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Immunology Test Two
Dr. Suh
116
Immunology
Undergraduate 4
02/14/2011

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Term
Antigen (Ag)
Definition
a substance that can bind specifically with an antibody (Ab) or a T cell (TCR)
Term
What makes a good antigen (Ag)?
Definition
1. Foreigness
2. Size
3. Complexity
4. Degradability
Term
Foreigness
Definition
Specificity to a Certain Group
Ex. Serum, Albumin (good examples)
Cytochrome C (Bad example)
Term
Size
Definition
Larger molecules generally are better
~100,000 Daltons
Term
Complexity
Definition
chemically or structurally complex
DNA is not a good antigen but Proteins are
Term
Degradability
Definition
Proteins have Proteases that degrade molecules
Term
Bovine Serum Albumine (BSA)
Definition
good antigen, very complex, has 25 different epitopes at least for its 582 amino acids
Term
Epitope or Antigenic Determinate
Definition
PARTS of a protein that antibodies recognize
Term
Number of Epitopes
Definition
does NOT equal number of antibodies because there are more than one antibody that can recognize the same epitope
Term
Immunodominate
Definition
epitopes that are recognized by many different antigens
Term
Bell Cell Epitopes
Definition
recognized by antibodies and are generally on the surface of intact antigens
maybe sequential or non sequential
Term
Examples of NOT good antigens
Definition
Lipids, DNA, Polysaccarides
Term
Can Non Sequential Eptopes be Lost?
Definition
only when a protein becomes denatured
Term
Antibody Structure
Definition
4 Polypeptides Subunits
(2 Identical Heavy Chains and 2 Identical Light Chains)
Term
Antibody Function
Definition
Bind antigens (B cell Receptor) and eliminate antigens
Term
What chains contribute to Binding?
Definition
Both light and dark chains
Term
2 Different Types of Light Chains
Definition
1. Lambda
2. Kappa
Term
5 Different Dark Chains
Definition
also known as isotopes

1. IgA - alpha - gut
2. IgE - allergies
3. IgD
4. IgM - blood
5. IgG - most common researched
Term
Light Chains Structure
Definition
two loops with disulfide bonds
60-70 Amino Acids inside each loop with ~220 amino acids all together KNOWN as its structural motif
Term
Heavy Chain Structural Motif
Definition
3-5 Loops instead of 2
Term
Ig Domains (Structural Motif) of the Ig Light Chain
Definition
composed of Beta pleated sheets connected by loops
Term
Two Types of Ig Domains(Structural Motif)
Definition
1. Variable Domains = amino acid sequence varies, light and heavy chains, antigen binding
2. Constant Domains = amino acids sequence does not vary, heavy chain, biological functions
Term
Plotting Variable Domains
Definition
amino acid number vs. number of different amino acid at that point
3 Hypervariable Regions both heavy and light also known as CDR (Complementary Determining Regions)
Term
CDRs Location
Definition
located on flexible loops and no variety on Beta Pleated Sheets to which the loops are what makes contact with antigen
Term
Change CDR ...
Definition
Change Epitope Binding Affinity
Term
Antigen Binding Domain
Definition
determine by CDRs on both light and heavy chains (3 on each)
**at least 4 stay in contact with the epitope but normally 5-6 all at once**
Term
Antigen Binding
Definition
like velcro, one or two interactions easy to pull apart but more together harder to seperate
-non covalent
-reversible
-mediated by interactions over short distances
-many interactions
Term
Binding Requires ...
Definition
Surface Complementary (close together with 15-22 A.A.)
- antibodies form a bumpy topology on surface and must complement that with epitope until match found
Term
Change Amino Acids
Definition
Change Binding Affinity
High = Good
Low = Bad
Term
Antibodies and Antigen Bind Together and Leave ...
