Blood and antibodies

Fox Chapter 15 (immune system)
also part of Chap 13 (for blood)
A figure from Chapter 20

Fig. 13.1

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)
Albumins
Globulins
Fibrinogen

II. Hematocrit
Erythrocytes 5-6 million/ml
Leucocytes 5-10 thousand/ml
Platelets 250,000-400,000/ml formed from megacaryocytes
(antibodies) ions, wastes, hormones

Blood clotting

Fig. 13.9
Platelets 250,000/ml from megacaryocytes
Clotting Platelet adhesion then fibrin (from fibrinogen)
Cascades
activated Hageman factor
prothrombin -> thrombin
fibrinogen ->fibrin
Hemophelia is famous disorder

Hemophelia (4 SLIDES)
Pix from Curtis and Barnes also Ritchie and Corola also Johnson et al textbooks long ago
pedigree
Victoria, family
Nicholas II & Alexandra - Alexis, Family
Rasputin
on X
problem with AIDS for clotting factor

Erythrocytes

Fig. 13.3
Red blood cells (corpuscles) (erythrocytes)
no nuclei
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

Polymorphonuclear granulocytes

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

Fig. 15.2
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

Fig. 15.1
Phagocytosis (cell eating), fusion of primary lysosome, formation of secondary lysosome

SLIDES:
blood cells (SEM= scanning electron micrograph))
white blood cell engulfing bacterium (Light Micrograph) (Ritchie and Corola)
white blood cell engulfing bead (SEM)
Pix from Jaret paper, June1986 National Geographic
macrophage eating E. coli
macrophage - asbestos
fibrin SEM
fibrin LM (Ritchie and Corola)

Monocytes

Fig. 15.6
Mononuclear cells
monocytes (5%) (as in mononucleosis) (phagocytosis)
late chemotaxis become macrophages
alveolar macrophages in lungs
Kupffer's cells in liver

Inflammation

Fig. 15.5
Inflammation and phagocytosis
Triad redness, warmth, swelling
Histamine (from mast cells, platelets)

lymphocytes:

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 cells)
antibodies

Blood groups

Fig. 13.5
Blood groups
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

Rh factor

- 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 immunity

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, cowpox
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)

Fig. 15.13
lymph system and nodes

Antibodies

Humoral immunity - B cells

Fig. 15.21
clones of plasma cells and memory cells derived from B cells for specific antigens

Fig. 15.7
Another version of this figure

Fig. 13.4
(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

Fig. 15.8
Antigen (virus or bacterial coat, usually not self)
Antigenic determinant (epitope 5-15 anino acids)
IgD on B cells, antigen receptors

Fig. 15.8b
Antibody
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

Fig. 20.54
Antibodies cross placenta, also in mother's milk, and late weaning covers until child's own antibodies are formed.

Fig. 15.23
IgE allergy, bind to mast cells (histamine)

T-cells

Fig. 15.15
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

Fig. 15.16
cytotoxic (killer) T cells express CD8
Class I MHC - actually on lots of cells (including the infected cellsshown here)
[try to match MHC (tissue typing) for transplantation]

Fig. 15.17
Interleukin-2 is released by helper T cells to cause killer and helper cells to proliferate

In the biology department,
Prof Shornick is our expert in immunology
and Profs Janowiak and Kennell 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?

macrophages, phagocytosis

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 determinant

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 around 1980?

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?

phagocytosis, chemotaxis

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 to smallpox?

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?).

memory cells

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 Alexis. How?
 
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?
 
macrophage
 
What does type O blood have or lack that permits type O individuals to be universal donors?
 
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.
 
IgD
 
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?
 
anemia
 
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 substance?).
 
histamine
 
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?

monocyte

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.")

antibody

In a neutrophil or macrophage, after phagocytosis of a bacterium, what cellular organelle full of enzymes fuses with the phagosome to destroy the bacterium?

lysosome

A B lymphocyte develops into what protein-producing cell?

plasma

When it is needed, what important protein does a plasma cell export?

antibody

What cell is specifically depleted in AIDS?

Helper T

The first vaccination was for what disease?

small pox

What are the two types of lymphocytes?

B&T

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.

lysosome

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?

monocytes

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 clumping called?

agglutination

What is the chemical signal that the helper T cell uses to cause the appropriate type of killer T cells to proliferate?

interleukin 2

Which specific antibody crosses the placenta to give the baby the mother's immunities early in life?

IgG

In what way is IgG different from IgM with regard to the placenta and blood groups?

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 syndrome)?

CD4-expressing (helper)

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?

passive

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 human population?

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?

histamine

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?

allergy

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?

monocytes

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?

antibody molecules

What type of cells are the memory cells that can jump-start the response to the next exposure to an antigen?

B lymphocytes

What kind of protein is the antigen receptor on the surface of a B lymphocyte?

antibody (IgD)

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 infection?

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 epitope?

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.

CD4

Why did AIDS, in the first few years, create a new "selection pressure" against hemophiliacs?

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" it?

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 imply?

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 mother. How?

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 epidemic?

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 count?

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 microbe?

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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this page was last revised 6/23/15