpox itself
A naive B cell is exposed to an antigen and develops into a clone of plasma
cells that produce antibodies plus (what other important type of cell?).
At and after birth, an infant has the mother's immunities. Describe one
of the two ways this happens with reference to the specific antibody involved
in the mechanism you are describing.
IgG through placenta then IgA from breast milk
It was argued that Rasputin may, in fact, have been able to help Czarevitch
The hemopheliacs bleeding might might have been decreased by getting vasoconstriction
by controlling his sympathetic output to arterioles
What type of cell do monocytes (mononuclear cells) become after they are
outside the circulatory system?
What does type O blood have or lack that permits type O individuals to be
Type O red blood cells lack antigens, so that blood can be transfued into
any recipient regardless of whether that person has antibodies
A molecule on the surface of a B cell was shown in one diagram as Y-shaped;
it was called a "B cell receptor" and it was shown as binding
to an antigen on a pathogen (probably a bacterium). What was this molecule?
Be as specific as you can.
How does class-2 MHC assist a macrophage "tell" a B cell what
antigens to "worry" about?
MHC-2 and CD4 corepressor are involved in the communication from the antigen
presenting macrophage to the T cell
Hageman factor, prothrombin, thrombin, fibrinogen
What is the general term for blood that is deficient in red blood cells,
hemoglobin, or iron?
After a white blood cell phagocytoses a bacterium, what does the white blood
cell do to dispose of the ingested bacterium?
Combine this endosome with lysosomes
Mast cells help to mediate the inflammatory triad because they release (what
Address ONE of the following differences between ABO blood groups and Rh
factor: (1) Whether antibodies are made after first exposure vs. they are
already present. (2) Whether the couple might have to worry about a mismatch
when having children. Or (3) Whether the antibody crosses the placenta.
Already present only for ABO, Worry for Rh only, IgG crosses placenta for
Rh, not IgM for ABO
A naive B cell is exposed to an antigen. Describe the constituents of the
clone of cells that develops from this cell.
Plasma cells make antibody, memory cells preserve the information
"Class-2 MHC molecules are expressed on macrophages and B cells."
By contrast, where are class1 MHC molecules expressed?
Lots of cells
How do helper T cells assist killer T cells in their mission to destroy
lots of cells that have been infected by the identified pathogen?
Via interleukin 2, they signal killer cells to proliferate
Say something you learned about EITHER IgA or IgE.
IgA is transferred to infant via breast feeding, IgE is involved in allergies
What kind of cell becomes a macrophage?
Presence of what in type O people would lead to agglutination if there were
a transfusion with any other type of blood?
anit-A and anti-B antibodies
Presence of what in type O people would lead to agglutination if there were
a transfusion with any other type of blood?
anit-A and anti-B antibodies
Eosinophils are a type of polymorphonuclear granulocyte. What is eosin?
a histological stain
What kind of molecule is IgG? (Be more specific than "protein.")
In a neutrophil or macrophage, after phagocytosis of a bacterium, what cellular
organelle full of enzymes fuses with the phagosome to destroy the bacterium?
A B lymphocyte develops into what protein-producing cell?
When it is needed, what important protein does a plasma cell export?
What cell is specifically depleted in AIDS?
The first vaccination was for what disease?
What are the two types of lymphocytes?
For Rh, a second exposure is very serious. Why is a first exposure, like
a transfusion of the wrong blood group, bad in ABO blood groups?
there are already antibodies
A bacterium is engulfed into a vacuole in a phagocytic white blood cell.
What cellular organelle, a bag of acid hydrolases, fuses with this endosome
to destroy the bacterium.
Like neutrophils, monocytes infiltrate the injury site, attracted by chemotaxis.
What is the difference in timing?
monocytes are later
Considering how much fibrin is around when clotting is needed, how come
fibrin does not make blood clot all the time?
unless cleaved by clotting cascade, fibrinogen is inactive
Macrophages are derived from what type of white blood cell?
Why are the prospects for worldwide elimination of flu by immunization more
elusive than for smallpox or polio?
evolution of virus in alternative hosts like birds and pigs
Antibodies produced by plasma cells are ineffective against infected cells.
