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306 Cards in this Set

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  • Back
What part of the immune system does not require prior exposure to antigen for expression of its activity?
Innate immunity - also called innate resistance
Name two major classes of lymphocytes that participate in the adaptive immune response.
T-cells and B-cells
Name three major cell types that participate in innate immunity.
Polymorphonuclear leukocytes Macrophages NK cells
What is the name of the lymphoid organs were T- and B-cells develop?
Central lymphoid organs
Where does T-cell development take place?
In the thymus
What is the site for B-cell development?
The bone marrow
Where do lymphocytes respond to stimulation with antigen?
The peripheral lymphoid organs (spleen, lymph nodes, MALT, BALT, GALT).
What cells transport antigens from a site of infection to the draining lymph nodes?
Dendritic cells
List the 7 major components of the innate immune response.
Natural barriers
What opsonin(s) does the liver produce that contribute(s) to innate immunity?
C reactive protein (CRP)
What is an opsonin?
A substance that binds to a pathogen and enhances its ability to be engulfed by phagocytes.
What is the response of the phagocytic cell after engulfment of a bacterium?
The oxidative burst
List five mechanisms used by phagocytes to kill bacteria intracellularly.
Hydrogen peroxide Singlet oxygen Superoxide anion Nitric oxide Lysosomal enzymes
What is the major activity of IL-1 in the inflammatory response?
Activation of endothelial cells to upregulate expression of adhesins.
What is the major activity of IL-8 during the innate immune response?
Chemotactic activity for polymorphonuclear leukocytes
What is the major activity of IL-12 during the innate immune response?
Activation of NK cells
What cells produce interferon-alpha and interferon-beta?
Most cells in the body
What cells of the body produce interferon-gamma?
Cells of the immune system: T cells, NK cells and macrophages
What are the effects of the interferons on macrophages and NK cells?
Increase expression of MHC I and MHC II molecules on both. Activation of NK cells. Activation of macrophages.
List three general characteristics of innate defenses.
Does not require an induction period. Is not specific for antigen. No memory.
List three general characteristics of adaptive immunity.
Requires induction with antigen. Response of an antigen specific lymphocyte. Has memory.
Give an example of active immunity that is naturally acquired.
Infection followed by recovery from an infectious disease.
Give an example of active immunity that is artificially acquired.
Vaccination of an individual who is not immune.
Give an example of passive immunity that is naturally acquired.
Transfer of IgG from mother to fetus.
Give an example of passive immunity that is artificially acquired.
Injection of immunoglobulin into an individual who is not immune.
Name the three different complement pathways.
Classical pathway. Alternative pathway. BM-lectin pathway.
Name the components of the classical complement pathway that precede C3 in order of their activation.
C1q, C1r, C1s, C4, C2
Name the C3 convertase of the classical complement pathway.
Which of the split products of the complement pathway have chemotactic activity?
C3a, C4a, C5a
Which split product of the complement pathway is the MOST active chemotactic substance?
Name three factors that are unique to the alternative complement pathway.
Factor D Factor B Factor P (properdin)
What is the C3 convertase of the alternative complement pathway?
Why does complement activation by pathogens and/or antigen-antibody complexes not cause the cells of the host to undergo lysis?
Various inhibitors of the complement pathway prevent this from happening (for example CD59 on host cells).
What is the role of factor P (Properdin) in the alternative complement pathway?
It stabilizes the C3b,Bb complex (C3 convertase) on the pathogen surface.
List three biological activities of C5a.
Chemotactic. Activates macrophages for enhanced phagocytosis and killing. Activates mast cells to release inflammatory mediators (TNF-alpha and histamine).
Which of the complement components constitute the membrane attack complex?
C5b, C6, C7, C8, C9
What causes the disease Hereditary Angioneurotic Edema (also called Hereditary Angioedema)?
A deficiency of C1 inhibitor (C1INH).
The edema that forms during C1INH deficiency is due to what two pharmacologically active mediators?
