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179 Cards in this Set

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  • Back
What are the four stem cell levels?
What are the characteristics of hematopoeitic stem cells?
Self renewing - maintain population
Generate granulocytes, erythrocytes, RBC, platelets, etc.
List the location of CD34+ found in the body in terms of decreasing population.
1. Bone marrow, cord blood
2. Peripheral blood
Describe the HIM (Hematopoeitic Inducing Environment).
Cellular matrix and GF
- GF provided by macrophages and T cells
- Some are soluble
- Some require
Which cells are CD34+?
Myeloid SC
Lymphoid SC
How are stems cells detected?
Using flow cytometry to sort cells by nucleation, CD34+, and CD35+ markings.
Who makes CSF (G-CSF, GM-CSF)?
Who makes IL-3?
Who makes IL-7?
Who makes Stem cell factor?
1. Macrophages, T cells, endothelial cells, and stromal
2. Made by T cells
3. Made by Stromal cells
4. Made by Stromal cells
What are stromal cells?
Non-hematopoeitic cells which support growth and differentiation of hematopoeitic cells.
Give an example of a few GF. What are their functions?
CSF (colony stimulating factor)
- induces formation of distinct HSC line

- Promotes division of most developing cells

- Acts on developing B Cells

Stem Cell Factor
- Acts on stem cells

Erythropoietin (EPO)
- Induces terminal development of erythrocytes & regulates RBC production
What are GATA-1, GATA-2, PU-1, and BM11?
Transcription factors essential for hematopoeitic lines
Which lineages do GATA-1, GATA-2, PU-1, and BM11 affect?
GATA-1: Erythroid
GATA-2: Erythroid, myeloid, lymphoid
PU-1: Erythroid, myeloid, ...
BM11: Myeloid, lymphoid
How is hematopoeisis important for homeostasis?
1. Bone marrow stromal cells
2. Cytokines (GF) activated by T cells and macrophages
3. Regulation of cytokine receptors
4. Removal of cells by apoptosis
How do necrosis and apoptosis differ?
Apoptosis does not result in disintegration and release of intracellular content to extracellular environment.

No inflammation results.
Plot a graph of survival rate of radiated mice with no immune system against number/type of stem cells.
Fully enriched stem cells are few in number.

Partial or unenriched stem cells are larger in number.

Fully enriched stem cells are equivalent to partially or unenriched stem cells in terms of reviving the immune system.
What are autologous cells?
Stem cells taken from the patient to treat the patient.
Why use autologous cells?
1. Prevent rejection by host
2. Prevent graft from rejecting the host
Why use stem cells from blood rather than marrow?
1. Easier to retrieve cells
2. Low costs
3. Less invasive
What are primary lymphoid tissues?
* Bone Marrow
* Thymus
What are secondary lymphoid tissues?
* Tonsils
* Lymph nodes
* Spleen
Describe the Thymus.
* Bi-lobed organ
* Site of T cell development
* Stromal cell network of thymic nurse cells, dendritic cells, macrophages aid in growth and maturation
What is in the Thymic Cortex?
Densely populated with immature thymocytes and thymic nurse cells.
What is in the Thymic Medulla?
Sparsely populated with mature thymocytes. Cells express higher levels of MHC I and MHC II.
At what age does the weight of the Thymus peak?
10 years
On which cells do CD4 and CD8 molecules generally appear on?
CD4 = Th
CD8 = Tc
What are antigen specific cells?
Cells that have specificity for the antigenic determinant.

Example: T and B cells
What are accessory cells?
Cells must interact with T cells before an acquired immune response can take place.

These are also called APC (antigen presenting cells).

Example: Macrophages, B cells, and Dendritic cells
What are effector cells?
Cells that carry out a function directly or indirectly.