What specific type of lymphocyte destroys such cells loaded with foreign
bacteria or viruses?
killer (cytotoxic) T lymphocytes
Class 1 & 2 MHC (major histocompatibility complex) molecules are expressed
on the surfaces of various cells. Why is it almost guaranteed that yours
are different from mine?
many genes, many alleles of each
If type A red blood cells are transfused into a type B person, antibodies
in the type B blood will cause the red blood cells to clump. What is this
What is the chemical signal that the helper T cell uses to cause the appropriate
type of killer T cells to proliferate?
Which specific antibody crosses the placenta to give the baby the mother's
immunities early in life?
In what way is IgG different from IgM with regard to the placenta and blood
IgG for Rh cross, IgM for ABO not cross
"Monocytes have a late chemotaxis and form macrophages." Translate.
these white blood cells are attracted to the site of injury after polymorphonuclear
granulocytes and further develop into big phagocytic cells
Which specific type of white blood cell is depleted in AIDS (acquired immunodeficiency
Why are lysosomes an important part of phagocytic leukocytes?
they merge with endosomes to digest them
What kind of immunity does RhoGAM confer in the treatment for Rh- mothers?
Why is there a major difference between small pox and flu (influenza) with
respect to the prospects for total elimination of the disease from the worldwide
flu evolves and has alternative animal hosts
What purpose does IgD on the surface of B cells serve?
it is the antigen receptor
An allergen binding to IgE on the surface of mast cells causes the release
of what substance from its granules?
Class II MHC (major histocompatability complex) is expressed only on macrophages
and B lymphocytes. What about class I?
all cells, involved in attack on infected cells
Why is AB the universal recipient?
no A or B antibodies
Neutrophils, eosinophils and basophils are all white blood cells. Name a
different type of white blood cell.
monocytes, lymphocytes (B and T)
Why is there so much variability in the MHC (major histocompatability complex)?
20 genes, 50 alleles each
Why is it beneficial for the infant that IgG crosses the placenta and that
IgA is in mother's milk?
passive immunity from mother
CD8 vs. CD4 coreceptors distinguish what types of cell?
Killer vs helper T cells
What is agglutination as it applies to antibodies and the blood groups?
antibody causes cells to clump
We don't worry so much about blood type (ABO) of the fetus vs the mother,
but we do worry about Rh factor. Why the difference?
IgM does not cross placenta, IgG does
For what is IgE most relevant?
How can MHC be so variable?
20 genes 50 alleles each
If all goes as "intended," what happens to a bacteria-containing
endosome in a white blood cell?
becomes secondary lysosome after merging with primary lysosome (etc.)
Which blood cells are the precursors of macrophages?
Some bacteria come in through a small skin injury. How do phagocytitc cells
get from an intact capillary to the site of the injury?
chem,otaxis, slither between endothlial cells
What is the major product exported from the B lymphocyte?
What type of cells are the memory cells that can jump-start the response
to the next exposure to an antigen?
What kind of protein is the antigen receptor on the surface of a B lymphocyte?
What is the difference between an epitope and an antigen?
epitope (antigenic determinant) is the small portion of the antigen to which
the antibody binds
How can an infant be immune to some diseases between birth and weaning?
IgG across placenta, IgA in milk
How would a blood count help to determine if you had a systemic bacterial
There are more neutrophils in bacterial infection
Explain what agglutination is using transfusion of type A blood into a type
B recipient as your example.
Antibodies would cause red blood cells to clump together
How can your immune system (conceivably) develop antibodies to every possible
The genes themselves get spliced to make the many variable regions
Class 2 MHC on the surface of an antigen-presenting macrophage acts in conjunction
with (what?) on the surface of a helper T cell to activate it.
Why did AIDS, in the first few years, create a new "selection pressure"
before AIDS, the "environment" was one where clotting factor was
available through medical technology; after AIDS (before the blood banks
were better secured) this factor from multiple blood donors had a grim chance
of being infected
What does a phagocytic cell do to destroy a bacterium after it has "swalled"
presumably the endosome with the bacterium fuses with a primary lysosome,
though some bacteria have evolved tricks to escape the endosome
"Monocytes have a late chemotaxis." Explain: either (1) later
than what? Or (2) just what do are they doing that is called chemotaxis?
