Specificity: Any particular adaptive immune response acts only against one particular molecular shape and not against others. Adaptive immune responses are precisely tailored reactions against specific attackers.

Inducibility: Cells of adaptive immunity activate only in response to specific pathogens.

Clonality: Once induced, cells of adaptive immunity proliferate to form many generations of nearly identical cells, which are collectively called clones.

Unresponsiveness to self: As a rule, adaptive immunity does not act against normal body cells; in other words, adaptive immune responses are self-tolerant. Several mechanisms help ensure that immune responses do not attack the body itself.

Memory: An adaptive immunity response has "memory" about specific pathogens; that is, it adapts to respond faster and more effectively in subsequent encounters with a particular type of pathogen or toxin.

Lymphocytes - are the smallest WBC and each is characterized by a large, round, central nucleus surrounded by a thin rim of cytoplasm.

B lymphocytes - arise and mature in the red bone marrow of adults. B= bursa of Fabricius found in birds, mammals do not have bursa.

T lymphocytes - begin in bone marrow as well but do not mature there. T cells travel to and mature in the thymus, located in the chest near the heart.

These proteins allow lymphocytes to recognize specific pathogens and toxins by their molecular shapes, and the proteins play roles in intercellular communication amoung immune cells.

Humoral immune responses: Descendants of activated B cells are the main defensive cells of humoral immunity. Once induced, they secrete soluble proteins called antibodies that act against extracellular pathogens such as bacteria and fungi in the body's fluids.

Cell-mediated immune responses: T cells regulate adaptive immune responses or attack intracellular pathogens, such as viruses replicating inside a cell. T cells mount cell-mediated immune responses and do not involve antibodies.

Lymph arises from fluid that has leaked out of blood vessels into the surrounding intercellular spaces. Unlike blood which supplies nutrients, lymph contains wastes such as degraded proteins and toxins.

From the lymphatic capillaries, lymph passes into increasingly larger lymphatic vessels until it finally flows via two large lymphatic ducts into blood vessels near the heart. One-way valves ensure that lymph flows only toward the heart.  The flow of blood is circular flowing.

Primary - red bone marrow and thymus

Secondary - lymph nodes and spleen

Antigens bind to lymphocytes and can trigger adaptive immune responses. The body recognizes antigens by the three-dimensional shapes of regions called epitopes, which are also known as antigenic determinants, b/c they are the actual part of an antigen that determines an immune response.

Antibody Function: Activation of Complement and Inflammation, Neutralization, Opsonization, Killing by Oxidation, Agglutination, and Antibody-Dependent Cellular Cytoxicity (ADCC)

The surface of each B lymphocyte is covered with about 500,000 identical copies of a protein called the B cell receptor (BCR). A BCR is a type of immunoglobulin.

They have a strong, noncovalent, hydrophobic interaction.

Contain four polypeptide chains (heavy chains and light chains refer to their relative molecular masses).

Disulfide bonds which are covalent bonds link the light chains to the heavy chains in such a way that a simple immunoglobulin looks like the letter Y. The transmembrane portion anchors the BCR in the cytoplasmic memberane and consists of the stem of the Y (composed of the tails of the two heavy chains) and two other polypeptides. All the BCRs of any particular cell are identical b/c the variable regions of every BCR on a single cell are identical - BCRs of one cell differ from the BCRs of all other B cells, much as each snowflake is distinct from all others.

Cytotoxic T Cells (Tc or CD8 Cell): These lymphocytes directly kill other cells - those infected with viruses and other intracellular pathogens, as well as abnormal cells, such as cancer cells.

Helper T Cells (Th or CD4 Cells): Their function is to assist in regulating the activity of B cells and cytotoxic T cells during immune responses by providing necessary signals and growth factors. 

Type 1 Helper T Cells - assist cytotoxic T cells and innate macrophages.

Type 2 Helper T Cells - function in conjunction with B cells.

Regulatory T Cells (Tr Cells): suppressor T cells, repress adaptive immune responses and prevent autoimmune diseases. Tr cells express CD4 and CD25 glycoproteins.

