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90 Cards in this Set

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Which two properties distinguish adaptive from innate immunity?
1) SPECIFICITY for particular foreign molecules (antigens), which also involves distinguishing self from nonself molecules

2) MEMORY for most previously encountered antigens so that a second encounter prompts an even more rapid and vigorous response
Where does the T in T cell come from?

The B in B cell?
T cells are so-named because they mature in the thymus.

B cells are so-named because in birds they mature in an organ called the bursa of Fabricus. In humans they mature in red bone marrow.
What features must maturing B and T cells develop in order to achieve immunocompetence?
B and T cells must begin to make several distinctive proteins that are inserted into their plasma membranes. Some of these proteins function as antigen receptors, which are molecules capable of recognizing specific antigens.
What are the two major types of T cells?
The two types of T cells are helper T cells (CD4 cells) and cytotoxic T cells (CD8 cells).
What's another name for helper T cells?
Helper T cells are also called CD4 cells.
What's another name for cytotoxic T cells?
Cytotoxic T cells are also called CD8 cells.
What are antigen receptors?
Antigen receptors are molecules on the surface of immune cells capable of recognizing specific antigens.
What is clonal selection?

Why is clonal selection necessary?
Clonal selection is the process by which a lymphocyte proliferates and differentiates in response to a specific antigen.

Initially there are usually many copies of an antigen in the body's tissues and fluids, with the numerous copies of the antigen outnumbering the small group of helper T cells, cytotoxic T cells, and B cells with the correct antigen receptors to respond to that antigen. Proliferation through clonal selection is therefore necessary to catch up and overtake the antigen.

Before first exposure to an antigen only a few lymphocytes are able to recognize it, but once clonal selection occurs there are thousands that can respond to that antigen.
The receptors on immune cells that recognize specific antigens are called what?
Antigen receptors
Name three types of effector cells in the adaptive immune system:
1) Active helper T cells
2) Active cytotoxic T cells
3) Plasma cells
A lymphocyte that undergoes clonal selection gives rise to which two major types of cells in the clone?
Lymphocytes that undergo clonal selection give rise to 1) effector cells and 2) memory cells.

The effector cells carry out activities that ultimately result in the destruction or inactivation of the antigen (e.g. active helper Ts, active cytotoxic Ts, plasma cells).

Memory cells do not actively participate in the initial immune response to the antigen. However, if the same antigen enters the body again in the future, the thoussands of memory cells of a lymphocyte clone are available to initiate a far swifter reaction than occurred during the first invasion.

The response of memory cells to the antigen is rapid proliferation into more effector and memory cells.

Examples of memory cells include memory helper T cells, memory cytotoxic T cells, and memory B cells.
What is an epitope?
An epitope is the small part of a larger antigen molecule that actually triggers the immune response.
What is an antigen?
Technically speaking, immunologists define antigens as substances that possess reactivity.

Reactivity is the ability of a substance to react specifically with the antibodies or immune cells it provoked.

Complete antigens possess both immunogenicity and reactivity (the ability to provoke immune responses and then react to them)
What is a complete antigen?
Complete antigens are those that possess both immunogenicity and reactivity.
What is the difference between immunogenicity and reactivity?
Immunogenicity refers to an antigen's ability to stimulate the production of specific antibodies or to stimulate the proliferation of specific T cells (or both).

Reactivity, on the other hand, refers to the ability of the antigen to react specifically with those immune elements previously provoked.

For example, if an antigen stimulates the production of specific antibodies against it, that antigen possesses immunogenicity.

