Adaptive Immunity Mechanisms

Describe the anatomy of the lymphoid system. What are the primary and secondary lymphoid organs?

1) Primary lympoid organs are where immune cells develop from stem cells. These are the bone marrow (hematopoiesis) and the Thymus (T-cell development) 2) Secondary lymphoid organs are where immune cells gather to coordinate their activites. Examples of this are the lymph nodes, spleen, peyers patches (large intestine), and others.

Describe the process of B-cell class switching (affinity maturation)

1. Affinity maturation: the process of becoming more specific; these are programmed mutations of antibody variable genes. Most mutations result in the decrease or no change of affinty for the BCR. Some mutations result in a higher affinity BCR and these outcompete the lower affinity antibodies, resulting in evolution through mutations. 2. Generation of the memory B cells result from the antibody with the highest affinty through Helper T cell activation.

Describe the structure and properties of antibodies. What are the different regions?

1. Fab region (variable region): antigen binding region composed of light chains 2. Fc region (constant region): phagocyte binding region composed of heavy chains

When it comes to all 5 classes of antibodies, what are the most defining characteristics of each class?

1. IgG is the most prominent in serum and the only antibody that is able to cross the placenta. 2. IgA is the most abundant antivody produced in mucousal/secretory regions and through breast milk 3. IgD is not known to be produced in soluble form, only in the form of a BCR 4. IgE is known to be associated with degranulation of granulocytes and mast cells. This is involved in allergies, worms, and helminth infections.

What are the 6 effects of an antibody binding to an antigen within the body?

1. Neutralization: blocks the biologically relavant portion of the antigen, rendering it inactive. 2. Immobilization and prevention of adherance. 3. Agglutination and precepitation (solid formation): clumping antigens together makes them more easily recognized 4. Opsinization facilitates phagocytosis. This is the flagging of an antigen for destruction. The Fc region of the antigen is what does this opsinization. 5. Complement system activation: Antibody attaches and causes complement polymerization (lysing) which in turn forms a pore in the membrane of the infected cell. 6. Antibody-dependent cell cytotoxicity (ADCC): usually NK cells work together with antibodies to kill the infected cell.

What are the two different types of adaptive immunity? What cells are associated with each type?

1. Type 1 immunity (formerly cell-mediated immunity): T cells are associated with this 2. Type 2 immunity (formerly antibody or humoral immunity): B cells are associated with this type.

Describe the process of what happens when a pathogen enters the body in terms of type 2 immunity?

1. Upon the pathogen entering, the B cell will bind to this pathogen using its BCR 2. Antigen recognition plus a secondary signal from a Th cell results in the activation and maturation of the B cell into a plasma cell. (Plasma cells then begin to secrete soluble, free floating versons of it's surface bound antibody. 3. These antibodies (Ab) can ciruclate in the blood and lymph for years 4. If the free floating antibody binds to a pathogen, it makes it a target for destruction.

How many signals does a B-cell need to fully activate?

A B-cell needs 2 signals to fully activate 1) Recognition of the antigen (binding) 2) Must also recieve a signal from the Helper T cell in the form of cytokines These two steps turn the B cell into a plasma cell that secretes soluble, free floating versions of the surface Ig (BCR): antibodies and a memory B cell that will stay in the blood to monitor for future infections

Clicker Q: Which type of adaptive immune response would be most helpful during an influenza virus infection? A) Type 1 B) Type 2

A) Type 1 Cytotoxic T cells are the big responders in viral infections

What is the difference between active and passive adaptive immunity?

Adaptive immunity includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells. Active immunity is aqcuired through direct infection and passive immunity is acquired through maternal antibodies.

Describe the process of antibody class swtiching. Why does this occur?

After the intial production of IgM, the immune system switches to IgG production. This is due to the fact that after more exposure to the infection, the affinity can be increased and a monomer can be produced instead og a pentomer. (higher affinity)

Describe the nature of antibodies. What are these composed of?

Antibodies are glyciproteins. These are composed of carbohydrates and tetrapeptides (carbs and protein) Each antibody possesses 2 heavy chains and 2 light chains.

What is an antigen?

Anything that solicites an immune response; it takes time to develop B and T cells to develop against these antigens because they are so specific.

Describe the immune tolerance process that happens in conjunction with the proliferative stage of clonal selection.

At the same time as the proliferative stage, any lymphocytes that develop a specificity for self-molecules and could be harmful are eliminated from the pool of cells in a process called immue tolerance. An issue with this stage can lead to an autoimmune disorder

Clicker Q: A B cell's antibodies become more efficient at binding to an antigen during the process of: a) Class switching b) Affinity maturation c) Clonal expansion

B

Clicker Q: A Helper T cell will be activated by the recognition of: A) Intracellular antigen on MHC 1 receptors B) Extracellular antigen on MHC 2 receptors

B

What cell is associated with the type 2 adaptive immune response? What do these cells possess on their surfaces?

B cells are the big responder in this type of immunity! B cells are covered with thousands of copies of a membrane-bound immunoglobulin. This membrane bound immunoglobulin is called a B-cell receptor (BCR) or surface Ig (sIg)

What type of antigens do the different types of adaptive immune cells respond to?

B cells respond to extracellular antigens while T cells respond to antigen infected cells as they present cytoplasmic proteins on their cell surface.

What are the different professional antigen presenting cells (PAPC's)?

Dendritic cells, macrophages, B cells

How do the very few cells that have the receptor bind to the specific antigen?

Each genetically unique line of lymphocytes arising from extensive recombinations of surface proteins is termed a clone. This proliferative stage of lymphocyte development doesnt require the actual presence of foriegn antigens.

