Immunology

Histamine:

Stored in preformed granules in mast cells, basophils and platelets, histamine is released and causes vasodilation and increased vascular permeability.

Adjuvants containing microbial components make the best adjuvants.

True

Only aluminum hydroxide and aluminum phosphate are used for licensed human vaccines in the U.S.

True

True or False: Clinical lab tests can detect either antigen or antibody in a patient's serum sample.

True

______________, also called Immunoblots, can be used to identify specific Abs in patient serum. The Ag proteins of interest are separated by electrophoresis and transferred to a solid surface such as nitrocellulose membrane. Diluted patient serum is then applied to the Ag coated solid surface, followed by a secondary anti-Ig Ab bound to a "detection" enzyme. Addition of substrate will result in visible band(s) if Abs specific for the Ags of interest are present in patient serum.

Western Blots

Primary Ag-Ab interaction between a single Ag epitope and an Ab binding site are a result of noncovalent bonds that are relatively weak, and these bonds are reversible. Therefore, successful Ag-Ab interaction requires ___________.

a "good" or close fit over a large area

effector cell:

a cell that has recognized an antigen, resulting in activation, and (in the case of lymphocytes) proliferation and differentiation into cells that can cause "effects", i.e. secrete antibodies (B cells), produce cytokines to help (T helper cells), or cause lysis of target cells Cytotoxic T cells).

Affinity:

a measure of the strength of binding between one antigenic epitope and one Ag-binding site on an Ab.

After activation by contact with antigen/pathogen, the B lymphocyte will become an "effector" B cell and begin producing soluble proteins called ____________ that circulate in the body humors (fluids) and help destroy the antigen/pathogen.

antibodies

T cell activation of B cells requires the T cell to recognize and respond to the same ______________ recognized by the B cell.

antigen

IgE

attaches via Fc receptors to mast cells and basophils

The spleen traps antigens carried by the ___________, and lymph nodes trap antigen primarily carried by ___________ coming from _____________.

blood lymph tissues

B cells mature in the _____________.

bone marrow

Stem cell progenitors, which produce all blood cells (WBC, RBC) are found in the:

bone marrow

Pluripotent:

capable of giving rise to several different cell types

Vasodilation:

causes enlargement of the diameter of a vessel, to allow more blood to flow to a particular area, and slows blood flow to allow cell adhesion and extravasation.

T lymphocytes mediate ___________ immunity.

cell-mediated

Movement of WBC from the blood, through the vascular endothelium and into the surrounding tissues is called _____________.

diapedesis/ extravasation

Phagocytosis:

engulfing and ingestion/ destruction of large foreign particles, such as microorganisms, by phagocytes.

T and B cells can recognize different __________ from the same molecule, or antigen.

epitopes

IgM

found in serum as a pentamer structure.

The generation of antigenic specificity within the BCR/ TCR of B and T lymphocytes results from a series of unique ________ that is not known to occur in any other cell type.

gene rearrangements

Activation of B cells by T-dependent antigen occurs primarily in the _____________________ in lymph nodes, where B cells (after exposure to antigen and interaction with T cells) undergo intense proliferation, somatic hypermutation/affinity maturation, isotype (class) switching, and ultimately, differentiation into effector cells (plasmablasts, plasma cells) and memory cells.

germinal centers

All white blood cells (leukocytes), including B lymphocytes are derived from a single cell type, the_____________________ found in the ___________________ in the neonatal through adult stage.

hematopoietic stem cell; bone marrow

B lymphocytes mediate ___________ immunity.

humoral

There are 3 _____________ regions within both the VH and VL regions. These regions combine to form the __________ on each arm of the N-terminal region of Ab.

hypervariable antigen binding site

Vascular permeability:

increased permeability of vessels facilitates movement of fluids, macromolecules, and cells from blood into tissue to help at the site of inflammation.

Molecules such as lipids and nucleic acids that are not normally immunogenic can be made immunogenic by attaching them to _____________.

large protein carriers

memory cell:

long-lived cells that have been activated previously by a specific antigen. These cells remain dormant until subsequent encounter with the same antigen. The memory cells then respond more quickly and strongly to the antigen to prevent infection.