Definition
"Wiggle Room" because of induced fit till the CDRs change to make a tighter fit
Term
Antibody Function
Definition
1. Membrane Bound as B cell antigen Receptors (IgM, IgD)
2. soluble form for tissues, blood, breast mil, gut soluble proteins known as EFFECTOR MOLECULES that eliminate antigens
Term
IgM, IgG
Definition
activate complement, enhance adaptive immunity to what innate already does
Term
IgG
Definition
most common, bind to receptors on phagocytosis
Term
IgA
Definition
gut, prevent toxins and pathogens from binding
Term
IgE
Definition
responses mediated by mast cells and eosinophils
Term
IgM
Definition
agglutinate bacteria
Term
IgD
Definition
act as receptor for B cell antigen
Term
Adaptive Immune System
Definition
1. Physical Barriers
2. Cells
3. Soluble Factors
Term
Adaptive Immune System Cells
Definition
1. T Cells
2. B Cells
3. Dendritic Cells
Term
Adaptive Immune System Soluble Factors
Definition
1. Antibodies
2. Cytokines
Term
Pre B Cells and Pre T Cells that do not have a functional receptor that bind to antigens Lead To ...
Definition
Maturation into B Cells and T Cells (T Helper and CTLs)that have functional receptors
Term
Exposure To Antigen
Definition
B Cells and T Cells bind to antigens that activate and proliferate into plasma cells T helper cells and CTLs
Term
T Helper Cells activate What???
Definition
T Helper cells via secretion of cytokines activate 3 Things:
1. Plasma Cells to secrete Antibodies
2. CTLs to migrate to sites of infection and kill infected host cells
3. Other Immune Cells
Term
4 Molecules Bind to Receptors
Definition
1. Antibodies
2. B cells
3. T Helper Cells
4. CTLs
Term
Antigen
Definition
binds to antibody or T cell Receptor
Term
Antigen
Definition
binds to antibody or T cell Receptor
Term
Immunogen
Definition
substance that can induce a specific immune response
Term
All ______ are _______
BUT NOT
All _______ are ______
Definition
Immunogens are Antigens
Antigens are Immunogens
Term
Hapten
Definition
a very small molecule that has antigenicity but not immunogenicity
(too small alone but conjugated to a larger molecule and it can become an immunogen)
Term
Epitope
Definition
specific portion of antigen recognized by antibody
aka antigen determinant
very small = Proteins < 15 A.A. (5-6 A.A.)
Polysaccarides ~4 Residues (sugar units)
Term
Antibody
Definition
a specific protein produced in response to an immunogen and binds antigen
Term
Large Protein with Several Epitopes Injected into Rabbit A
Definition
Rabbit A Produces Antibodies that Bind Epitopes
Term
Large Protein but Degraded with Epitopes Still Intact Injected into each piece into a Different Rabbit
Definition
No Immune Response
Term
Most Potent Immunologen
Definition
Proteins then Polysaccarides
Term
2 Types of Complexity
Definition
1. Chemical
2. Structural
Term
Complexity
Definition
more is better and makes better Immunogens
Term
Chemical Complexity
Definition
how many different building blocks
Proteins - 20 A.A. - 30 to 1000 A.A.
Polysaccarides - 2 to 10, 100 - Repeating Structures
Term
Structural Complexity
Definition
shape conformation
Term
Epitopes and Relationship to Protein Structure
Definition
1. Larger Proteins tend to have more Epitopes than smaller proteins
2. Epitopes may overlap
3. Epitopes tend to be on the surface of the molecule
4. Epitopes can be linear (continuous and Sequential) or non linear (non continuous and non sequential)
5. some epitopes are are better at inducing an immune response than others related to binding characteristics
6. the more epitopes (larger molecule) an immunogen has, the better immune response
Term
Epitopes Location
Definition
can be inside or outside molecule but the inside ones are not good binders
Term
Denaturing Proteins ...
