Lectures 1-4 Flashcards Preview

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Flashcards in Lectures 1-4 Deck (56):
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Recognition mechanisms of innate immunity

Rapid response, fixed, limited number of specificities, constant during response

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Recognition mechanisms of adaptive immunity

Slow response, variable, numerous highly selective specificities, improves during response

Involves antibody, T cell recognition, and cell mediated activation of the innate immune system

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Antibody

Serum proteins that result from specific immune responses. High affinity binding sites for antigen at one end and the other end are Fc regions which are sites for effector cells or proteins to bind.

Flexible specific adaptor between the target and the effector

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Opsonization

When a specific antibody is present a high affinity bridge is formed enhancing phagocytosis. Antibody types responsible are sometimes called opsonins.

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CD3

Mature T cells

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Complement

Group of serum proteins that can either recognize certain types of microorganisms directly or bind to an recognize bound antibody molecules. May result in lysis of the target cell. Attracts an effector cell.

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CD4

T helper cells

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CD8

T cytotoxic

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Neutrophils or polymorphonuclear leukocytes

Most abundant leukocyte (60-70%) of circulating white blood cells. Does not divide. Only circulate for 12 hours. Enter tissue during inflammation to complete their life cycle.

Contain many granules: primary or azurophilic and secondary or specific granules. Contain the bactericidal and hydrolytic enzymes of the cell.

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Eosinophils

1-3% of circulating lymphocytes. Half life of only 30 minutes, can survive up to 12 days in tissue. Contain eosinophilic basic protein (EBP) which is important in the clearance of parasitic worms. Do much of their work through extracellular mechanisms.

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Macrophages-monocytes

Derived in the bone marrow and circulate in the blood. Called macrophages once they enter tissues. May exist in tissues without any inflammation. Capable of both intracellular and extracellular killing. Antibody and complement can enhance killing.

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Kupffer cell

Liver macrophage

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Histiocyte

Skin/connective tissue macrophage

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Microglial cell

Brain macrophage

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Osteoclasts

Bone macrophage

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Synovial type A cells

Joint macrophages

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Alveolar macrophages

Lung macrophages

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B Lymphocyte

Small lymphocyte that expresses immunoglobulin (antibody)

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T Lymphocyte

Thymus derived cell critical in regulating immune responses as well as effector function of killing infected cells

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Cytotoxic T cells

Important role in the regulation of the immune response and also acts as an effector cell. CD8 surface marker. Antigen specific process. Most restricted to killing cells that have self antigen in addition to the foreign antigen (targets mainly infected cells and tumor cells).

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Natural killer cells

Large granular lymphocytes. Kill tumor cells and some virally infected cells without apparent specificity

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Immunoglobulin G

Predominant class in serum. Toxin neutralizing, agglutinating, opsonizing, bacteriolytic with aid of complement system. Subclasses IgG1, IgG2, IgG3, IgG4. Intrachain disulfide bonds occur between the same residues.

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Immunoglobulin M

Predominant class in primary immune response. Antigen receptor on B-lymphocyte and agglutinating. With the aid of the complement system can be opsonizing and bacteriolytic. Immune cells do not have IgM receptors. 5-10% of serum Igs. 4 heavy chain domains with no hinge region. J chain.

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Immunoglobulin A

Predominant class in secretions. Found as monomer, dimers, and trimers. 15% of serum Igs. Secretory piece (T piece)- resists acid hydrolysis. J chain. Agglutinating and opsonizing.

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Immunoglobulin D

Located on surface of human immature B-lymphocytes. Associated with some tumor cells. 0.2% of serum Igs. Co-expressed with IgM on surface of B-lymphocytes. May function as an antigen receptor.

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Immunoglobulin E

Immediate hypersensitivity. Fixes to mast cells. 0.1% of serum Igs. Mediates changes is vascular permeability. May be involved in host defense against parasitic infection.

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Proteolytic degradation of immunoglobulins

Papain digests the hinge region which contains the interchain disulfide bonds. Yields 3 fragments. One fragment can be crystallized and contains most of the IgG specific antigenic determinants- Fx. The other two regions retain the ability to bind antigen and are not crystallized- Fab.

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Variable region of immunoglobulin

Contains the amino acid sequences coding for the antigen binding site.

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Framework residues

Part of the V region. Do not vary from one protein to another. Most likely not directly involved in antigen binding but are essential in producing the folding of the V region producing the antigen binding site.

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Hypervariable regions

Provide the sequence of the very specific antigen binding site. Heavy and light chain V regions contain three hypervariable regions each. Regions are on two separate chains but lie close together in the antigen binding site due to the way they fold.