C2 kinin Bradykinin
What are some of the triggers for the symptoms in patients with Hereditary Angioneurotic Edema?
Stress. Minor trauma. Surgery. Dental Procedures.
What is the best treatment for Hereditary Angioneurotic Edema?
Androgen daily for one week prior to surgery, or C1 inhibitor concentrate (or plasma) immediately before surgery.
What activates the classical complement pathway?
Antigen-antibody complexes.
What activates the alternative complement pathway?
Binding of C3b to microbial surfaces
What is the fluid phase C3 convertase of the alternative complement pathway?
How are immune complexes removed from circulation?
They attach to the CR1 receptor on RBCs. The complex is removed from the RBC by Kupffer cells in the liver or by splenic macrophages.
Which route of injection of an antigen is the least likely to induce an effective immune response?
Which route of antigen injection is the most likely to result in induction of an effective immune response?
Subcutaneous or intramuscular
Which are more immunogenic, proteins or polysaccharides?
What is an adjuvant?
A substance that increases the immunogenicity of an antigen when injected with antigen.
What is a hapten?
A small molecule that does not induce an immune response when injected alone but will induce an immune response if conjugated to a carrier molecule.
Are antibodies that are produced by injection of animals monoclonal or polyclonal?
How many different epitopes react with a monoclonal antibody?
How are monoclonal antibodies made?
Fusion of immune mouse B cells with a mouse myeloma cell line, followed by cloning of the fusion product. The antibody is secreted into the medium used to grow the fusion product.
What are usually the best conditions for the interaction of antigens with antibodies?
Those found in the body: pH 7.2, 37 C, physiological salts concentrations.
The reaction between a bacterial cell and antibodies that interact with molecules on the cell is?
What happens when a mammalian cell that is coated with antibody interacts with the complement system?
Usually results in lysis of the cell (may depend upon the density of the antigen on the cell).
What happens when an antibody interacts with the active site of a bacterial toxin?
Neutralization of the toxin.
What is the reaction that occurs when an antibody reacts with an insoluble particle?
What is the reaction that occurs between a soluble antigen and an antibody specific to that antigen?
What is the titer of an immune antiserum?
The highest dilution of the antibody that results in a visible reaction.
What is meant by the term "indirect hemagglutination"?
An agglutination reaction that occurs when antibody coated cells are agglutinated by addition of antibody specific for the antigen-specific antibody (i.e. anti-human IgG used in the Coombs test)
In the complement fixation assay a positive test is indicated by?
No lysis of indicator red blood cells showing that complement was consumed by a soluble antigen-antibody reaction.
The complement fixation assay is quantitative.
The correct answer is: True
In relative terms, which is the most sensitive assay - complement fixation or agglutination?
Complement fixation
In relative terms, which is the most sensitive assay - ELISA assays or precipitation assays?
What two conditions result in a false negative precipitation reaction?
Antigen excess Antibody excess
What precipitation reaction usually eliminates concerns about antigen excess and antibody excess?
Precipitation in gels
Name an immunological assay used for studying complex mixtures of antigens and antibodies that allows identification of specific antigens and/or antibodies.
Double diffusion in gel
Which of the precipitation reactions is good for quantitation of antigens?
Radial immunodiffusion
What is the most common and accurate method used for quantitation of the most abundant serum immunoglobulins (IgG, IgA and IgM)?
What types of immunological assays are sensitive enough to detect molecules that are present in very low concentration?
Enzyme Linked Immunoassay - ELISA Radioimmunoassay - RIA
What type of assay is very sensitive and allows specific detection of a mixture of molecules when an antiserum of known specificity is used?
Western Blotting
Name two immunological assays that allow visualization of antigens on the surface of cells.
Fluorescence microscopy Flow cytometry
What is it that allows visualization of the antigen-antibody reaction in flow cytometry?
A fluorescent tag on the antibody.