If the the antigen then reacts with those antibodies, the antigen is said to have reactivity.
What is a hapten?
A hapten is a substance that lacks immunogenicity but has reactivity. A hapten can stimulate an immune response only if it is attached to a large carrier molecule.
What two terms is the word antigen derived from?
Antigen is a portmanteau from antibody generator.
What's the name for the small part of the larger antigenic molecule that actually triggers the immune response?
These small, immune response-generating pieces are called EPITOPES.
What's the name for a substance that has reactivity but not immunogenicity?
These substances are called haptens. They only stimulate an immune response when attached to a larger carrier molecule.
What are the only body cells that do not possess MHC molecules?
Red blood cells
Which cells possess MHC-I molecules?
All body cells except red blood cells display Class I MHC molecules on their plasma membranes.
All normal body cells, with the exception of red blood cells, possess which class of MHC molecule?
All body cells except red blood cells have Class I MHC molecules built into their plasma membranes.
Which class of MHC molecule do antigen-presenting cells (APCs) display in their plasma membranes?
APCs have MHC-II molecules while all other body cells (except RBCs) have MHC-I molecules.
What is an exogenous antigen?
Exogenous antigens are extracellular antigens present in fluids outside body cells.
What special class of cells processes and presents exogenous/extracellular antigens?
Antigen-presenting cells (APCs)
What do APCs do after processing an antigen?
After processing an antigen and presenting the peptide fragments on its MHC-II molecules, APCs MIGRATE from wherever they found the antigen to lymph tissue where they present the antigen-MHC complex to helper T cells.
Describe the process of processing and presenting of an exogenous (extracellular) antigen:
1) Ingestion of antigen (phagocytois/endocytosis) by APCs

2) Digestion of antigen into peptide fragments

3) Synthesis/packaging of MHC-II molecules

4) Insertion of antigen-MHC-II complexes into plasma membrane
What is meant by antigen processing?
In antigen processing, antigens are taken up into cells (via endocytosis/phagocytosis), broken down into smaller peptide fragments, and combined with MHC molecules (class I or II) to form antigen-MHC complexes.
What are TCRs?
TCRs are T cell receptors.

These are antigen receptors on the surface of T cells that recognize specific antigens presented in the form of peptide fragments in MHC molecules (antigen-MHC complexes).
What are coreceptors in the immune system and what do they do?
The CD4 and CD8 surface proteins present on helper and cytotoxic T cells, respectively, are called coreceptors.

They interact with antigen-MHC complexes and help maintain TCR-MHC coupling.

Antigen recognition by a TCR with CD4 or CD8 proteins is the first signal in the activation of all T cells.
What is the function of the CD4 and CD8 surface proteins present on helper and cytotoxic T cells?
The CD4 molecule in helper T cells and CD8 molecule in cytotoxic T cells interact with antigen-MHC complexes and help maintain TCR-MHC coupling.

Antigen recognition by a TCR with the help of CD4 or CD8 proteins is the first signal in activation of all T cells.
Describe a type of costimulation of T cells OTHER than cytokine stimulation.
Another type of costimulation is paired plasma membrane molecules, one on the surface of the antigen-presenting cell and one on the surface of the T cell, that enable the two cells to adhere to one another for a period of time.
What is costimulation?
Costimulation refers to the second signal necessary in the activation of T cells.

There are over 20 known co-stimulators. One type of costimulation is cytokine stimulation. IL-2 is an important cytokine co-stimulator.

Another type of costimulation is paired plasma membrane molecules, one on the surface of the antigen-presenting cell and one on the surface of the T cell, that enable the two cells to adhere to one another for a period of time.
What is anergy?
Anergy is a prolonged state of inactivity that T cells can enter if so instructed by their co-stimulator.
What is the prolonged state of inactivity that T cells can enter called?
Anergy
What is the first signal in the activation of both helper and cytotoxic T cells?
The first signal in the activation of both helper and cytotoxic T cells is antigen-TCR coupling (aided and maintained by CD4 or CD8 proteins).
Name an important cytokine costimulator of T cells:
IL-2
How many different epitopes does the human immune system possess specific antigen receptors for?
The human immune system can recognize and bind to at least a billion different epitopes!
What do memory T cells possess that allows for a quicker response the next time the antigen is encountered?
They possess one simple thing: the antigen receptor needed to recognize that antigen. Before first exposure there were just a few cells with that receptor. After, through clonal selection and proliferation, there are many.
Describe the activation and clonal selection of helper T cells:
First, an antigen-presenting cell (APC) must take up the exogenous (extracellular) antigen, process it, and display it on its surface as part of an antigen-MHC-II complex.