Clonal Deletion of T Cells: 1. Stem cells in the red bone marrow generate a host of lymphocytes that move to the thymus. 2. In the thymus, each lymphocyte randomly generates a TCR with a particular shape. 3. T cells pass through a series of "decision questions" in the thymus: Are their TCRs complementary to the body's MHC I protein? If "no" they undergo apoptosis - clonal deletion. If "yes" they survive. 4. Do the surviving cells recognize MHC I protien bound to any autoantigen? If "no" they survive and become the repertoire of inmature T cells. If "yes" then most undergo apoptosis; a few survive as regulatory T cells (Tr).

Clonal Deletion of B Cells: 1. Stem cells in the red bone marrow generate a host of B lymphocytes. 2. Each newly formed B cell randomly generates a BCR with a particular shape. Note that each cell's BCR binding sites differ from those of other cells. 3. Cells whose BCR is complementary to some autoantigen bind with that autoantigen, stimulation the cell to undergo apoptosis. Thus, an entire set of potential daughter B cells (a clone) that are reactive with the body's own cells are eliminated - clonal deletion. 4. B cells with a BCR that is not complementary to any autoantigen are released from the bone marrow and into the blood. 

Cytokines are soluble regulatory proteins that act as intercellular messages when released by certain body cells including those of the kidney, skin, and immunity.

Types:

Interleukins - signal among leukocytes

Interferons - antiviral proteins, may also act as cytokines; potent phagocytic activator secreted by Th1 cells.

Growth Factors - stimulate leukocyte stem cells to divide, ensuring that the body is supplied with sufficient white blood cells of all types.

Tumor necrosis factor - Macrophages and T cells secrete TNF to kill tumor cells and to regulate immune responses and inflammation.

Chemokines - are chemotactic cytokines; they signal leukocytes to move.

Importanat in determining the compatibility of tissues in successful grafting. Are glycoproteins found in the membranes of most cells of vertebrate animals. MHC are genes coded in clusters. 

Class I MHC molecules are found on the cytoplamsic membranes of all nucleated cells. RBC do not have nuclei, therefore they do not express MHC class I molecules.

Antigen-presenting cells (APCs) have class II MHC proteins. Also known as B cells, macrophages, and dendritic cells (have many long, thin cytoplasmic processes called dendrites). Dendritic cells are found under the surface of the skin and mucous membranes. Once antigens are acquired they migrate to lymph nodes to interact with B and T lymphocytes.

Immunoglobulin M (IgM) - Every B cell begins by attaching its variable region gene to the gene for the mu Fc region and thus begins by making class M. Most IgM are secreted during the inital stages of an immune response. IgM is most efficient at complement activation, which also triggers inflammation, and can be involved in agglutination and neutralization.

Immunoglobulin G (IgG) - In a process called class switching, a plasma cell then combines its variable region gene to the gene for a different Fc region and begins secreting a new calls of antibodies. The most common switch is to the gene for heavy chain gamma; that is, the plasma cell switches to synthesizing immunoglobulin G. IgG is the most common and longeset lasting class of antibody in the blood. IgG play a major role in antibody-mediated defense mechanisms, including complement activation, opsonization, neutralization, and antibody-dependent cellular cytotoxicity.

Immunoglobulin A (IgA) - which has alpha heavy chains, is the immunoglobulin most closely associated with various body secretions. Plasma cells in the tear ducts, mammary glands, and mucous membranes synthesize secretory IgA, which is composed fo two monomeric IgA molecules linked via a J chain and another short polypeptide. Secretory IgA agglutinates and neutralizes antigens and is of critical importance in protecting the body from infections arising in the gastrointestinal, respiratory, urinary, and reproductive tracts.

Immunoglobulin E (IgE) - two epsilon heavy chains - Act as signal molecules - they attach to receptors on eosinophil cytoplasmic membranes to trigger the release of cell-damaging molecules onto the surface of parasites (Parasitic worms).

Immunoglobulin D (IgD) - delta heavy chains - are not secreted but are membrane-bound antigen receptors on B cells that are often seen during the initial phase of a humoral immune response.

PG. 470 Table 16.1

Exogenous - include toxins and other secretions and components of microbial cell walls, membranes, flagella, and pili.

