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186 Cards in this Set

  • Front
  • Back
Antigens and Immunogens are distinctly what?
different
What is an immunogen?
any substance that can induce a cell-mediated or humoral immune response
What is an Antigen (Ag)?
substance that is recognized by a particular surface Ig (B-cell receptor) or TCR, and is a target of an immune response.
All Ags are ? but all ? are not Ags.
immunogens, immunogens
Why are all Ags considered immunogens?
because they can induce cell-mediated or humoral responses
Haptens are ? but not ?.
they are antigenic but not immunogenic
What is a hapten?
a small molecule which can elicit an immune response only when attached to a large carrier such as a protein (the carrier may be one that does not elicit an immune response by itself)
What does a hapten need in order to be considered antigenic?
needs to be coupled to a large protein
What is urushiol?
a toxin found in poison ivy that is a known hapten
What can some hapten's illicit? Give 2 examples.
Autoimmunity

1. Hyralazine can induce a lupus like rash

2. Halothane can induce hepatitis
How many molecules can as haptens?
more than 7000
Name 9 products that illicit hapten like immune responses?
1. penicillin

2. neuromusc. blocking agents

3. succinylcholine

4. aspirin

5. alpha-methyldopa

6. cimetidine

7. NSAIDS (ex. Bextra)

8. sulfur based antibiotics

9. latex

(all these products have the ability to form hapten-protein complexes)
What molecules are the best immunogens?
large proteins (>10,000 MW)

-the most foreign to the host, the better the immunogen
What are the least immunogenic molecules?
1. polysacch.s

2. short polypeptides

3. lipids

4. organic polymers
What molecules are not usually immunogenic?
very small molecules (unless attached to a carrier like haptens), short amino acid chains, monosaccharides.
When it comes to the properties of immunogens what is key?
"complexity is key"...the more complex the protein the greater the immunogenicity
How is "tolerance" related to the properties of the immunogen?
if you don't learn to tolerate you can have an auto-immune response of you will get coupled haptens
5 factors that affect the response of the immune system to immunogens?
1. Amount of immunogen

2. Route of exposure

3. Genotype of recipient

4. Repetition

5. Adjuvants
How does the amount of immunogen affect the response of the immune system to immunogens?
Excessively large doses can lead to tolerance and too little will not elicit a response.
Name 4 different routes of exposure?
1. IV (goes to spleen)

2. IM (goes to lymph nodes)

3. SC (goes to lymph nodes)

4. Oral (goes to gut mucosa)
Give an example of how the route of exposure affects the response of the immune system to immunogens?
Oral exposure evokes a different response than parenteral exposure. All exposures give a unique response.
Explain how the genotype of a recipient can affect the response to immunogens?
The type of MHC, B-cell, T-cell genes will influence the degree of reactivity or you may not react at all.
How does repetition affect response to immunogens?
Boosting tends to increase response. It is important to give progressively more. If you are allergic to something you will not have a response to it on first exposure.
Administration with other immunogens or ? can alter the immune response.
adjuvants
What is the only adjuvant approved for use by the FDA?
Alum
Where are adjuvants often used?
They are often used in studies but not with people.
Define adjuvant?
Substances that when mixed with and co-injected with Ag enhance the immunogenicity of that Ag.
List 4 effects of adjuvants.
1. Ag persistence is prolonged

2. Co-stimulatory signals (that help the immune response) are increased.

3. Local inflammation is increased

4. Nonspecific proliferation of lymphocytes is stimulated at the area of injection.
List 2 examples of adjuvants.
1. Alum