Example: NK cells, mast cells, granulocytes, macrophages, Tc cells, and plasma cells.
How would the loss of T cells affect a person's ability to fight off infections or possibly tumors?
Mature T cells have antigenic specificity towards any one infection. As a result of the loss, the body's adaptive immunity will not be activated . This would like to chronic or debilitating infections for that individual's lifetime.
What would happen if the thymus were removed at birth or at a young age?
The removal of the thymus would lead to NO mature T cells and therefore would deactivate the adaptive immune system.
Up to 99% of thymocytes die in the thymus. Why?
Thymocytes are educated to not recognize self antigens and act against them. Those thymocytes that survive can recognize SELF MHC + foreign Antigenic peptides.
Which molecules/markers are specific for T cells?
TCR, CD3 molecule, and IL-2 Receptor
Which molecules/markers are specific for T helper cells?
Class II MHC molecule
Which molecules/markers are specific for T cytotoxic cells?
Class I MHC molecule
In mammals and birds, where does B cell development take place?
1. Mammals: fetal liver first and then bone marrow
2. Birds: Bursa of Fabricius
Why do B cells develop independent of antigen?
B cells rearrange their immunoglobulin genes in bone marrow to allwo for diversity in the V region of the antibody molecule.
Which immunoglobulins are produced on the surface of and in the membrance of immature B cells?
IgM and IgD
Are B cells educated? If yes, how so?
Yes. They are educated in much the same way as T cells but in the bone marrow.

Some self recognizing B cells are released into the body but are most often unresponsive to self antigen.
How are B cells identified?
CD19 or CD20 molecules
What two ways do lymphocytes enter a lymph node?
HEV and afferent lymphatics
Through which areas of the lymph node do the antigens travel?
1. Afferent lymphatics
2. Subcapsular sinus
3. Cortex
4. Paracortex
5. Medulla
6. Efferent lymphatics
What is found in the cortex?
B cells are contained in primary follices. Cells in the primary follicles when activated become secondary follicles.

The secondary follicles have a site of cell proliferation called the Germinal Center.
What is found in the paracortex?
T cells in close association with interdigitating dendritic cells.
What is found in the medulla?
T cell, B cells, and plasma cells.
What is the red pulp area?
An area of the spleen where large amount of erythrocytes and macrophages aggregate.
What is the white pulp area?
An area of the spleen where lymphocytes aggregate. It is an artery surrounded by the periarteriolar lymphatic sheats (PALS). The B cell area is follicles with germinal centers next to the artery. The T cells surround the B cell areas.

A marginal zone on the outside of the PALS contains macrophages and APC.
Does the spleen have an HEV and/or afferent lymphatics?
What is the purpose of the spleen in the body's fight against pathogens?
1. Stimulate immune response to microbes by trapping bloodborne antigen in the white pulp.

2. Remove old RBCs
What is the function of the HEV?
Most lymphocytes from the blood selectively bind to the endothelium of the HEV.

Very few polymorphonuclear leukocytes and RBC enter the lymph node.
How do lymphocytes attach to the HEV?
1. L-selectin present on lymhpocytes
2. Adheres to a vacular addressin (CD34 or GlyCAM-1)


1. Chemokine produced by HEV bind to lymphocytes
2. Activates LFA-1
3. Resulting in binding to ICAM-1
What are the two groups of chemokines?
C-C and C-X-C
What are chemokines?
Small polypeptides that control where cells move in the tissues.

Produced by lymphoid and non-lymphoid cells.
How do chemokines affect cell migration?
Chemokine gradients cause cells to move in tissues.

By binding to chemokine receptors on the cell membrane and promoting production of integrins -- facilitate adherence to vascular endothelium.
What are chemokine receptors?
Molecules on the cell membrance that:

1. Traverse the membrance 7 times
2. Activate signal transduction pathways
What are the chemokine receptors designated as?
Compare and contrast innate and acquired immunity when it comes to specificity, timing, and memory.
Innate: no, fast, no
Acquired: yes, slow, yes
Which cells are the first line of defense for innate immunity?
Macrophages and polymorphonuclear leukocytes.
Does the antigen select the B/T cell OR the B/T cell select the antigen?
Antigen selects the B/T cell
Other than antigens, what molecule drives B cell activation and division?
What are cytokines?
Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis.
Name four properties of neutrophils and macrophages.
1. Chemotactic response - chemokines and chemokine receptors
2. Attachment and opsonization
3. Membrance activation and engulfment
4. Destruction by 02 dep. or 02 indep. killing
What is opsonization?
The act of making bacteria more "delicious" by coating with complementary and antibody molecules.
What is the movement of leukocytes from the blood vessel to the tissue called?
What is the shape of the neutrophil nucleus?
What is the shape of the macrophage nucles?
How does a macrophage engulf bacteria?
1. Bacterium coated with complements and antibody
2. Attachment of macrophage to bacterium (due to complements)
3. Zippering process
4. Engulfment occurs
What happens to a bacteria engulfed by a macrophage?
1. Bacteria is engulfed within a phagosome
2. Lysome later bind with phagosome
3. Phagolysosome is produced
4. Peptides are later associated with MHC II
What marker is found on macrophages and monocytes?
What are the differences between macrophages and monocytes?
1. Macrophages in tissue
2. Monocytes in blood
3. Different names in different tissues; e.g. kidney, brain, ...
What is the size of macrophages and monocytes?
55,000 daltons
IL-1, IL-6, TNF, CSF, Interferon Alpha, and hydrolytic enzymes are released by which cells?
Describe follicular dendritic cells.
Long, beaded tentacles coated with antibody-antigen complex.