1-neutrophils, 2-slither out between endothelial cells
In what way do different antibodies create different risks for the fetus,
comparing the ABO blood groups vs. Rh factor.
IgM not cross placenta but IgG does so 2nd Rh+ fetus is a problem for an
Rh- mother unless she has antibodies after the first is born
"Clone" is a term applied in the discussion of the development
of plasma and memory cells from B lymphocytes. What is that term meant to
tha after a B cell is subjected to a particular epitope, a bunch of plasma
and memory cells responsive to that epitope will form
To what fraction or portion of an antigen does an antibody bind?
epitope, 5 to 15 amino acids (also groups attached to them) near eachother
Address an infant's immunity answering either (1) what kind of antibody
gave the newborn some of the mother's immunities at the moment of birth,
OR (2) what kind of antibody from the mother can prolong the infant's immunity
(that the mother had developed) for some time after that?
(1) IgG, (2) IgA
Address allergies with either (1) what kind of antibody is released from
a plasma cell, (2) to activate what kind of receptor on the surface of a
mast cell, OR (3) to release what substance from a mast cell.
(1) IgE (2) IgE receptor (3) histamine
CD8 coreceptor on a killer T cell acts in conjunction with (what?) on the
surface of an infected cell to destroy that cell.
Class 1 MHC (also viral antigen)
What is the role of lysosomes in a polymorphonuclear leukocyte (granulocyte)?
they merge with ingested bacteria to "digest" them
What is agglutination, and why would you expect that reaction for a transfusion
mismatched for ABO blood type?
clumping of red blood cells, happens because Y-shaped antibody molecule
can stick several cells or clumps of cells together
At the moment of birth, an infant has some of the immunities of his or her
IgG crosses the placenta
A killer T cell is activated by an antigen-presenting macrophage to kill
cells infected with a microbe. It would sure be nice if a whole lot of killer
T cells knew to kill cells with the antigens of that microbe. How does the
immune system signal that proliferation?
interleukin-2 from a helper T cell
Why were hemopheliacs at particular risk for AIDS in the early days of the
clotting factor needed to be produced from multiple blood donations before
they knew to police the blood banks
In sexual dimorphism, why is the early development in the female considered
to be the default pathway?
without TDF, indifferent gonads become ovaries, without MIF, Mullerian duct
becomes uterus and tubes, without testosterone, embryonic structures become
vagina, labia, clitoris
Suppose you get sick. What would they be looking for if they ordered a blood
white blood cell count increased in (bacterial) infection
For inflammation, answer either (1) What are the three components of the
triad? Or (2) What chemical mediator from mast cells contributes to inflammation?
warmth, redness, swelling, histamine
What white blood cell was conspicuously reduced in AIDS?
helper (CD4 coreceptor expressing)
If an Rh- mother has an Rh+ child there is definitely a concern in later
pregnancies. Not so if the child's ABO blood type does not match the mother's.
Why the difference?
IgG crosses placenta, IgM does not
Smallpox and polio could be eradicated worldwide. Why not influenza (flu)?
flu mutates (changes) and has alternate hosts, especially birds and pigs
How does a B cell "learn" that it needs to initiate its response
(making targeted plasma and memory cells) in response to a specific newly-"seen"
antigen (that is out in the blood plasma)?
it binds that antigen with an antigen receptor that is an IgD
You get infected with the novel Stark-virus whose astounding property is
that it has only one surface protein, and yet you develop many different
clones of memory cells to protect you next time you are exposed. How could
they be different when there is only one protein?
they would be against specific epitopes (antigenic determinants
A "microbe" is phagocytosed by a macrophage. How is it that a
B cell can "learn" to make antibodies to the antigens on that
macrophage presents antigen and helper T cell presents it to the B cell
In cooperation with the CD8 expressing T cell, why is it important that
MHC class 1 be expressed on cells in tissues that might be infected (in
contrast with MHC class 2 that is only on macrophages [and B cells])?
MHC1 is part of the communication allowing this killer T cell to recognize
and kill the infected cell
Why is there so much diversity in MHC?
20 genes 50 alleles each
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