What allows detection of the antigen-antibody reaction in an ELISA assay?
An enzymatic tag on the specific antibody. The enzyme converts its substrate to a color that can be seen visually or read on a spectrophotometer.
What allows detection of the antigen-antibody reaction in a radioimmunoassay?
A radioactive tag on the antibody molecule. The tag can be detected with an appropriate detector for the radioactive nuclide.
What is the BEST assay to use for enumeration of T cell subsets present in a patient's blood?
Flow cytometry - due to the fact that large numbers of cells can be evaluated in a short period of time.
Name three assays that will measure the function of T lymphocytes?
Lymphocyte proliferation to T cell mitogens or recall antigens. Mixed lymphocyte response (MLR). Chromium release assay for cytotoxic T cells.
Which mitogen induces proliferation in human B cells and causes them to secrete immunoglobulin?
Pokeweed mitogen
In the mixed lymphocyte reaction (MLR), T cells of a potential transplant recipient proliferate in response to what class of molecule on the cells of a potential donor?
MHC class II
Immunoglobulins are secreted by?
Plasma cells
Plasma cells are derived from?
Antigen activated B lymphocytes
Which class(es) of immunoglobulins have subclasses?
IgG - IgG1, IgG2, IgG3, IgG4 IgA - IgA1, IgA2
The antigen combining site of an immunoglobulin is composed of what regions?
The VH region of the heavy chain and the VL region of the light chain.
What is function of the Fab region of an IgG molecule?
It binds to antigen.
F(ab')2 describes a molecule that has how many antigen combining sites? What is missing from this molecule?
2 combining sites. There is no Fc region.
What is the most abundant immunoglobulin class in serum?
What is the 1/2 life of IgG in the body?
about 21 days
Which antibody class(es) can strongly bind complement?
IgG and IgM
Which immunoglobulin class(es) pass(es) the placenta?
Which immunoglobulin class is a pentamer of the basic Ig structure?
Which immunoglobulin class is primarily a cell surface receptor?
What is the sedimentation rate of an IgM molecule?
What is the sedimentation rate of an IgG molecule?
What class of immunoglobulin is found during the primary immune response?
What is the predominant immunoglobulin class found in a secondary immune response?
Which immunoglobulin molecule is a dimer of the basic Ig structure?
secretory IgA
What is the primary function of secretory IgA?
To provide immunity at mucosal surfaces.
Which immunoglobulin class(es) have a J chain?
IgM and IgA
What is the function of secretory component?
Transport of IgA across the mucosal epithelium. Protects IgA from proteolytic digestion.
What are two activities of IgE?
Elicits the immediate hypersensitivity reaction. Provides immunity to helminthic parasites.
What is the function of Ig-alpha and Ig-beta?
They transmit signals into the interior of a B cells after antigen interacts with mIg.
What is the funcion of the tri-molecular complex, CD81:CD19:CR2?
It is the co-receptor for the B lymphocyte.
What is the difference in mIgG and secreted IgG?
A change in the last constant region of the heavy chain. This allows the immunoglobulin molecule to be secreted or inserted into the membrane of the cell.
What are the names of the light chains of immunoglobulin molecules?
Lambda and kappa
What are the names of the heavy chains of the 5 immunoglobulin classes?
Mu, gamma, alpha, delta, epsilon
What cell binds IgE?
Mast cells
A difference in the constant region of the various immunoglobulin classes is called?
An isotypic difference.
A difference in the constant regions of IgG molecules that occur between individuals of the same species is known as?
An allotypic difference.
The difference that occurs in the variable regions of immunoglobulins of the same class is called?
An idiotypic difference
The diversity of the variable regions of immunoglobulins can be attributed to?
Variation in the three complementarity determining regions (CDRs) of the heavy and light chains.
Gene rearrangements that occur in heavy chain genes are named?
DJ and V-DJ
Gene rearrangements that occur in light chain genes include?