2. Freund's Adjuvant
What is the only adjuvant approved for human use?
Alum
What does Alum act like?
It acts kind of like a carrier and allows phagocytosis to occur quicker.
What does Alum do to the time of exposure to an Ag?
It causes the time of exposure to Ag to increase from days to weeks. (so gives more time and slows down the immune response)
What does Alum do to the size of Ag? Why does it do this?
It increases the size of Ag making it amenable to phagocytosis.
What can Alum cause?
Like MOST adjuvants it can cause granulomas.
What is a granuloma?
Occurs when macrophages flow to the area of adjuvant and form a cluster of cells. (Appears lumpy)
Which of the two listed adjuvants is typically used in the lab?
Freund's adjuvant
Why do studies utilize adjuvants?
Immunological studies look more effective when you use adjuvants.
Epitopes are ? determinants.
antigenic
In general terms, what induces an immune response best?
Large molecules.
What is an epitope?
Part of a macromolecule that is usually non-self and is recognized by an immune system cell. The whole molecule is not recognized, just the antigenic epitope. Ags may contain several distinct epitopes.
Ab or TCR will target how many epitopes.
They EACH will target ONE epitope.
One epitope may be ?% of the total surface of the protein.
10%
What must epitopes and Abs have for short-range binding (Van der waals) forces to operate?
complementary shapes
The development of B-cells occurs where?
In the bone marrow.
The development of T-cells occurs where?
In the thymus.
What is Ig?
Immunoglobulin. Antibodies found in the plasma.
B-cells can recognize what kind of Ag?
soluble Ag
Epitopes are ? ? sites.
highly accessible
T-cell epitopes are ? peptides.
breakdown
What are B-cell epitopes composed of?
They are composed of hydrophilic a.a. on the protein surface that protrude from the surface.
B-cell epitopes tend to be located in what kind of regions of an Ag?
In flexible regions. This makes it easier for Abs to fit into.
Complex proteins may contain ? B-cell epitopes. This may cause them to be what?
May contain multiple B-cell epitopes and some are immunodominant (produce a more pronounced immune response than a smaller immune response)
The interaction of a B-cell with an antigen involves what kind of complex?
A binary complex of membrane Ig and Ag
The interaction of a T-cell with an antigen involves what kind of complex?
A ternary complex of T-cell receptor, Ag, and MHC molecule.
Are B-cells able to bind soluble antigen?
Yes
Are T-cells able to bind soluble antigen?
No
Are MHC molecules involved in Ag recognition by B-cells?
None reqd
Are MHC molecules involved in antigen recognition by T-cells?
Yes, they are reqd to display processed Ag.
The chemical nature of Ags recognized by B-cells? (3)
1. protein

2. polysaccharide

3. lipid
The chemical nature of Ags recognized by T-cells? (3)
1. proteins (mostly)

2. lipids (some)

3. glycolipids presented on MHC-like molecules (some)
The epitope properties for antigens that are recognized by B-cells?
Accessible, hydrophilic, mobile peptides containing sequential or nonsequential amino acids
The epitope properties for antigens that are recognized by T-cells?
Internal linear peptides produced by processing of Ag and bound to MHC molecules.
Epitopes are in association with ? on an APC (a processed Ag). Explain.
Epitopes are in assoc. with MHC on an APC. T-cells rarely recognize specific conformational features on native Ag. An APC may only present a few of the conceivable epitopes.
TCRs depend on what for complimentarity of binding?
The depend on both epitope and MHC.
Processed Ag has how many binding sites? Name and describe them briefly.
2 binding sites:

1. One that interacts with TCR - the epitope

2. One that interacts with the MHC - the agretope
Immunoglobulins are ?.
Antibodies. They are a group of glycoproteins found in the tissue and serum of all mammals.
Immunoglobulins are involved in what?
The immune response
What is necessary for B-cells to develop into plasma cells? Once developed what can they secrete?
Contact between B-cell and Ag (and Th) are needed to cause B-cells to dev. into plasma cells which then can secrete large amounts of soluble Ab that can recognize a particular Ag.
How many distinct classes of immunoglobulins exist? Name them.
5 classes of IGs:

1. IgM

2. IgG

3. IgE

4. IgA

5. IgD
What distinguishes the different Immunoglobulin classes from one another?
They differ in size, charge, a.a. composition and CHO content. However, there is also heterogeneity between all 5 classes.
Describe 5 components of a typical Ig structure?
1. 2 INTRAchain disulfide bonds in light chain - one in V region, one in C region.