IgG

longest half-life of any immunoglobulin

Movement of antigen, immune cells, and cytokine signaling molecules through the body is essential for immunity. Two systems that are vital in immune trafficking include the __________ system and the _____________ system.

lymphatic circulatory

The stem cell can differentiate into cells of either the _______________ or ________________ lineage.

lymphoid myeloid

Myeloid progenitors can become:

megakaryocytes, erythrocytes, granulocytes

After activation by contact with antigen/pathogen, some B and T lymphocytes will become ______________________ cells, which are long-lived and produce a larger and more rapid response upon subsequent encounter with the same antigen.

memory

Hybridoma technology has greatly benefited the clinical lab by producing an abundant supply of ________________ with high specificity.

monoclonal antibodies

Secondary Ag-Ab interactions such as agglutination and precipitation are dependent upon optimal cross-linking events which require both ___________ Ag and ____________ Ab.

multivalent

Pinocytosis:

nonspecific membrane invagination in which macromolecules are brought into the phagocyte and are destroyed.

Agglutination results from cross-linking of Ab with _______________ Ag, and precipitation results from cross-linking of Ab with ____________ Ag.

particulate soluble

As a test for Strep infection, a patient's serum (possibly containing anti-Strep O antibody) is mixed with commercially available latex beads coupled with Strep O antigen. Visible clumping of the latex beads would indicate a positive result/strep infection due to the presence anti-strep O Ab in the patient's serum. This type of testing is an example of ________________.

passive agglutination

Hematopoietic:

pertaining to the formation of blood or blood cells

T-Independent antigens are typically:

polysaccharides

IgA

present as a dimer on mucosal surfaces

IgD

present with IgM on the surface of naïve, mature B cells

In both the spleen and lymph nodes, naïve B cells reside primarily in the __________________ and activated B cells/ plasma cells are found in _____________.

primary follicle germinal centers of secondary follicles

T cells respond only to protein fragments (peptides) as antigens because TCR must recognize antigen that has been ___________ by APC and presented in the context of ____________ molecules on the surface of APC.

processed MHC/HLA

Only __________ serve as immunogens for cell-mediated immunity.

proteins; Cell-mediated immunity is controlled by TH and Tc cells. These cells primarily recognize peptide antigens presented by MHC Class I or II. The antigen, thus must be a protein, or have a protein component.

Serial dilution of a patient's serum containing possible agglutinating Ab is important to rule out an erroneous negative agglutination result due to ___________________.

prozone or postzone effects

A single B cell clone that undergoes Ig isotype switching:

retains the same antigenic specificity

Receptor-mediated Endocytosis:

selective binding of foreign microbial antigens to Pattern Recognition Receptors (PRRs) and ultimate membrane invagination, resulting in internalization and degradation of foreign antigens in the phagocyte.

Explain the interrelationship between innate and acquired immune responses with respect to:

1. Antibodies: such as IgG, produced by B cells (acquired immunity) can serve as "opsonins", binding to and "tagging" foreign substances to enhance phagocytosis by phagocytes (of innate immunity) 2. Cytokines: Macrophages (innate immunity) produce cytokines like IL-1 that can activate T lymphocytes (acquired immunity). In turn, T lymphocytes produce cytokines like IFN-gamma that promotes NK cell (innate immunity) activity, and can activate macrophages to be better phagocytes and antigen presenting cells. 3. Antigen Presenting Cells (APC): Dendritic cells and macrophages (both phagocytes of innate immunity) also play an essential role in presentation of antigen to T lymphocytes (acquired immunity) to activate the T cells to action.

Explain why antigens with multiple epitopes and multiple specificities are better able to stimulate an immune response.

1. Antigens with multiple epitopes are able to cross-link receptors on the surface of lymphocytes. This cross-linking results in activation of the lymphocyte. 2. Antigens with multiple epitope specificities are able to stimulate a greater percentage of lymphocytes into action.

Describe 3 applications for Flow Cytometry / Fluorescence-Activated Cell Sorting (FACS) in the laboratory.