The expression of what two genes is essential for lymphocytes to rearrange their antigen-specific receptors?
RAG-1 and RAG-2
What happens to bring the genetic information generated by the VJ or VDJ rearrangements of H and L chains in close proximity to genetic information encoding the constant region?
RNA splicing of the primary RNA transcript.
Name two mechanisms whereby genetic diversity of immunoglobulin genes occurs besides rearrangement of V, D and J genes.
N-nucleotide additions. P-nculeotide additions.
What are the characteristics of a pre-B cell?
No detectible surface immunoglobulin. (they do have a pre-B cell receptor) Rearranged VDJ genes. Can have cytoplasmic mu chains.
What must a B cell express before it can be considered a mature B cell?
Surface IgM
What is the mechanism of immunoglobulin diversity that occurs during stimulation of antigen-specific B cells with their specific antigen?
Somatic hypermutation.
What is the name of the mechanism whereby a B cell becomes capable of producing a new class of immunoglobulin?
Isotype switching.
The specificity of the antibody produced after isotype switching is changed.
The correct answer is: False
Name the anatomical location for T cells in lymph nodes.
Name the anatomic location for B cells in lymph nodes.
Germinal Centers. Also, primary or secondary lymphoid follicles.
Name the anatomic location for T cells in the spleen.
Periarteriolar lymphoid sheaths (PALS).
Name the anatomic location for B cells in the spleen.
In the corona, next to the PALS.
Which three cells are needed to initiate an antibody response?
Helper T cells. B cells. Antigen presenting cells.
Name the three types of "professional" antigen presenting cells.
Dendritic cells. Macrophages. B cells.
What receptors are utilized by macrophages to internalize antigens?
Fc Mannan Glucan
What receptor(s) are utilized by B cells to internalize antigen?
Surface immunoglobulin
What serves as a co-receptor for the T cell receptor? Name the chains of the co-receptor.
CD3 gamma, delta, epsilon, zeta, eta
What is the predominate T cell receptor found on T cells in the human?
alpha, beta T cell receptors
Which chain of CD3 is responsible for transmission of activation signals to a T cell?
The zeta chain of CD3.
Which cytokines are unique to the Th1 subset?
IFN-gamma, IL-2, TNFbeta
Which cytokines are made by Th2 cells and not by Th1 cells?
IL-4, IL-5, IL-6, IL-10
Which Th1 cytokine(s) down-regulate(s) the Th2 response?
Which type of helper cell functions in the development of most antibody responses including IgE?
Th2 cells
Which type of helper cell is responsible for the development of cell-mediated immunity and the IgG2 response?
At about what age is most of maternal immunoglobulin lost from the circulation of a newborn?
6 months of age
Which MHC molecules present antigen to CD8+ T cells?
MHC class I
Which MHC molecules present antigen to CD4+ T cells?
MHC class II
Antigens that enter the APC from the exterior of the cell are presented by?
MHC class II molecules
Antigens that are synthesized within the cell are presented by?
MHC class I molecules
What co-stimulatory signal is most important for activation of a T cell?
The interaction of B7 on the APC with CD28 on the T cell.
What APC derived cytokines contribute to the activation of T cells?
IL-1 TNFalpha IL-12
What common function do the following molecules play in the activation of T cells - ICAM-1, LFA-1, LFA-2, LFA-3?
They are primarily adhesions but may also provide activation signals.
Which cytokine provides growth signals after a T cell is activated?
What is the name of the intracellular molecule that interacts with the zeta chain of CD3 and participates in activation of T cells?
ZAP 70
When a foreign tissue is transplanted into a recipient, what type of cell activates CD8+ cells of the recipient?
Dendritic cells that are derived from the grafted tissue.
When a foreign tissue is transplanted into a recipient, what type of cell activates CD4+ cells of the recipient?
Recipient APC that have processed soluble antigens of the grafted tissue.
Which molecules on T cells and B cells must interact before class switching will occur?