2. 4 INTRAchain disulfide bonds in heavy chain

3. 2 INTERchain disulfide bonds

4. CHO attached to CH region

5. Variability in Vh and Vl regions accounts for binding diversity.
What accounts for the binding diversity of a typical Ig structure?
Variability in Vh and Vl regions
How are disulfide bonds involved in the structure of the typical Ig molecule?
The hold the light chain and heavy chain regions together and provide stability to the Ig.
What does the V stand for in Vh and Vl?
Variable
What does the C stand for in the C-region of an Ig structure?
Constant
What makes the light chains of an Ig light?
They have less a.a.'s.
The V-regions of Ig have how many a.a.'s?
100-110
The V-regions of Ig differ in their ability to do what?
They differ in their ability to recognize Ag and they vary from Ab to Ab.
When compared to the V-regions the C-regions are ? in size.
larger
Why are the V-regions considered 'variable' and the C-regions considered 'constant'?
V-regions vary between Abs and C-regions are more constant with very limited variation between Abs.
All Abs are what?
Igs
IgG stands for what?
Immunoglobulin gamma
How many subclasses does IgG have?
4 (IgG1, IgG2, etc)
Of the 4 subclasses of IgG which has a long hinge region and longer half life?
IgG3
IgG is the major Ig found where?
In normal human serum.
Average molecular weight of IgG?
146,000
MW of IgG3?
170,000
Where is IgG distributed?
It evenly distributes between intravascular and extravascular space.
IgG is the major Ab of what response.
The major Ab of the secondary immune response.
IgG is the exclusive ? class of the Igs?
The exclusive antitoxin class.
IgG crosses the placenta to confer ? ? to a fetus from the mother.
It confers passive immunity.
IgG plays a key role in ? and activates ?.
Plays a key role in opsonization and activates complement.
IgM size compared to IgG?
IgM is about 8 times larger than IgG.
IgM has a ? configuration.
Has a crab-like configuration, J-joining chain.
IgM comprises what percentage of total Ab?
10%
MW of IgM structure? What does this weight hinder.
970,000 (So it can't diffuse well and it does not cross the placenta)
Where are IgMs typically found?
In the intravascular pool.
IgM is involved mostly in the ? immune response.
Mostly in the primary immune response.
IgM is frequently seen in the immune response to what?
The immune response to antigenically complex infectious organisms.
Which activates complement better IgG or IgM?
IgM
IgM has a crab-like structure in the plasma but sometimes it has a different structure. Explain.
It is a secretory IgM. When attached to a B-cell it looks more like a dimer (molecule composed of two simpler molecules)
IgA has how many subclasses?
2
IgA composes what percentage of total Ig?
15-20%
What is the MW of IgA?
160,000 (so it is about the size of IgG)
How can IgA exist?
1. monomer