1. Can determine % of lymphocyte phenotypes in a cell population based on CD (clusters of differentiation) markers 2. Can sort labeled from unlabeled cells to generate a homogeneous cell population 3. Can measure the relative amount of CD Ag on each cell surface

Three types of antigen presenting cells (APC) are:

1. Dendritic Cells 2. Macrophages 3. B Lymphocytes

Describe 4 factors affecting immunogenicity with regard to the nature of the immunogen:

1. Foreignness: Substance is nonself. The greater degree of "foreignness" the more immunogenic a substance will be. 2. Molecular Size: Typically at least 6000 Da. Larger molecules are usually more immunogenic. 3. Chemical complexity: More complex molecules are typically more immunogenic. 4. Degradability: T cells "see" degraded foreign antigens in the context of MHC on the surface of APC. Therefore, for "T dependent" immune responses, it is important that the antigen is degradable or can survive the degradative process and bind to MHC.

Describe 4 factors affecting immunogenicity with regard to the nature of the biological system:

1. Genotype of Individual: An individual's genetic makeup (esp. HLA genes) can affect his/her ability to react to different antigens. 2. Immunogen dosage: Intermediate doses tend to be more immunogenic. High and low doses may elicit immune "tolerance". 3. Route of Administration: Subcutaneous > I.P. > I.V. > Oral 4. Use of Adjuvants: Adjuvants serve to enhance the immune response to antigens.

Describe 3 mechanisms of killing by phagocytes:

1. Lysosomes, containing degradative enzymes such as proteases, nucleases and lipases. 2. Respiratory Burst, producing toxic oxygen products. 3. Extracellular release of antimicrobial substances.

Antibodies bind antigen with specificity and, depending upon the nature of the Ab isotype (heavy chain constant region), can produce a number of biologic effects. Describe nine different biologic effects associated with antibodies:

1. Neutralization of toxins and viruses 2. Immobilization of microorganisms 3. Agglutination 4. Precipitation 5. Opsonization 6. Complement fixation/activation 7. ADCC: antibody-dependent cell-mediated cytotoxicity 8. Transfer of IgG across the placenta from mother to baby 9. IgE degranulation (histamine release) of mast cells and basophils: allergy/ anaphylaxis

Cells involved with the innate Immune response include:

1. Neutrophils 2. Monocytes / Macrophages 3. Dendritic Cells 4. Natural Killer Cells

Explain 5 features of a B cell response to T-Independent Ag that differs from a B cell response to T-dependent Ag.

1. No T cell help required 2. Response is rapid 3. Typically only IgM (membrane-bound and secreted) 4. Memory cells not generated 5. Antigen is often polysaccharide

Fc Receptors are found on a variety of cell types and bind to the Fc region of antibodies. This receptor-mediated binding is important for a number of biologic effects involving antibodies, including:

1. Opsonization 2. ADCC 3. Transfer of IgG across the placenta from mother to baby 4. IgE bound to mast cells in allergy/ anaphylaxis

Four hallmark features of the acquired immune response distinguish it from other systems of the body. List and explain the importance of each of these 4 features:

1. Specificity: Each T or B lymphocyte bears antigen-specific receptors on their surface that can respond to only one specific antigen. These receptors are generated early in cell development by a series of amazing gene rearrangements, resulting in each lymphocyte bearing a unique receptor specific for only one antigen. 2. Adaptiveness/Diversity: The body produces a huge "repertoire" of specific T and B lymphocytes so that the body can respond to virtually any foreign substance it encounters. 3. Self / Nonself Discrimination: The immune system can distinguish between "self" and "nonself". Early in their development, T and B lymphocytes that can react to "self" molecules are eliminated. "Non-self"-reactive lymphocytes proliferate. 4. Memory (Anamnestic Response): After T and B lymphocytes have seen a foreign substance, memory cells are produced that are long-lived and capable of responding to the specific non-self substance again during a subsequent encounter. This secondary response is more rapid and larger than the initial, primary response.

Describe 2 signals required for T lymphocytes to become activated by antigen presented by antigen presenting cells.

1. The TCR must bind antigen presented in the context of MHC molecules on the surface of antigen presenting cells. 2. Co-stimulatory molecules on the T cell and APC must be ligated.

Describe two main functions of secondary lymphoid organs/ tissues:

1. Trap and concentrate foreign antigens 2. Main site of antigen encounter and activation of both B and T lymphocytes

The two types of acquired (adaptive) immunity are:

1. humoral 2. cellular or cell-mediated

naïve cell:

A cell that has not yet encountered antigen

What is the Immunoglobulin Superfamily? Name three members of this family.