CD40 on the B cell and CD40L on the T cell.
Which cytokine(s) primarily drive(s) the development of Th1 cells?
IL-12, IFN-gamma
Which cytokine primarily drives the development of Th2 cells?
What is the difference in generalized immunosuppression and immunological tolerance?
Immune tolerance occurs to an individual epitope of an antigen while generalized suppression results in lack of responsiveness to all antigens.
Why are many of the agents that are used to treat cancer also immunosuppressive?
They are agents that interfere with DNA synthesis. They preferentially kill rapidly proliferating cells such as cells of the immune system.
Name 4 disease states that can result in generalized immunosuppression.
Cancer Immune deficiency diseases Some chronic infections Malnutrition
What is the immunophilin that binds cyclosporin A?
What is the immunophilin that binds FK506?
FK binding protein (FKBP)
What is the mode of action of cyclosporine and FK506?
Both inhibit the activation of calcineurin.
What is the mode of action of corticosteroids?
Steroids bind to an intracellular steroid receptor. The complex then travels to the nucleus of the cell where it binds to regulatory elements of genes on DNA.
Which monoclonal antibodies are used for immunosuppressive therapy?
Anti-CD3. Anti-CD4 and anti-CD8 have also been used. Anti-TNFa Others.
What is RhoGham used for?
To prevent the development of anti-Rh in Rh- mothers who deliver an Rh+ child.
What is an anti-idiotypic antibody?
An antibody that interacts with the antigen combining site of another antibody.
How can anti-idiotypic antibodies influence the immune response?
Depending on dose, they can inhibit or augment the immune response.
What is the function of CTLA-4 on an activated T lymphocyte?
It interacts with B7 molecules on antigen presenting cells. This sends a signal to the T cell to stop producing cytokines or to "turn off".
What mechanism is used in the thymus to ensure that self-reactive T cells do not develop?
Cells that bind tightly to MHC are eliminated - The mechanism is called clonal deletion.
If self-reactive T cells are not eliminated in the thymus, what mechanisms can be used to ensure that they do not cause autoimmune disease?
Regulatory T cells (Tr). Induction of clonal anergy. Death of anergic cells.
What happens to B cells that interact with self-antigen in the bone marrow?
Death by apoptosis. Induction of a change in their specificity by "receptor editing". This change results in B cells that do not react with self.
What mechanisms are used to ensure that B cells that might react with self antigen are eliminated in the peripheral lymphoid tissues?
Interaction with antigen without helper T cell activity leads to induction of anergy in the B cell. Partial activation of the B cell results in failure to move into the germinal center and develop into a plasma cell.
What is a tolerogen?
A form or dose of antigen that induces immunological tolerance (unresponsiveness) to a specific antigen.
What type of cell (T or B) is most sensitive to induction of immune tolerance after injection of soluble antigen?
T cells.
Which cell type (T or B) remains tolerant the longest without re-exposure to antigen?
T cells.
What explains the ability of antigens that cross-react with self antigens to break tolerance?
This can occur when B cells are not tolerant of the self antigen and T cells are tolerant of the self antigen. The cross-reacting antigen will contain some epitopes that are not the same as self and these will stimulate a T helper response. This later response will provide help for the B cell that is not tolerant to self and cause it to secrete antibody that reacts with self.
Which would be expected to induce tolerance more easily - a soluble protein antigen or a polysaccharide antigen?
What routes of antigen exposure favor tolerance induction?
Whole body, such as intravenous and intraperitoneal. Oral.
What doses of antigen favor tolerance induction?
High doses.
In regard to protein antigens, what form of the antigen is more tolerogenic?
Soluble proteins are tolerogenic, aggregated proteins are immunogenic.
What are the three mechanisms that can be responsible for induction of acquired tolerance?
Clonal deletion. Anergy. Regulatory T cells.
Define type I hypersensitivity.
Allergic reactions due to IgE antibodies attached to mast cells. Interaction with specific antigen results in mediator release from the mast cell.