Definition
looses nonconinous epitopes while continous one stays intact
Term
Affinity
Definition
the strength of binding of antibody to antigen
Function of the number of types of noncovalent bonding
Term
Avidity
Definition
the overall strength of antibody binding to antigen
Function of how many antibody sites are occupied
Term
Multimers
Definition
IgA (4 Possible Binding Sites) and IgM (10 Possible Binding Sites)
Term
Early Structure Functions Studies (1950s)
IgG From Rabbit Blood
Purpose:
Definition
to assign a function to a particular domain, separate domains, and test for function
Term
Early Structure Function Studies (1950s)
IgG From Rabbit Blood
Tool
Definition
2 Proteases:
1. Papain
2. Pepsin
Term
Papain Function
Definition
Breaks apart First
Bind Antigen (monovalent) therefore each antibodies bind two antigens on the FAB section composed of heavy and light chains (Fragment Antigen Binding)
FC Fragment crystalizable also are formed and they preform a function in effector and are composed of heavy chains only
Term
Pepsin Function
Definition
Breaks apart
two sections formed
1. F(ab')2 which is a divalent that bind to two antigens
2. small fragments
Term
Each Antibody (Monomeric) Binds ...
Definition
Two Antigens
Term
Antigen Binding Site is ...
Definition
FAB that has both heavy and light chains
Term
FC
Definition
heavy chains that serves as effector function
Term
Binding of FAB to Antigens will...
Definition
change the conformation of FC and expose binding sites
Term
Immune Cells and Components have ....
Definition
FC Receptors when they bind antibodies which leads to elimination of antigen
Term
FcER
Definition
Fc Receptor for IgE
Term
Differences in FC Portion serves in ...
Definition
distribution function because there are 10^9 different B cells
Term
Isotypes in Blood
Definition
IgG, monomeric IgA, and IgM
Term
Secretion Isotypes
Definition
Dimeric IgA
Term
Transferred from Mother to Fetus Isotype
Definition
IgG
**Only one to cross the placental barrier**
Term
Bound to Mast Cells in Submucosal, subcutaneous, and subendothelial Areas Isotypes
Definition
IgE
-Also do not have eosinophils
Term
IgG
Definition
functions as a monomer, predominate antibody in the blood (80% of blood antibodies), lymph, cerebrospinal fluid, peritoneal fluid, and interstitial fluid, has the longest 1/2 life =25 days which therefore functions in passive immunizations,primary antibody of secondary responses, has the most functions: neutralization, ADCC, agglutination, activation of complement, opsonization, relatively small, can enter tissues during inflammation
Term
IgG Role in Newborns
Definition
Protects from infection during a vulnerable period and moves across the placenta from mother to fetus in the last part of gestation.
Term
Infants Producing Ig
Definition
all Ig have come from their mothers, passively protecting infants from pathogens the mother has previously encountered. infant begin to make Ig on their own after birth with amounts rising slowly but progressively over years
Term
IgM
Definition
Two Forms:
1. Monomer-B Cell Receptor
2. Pentame-5IgMs connected via J-chain which is also secreted by plasma cells

Pentamer=Largest Ig, cannot enter tissues during inflammation
3rd most common antibody in blood
1st antibody made during an immune response
low affinity and high avidity
first antibody made by newborns at 5 months
cannot cross placental barrier because of its size
Term
IgM Functions
Definition
Pentamer = neutralization, agglutinations, activation of complement
Term
IgA
Definition
Two Forms:
1. Blood IgA - monomer, second most common antibody in blood with an unknown function maybe in neutralization
2. Secreted IgA (slgA) present as a dimer, predominate antibody in body secretions like mucus, tears, saliva, colostrim, milk
Term
slgA
Definition
major antibody in the body, functions in mucosal immunity, and is responsible for passive immunization of breast feeding babies
Term
In Body .. More Mucus or More Blood?