Role as B cell activator.

Does not express MHC II moecules, instead presents antigen to B cell.
Describe interdigitating dendritic cells.
Antibody-antigen complex.

Role as Th cell activator.

MHC II molecules present antigen to Th cell.
What are the markers of a NK cell?
CD16 molecule, IL-2 receptor, and CD56 molecule.
What do CD16 and CD56 function as?
CD16: cell adhesion
CD56: NCAM receptor
What is the function of a NK cell?
Attach to foreign microorganisms (viruses), release perforin, and breakdown cell membrane.
What is the function of mast cells and basophils?
Cells have a Fc receptor and use to to bind to the Fc portion of IgE.

Release mediators involved in inflammation (e.g. histamine).
What is the function of eosinophil?
Release contents of granules to harm large parasites invading host organism.
Who is Jules Bordet and what did he do?
Researcher at Institut Pasteur 1890s.

Inoculated vibrio cholera with sheep antiserum leading to lysis of bacteria.
Heated antiserum does what?
Destroy activity but antibody remains.
Heated antiserum + sheep serum without antibody did what?
Caused lysis because complement added to antibody.
Sheep serum without antibody did what?
Destroyed activity but complement remains.
What is complement?
Components are produced by macrophages/monocytes, epithelial cells of GI, and liver hepatocytes.

Often circulate in blood as zymogen and only become activated enzymes when cleaved.
Cleavage of a zymogen produces two fragments, what are they?

What is the exception to this model?
A: small fragment
B: large fragment

C2 is the exception.
What are the activities of the complement system?
1. Lysis
2. Opsonization
3. Activation of inflammatory response.
4. Clearance of immune complexes
What activates inflammation?
What are the effects of inflammation?
1. Mast cell degranulation
2. Macrophage activation
3. Chemotaxis
4. Platelet aggregation
What are the three complement pathways?
1. Classical
2. Alternate
3, Lectin
The complement pathways are what kind of systems?
Cascade systems
Complement components are ________________
What activates the classical pathway?
1. Antibody binds with antigen; conformational change occurs in Fc portion of Antibody
2. C1q must bind to two Fc regions
3. C1q can bind to either two IgG molecules (correct distance apart) OR one IgM.
4. Pathway is activated
What is the MAC?
It is composed of C5b, C6, C7, C8, and C9.

It inserts into the lipids of the cell membrance creating a small hole leading to lysis.
Does the MAC attahc of the antigen-antibody complex is a soluble complex?
No. It mya instead fall off and hurt cells in the vicinity.
List the complement components of the classical pathway.
C1q, C1r, C1s, C4, C2, C3,
C5, C6, C7, C8, C9
List the complement components of the alternative pathway.
C3, Factor B, Factor D, C5, P,
C6, C7, C8, C9
What are the differences between the classical and alternative pathways?
1. C3 is the initiator of the alternative, while C1q is the initiator of the classical
2. Serum proteins B, D, and properdin are involved in the alternative only.
What activates the alternative pathway?
Substances that are foreign to the body:

* Bacteria
* Viruses
* Fungi
* Cobra venom
Why don't normal body cells activate this pathway?
Body cells have sialic acid and thus neutralize the C3b component that lands on the cell.
What regulates the complement pathways?
1. Failure to move fast enough through subsequent steps in the cascade.
2. Regulator proteins
What are the regulatory proteins of the complement pathway and what is their function?
C1q inhibitor: dissociated C1q from C1rs

Decay accelerating factor: dissociates C4b2b

C4b binding protein: allows cleavage of C4b by Factor I
What are complement receptors?
Molecules on the membranes of cells which can interact with various complement components.
What are the five complement receptors?
What is the function of complements?
1. Help with phagocytosis
2. Act as an opsonin
Which complement fragments act as an opsonin?
C3b (most important), iC3b, c4b
What are two types of C3 convertase?
C4b2b, C3bBb
What are two types of C5 convertase?
C4b2b3b, C3bBb3b
Which complement fragments act as anaphylatoxin?