2. dimer

3. trimer

4. tetramer

5. Secretory
MW of Secretory IgA? What does this indicate?
385,000. This means it is larger then when it is attached to a B-cell.
What is Secretory IgA made of?
It is composed of epithelial cells.
What would indicate that an IgA was secretory?
It would have a J-chain. This is the secretory component.
Secretory IgA is a ?.
It is a dimer.
Where is secretory IgA found? When is it found?
It is found in breast milk, saliva, tears, and mucus. It kicks in when food is infected with salmonella, Vibrio cholerae, influenza, and gonorrhea.
IgD is not very ?.
Not very stable.
IgD comprises what percentage of total Ig?
<1%
MW of IgD?
185,000
IgD is more susceptible to what than the other Igs are?
IgD is more susceptible to proteolysis. It has a tendendency of undergoing spontaneous proteolysis. (the breaking down of proteins into simpler compounds)
IgD may play a role in Ag-triggered what?
May play a role in Ag-triggered lymphocyte differentiation. (But no one really knows the function it plays in this)
IgD was discovered in association with what?
multiple myeloma
MW of IgE?
190,000
Where is IgE scarce?
Scarce in the serum.
Where is IgE found?
On the surface of basophils and mast cells.
IgE is commonly associated with what?
Associated with allergies.
IgE may play a role in what?
May play a role in Immunity to helminthic parasites.
IgE has ? ? activity?
Potent biological activity
Degranulation (related to IgE's potent biological activity) is associated with what?
It is assoc. with hypersensitivity rxns that are responsible for the symptoms of hay fever, asthma, hives and anaphylatic shock. (ex. histamine degranulation)
What is an assay for IgE activity?
P-K reaction. ("Prawnst & Kustner" discovered the "wheel and flare" reaction : Injected people who were not allergic to something from allergic people)
MW of IgM?
900,000. The largest MW of all the Igs.
Which Igs cross the placenta?
1. IgG1

2. IgG2 (sometimes)

3. IgG3

4. IgG4

So all the gamma immunoglobulins have the ability to cross the placenta.
Which Igs cannot cross the placenta?
IgA1, IgA2, IgM, IgE, IgD. None of them can except for the IgGs.
Which Ig induces mast cell degranulation?
Only IgE.
Which Igs are present on the membrane of mature B-cells?
Only IgM and IgD are present on the membrane of mature B-cells.
Igs have ? deteminants?
Igs have antigenic determinents (epitopes).
What do Igs have the ability to do when injected cross-species?
Ability to elicit an immune response.
Name the three classes of Epitopes?
1. Isotypic

2. Allotypic

3. Idiotypic
What region are Isotypic epitopes found in?
They are found in the constant region.
What do isotypic epitopes define?
The define each heavy chain class and subclass (alpha, gamma, mu, delta, and epsilon)
Within a species, each normal individual will express ? ? in the serum.
Will express all isotypes in the serum.
Allotypic epitopes have subtle ? ? differences.
Have subtle a.a. differences.
Allotypic epitopes are found in ? ? ? ? members of a species.
They are found in some but not all members of a species.
Give an example of an Allotypic epitope?
Abs to an allotypic epitope can be produced by a mother in response to paternal allotypic epitopes on fetal Ig. So this is an immune response to the fetus itself.
Idiotypic epitopes are ? ? than allotypic isotypes?
They are less common.
How are Idiotypic epitopes generated?
By conformation of the a.a. sequences of the H and L-chain variable regions.
Each Ab has ? idiotopes. What are these called?
Each Ab has multiple idiotOpes. These are called the idiotYpe of the Ab.
Which epitope is related to blood transfusion matches?
Idiotypic epitopes
BCR is a ? ? complex. What is it composed of?
BCR is a transmembrane protein complex. It is composed of mIG (membrane bound Ig) and disulfide linked heterodimers.
What is an FcR?
An Fc Receptor is a glycoprotein that has an affinity for the Fc region of soluble Abs.
What are FcRs essential for?
The are essential for many of the biological functions of Abs.
What do FcRs do to Abs. What do they do to IgG?
They move Abs across cell membranes and transfer IgG from mother to fetus across the placenta.
FcR provides a means for Abs to recruit what?
Provide a means for Ab to recruit cellular elements of innate immunity.
Is there a single type of FcR?
No, there are many types.
What can FcRs signal?
phagocytosis
What does Ag bind to?
Each Ig binds to a specific antigenic determinant found on bacteria, pathogens, and viruses.
What is the Valency of an Ab?
Valency refers to the number of antigenic determinants that an individual Ab can bind (at least 2, divalent, and sometimes more)
The effector functions of Ig enable it to fixate to what?
Complement
The effector functions of Ig allow for complement fixation and binding to various cell types. Name 6 of the cell types that have receptors that bind Igs.
1. Phagocytes