The APC then migrates to lymph tissue, where the antigen-MHC-II complex is presented to helper T cells until it gets to one with a corresponding TCR.

MHC-TCR coupling, with the help of the helper T-cell's CD4 molecule, represents the first signal in helper T cell activation.

After the first signal, costimulation must occur. This happens either through cytokine stimulation (IL-2) from an already-activated helper T cell or through the coupling of paired proteins on the surface of the helper T cell and the APC.

Once costimulation has occurred, the helper T cell undergoes clonal selection and proliferates and differentiates into effector and memory helper T cells.

Effector T cells release IL-2. What about IFN-gamma?
What do effector helper T cells do?
Effector T cells release IL-2 which can act as a co-stimulator for B-cell, helper T cell, or cytotoxic T cell activation.

What about IFN-gamma?
What do memory helper T cells do?
Memory T cells don't participate in the initial fight against the antigen. They possess the specific TCR (antigen receptor) necessary to recognize that antigen in the future, however.
Describe the activation and clonal selection of cytotoxic T cells:
First, body cells containing non-self proteins (either from foreign invaders or from mutations) process these antigens and pair them with MHC-I molecules, displaying them on their surface as antigen-MHC-I complexes.

Next, these cells present their antigen-MHC-I complexes to cytotoxic T cells until they get to one that has a matching TCR.

Recall that cytotoxic T cells don't stay in lymph tissue but rather seek out infected cells. Thus TCR-MHC coupling can occur outside lymph tissue in the body.

TCR-MHC-I coupling, aided by the T cell's CD8 molecule, is the first signal in cytotoxic T cell activation.

Next, cytotoxic T cells require co-stimulation, usually in the form of cytokine stimulation. IL-2 is a common costimulating cytokine. Note that these cytokines are released by ALREADY ACTIVATED helper T cells, so optimal activation of cytotoxic T cells requires activation of helper T cells.

Once activated, cytotoxic T cells undergo clonal selection with differentiation and proliferation.

Effector cytotoxic T cells kill cells directly.
Explain why maximal activation of cytotoxic T cells requires both presentation of antigen-MHC-I complexes and antigen-MHC-II complexes.
After the first signal (TCR/MHC-I coupling), cytotoxic T cell activation requires costimulation, usually in the form of cytokine stimulation (e.g. from IL-2).

These cytokines are typically released by effector (already activated) helper T cells. In order for these helper T cells to become active however, they must have already been presented with MHC-II molecules.
What are the three types of lymphocytes?
The three types of lymphocytes are B cells, T cells, and natural killer (NK) cells.
Which class of molecules are the TCR of helper T cells capable of recognizing?
Helper T cell receptors recognize antigen-MHC-II complexes.
Which class of molecules is the TCR of cytotoxic T cells capable of recognizing?
Cytotoxic T cell receptors recognize antigen/MHC-I complexes
How do active cytotoxic T cells kill their target?
Once an ACTIVE cytotoxic T cell recognizes and binds to an infected cell, it kills the cell in one of two ways.

1) The cytotoxic T cell can release granzymes, which are protein-digesting enzymes that trigger apoptosis in the infected cell.

2) Alternatively, cytotoxic T cells can release perforin, which inserts into the plasma membrane of the target cell causing influx of water and cytolysis.
Name three types of proteins released by T cells in order to kill their targets:
1) Granzymes (protein-digesting proteins that induce apoptosis)

2) Perforin (allows water to flow in, causing cytolysis)

3) Granulysin (creates holes in plasma membrane, causing cytolysis)
What are toll-like receptors?
Are these TCRs?
What are B cell receptors?
Is this IgG?
Describe the activation of B lymphocytes.
Different sorts of antigens activate B cells in different ways. Some do not require T cell help and are known as T-independant (Ti antigens). There are two types of Ti antigens: those with intrinsic mitogenic activity (Ti I antigens, e.g. LPS) and those with repeated identical antigenic determinants that bind to and link together several surface B cell immunoglobulin receptors (Ti II antigen). In both cases, Ti antigens induce B cells to divide and produce antigens without further activation.