A group of proteins that all have similar domain structure, suggesting that these molecules evolved from a common primordial gene. Examples include: Immunoglobulin, Igα/IgΒ, TCR, CD3, MHC I & II, Poly-Ig Receptor

Bradykinin (Kinin System):

A vasoactive protein that is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain.

Compare B and T cell antigen recognition with regard to:

A. Ag-Receptor Complex: B cells: bimolecular complex: Ag + BCR T cells: trimolecular complex: Ag - MHC (HLA) + TCR B. Epitope Location: B lymphocytes typically bind directly to exterior hydrophilic components of the intact or "native" molecule. T lymphoctyes must recognize fragments of proteins degraded and presented bound to MHC/HLA molecules on the surface of antigen presenting cells. These fragments tend to be more hydrophobic and on the interior of the protein. C. Epitope Type: B cells: Can recognize either linear determinants or conformational epitopes created by the protein structure (1o, 2 o, 3 o, 4 o). Epitopes can be either sequential portions of the molecules or created from nonsequential or discontinuous portions of the molecule. T cells: Recognize only linear protein fragments in the context of MHC. D. Classes of Antigen: B cells: Proteins, Carbohydrates, and to a lesser extent: (Lipids, Nucleic Acids) T cells: Protein fragments or "peptides".

Cytokine - IL-6:

Acts on liver cells, affecting systemic production of acute phase proteins such as C-Reactive Protein.

Explain somatic hypermutation:

After B cell activation with T-D antigen, mutations occur at high frequency in the hypervariable regions of rearranged Ig gene DNA, resulting in variant BCR/Abs, some of which have a higher affinity for Ag.

How are B cell hybridomas generated, and what do they produce?

An antibody-producing B cell is fused with a myeloma cancer cell to create an immortalized cell line that proliferates continuously and secretes monoclonal antibody.

Define cross-reactivity? How is it useful to us?

An immunologic reaction in which immune components, such as lymphocytes or antibodies react with two molecules that share epitopes or epitope structural similarities but are otherwise dissimilar. This is called cross-reactivity: when 2 different antigens appear similar to the immune system. Cross reactivity results when: 2 antigens share a common epitope, OR 2 antigens share a structurally similar epitope.

Autoantigens:

Antigens derived from the same individual or "self". People with autoimmune disease respond to self-antigens. For example, Systemic Lupus Erythematosus (SLE) is a disease in which a person develops antibodies against components of his/her own cell nucleus.

Heteroantigens or Xenoantigens:

Antigens that originate from a different "species" and produce an immune response in another species. The term is sometimes used loosely and can refer to an immune response to single-celled organisms also, though they are grouped as phylotypes, not "species". An example: If a person gets a mitral valve replacement, they may receive a porcine (pig) valve. This is an example of a xenograft.

Alloantigens:

Antigens that vary within a species. An example is MHC/HLA antigens expressed on the cell surface in organ transplants in humans. Each person expresses different combinations of MHC/HLA antigens. Therefore, it is important to match these "alloantigens" between transplant recipient and donor as closely as possible in order to avoid the recipient generating an immune response against the alloantigens and rejecting the transplanted organ.

What are the primary lymphoid organs?

Bone Marrow Thymus

Describe a laboratory test to detect and track inflammation:

C-Reactive protein (CRP) levels CRP levels increase in plasma during inflammation. Complete Blood Count (CBC) WBCs may increase in plasma during inflammation Erythrocyte Sedimentation Rate (ESR) Faster RBC sedimentation in presence of increased inflammatory proteins in plasma

Complement Components:

C3b: An opsonin; binds to bacterial cell walls which "tags" the invader as a target for phagocytosis. C5a: Both C5a and C3a are "anaphylatoxins" which are potent mediators of inflammation, initiating release of histamine by mast cells resulting in vasodilation and vascular permeability. C5a is also a chemokine and serves as a chemoattractant, directing cells to the site of inflammation. membrane-attack complex: Complement proteins C5b, C6, C7, C8, and C9 form a complex that insert into bacterial cell walls resulting in cell lysis.

Simultaneous binding of the BCR to a pathogen epitope and the B cell coreceptor binding to __________, (a degraded complement component) covalently bound to the same pathogen, results in a(n) ________________ (100-10,000 fold) B cell response.