Define type II hypersensitivity.
Immune reactions due to IgG antibodies interacting with antigens on the surface of cells. The interactions could result in complement mediated lysis or phagocytosis of the antibody coated cell.
Define type III hypersensitivity.
Immune injury that occurs due to deposition of immune complexes in tissues.
Define type IV hypersensitivity.
Immune damage due to the activity of activated Th1 cells. This results in granulomatous inflammation and generation of cytotoxic T cells.
What is the role of the mast cell in type I hypersensitivity?
The mast cell with IgE bound to its surface releases pharmacologic mediators that are responsible for symptoms in the patient. Mast cells also release IL-4 that potentiates the IgE response.
What types of mediators do mast cells release during an allergic attack?
Chemoattractants. Activators (histamine and others). Spasmogens. Lipid mediators.
Name five conditions that are attributed to type I hypersensitivity.
Allergic rhinitis. Acute urticaria. Asthma. Food allergy. Systemic anaphylaxis.
What is the cause of systemic anaphylaxis?
The entry of allergin into the systemic circulation of an allergic patient. This can occur by routes such as injection, insect bite, etc. Mediators of type I hypersensitivity are released in large amounts systemically.
What are the most important target organs for systemic anaphylaxis in man?
The lung, cardiovascular system and gut.
What is the timing of the early response seen during skin testing for allergies?
Within 30 minutes.
What is the timing of the late response seen during skin testing for allergies?
8 hrs and can persist for a number of hours.
What is the main pharmacologic mediator of the early response during an allergic attack and what is the treatment?
Mediator: Histamine. Treatments: Sodium chromoglycate, anti-histamines.
What are the mediators of the late phase type I hypersensitivity response and what is the best treatment?
Mediators: Chemotactic factors - LTB4, platelet activating factor and other cytokines. Treatments: Steroids and indomethacin.
What are the four diagnostic methods used to evaluate the patient with type I hypersensitivity problems?
Clinical evaluation and history. Skin testing. RAST testing. IgE levels - indicate severity of disease.
What is the RAST test? What type of immunological assays can be used for RAST testing?
An in vitro assay that measures IgE antibodies in the serum that bind to specific allergins. Requires a sensitive assay such as RIA or ELISA.
What treatments are available for allergic rhinitis?
Avoid contact with the allergin. Anti-histamines. Hyposensitization with specific antigen.
What are the possible mechanisms of hyposensitization therapy for allergic rhinitis?
Production of IgG blocking antibodies - primary mechanism. Induction of a strong Th1 response. Induction of suppressor cells.
List 4 immunological mechanisms that contribute to type II hypersensitivity reactions.
IgG and IgM antibodies interact with a cell. Lysis of the cell by complement. Phagocytosis of the antibody coated cell. Killing of the cells by the ADCC (antibody-dependent cell-mediated cytotoxicity) mechanism.
List four clinical manifestations of type II hypersensitivity.
Transfusion reactions. Hemolytic disease of the newborn. Hyperacute graft rejection. Drug reactions that result in clearance of RBC or platelets.
List four conditions where type III hypersensitivity plays a role.
Persistent infections Autoimmune diseases - especially collagen vascular diseases. Inhalation of antigens (such as Farmer's lung). Treatment with heterologous antiserum.
What are the mechanisms of injury in type III hypersensitivity?
Deposition of immune complexes. Complement split products cause basophils and platelets to release vasoactive amines. Platelet aggregation and microthrombi. Damage by the enzymes of neutrophils.
What causes the Arthus reaction and when does the peak of the response occur?
Antigen injected into the skin interacts with IgG antibodies. 12 hrs.
What causes serum sickness?
Formation of antigen-antibody complexes in the circulation. Deposition of complexes in vessel walls producing systemic symptoms. Anaphylactic-like symptoms are produced by release of complement split products.
What are the mechanisms that contribute to the damage that occurs in type IV hypersensitivity?