Endogenous - Protozoa, fungi, bacteria, and viruses that reproduce inside a body's cells produce endogenous antigens. The immune system cannot access the health of the body's cells; it responds to endogenous antigens only if the body's cells incorporate such antigens into their cytoplasmic membranes, leading to their external display.

Autoantigens - Antigenic molecules derived from normal cellular processes are autoantigens or self-antigens. Immunce cells that treat autoantigens as if they were foreign are normally eliminated during the development of the immune system. This phenomenon, called self-tolerance prevents the body from mounting an immune response against itself.

Exogenous Antigens - a dendritic cell internalizes the invading pathogens and enzymatically catabolizes the pathogen's molecules, producing peptide epitopes, which are contained in a phagolysome. This occurs outside the body's cells.

Endogenous Antigens - epitopes from all polypeptides synthesized within a nucleated cell load onto complementary MHC I Proteins, which are exported to the cytoplasmic membrane.

Activation of T Cell Clones follow these steps: Antigen presentation, Helper T cell differentiation, Clonal expansion, and Self-stimulation.

CD95 cytotoxic pathway - involves an integral glycoprotein called CD95 that is present in the cytoplasmic membranes of many body cells. Activated Tc cells insert CD95 into their cytoplasmic membranes which then activates enzymes that trigger apoptosis, killing the target cells.

Perforin-Granzyme Cytotoxic pathway - two key proteins - when a cytotoxic T cell first attaches to its target, vesicles containing the cytotoxins release their contents. Perforin molecules aggregate into a channel through wich granzyme enters, activating apoptosis in the target cell.

The binding of a virus-infected cell by an active cytotoxic T (Tc) cell.

The perforin-granzyme cytotoxic pathway. After perforins and granzymes have been released from Tc cell vesicles, granzymes enter the infected cell through the perforin complex pore and activate the enzymes of apoptosis.

The CD95 cytotoxic pathway. Binding of CD95L on the Tc cell activates the enzymatic portion of the infected cell's CD95 such that apoptosis is induced.

The body carefully regulates cell-mediated immune responses so that T cells do not respond to autoantigens.

T-independent antigens

- Fast, do not depend on interactions with Th cells.

- relatively weak, disappears quickly, and induces little immunological memory.

The effects of the binding of a T-independent antigen by a B cell. When a molecule with multiple repeating epitopes cross-links the BCRs on a B cell, the cell is activated: it proliferates, and its daughter cells become plasma cells that secrete antibodies.

T-dependent antigens lack the numerous, repetitive, and identical epitopes and the large size of T-independent antigens, and immunity against them requires the assistance of type 2 helper T (Th2) cells. A T-dependent humoral immune response involves a series of interactions among antigen-presenting cell, helper T cells, and B cells, all of which are mediated and enhanced by cytokines.

Most members of a clone become plasma cells. The initial plasma cell descendants of any single activated B cell secrete antibodies with binding sites identical to one another and complementary to the specific antigen recognized by their parent cell.

Active B cells with BCRs that bind the epitope more closely survive at a higher rate. Thus, as the humoral immune response progresses, there are more and more plasma cells, secreting antibodies whose fitness gets progressively better.

In a primary response relatively small amounts of antibodies are produced, and it may take days before sufficient antibodies are made to completely eliminate the toxoid from the body. Though some antibody molecules may persist for three weeks, a primary immune response basically ends when the plasma cells have lived out their normal life spans.

The newly differentiated plasma cells produce large amounts of antibody within a few days, and the tetanus toxin is neutralized before it can cause disease. Since many memory cells recognize and respond to the antigen, such a secondary immune response is much faster and more effective than the primary response.

When the body mounts a specific immune response against an infectious agent, the result is called naturally acquired active immunity.

The passing of maternal IgG to the fetus and the transmission of secretory IgA in milk to a baby are examples of naturally acquired passive immunity.

Artificially acquired active immunity is achieved by deliberately injecting someone with antigens in vaccines to provoke an active response, as in the process of immunization.

Artificially acquired passive immunotherapy involves the administration of performed antibodies in antitoxins or antisera to a patient.