Definition
More Mucus so IgA is the most present in the body
Term
Two Proteins of slgA
Definition
1. J-chain to connect the two monomers together which is the same J-chain that binds IgM pentamer
2. Secretory Piece - made in peithelial cells and is added to IgA as it passes into secretions
Term
Secretory Piece Functions:
Definition
1. Transport IgA across the Mucosa
2. Stabilize IgA and prevent it from being degraded by substances in secretions
Term
Formation of Secretory IgA
Definition
two IgA molecules covalently linked by J chain and with the secretory component
Term
Secretory Component Formation
Definition
polymeric IgA produced by plasma cells located in the submucosa binds to the poly-Ig Reeceptor on epithelial cells, and the complex is transported to the luminal surface of the mucosa. The poly - Ig receptor is enzamatically cleaved during the transport process and becomes the secretory component of secretory IgA
Term
IgE
Definition
functions as a monomer, unbound monomer is rare in the blood, most igE is attached to mast cell surface and eosinophils, found in tissues and associated with mucosal surfaces
Term
IgE Functions
Definition
antiparasitic defense and is responsible for allergies
Term
IgD
Definition
functions as a monomer, attached to B cell surface, may be present in blood in low concentrations
Function=UNKNOWN thought to be a substitute for B cell Receptors and help development of plasma and memory B cells
Term
FcER
Definition
high affinity (nearly covalent) assures that much of the IgE in body is bound to mast cells and eosinophils in tissues
Term
Mast Cells
Definition
polyspecific antibody (coated loaded gun)
Term
Neutralization vs. Optimization
Definition
size = neutralization does small molecules/proteins/toxins
Term
Neutralization
Definition
DOES NOT eliminate only breaks down and lets phagocytes eliminate
Term
Antibody Kinetics
Definition
rate of change
change on numbers and types of antibodies overtime which can be used to measure an immune response
Term
Primary Immune Response Phases
Definition
1. Lag
2. Log
3. Plateau
4. Decline
Term
Lag Phase
Definition
antibodies not produced antigen enters body
B cells and T cells recognize antigen activation, proliferation, and differentiation
Term
Lag Phase Duration
Definition
2 Days to Months
Avg. 4 - 7 Days
Term
Log Phase
Definition
Exponential Phase
describes the rate at which antibodies are produced. plasma cells produce antibodies
Term
Plateau Phase
Definition
antibodies productions is balanced by antibody decay
Term
Avg. 1/2 Life of Antibody (Plateau Phase)
Definition
2 - 6 Days with no net gain in antibodies
Term
Decline Phase
Definition
overall decline in antibodies plasma cells have 1/2 life ~4-5 Days
production of memory B cells
Term
Secondary Immune Response Phases
Definition
1. Lag Phase
2. Log Phase
3. Plateau Phase
4. Decline Phase
Term
Lag Phase - Secondary
Definition
generally a much shorter phase compared to Primary Response because Memory B Cells
Term
Memory B Cells - Secondary Response
Definition
Memory B Cells still go through activation, proliferation, and differentiation but is a quick response because they do not need T cell Input
Term
Log Phase - Secondary
Definition
antibodies produced at a faster rate and more antibodies are produced
Term
Plateau Phase - Secondary
Definition
no net increase in antibodies
Term
Decline Phase - Secondary
Definition
less rapid in secondary response than primary, antibodies can persist for months
Term
Primary Response Characteristics
Definition
1. slow response because long lag phase
2. low concentration of antibodies produced
3. rapid decline
4. IgM Major Antibody
5. Low affinity antibodies made
Term
Secondary Response Characteristics
Definition
1. Fast Response because Memory B Cells
2. High Concentration of antibodies produced
3. slow decline
4. IgG or IgA or IgE is the major antibody
5. high affinity antibodies because affinity maturation
Term
T Cells Secretion
Definition
cytokines to B cells to tell time for proliferation and go with response
Term
Affinity Maturation
Definition
mutations in DNA coding that can improve antigen binding for higher affinity antigens
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