Activation of macrophages. Activation of CD8+ cytotoxic T cells. Granulomatous inflammation.
List two cytokines that are important for the expression of type IV hypersensitivity.
IFN-gamma TNF-alpha
What type of hypersensitivity results in the delayed-type hypersensitivity (DTH) skin test reaction and when does the peak response occur?
Type IV hypersensitivity. 48-72 hours.
What form of antigen is recognized by T cells?
Peptide fragments bound to MHC molecules. No recognition of conformational epitopes.
What form of antigen is recognized by B lymphocytes?
Native, unprocessed antigen. Recognition of conformational epitopes is possible.
What parts of MHC II molecules form the peptide binding groove?
The membrane-distal domains, alpha 1 and beta 1.
What part of the MHC I molecule forms the peptide binding groove?
The membrane-distal domains, alpha 1 and alpha 2.
Antigenic peptides associate with MHC class I molecules in what part of the cell?
Within the endoplasmic reticulum.
Antigenic peptides associate with MHC class II molecules in what part of the cell?
Within the vesicular endosomal compartments.
Name some examples of the source of antigens that are presented by MHC class I molecules.
Endogenous antigens: self peptides, viral peptides, tumor antigens, and intracellular bacteria.
Name some examples of the source of antigens that are presented by MHC class II molecules.
Exogenous antigens that are phagocytized - includes extracellular bacteria and protozoa.
What is the MHC?
A genetic locus. It contains the genetic information for making MHC class I and class II proteins as well as other molecules involved in immunity such as complement proteins and TNF.
What are the names of the three MHC loci in man?
What are the names of the MHC class II loci in man?
Do HLA loci have very few or many alleles?
What is an autograft?
Transplantation of tissue from one site to another site on the same individual.
What is a syngraft (isograft)?
Transplantation of tissue between genetically identical individuals.
What is an allograft?
Transplantation of tissue between genetically dissimilar individuals of the same species.
What is a xenograft?
Transplantation of tissue between members of two different species.
What types of grafts would be expected to experience rejection?
Allografts and Xenografts
What types of immune cells play a major role in graft rejection?
CD4+ and CD8+ T cells
What is meant by the term "first set rejection"?
Rejection of the first graft given to an individual. Is not due to failure of engraftment. Occurs 10 to 21 days after transplantation and is immunologically mediated.
What is meant by the term "second-set rejection"?
Occurs after giving a transplant to a recipient who is already sensitized due to exposure to a previous transplanted tissue. Occurs rapidly - 6 to 8 days after transplantation. Immunologically mediated.
How do the CD4+ cells of a graft recipient become sensitized to the grafted organ?
Exposure to class II antigens of the graft donor that are transferred along with the graft (found on dendritic cells, macrophages, B cells).
How do the CD8+ cells of a graft recipient become sensitized to the grafted organ?
Exposure of the recipient's CD8+ cells to the MHC I molecules on the engrafted tissue.
What is the mechanism for hyperacute rejection of a graft?
A rapid second-set rejection occurs minutes to hours after transplantation. This results from the presence of pre-existing cytotoxic antibodies in the circulation of the recipient.
How do you prevent hyperacute rejection?
Cross-matching of recipient antibodies with donor cells prior to transplantation.
What accounts for chronic rejection of a graft?
T cells and antibodies. May be due to recognition of minor histocompatibility antigens.
Besides graft rejection what is another major concern for patients undergoing bone marrow transplantation?
Graft Versus Host Disease. Immunocompetent T cells in the engrafted marrow recognize antigens of the host and respond to them.
Why is it sometimes beneficial to have a mild form of GVHD to occur in leukemic patients who are treated with a bone marrow transplant?
The GVHD provides an anti-leukemic effect and results in a lower incidence of relapse of the leukemia.
What types of evaluations are done prior to transplantation which will maximize donor-recipient compatibility?