The majority of antigens, however, are T cell dependent. In these cases B cells are activated in much the same way as T cells, with a first signal and costimulation.


The initial signal comes in the form of an antigen binding to the BCR.

Subsequently, the B cell, as an APC, will take the antigen up, process it, and display it in antigen-MHC-II complexes.

Costimulation occurs from cytokines (e.g. IL-2, IL-4, IL-5, IL-6) released from already active effector CD4 cells.

Once they receive costimulation, B cells undergo clonal selection, resulting in plasma cells and memory B cells.

Plasma cells work as antibody factories, pumping out antibodies against the specific pathogen. Memory cells lie in wait for the next time the antigen is encountered.
What event serves as the first signal in the activation of B cells?
The first signal in the activation of B cells is the binding of an antigen to the surface B cell receptor (BCR).

Is this IgG?

As an APC, the B cell will subsequently process and display the antigen as part of antigen-MHC-II complexes. This step is not necessarily a part of activating this B cell but rather more a part of the B cell's duty as APC.
What serves as costimulation in the activation of B cells?
Like helper T cells and cytotoxic T cells, B cells are costimulated by cytokines released from active helper T cells.

The B cell may help to activate the helper T cells themselves by presenting antigen to them or the helper T cell could have been activated by another cell altogether.
What are antigenic determinants?
...
How long after activation does a plasma cell secrete antibodies for?
Plasma cells continue to secrete antibodies for about 4-5 days until they die.
How many antibodies do plasma cells secrete on a daily basis.
Plasma cells secrete hundreds of millions of antibodies each day for 4-5 days until they die.
How many antigens are the B cells of a clone capable of secreting antibodies against?
Just one. The B cells will secrete only antibodies specific to the original antigen encountered.
Give another name for antibody.
Antibodies are also known as immunoglobulins.
Give another name for immunoglobulin.
Immunoglobulins are also known as antibodies.
What are Igs?
Igs are immunoglobulins, also known as antibodies.
Which is the part of the antibody that recognizes and attaches specifically to a particular antigen?
This region, located at the tips of the heavy and light chains, is called the variable region because it is specific to a particular antigen.

The rest of the heavy and light chains are referre
Describe the structure of a monomeric antibody:
Antibodies consist of two long heavy chains arranged in an Y fashion. Outside the heavy chains, at the top of the why, are two light chains.

The crux of the Y is called the hinge region because arms of the antibody can bend here. The remainder of the antibody is called the stem.

The tips of the heavy and light chain are called the variable region and bind to a specific antibody. The rest is referred the constant region and varies only between types of antibody (i.e. between IgG, IgA, IgM, IgD, IgE)
Which class of antibody is most abundant in the blood?
IgG (80% of blood antibodies)
Where can IgA typically be found?
IgA is present in secretions such as sweat, tears, saliva, breast milk, and gastrointestinal secretions. Smaller quantities are found in the blood and lymph.
After IgG, which is the most prevalent antibody found in blood?
IgA (10-15% of antibodies in blood)
Describe the structure of IgM.
IgM occurs ans pentamers, or arrangements of 5 monomeric units in a star-like pattern.
Which is the first class of antibodies to be secreted by plasma cells after initial exposure to any antigen?
IgM
Where can IgD be found?
IgD is mostly found on the surfaces of B cells functioning as an antigen receptor (B cell receptor, or BCR)
What is the principle function of IgA?
IgA provides localized protection of mucous membranes against bacteria and viruses.
Which is the only class of antibody to cross the placenta from mother to fetus, conferring considerable immune protection in newborns?
IgG
Describe the structure of IgA?
IgA monomers are usually arranged back to back in dimeric molecules.
How long until maternal IgG passed on to the newborn is completely gone?
This IgG is almost completely gone after 6 months.
What is the function of IgD?
IgD functions mostly as a B cell receptor (BCR) rather than in circulation. Its thus contributes to the activation of B cells.
Name the 5 classes of immunoglobulins in order of highest to lowest prevalence in serum.
IgG