Which of those work as chemotactic factors?
C5a (most potent), C3a, C4a

C5a, C3a
How does the immune system remove immune complexes?
The same system as opsonization:

1. Complements (C3b, C4b) attaches to complex
2. CR1 receptor attaches to C3b and C4b
3. Leukocyte engulfs complex
CR3 and CR4 bind which complement?
What is the function of the iC3b complement?
1. Cell adhesion
2. Extravasation
3. Phagocytosis

See table 13-4 of Kuby
What is a Free Split Complement Fragment?
The unused portion of the complement fragment in the cascade system. It acts alone.

See C5a, C3a, C4a
Which complement causes increased phagocytic capability?
Complement activation leads to _________________ ?
Cellular activation
What is cellular activation?
1. Respiratory burst in phagocytic cells
2. Release of granule contents in phagocytes
3. Mast cell degranulation caused by C3a, C5a
4. Increased vascular permeability
5. Increased chemotaxis
6. Smooth muscle contractions
Which lymphocyte is under innate immunity?
Large granular lymphocyte or otherwise known as NK cell
In the early stages of inflammation, which cell type is predominantly infiltrating tissue?
How fast and how much of neutrophils are evident in inflammation.
In the first 6 hours, neutrophil count increases from 10^10 to 10^11 (10 fold increase).
Which molecules allow more neutrophils to extravasate to the region of inflammation?
Thrombin and histamine: produce p-selectin

IL-1 and TNFa: produce e-selectin

Neutrophils express PSGL-1 to bind to p- and s-selectins
What is C reactive protein?
An acute phase protein useful as a chemical mediator in response to injury.

Bind to polysaccharides and glycolipids, damaged membranes, and exposed nuclear antigen.

Leads to classical pathway -- binds C1q to Cr and Cs components
What are the two subgroups of chemokines?
The a chemokines, also known as CXC chemokines, contain a single amino acid between the first and second cysteine residues; ß, or CC, chemokines have adjacent cysteine residues.
What is the function of CXC chemokines?
Most CXC chemokines are chemoattractants for neutrophils.
What is the function of CC chemokines?
CC chemokines generally attract monocytes, lymphocytes, basophils, and eosinophils.
How do chemokines compare to cytokines?
Chemokines are a sub-type of cytokine used effectively to marshal leukocytes to the site of inflammation.
What is bradykinin?
An inflammatory mediator created by:

1. Activated Hagemen Factor activating prekallikrein
2. Prekallikrein forming kallikrein
3. Kallikrein cleaving kininogen
4. Bradykinin formed
What is fibrin?
Fibrin are insoluble strands that when criss-crossed form a clot -- barrier against spread of infection.

Thrombin acts on insoluble fibrinogen.
What is the oxygen independent killing system?
A microorganism engulfed becomes a phagosome. This later fuses with a lysosome to form a phagolysosome. The hydrolytic enzymes in the lysosome destroy the microorganism by dropping the pH.
What is the oxygen dependent killing system?
NADPH oxidase in the membrane of the phagolysosome activates the oxygen. OH-, O2-, O, and H202 are produced and act on unsubstances within the structure.
What is the peroxidase dependent system?
Peroxidas, H202, and halides react to form toxic oxidants.

This occurs only in neutrophils and NOT in macrophages.
How do macrophages present antigen to T cells?
The macrophages does not desotry all of the peptides in the phagolysosome. Instead, the antigenic peptide is associated with the MHC II molecule and expressed in the surface fo the macrophage.
This cell type is one of the first lines of defense against virus infected cells, what is it?
NK cells (innate immunity)
What are the components of blood when centrifuged?
* Plasma & components
* Serum when plasma is allowed to clot; fluid part contains proteins and antibody
What happens to serum when it is placed in an electric current?
The proteins within the serum separate into alpha, beta, and gamma globulins.
What is the largest (in terms of number) Ig?
Gamma globulin (IgG)
Describe the basic Ig molecule.
Two light chains and two heavy chains held together by disulfide bonds.
How was the basic Ig structure determined?
Enzymatic cleavage and reduction of disulfide bonds.
This enzyme breaks the Ig molecule into Fab and Fc parts.
This enzyme breaks the Ig molecule into F(ab')2.
This reducing agent breaks the Ig molecule into is components parts.
Where are the V and C regions of the Ig located?
V region is located at the very edge of the Fab arms.