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Affinity

The expression of the sum of all the interactions between an antibody binding site and its homologous antigenic determinant. Only a precise term in a monovalent antigen-antibody system with a monoclonal antibody. Can be expressed using the law of mass action. K=[AbAg]/[Ab][Ag]

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Avidity

Strength of binding of multivalent antiserum to multivalent antigen.

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Techniques used to eliminate cross reactivities

Absorption and affinity chromatography--create a specific antibody

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Absorption

Say you want only T cells but the antiserum also recognizes B cells--Isolate B cells and mix with your antiserum. Then centrifuge the B cells along with the bound antibodies. The remaining antibody will now only bind T cells.

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Affinity chromatography

Say you only want to recognize T cells that are CD4 positive but have an antiserum with a lot of cross reactions. Obtain some pure CD4 protein, bind to agarose, then pass your antiserum over it. The antibodies you want will be bound.

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Monoclonal antibody

Single clone of one B cell is produced by fusing that cell to a tumor cell (which has unlimited growth potential) and isolating the clone with the antibody specificity of interest.

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Preparation of monoclonal antibody

1. Immunize an animal.
2. Isolate spleen cells from immunized animal.
3. Fuse the spleen cells to plasmacytoma tumor cells.
4. Select for only those cells that are hybrids of tumor cells and B cells.
5. Clone the hybridomas so that each single cell grows up independently.
6. Select the individual clone with the specificity that you are interested in.

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Chimeric monoclonals

Variable regions are from the mouse monoclonal, the constant regions are human. Suffix -ximab (omab is murine monoclonal antibodies)

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Humanized monoclonals

Only the points of contact with the antigen remain mouse. Suffix -zumab

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Human monoclonals

Generally totally made through molecular techniques to be completely human. Suffix -umab

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ELISA

Antigen stuck to bottom of well. Antibody added, allowed to incubate, and the unbound antibody is washed away.
A second antibody with an enzyme molecule attached that will bind the first antibody is added. Unbound second antibody then washed away. Amount of second antibody bound is detected by adding a chemical reagent that turns color in the presence of the enzyme bound to the second antibody. Can be used to assay for antibody or antigen.

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Immunofluorescence

Cells reacted with antisera specific for a cell marker or pathogen. Second antibody attached to a fluorescent molecule specific for first antibody is added. Fluorescence can be used to identify a pathogen.

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Flow cytometry (FACS)

Automated immunofluorescence. Scan large number of cells and analyze/sort cells.

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Western immunoblot

Mixtures of proteins separated electrophoretically. Separated proteins bound to nitrocellulose paper. Antibody to the protein of interest is reacted, other antibodies washed away, and specific antibodies detected like in ELISA. Both quantitative and qualitative results. Can tell amount of antigen, molecular weight, and different forms of antigen.

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Lag/inductive/latent phase

Period of time before antibody can be detected after initial exposure to immunogen.

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How does the secondary response differ from the primary response?

1. Shorter lag time
2. Higher rates of antibody synthesis
3. Higher peak of antibody titer
4. Longer persistence of antibody
5. Predominance of IgG class molecules
6. Higher affinity of antibody
7. Requires less antigen

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Idiotype

Single variable region expressed by a B-cell.

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Antigen presenting cells

Initiates the interaction with antigen by endocytosis or phagocytosis. May be enhanced by interaction with complement, pre-existing antibody, or with specific receptors that recognize pathogens. Uptake of antigen is followed by antigen processing/digestion and antigen presentation where antigen is deposited on the surface of the presenting cell. Antigen is presented by cells that bear MHC antigens. Must also provide a co-stimulatory signal to induce immunity.

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CD28

Recognition of presenting cells

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CD40

Co-stimulatory molecule

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CD40L

Ligand for CD40

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CD25

IL2 receptor (high affinity)

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Serum sickness

-Type of hypersensitivity reaction
-Immune system reaction to medications, injected proteins, or antiserum
-Resultant from non-humanized monoclonals

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B-Cells

-B Lymphocytes express surface immunoglobulin.
-Each cell only expresses a single variable region or IDIOTYPE.
-Total population of B cells make up the repertoire of antibody specificities.
-Antigen is seen by B cells
-Selective expansion of clones with the highest affinity to antigen.

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Helper T cells

-Distinguished by CD4
-Mostly react to proteins or peptides
-Produce factors that stimulate B cells
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Antigen presenting cells

-Initiate the interaction with antigen by endocytosis or phagocytosis
-Enhanced by interaction with complement (C3b receptor mediated)
-Takes in antigen, processes, and presents it
-Presented by cells that bear MHC2 antigens (MHC/antigen complex is presented)
-Must provide co-stimulatory response too!!!! (CD28:B7 is the most important for generation of an immune response)
-Dendritic cells and langerhans cells are examples