C3dg; augmented

The B Cell coreceptor is composed of __________________ and results in additional signal transduction associated with the BCR, which _________________ the threshold needed to activate the B Cell.

CD21/CD19/CD81; lowers

Thrombin (Coagulation system):

Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a blood clot.

What is the general function of the constant and variable regions of Ig?

Constant: The more invariant C-terminal region of Ig heavy and light chains which contains the biological activity of the antibody. Variable: N-terminal portion of immunoglobulin heavy and light chains which contains the antigen binding sites, one on each arm of the Ig, resulting in a bivalent Ab.

Lattice Formation:

Cross-linking of multivalent Ab and multivalent Ag to produce a visible, stable aggregate of Ab-Ag complexes at optimal concentrations of both Ag and Ab.

Unique gene rearrangement of V region genes in all lymphocytes, resulting in a large repertoire of lymphocytes (each with a unique Ag-specific receptor), allowing the body to respond to many different Ags

Diversity/Adaptibility

_______ is a valuable and widely used solid phase immunoassay used to help diagnose diseases by identifying Ab or Ag in a patient's fluids. An indirect ELISA can detect anti-HIV Ab in a patient's serum by applying the serum to plastic microtiter wells coated with HIV Ags. A secondary anti-Ig Ab coupled to a detection enzyme is then added, followed by the enzyme substrate. A color change indicates a positive result if anti-HIV Abs are present in the serum and bound to HIV Ags on the wells.

ELISA (Enzyme-linked Immunosorbent Assay)

Adjuvants exert their effect by making the antigen they are mixed with pathogenic.

False

True or False: All antigens are immunogens

False

True or False: Tetanus toxin and tetanus toxoid are homologous antigens.

False

True or False: Adjuvants can make haptens immunogenic.

False

_________________ are low M.W. molecules that can bind to antibodies but cannot induce an immune response unless bound to a large protein carrier molecule.

Haptens

In the cell-mediated immune response there are different subtypes of T lymphocytes, including the Helper T cell and the Cytotoxic T cell. Describe the role of these two T lymphocyte subtypes.

Helper T lymphocytes: Activated Helper T cells produce cytokines to help activate, mobilize and regulate other immune cells such as phagocytes, natural killer cells, B cells and Cytotoxic T cells. Cytotoxic T lymphocytes: Activated Cytotoxic T cells bind directly to and kill cells infected with intracellular pathogens such as viruses, or tumor cells.

Interaction of CD40 (on B cells) and CD40L (ligand on T cells) plays a critical role in:

Ig isotype switching

found in abundance in secretions such as mucus, tears and saliva:

IgA

plays a role in immune defense against parasites (worms):

IgE

upon binding to antigen, results in mast cell and basophil degranulation and release of histamine, heparin, and other pharmacologically active compounds:

IgE

neutralizes bacterial toxins and crosses the placenta:

IgG

effective in neutralization of viruses:

IgG and IgA

Identify the antibody isotype(s) that may be produced after isotype switching occurs in response to primary (T-dependent) antigenic stimulation.

IgG, IgA or IgE

Identify the antibody isotype(s) that may be secreted during a second encounter with the same (T-dependent) antigen.

IgG, IgA, IgE

important opsonins, resulting in enhanced phagocytosis of extracellular pathogens:

IgG1 and IgG3

sensitizes NK cells to kill target cells through ADCC (antibody-dependent cellular cytotoxicity):

IgG1 and IgG3

Identify the antibody isotype(s) secreted initially after primary antigenic stimulation of naïve but mature B lymphocytes.

IgM

most effective at agglutination of antigen and complement activation:

IgM

dentify the antibody isotype(s) found to be membrane-bound on the surface of naïve but mature B lymphocytes.

IgM and IgD

In the B Cell Receptor Complex, the BCR is associated with _________________ which function as signal transduction molecules, transducing signals to the interior of the B cell when the B cell receptor binds antigen.

Igα/IgΒ

______________ is a technique used to detect the presence or absence of one or more proteins in patient serum. Proteins placed in a gel are separated based on charge, and then antibodies are applied to a trough and allowed to diffuse through the gel. Immunoprecipitate lines are visible when separated proteins bind to specific antibodies at the zone of equivalence.

Immunoelectrophoresis

____________ Immunity is the first line of defense against invasion of the body by foreign pathogens.

Innate

Encounter with antigen results in immunological memory?