C region is everything else.
Which factor cleaves C4b?
Factor I
Which factor cleaves C3b?
Factor H
What parts of the antigen and the antibody interact with one another?
The epitope and the antigen binding site
This area of the Ig is flexible and rich in proline.
Hinge region
The hinge region is only available in these Ig.
IgA, IgD, IgG (ADG)
How long are the light and heavy chains of the Ig molecule?

What is their respective weights?
The light chains are each 220 a.a, the heavy chains are each 440 a.a

The light chains are each 25000 KDa, the heavy chains are each 50000 KDa. The total weight of a Ig molecule is 150000 KDa.
How many CDRs are in the V region of each chain?
What are the Framework Regions?
They are ß pleated sheets of the V region. They are less variable than the CDRs and are found between them.
Can variable regions be divided into families? Based on what?
Yes, they can due to amino acid sequence similarities in the CDRs and Framework Regions.
What areas of the body do the five Ig classes function?
M: blood
A: secretions
D: not known
G: blood and tissues
E: Fc receptors on mast cells
The class or subclass designation of Ig molecules is dictated by the amino acid sequence of this _________
H chain constant region
The light chain of the different Ig classes can be either ____________ or ___________
kappa, lambda
These two researchers demostrated CDRs in action utilizing myeloma. Who are they?
Wu and Kabat
What is an isotypic determinant?
These determinants distinguish the C regions of the H chain classes (and subclasses) and the L chain types. Each isotype is encoded by a distinct gene that is characteristic for a particular mammalian species and is present in all members of that species.

Antibodies to these determinants may be raised by injecting IgG from one species into another species.
What is an allotypic determinant?
Allotypic determinants reflect genetic polymorphism of Igs within one species. They are found in the constant domains of IgG, k L chain, and one subclass of IgA.

Antibodies can be formed against an allotypic determinant by injecting Igs into another member of the species that does not possess the alloantigen.
What is an idiotypic determinant?
The third group of antigenic determinants of Igs exist as a result of unique structures generated by the CDRs on L and H chains.
How would one go about stopping an autoimmune disease?
Create anti-idiotypic antibody to the antigenic determinant in the combining site.
How many constant domains does a L chain have?
How many constant domains does a H chain have?
3, except for IgM and IgE which have 4
What are the secondary and tertiary structures of the Ig domain?
Two anti-parallel ß pleated sheets
Which of the Ig classes will cross the placenta? How does it do so?
IgG because it is the only class whose Fc will bind to cells of the placenta
Which portion of the Ig domain bind to C1q and controls its rate of catabolism?
Ch2 near the hinge region
Which of the Ig classes are monomers?
IgG (serum and secretions)
IgM (receptor for Ag on B cells)
IgA (serum)
IgD (receptor for Ag on B cells)
IgE (unknown)
Which of the Ig classes are multimers?
IgM (pentamer in serum)
IgA (dimer in secretions)
Which cell makes the J chain?
Plasma cells
What is the function of the J chain?
Aids in the polymerization of IgA
Is the secretory component of Iga produced by the same cell that makesthe antibody?
No. The secretory component is produced by intestinal epithelial cells.
What is the function of the secretory component of IgA?
The presence of the secretory component renders the IgA much less susceptible to proteolysis in the hostile mucosal environment.
Where is IgA predominantly found?
Breast milk, saliva, mucosal areas
What is the function of IgA?
Prevent bacteria and viral infections from reaching mucosa cells
This Ig class is the most abundant.
What are the four subclasses of IgG in order from highest to lowest serum concentration?
1. IgG1
2. IgG2
3. IgG3
4. IgG4
Which of the IgG subclasses fix complement?
IgG3 (most effective)
IgG1, IgG2 (somewhat)
Which of the IgG subclasses have affinity for macrophages/monocytes, PMNs, and lymphocytes with Fc receptor?
IgG3 (high affinity)
IgG2 (low affinity)
Which Ig class has 10 binding sites?
Which Ig class has 5 carbohydrates per H chain?
Which Ig class is the first to be produced by the fetus?
Which Ig class is the largest (in size)?
Where is IgD primarily found?
On the membrance of B cells
Which of the Ig classes do not have a hinge region?
IgM, IgE
What is the function of IgE?
1. Can bind to mast cells and basophils (def) where it mediates many allergic reactions -- inflammatory response

2. Can bind to eosinophils enabling opsonization against parasites and worms