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Immunology Exam 1, Part 4
The Immune Response; Immunogens and Antigens
59
Immunology
Professional
01/30/2012

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Term
What are the four stages of the immune response?
Definition
1. Lag phase
2. Exponential phase
3. Steady state phase
4. Decline phase
Term
How long does it take to reach protective levels of immunity?
Definition
1-3 weeks. This is a longer length of time than the immune response, because it takes time for memory cells to proliferate.
Term
Define the lag phase of the immune response
Definition

3 - 14 day period of cell proliferation and differentiation before antibody appears

 

Varies with such factors as the antigen, dose, route of administration, and the individual patient

Term
Define the exponential phase of the immune response
Definition
4 - 10 days when rate of antibody biosynthesis exceeds rate of catabolism
Term
Define the steady state phase of the immune response
Definition
Rate of antibody biosynthesis and catabolism are approximately equal
Term
In the immune response, which antibodies respond in greatest numbers first? Which respond second?
Definition
IgM, then IgG
Term
How do antibody levels change from the primary to secondary immune response?
Definition
Total Ab levels are much higher. IgM levels stay about the same, but there is a much greater IgG response because IgG are from memory cells and have greater binding affinity.
Term
Define the decline phase of the immune response
Definition
Antibody biosynthesis has essentially ceased and catabolism occurs.
Term
What two factors does the duration of effective immunity depend on?
Definition
1. The amount of antibody formed (ie, first order declined), and to a lesser extent,
2. Efficacy of the antibody
Term
Define secondary immune response
Definition
Subsequent exposure to the same antigen. The clones of specific immunogen-reactive cells grow after each exposure and the size of this population is the main determinant of the
speed and intensity of any secondary response.
Term
How do the stages of a secondary immune response compare to those of a primary immune response, in regards to time?
Definition
1. Lag phase- shorter
2. Exponential phase- steeper
3. Steady state phase- higher
4. Declining phase- longer (due to more Ab formed)
Term
Why will a secondary response not be seen if it is too soon after primary exposure?
Definition
Antibody interference
Term
Why will a secondary response not be seen if it is too long after primary exposure?
Definition
Memory is finite and long term
immunity requires repeated immunogenic exposure
Term
What cells allow T cells to form into effector T cells and B cells to form into plasma cells?
Definition
Helper T cells
Term
What are the broad functions of effector T cells in the efferent immune response?
Definition
Lymphokine release and/or cytotoxicity
Term
What are the broad functions of plasma cells in the efferent immune response?
Definition
Antigen-Antibody reactions (precipitation, agglutination, compartment-fixation, opsonization, virus neutralization
Term
List the four basic steps of the afferent immune response
Definition

1. Antigen capture by general APC (ex. dendritic cell) 

2. Antigen processing 

3. Antigen presentation via class II MHC to specific TH cell receptor

4. TH cell activation

Term
Once a TH cell is activated, what three things can it do in the efferent immune response?
Definition

1. Activate a B cell 

2. Become a memory TH cell

3. Activate a cytotoxic T cell via IL-2 receptor

Term
Once a cytotoxic T cell is activated, what can it do in the efferent immune response?
Definition

1. Become a memory Tc cell

2. Kill infected cells, which present antigen via a class I MHC

Term
Once a B cell is activated, what can it do in the efferent immune response?
Definition

1. Undergo differentiation to a plasma cell

 

 2. Undergo proliferation to a memory B cell

Term

Where are MHC class I receptors located?

Where are MHC class II receptors located?

Definition

MHC class I receptors (CD8): cytotoxic T cells

 

MHC class II receptors (CD4): helper T cells

Term
Give an example of positive selection (in the immune response)
Definition
Immunogen stimulation of lymphocytes is an example of positive selection that results in the proliferation of the cells.
Term
Define negative selection (in the immune response)
Definition
Immunogen stimulation of lymphocytes under some special circumstances results in death of the cell. This is of greatest importance in two areas which will be discussed in more detail later.
Term
Why is negative selection (cell death) in the immune response so important?
Definition
1. It limits the extent of a normal immune response
2. Discrimination of self and preventing attack of the host by autoreactive clones of cells
Term
Define apoptosis
Definition
Physiologic or programmed cell death

A physiologic signal programs the cell to die rather than the cell being killed by lysis, a metabolic toxin, etc.
Term
Define immunogen
Definition
A substance capable of inducing an immune response in a susceptible animal and reacting with the products of that response.
Term
What three things can an immunogen refer to?
Definition
1. Immunogenic substance
2. Immunogenic compound
3. Epitope
Term
Define immunogenic substance
Definition
Substance that contains one or more immunogenic compounds; e.g., microorganism, pollen
Term
Define immunogenic compound
Definition
A single molecule that may have more than one specificity
Term
Define epitope
Definition
A part of an immunogenic molecule that determines specificity and binds with an antibody or gives rise to the MHC-binding peptide that is recognized by the T-cell receptor.