Innate: No Acquired: Yes

System of physical barriers?

Innate: Yes:skin and mucus membranes Acquired: No

Humoral components

Innate: complement acute phase proteins and other soluble mediators Acquired antibodies, cytokines, and other soluble mediators

Response time: first encounter with antigen

Innate: immediate Acquired: lag time: several days to weeks

Cellular components

Innate: phagocytes and natural killer cells Acquired: B and T cells

Response time: subsequent encounter with antigen

Innate: the same Acquired: more rapid

Specific or nospecific?

Innate:No Acquired:Yes

Can identify self from nonself?

Innate:Yes Acquired:Yes

Prozone:

Lack of a visible agglutination or precipitation reaction due to the presence of excess antibody, which may result in a false-negative test result.

Postzone:

Lack of a visible agglutination or precipitation reaction due to the presence of excess antigen, which may result in a false-negative test result.

Natural Killer (NK) cells have Killer-cell Inhibitory Receptors (KIRs) which allow them to identify tumor cells and virally-infected cells as abnormal because these cells often lack __________ on their cell surface.

MHC class I

A majority of antigens are T-dependent. This means that the T helper (H) cell must interact with and provide help for the B cell to become activated and proliferate in response to the T-dependent antigen. The B cell serves as an APC for the TH cell, and presents Ag to the TH cell in the context of the B cell's _______________. After TH cell activation by the B cell, the TH cell begins to produce ______________ required for B cell activation.

MHC class II; cytokines

Ag-driven activation and differentiation of lymphocytes into quiescent, nonproliferating, long-lived cells ready to respond more rapidly and effectively to 2nd Ag encounter

Memory

______________ are the second phagocytes to arrive at the inflammatory site, within hours. They leave the blood and rapidly differentiate into ________________ in the tissues.

Monocytes macrophages

Prior to development of hybridoma technology, explain how patients with multiple myeloma aided studies of antibody structure?

Multiple myeloma is a malignant tumor within the bone marrow resulting from one individual cancerous plasma cell and producing an excess of monoclonal antibody. This monoclonal antibody can be isolated from patient serum and urine (light chains only in urine), and was used as a source of Ab to characterize Ab structure prior to the advent of hybridoma technology.

Describe how NK cells kill abnormal or infected body cells.

NK cells are "cytotoxic". Small granules in their cytoplasm contain perforins which are capable of forming pores in the target cell, and granzymes (proteases) which enter the cell and cause apoptosis: "programmed" cell death through DNA fragmentation.

There are 4 means of inducing or transferring acquired immunity in an individual. Give an example of each type.

Natural -Passive: Antibodies passed from mother to baby in utero or through breast milk. Natural - Active: Infection: the body encounters a pathogen and mounts an immune response. Artificial - Passive: Injection/transfer of specific antibodies or cells to an individual, i.e. Ready-made immunoglobulins (antibodies) specific for cytomegalovirus (CMV) are administered prophylactically to patients receiving kidney transplants to provide artificial immunity to prevent CMV infection. Artificial - Active: Vaccination: i.e. measles vaccine.

______________ are the first phagocytes to leave the blood and enter the tissue at the site of inflammation, usually within minutes.

Neutrophils

T cell precursors leave the bone marrow and go to the _______________ where they mature.

thymus

How many Ig isotypes can be membrane-bound and secreted by a single B cell clone after isotype switching has occurred?

Only one

In a semi-quantitative agglutination assay, a "relative" quantity of Ab that reflects the highest dilution showing visible agglutination is reported as a __________

titer

Induction of B cell activation, resulting in IgA Ab synthesis can occur in the _____________________ in GALT.

Peyer's patches

Immune cells that are prominent players in innate immunity are phagocytes. Describe the role of phagocytes in the innate immune response.

Phagocytes are capable of identifying foreign substances as nonself, and respond by ingesting/digesting and eliminating the foreign substance such as a pathogen. Another important function of phagocytes is housekeeping. They are capable of clearing away unwanted cell debris.