What types of antigens do Helper T cells respond to? Cytotoxic T?

Helper T cells respond to extracellular antigens presented by PAPC's. Cytotoxic T cells directly bind to infected cells by binding to them with T cell receptors on their surface.

How many binding sites does IgG have? What are the specific properties of this antibody class?

IgG has 2 binding sites, making it a monomer. This composes 80% of antibodies in the serum and has a halflife of 23 days. It is able to cross the placenta and contribute to passive immunity!

How many binding sites does IgM have? What are the specific properties of this antibody class?

IgM has 10 binding sites and it is a pentomer. It only makes up about 6% of the total antibody in the serum and has an average half life of about 5 days. It cannot pass the placenta therefore it doesnt play a role in passive immunity for the fetus.

Describe the nature of antigens. What are they composed of?

Proteins make the best antigens. These must be composed of proteins for the adaptive immune response to work because a) lipids are linked to other non-pathogenic macromolecules b) Carbohydrates are linked to other non-pathogenic macromolecules as well and the body doesnt want to attack good molecules. A polysaccaride capsule can be tricky for the adaptive immune response.

How are Helper T cells activated?

Respond to extracellular antigen; The extracellular antigen is captured and processed by professional antigen presenting cells (PAPC's) and shown to the Helper T cell in a fragment. The PAPC places the antigen on MHC 2 receptors and presents them on the surface of the cell. MHC 2 receptors help cells to recognize self from non-self. PAPC's are the only cells that can present on MHC class 2's.

What is the function of Helper T cells?

Secrete cytokines that mediate a local immune response (cytokines are hormone life proteins). These are the "generals" of the immune response, they direcgt what the fighters do (cytotoxic T cells and B cells)

What cell is associated with the type 1 adaptive immune response? What are the different subtypes of these cells?

T cells are the big responders in this immune response. The three different types of T cells in this response are: 1) Cytotoxic T cells (up regulation) 2) Helper T cells (up regulation) 3) Regulatory T cells (down regulation)

How is a T cell activated in the Type 1 adaptive immune response?

T cells must be "shown" to antigen by antigen presenting cells (T cells are blind, they cannot bind to an antigen on their own) The antigen must be in a small, linear peptide form. This is done by the antigen presenting cell capturing it, chewing it into small, linear pieces, and presenting it to the "blind" T cell.

How are Cytotoxic T cells fully activated?

The Cytotoxic cell must recieve a secondary signal in order to fully activate. Helper T cells provide this secondary signal; They secrete cytokines which provide a chemical signal for Cytotoxic T cell activation.

What comes after the proliferation and immune tolerance stages of clonal selection?

The specificty for a single antigen molecule is programmed into the lymphocyte and is set for the life of the given cell. The end result is an enormous pool of mature but naive lymphocytes that are ready to further differentiate under the influence of certain organs and immune stimuli.

What are the 5 different antibody classes? What portion of the antibody is this dependent upon?

There are 5 antibody classes dependent on the properties of the heavy chain portion of the antibody. These classes are: 1) IgG 2) IgM 3) IgE 4) IgA 5) IgD We will mainly focus on IgG and IgM as these are the most diagnostically relevant

How specific are the B cell receptors (BCR)?

These are very specific! They are programmed to bind to a certain surface molecule from a specific species of pathogen.

What is the function of cytotoxic T cells?

These physcially interact with cells harboring a pathogen (such as a virus). These are the "special forces" of the immune system (work on viral and internal bacterial infections) These are the fighters of the immune response

How are cytotoxic T cells activated?

These respond to intracellular antigens. Any cell in the body that is nucleated can present antigen to a cytotoxic T cell. Intracellular antigen is processed by the infected cell, and places on the MHC 1 receptor for presentation to the Tc cell. The Tc cell with a Tcell receptor (TCR) capable of recognizing the antigen will bind and start to become activated. Note: MHC 1 presentation is always happening, this just presents what is inside the cell. Not always bad!

What is the function of the Regulatory T cells?

These supress inflammtion as the immune response wanes (down regulation) This is necessary to prevent prolonged inflammtion once the threat is gone.

What is the biological function of IgG antibodies?

This is a monomer produced by cells in a primary response (first to respond!!) and by memory B cells responding to the second antigenic stimulus. This is the most prevalent antibody circulating through the tissue fluid and blood. It neutralizes toxins, opsintes, and fixes complement. Because IgG only has two binding sites, it has high affinity (strong bind) but less binding sites (avinity)

What is the biological function of IgM antibodies?

This is the first antibody produced in response to a new antigen entering the body; these can also serve as a B-cell receptor! The 10 binding regions strengthen the antibodies avinity for an antigen (avinity provides strength in numbers because there is more binding sites). This high avinity is good as a first response class because IgM is the first antibody produced in a soluble (free-floating) form at the site of infection.

Describe the Fc region of an antibody.

This is the region that is recognized by phagocytes (phagocytes have Fc receptors). The phagocytes bind to the antibody in the Fc heavy chain region once it has bound to the antigen to engulf it.

What comes after the naive lymphocyte stage after they have matured and entered certain lymphatic organs?

When an antigen enters the immune survaillence system, it encounters specific lymphocytes ready to recognize it . Such contact stimulates that clone to undergo mitotic division and expands into a larger population of lymphocytes, all bearing the same specificity.

Clicker Q: Which of the following would be potent viral antigens? a) Peplomers (spike proteins) b) Capsid (protein around DNA) c) membrane lipids d) A and B e) B and C

d) A and B These both have protein compositions which is best for antigen composition.

What is clonal selection?

the process through which immature B and T Cells go through so that only certain types are permitted to mature