(aka immunogenic determinant, antigenic determinant)
Term
Are all immunogens antigens?
Definition
Yes
Term
Are all antigens immunogens?
Definition
No
Term
Define antigen
Definition
A substance that can react with immune effectors (Ab or T-cell receptors)
Term
Define complete immunogen
Definition
Complete Immunogens are capable of inducing an immune response themselves.
These are usually proteins but may be polysaccharides.

1. The term immunogen implies that a substance is "complete"
Term
Define hapten
Definition
Haptens (Partial Immunogens) are not capable by themselves of inducing an immune response but may do so when covalently bound to a suitable carrier compound, usually a protein.
Term
Are haptens common?
Definition
Virtually any compound with the potential to covalently bind to protein is a possible hapten. This includes most conventional drugs and their metabolites.
Term
Are haptens active during an immune response?
Definition
Haptens serve as an epitope (or part of an epitope) and thus determine the specificity of the immune response.

Free haptens, while not inducing an immune response, will often react with the effectors (e.g., antibody) formed in the response.
Term
Why can most drugs cause allergy?
Definition
Because they act as haptens, serving as an epitope on a carrier protein.
Term
Are all haptens proteins?
Definition
No, virtually any chemical class can be a hapten
Term
Give an example of an antigen that is not an immunogen
Definition
A free hapten that is not bound to a carrier, but still interacts with effectors (antibodies) during an immune response
Term
How does penicillin usually become a hapten?
Definition
The lactam ring in penicillin is opened up (the penicilloyl configuration), which is a major antigenic determinant for antibodies and T cells.
Term
How is immunogenicity related to molecular weighr?
Definition
Immunogenicity usually increases with molecular weight

Around 10,000 is threshold, >100,000 is highly immunogenic
Term
List five physical characteristics that can lead to immunogenicity
Definition
1. Chemical class (protein)
2. Molecular size (larger)
3. Source (foreign)
4. Chemical complexity
5. Epitopes
Term
Define tolerance
Definition
The absence of an immune response to something that is immunogenic in others
Term
Variation in 1-2 amino acids away from the active
site of an enzyme or hormone generally has very little effect on the biological activity of a protein. Can it have a major effect on immunogenicity?
Definition
Yes, even though it might not even have a different structure
Term
If a single amino acid such as (Gly-Gly-Gly-Gly) is repeated in sequency, is it likely to be immunogenic?
Definition
No
Term
Which are more likely to be immunogenic, aromatic or aliphatic amino acids?
Definition
Aromatic amino acids
Term
Describe the chemical bond between antigen and antibody
Definition
Reversible, non-covalent
Term
Describe the valency and specificity of immunogens
Definition
Multivalent and multispecific

Important because we don't need to respond to every epitope- just a few is enough
Term
How large are most epitopes?
Definition
3-20 amino acid or monosaccharide units in size

It is interesting that this is a similar size to most conventional drugs (MW 250-1000)
Term
Define cross-antigenicity
Definition
The level of specificity in immune reactions is very high but nonetheless relative. Epitopes of similar size, shape and charge may crossreact
Term
Is a native epitope (in a macromolecule) identical to the same free epitope?
Definition
No, a free epitope may or may not react with antibodies induced by the complete immunogen
Term
What is the key difference between B cell immunogens and T cell immunogens?
Definition

B cell immunogens react directly with the B cells

 

T cell immunogens must be processed which includes hydrolysis to smaller fragments

Term
Define linear epitope
Definition
An epitope comprised of a linear sequence of amino acid or sugar residues (3-20 units) in a macromolecule
Term
Define discontinuous (conformational) epitope
Definition
An epitope created by individual units occupying a number of non-adjacent sites in the macromolecule that have been brought into proximity by the conformation of the molecule

Can be disrupted by protein denaturation
Term
Define immunodominance
Definition
A way to compare two epitopes within the same immunogen molecule.

Factors that determine immunodominance include position within chain, conformation, hydrophilicity, steric structure
Term
About how many epitopes can an individual respond to?
Definition
10^6 - 10^8 different epitopes
Term
Why does the typical immunogen have to be multivalent to generate a response?
Definition
The normal antibody response requires at least two determinants—one to trigger a T cell response and the second the B cell response.

(The usual antibody response is said to be thymic dependent and little or no antibody will be formed in the absence of helper function.)
Term
Define a thymic-independent antibody response
Definition
An atypical antibody response consisting mainly of IgM and no immunologic memory.
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