Surface barriers are vital in preventing entry of pathogens into the body. Give examples of the following:

Physical barriers: Skin, mucous membranes, Earwax, Mucus, cilia, cough/sneeze reflex Chemical/Molecular barriers: acid pH of sweat, stomach acids, urine, vaginal fluids Antimicrobial Proteins: (found in epithelial layers, phagocytes, body fluids) Lysozymes: enzymes in tears, saliva, phagocytes, epithelial layers; digest the cell wall of Gram + bacteria Defensins: Produced by small intestine cells and neutrophils. Penetrate microbial membranes and disrupt integrity Biological barriers: Normal Flora of skin and GI tract

Cytokines (such as TNF-alpha and IL-1):

Produced by immune cells such as macrophages. Cause general cell signaling, responsible for recruiting and regulating a variety of cells involved in inflammation. Consequences include fever, T cell proliferation and cytokine production, endothelial cell and fibroblast activation, chemotaxis, and leukocyte adherence.

Chemokines (such as IL-8):

Produced primarily by tissue macrophages, causes activation and chemoattraction of neutrophils to the site of inflammation.

___________ are the best immunogens because they meet all the requirements for good immunogens, and, in part, because they can be recognized by both B and T lymphocytes.

Proteins

____________ is a test based on precipitation of Ag-Ab complexes in gel. This test can be used to quantitate an unknown concentration of Ag in a patient's serum using dilutions of a sample with known Ag concentration.

Radial Immunodiffusion

Clonal deletion of self-reactive lymphocytes in early cell development

Self/Nonself Discrimination

What is the difference between serum and plasma?

Serum is the blood fluid (minus clotting factors) collected after centrifugation of clotted blood. Plasma is blood fluid (containing clotting factors) collected after centrifugation of blood that has been treated with anti-clotting agent (such as heparin...).

C-Reactive Protein:

Serves as an opsonin, binds to dead or dying cells and some bacteria, activates the complement system, and promotes phagocytosis.

Unique gene rearrangement of V region genes in a given lymphocyte, resulting in a unique Ag-specific receptor, which allows the lymphocyte to discriminate among different Ag epitopes/ bind to a specific Ag epitope

Specificity

What are the secondary lymphoid organs/ tissues?

Spleen, Lymph nodes, Mucosal-Associated Lymphoid Tissues (MALT)

Cell-mediated immunity is controlled by

T cells

Give an example of a lab test used by clinical laboratory scientists that measures or utilizes a component of the immune system, and explain how the test procedure relates to immunology.

The Rapid Strep A test makes use of specific anti-Strep A antibody binding to the Strep A bacterial antigens to detect the presence of the Strep A bacteria in a throat swab sample. The clinical laboratory has made extensive use of the antigen-antibody reaction as a tool to: 1. measure the concentration of analytes in serum or plasma- hormones, drugs, soluble proteins 2. detect cell surface molecules to identify cells 3. detect antigens or antibodies in serum/plasma or other body fluids/secretions to diagnose infectious or autoimmune diseases.

Explain the importance of Ab cross-reactivity in our immune defense against antigenic challenges.

The ability of a specific Ab to cross-react with a second "related" antigen allows for redundancy in the immune response, thereby reducing the number of different antibodies necessary to defend against a broad range of antigenic challenges.

Describe the importance of the hinge region of antibodies.

The hinge region permits flexibility between Fab arms to allow binding of Ag epitopes with a fixed distance on the same antigen

Describe affinity maturation:

The increase in affinity of the Ag-binding sites of BCR/Abs for Ag that occurs during the course of an adaptive immune response. It occurs due to somatic hypermutation causing variant BCR/Abs and consequent selection of these mutated B cells that have BCR with higher affinity for Ag.

Zone of equivalence:

The optimal concentration of both Ag and Ab that results in visible precipitation or agglutination.

Avidity:

The overall stability of an Ag-Ab complex as affected by all Ab binding site interactions with a multivalent Ag. Avidity represents the multiplicity of all affinities and is influenced by Ab valence. Therefore IgM pentamer (valence of 10) would have a greater avidity than IgG (valence 2) when binding identical multivalent Ag.

Which part of a virus can be immunogenic?

The protein component will definitely be immunogenic. If there is any RNA or DNA attached to a protein carrier, this may make the nucleic acid immunogenic as well.

What are the 4 classic signs of inflammation?

Heat, Pain, Redness, Swelling (Edema)

Pentameric IgM is an excellent agglutinin due to its _________.

high valency (10)/ high avidity