IgA

IgM

IgD

IgE
Where can IgE be found?
IgE is found on mast cells and basophils and is involved in allergic and hypersensitivity reactions.
Which class of antibody participates in allergic and hypersensitivity reactions?
IgE
Describe 5 ways in which immunoglobulins disable antigens:
1) Direct neutralization of antigen
-prevention of attachment to body cells, neutralization of toxins

2) Activation of complement
-antigen-antibody complexes initiate the classical pathway

3) Agglutination and precipitation of antigen
-antigen-antibody complexes may cross link together into clumps more readily phagocytosed

4) Immobilization of bacteria
-antibodies against antigens on cilia or flagella of bacteria will immobilize them

5) Enhancement of phagoyctosis
-the stem of the antibody acts as a flag attracting phagocytes
Which type of cells possess pattern recognition receptors, or PRRs?
Cells of the innate immune system, such as macrophages, possess PRRs in order to recognize PAMPs, or pathogen-associated molecular patterns, on the surface of invading microorganisms.

The family of toll-like receptors, or TLRs, are examples of PRRs.
What are the two principle phagocytic cells of mammals?
1) Macrophages (large)

2) Polymorphonuclear leucocytes (smaller)

Dendritic cells are also capable of phagocytosis
What's the difference between pattern recognition receptors (PRRs) and antigen receptors (TCRs and BCRs)?
Pattern recognition receptors are present on cells of the innate immune system, such as macrophages and polymorphonuclear cells. PRRs recognize pathogen associated molecular patterns (PAMPs). PAMPs occur commonly across a wide variety of microorganisms and are not specific. Examples of PRRs include the family of toll-like receptors (TLRs).

Antigen receptors recognize only one specific antigen. Examples of antigen receptors are T cell receptors (TCRs) and B cell receptors (BCRs).
What is opsonization?
Opsonization refers to the "marking" or "flagging" of pathogens with either antibodies or complement, a process that facilitates identification of the pathogen by phagocytes.
Which cell type is regardless as the primary interface between infectious organisms and the adaptive immune system?
Dendritic cells in their role as APCs.
How do dendritic cells and phagocytes recognize pathogens in order to imbibe them, process their antigens, and present these antigens to lymphocytes?
Dendritic cells and macrophages possess pattern recognition receptors, or PRRs. These surface receptors recognize pathogen-associated molecular patterns, or PAMPs, which are common molecular themes present on the surface of many pathogens (e.g. LPS, lipoteichoic acid).

Examples of PRRs include the toll-like receptor (TLR) family of receptors.
Name two cell types that release granzymes. What is the MOA of granzymes?
Granzymes are released by both NK cells and cytotoxic T cells to induce death in infected body cells.

Granzymes are proteases which induce apoptosis in the affected cell.
What is the MOA of granulysin?
Granulysin works by creating holes in the infected cell's membrane, causing influx of water and lysis.
Which type of helper T cell specializes in "helping" macrophages?

How do they help?
TH1 cells specialize in helping macrophages by releasing IFN-gamma.

IFN-gamma has an activating effect on macrophages, emboldening and inducing them to kill their intracellular pathogens.
Which type of helper T cell is most specialized to "help" B cells become activated?
TH2 cells help B cells by releasing cytokines such as IL-2 that act as costimulators in B cell activation.
Which is the most important cytokine in the activation of macrophages? What is the source of this cytokine?
IFN-gamma is the most important cytokine in the activation of macrophages.

This cytokine is released by TH1 CD4 cells and NK cells.
At least three distinct processes are meant by the term "cell-mediated immunity." Describe them.
"Cell-mediated immunity" refers to the destruction of intracellular ("endogenous") pathogens. This occurs in three ways.

First, natural killer (NK) cells can recognize and destroy cells harbouring pathogens.

Second, pathogens surviving within macrophages, such as mycobacteria, can be killed if the macrophages are activated by TNF-gamma (released by TH1 cells and NK cells).

Thirdly, pathogens within other body cells can be destroyed by cytotoxic T cells much in the same way that they are destroyed by NK cells.