2. Lymphocytes

3. Platelets

4. Mast cells

5. Basophils

6. Placental trophoblasts

The binding of an Ig allows these cells to perform a function. For example, the transfer of Ig across the placenta.
List 5 points about the basic structure of Igs.
1. 2 heavy and 2 light chains

2. Disulfide bonds to add stability

3. Have variable (V) and constant (C) regions

4. Hinge region (flexible) located at the "fork"

5. Oligosaccharides (are usually attaced to Ch region, and are almost always found here)
Comparison of a.a. sequences shows what two things about the V region?
1. Most variability resides in CDR (complementarity determining regions)

2. Found in both H and L-chains
Remember, Ab is a ?. This makes it susceptible to breakdown by enzymes.
Protein
Fab and Fc are formed from what?
Formed from papain digestion.
F(ab)2 is formed from what?
Formed from digestion with pepsin.
The Fc region is bound to what? This enables it to signal what?
Bound to the membrane. It signals extracellular effects.
Fab fragments contain what sites?
The Ag binding sites of the Ab
Each Fab is ? while the original molecule was ?.
Each Fab is monovalent while the original mol. was divalent.
The effector functions of Igs are mediated by what part of the molecule?
Fc (and different functions are mediated by different parts of this fragment). The type of Ab signals what the Fc region will do.
Fc Receptors are found where?
They are found on the surface of all effector cells of the immune system.

1. NK cells

2. Macrophages

3. Neutrophils

4. Mast cells

5. B-cells
Fc Receptors contribute to what functions of the immune system?
The protective function
Fc Receptors help in the elimination and identification of microbial pathogens by binding to what?
By binding to Abs that are ATTACHED to infected cells or invading pathogens. The binding occurs at the tail.
Carbohydrates play an important role in the binding of what?
In the binding of an Fc to an Fc Receptor.
Fc Receptors are only active when?
Only when they are bound to a cell.
What is associated with the Fc'gamma'RI receptor?
The cluster differentiation protein CD 64. The gamma indicates that this is associated with IgG.
The principal Ab ligand of Fc'G'RI?
IgG1 and IgG3
Fc'F'RI receptor has a ? affinity for IgG1 and IgG3.
High
The cell distribution of the receptor Fc'G'RI?
1. Macrophages

2. Neutrophils

3. Eosinophils

4. Dendritic cells
The biological effect of Fc'G'RI following it's binding to an Ab?
1. phagocytosis

2. cell activation

3. activation of burst (releases bleach)

4. induction of microbe killing
The principal Ab ligand associated with Fc'E'RI?
IgE
Is the Fc'E'RI affinity for IgE high or low?
High
The cell distribution of Fc'E'RI?
1. Mast cells

2. Eosinophils

3. Basophils

(So these are associated with allergic responses)
Fc'A'RI is associated with what?
CD89
What is the principal ligand associated with Fc'A'RI?
IgA
The affinity of Fc'A'RI for IgA is what?
Low
The cell distribution of Fc'A'RI?
1. Monocytes

2. Macrophages

3. Nuetrophils

4. Eosinophils
The biological effect of Fc'E'RI following its binding to an Ab?
Release of granules.
The biological effect of Fc'A'RI following its binding to an Ab?
1. Phagocytosis

2. Induction of microbe killing
The principal Ab ligand of FcRn?
IgG
The affinity for FcRn for IgG is high or low?
It is unknown.
The cell distribution for FcRn?
1. Monocytes

2. Macrophages

3. Dendritic cells

4. Epithelial cells

5. Endothelial cells

6. Hepatocytes
The biological effect of FcRn following its binding to an Ab?
1. Transfer IgG from mother to fetus via placenta.

2. Transfers IgG from mother to baby via milk.

3. Protects IgG from degradation.
The receptors serve as an example of this aspect of the immune system?
It is redundant. This aids in it's ability to compensate for itself when there are malfunctions.