ABO blood group compatibility. MHC class I and class II tissue typing. Cross-matching to detect preformed recipient antibodies.
Which molecules of donor cells are responsible for causing recipient cells to proliferate in the mixed lymphocyte reaction (MLR)?
MHC class II molecules.
What is the name for a tumor antigen that is recognized by cytotoxic T cells and is primarily responsible for rejection of tumors in immunized individuals?
Tumor Rejection Antigen - TRA
Do all tumor antigens elicit immune responses that result in rejection of the tumor?
Name three different categories of changes in the antigens of a tumor cells that might be responsible for expression of new peptide-MHC I that could function as a tumor rejection antigen.
Mutation of a normal antigen (self-protein) Overexpression of a normal antigen (self-protein) Expression of a viral protein
In human medicine, monitoring the blood levels of some oncofetal antigens such as CEA and AFP are useful for?
Establishing prognosis when measured at initial diagnosis. Monitoring the effectiveness of treatment and/or the possible return of disease.
Which immune effector cell is most likely to be responsible for immune surveillance?
NK cell
Which immunological effector mechanisms are most likely to participate in rejection of a solid tumor?
Cytotoxic T cells. NK and LAK cells. Activated macrophages.
What is the primary mechanism used by cytotoxic T cells to kill tumor cells?
Perforin and granzymes.
What are some secondary mechanisms that cytotoxic T cells might use to kill tumor cells?
TNF binding to TNF receptors on the tumor cell. IFN binding to IFN receptors on the tumor cell. FasL binding to Fas on the tumor cell. All of the above cause the cell to go through apoptosis (programmed cell death).
What mechanisms are used by CD4+ Th1 cells to eradicate tumor cells?
Activation of NK cells by secretion of IFN-gamma. Activation of macrophages by secretion of IFN-gamma. Secretion of TNF-beta that can directly kill tumor cells.
What mechanisms are used by NK and/or LAK cells to kill tumor cells?
Perforin + granzymes. TNF. IFN-gamma. NK cytotoxic factor (NKCF).
What mechanisms are used by activated macrophages to kill tumor cells?
TNF-alpha. Reactive oxygen intermediates - hydrogen peroxide, superoxide anion. Reactive nitrogen intermediates - nitric oxide (NO)
What two cell types participate in ADCC?
NK cells. Activated macrophages.
What properties of a tumor cell help it escape the effects of the immune system? (8 properties are possible)
Tumor heterogeneity
What is the specific molecular defect that results in Chronic Granulomatous Disease?
A deficiency or abnormality in one of four different polypeptide chains in the NADPH oxidase system.
What is the inheritance pattern of chronic granulomatous disease?
X-linked and autosomal recessive.
What is the primary immunologic defect in chronic granulomatous disease?
A failure of phagocytic cells to kill microorganisms intracellularly.
What type of repeated infections should be a sign to the clinician to consider examination of granulocyte function?
Staphylococcal skin infections.
What clinical test will evaluate the function of the NADPH oxidase system in polymorphonuclear leukocytes?
The nitrobluetetrazolium reduction (NBT) assay.
Why is the NBT test performed on the mother of a patient with chronic granulomatous disease?
To determine if she is a carrier of the genetic defect - about 50% of her granulocytes will fail to reduce the NBT dye.
What immune deficiency disease is characterized failure of phagosome-lysosome fusion and microtubular function?
Chediak-Higashi Syndrome.
What are the immunologic defects seen in Chediak-Higashi syndrome?
Defects in neutrophils including: Poor chemotaxis. Delayed intracellular killing. Defects in natural killer cell function.
What is the molecular basis for the leukocyte adhesion deficiency?
Absence of CD18 - the beta chain for the beta-integrins (LFA-1, CR3 and CR4).
What are the immunological defects found in Leukocyte Adhesion Deficiency (LAD)?
Lack of leukocyte adhesion. Lack of T cell function. Lack of B cell function.
What is the molecular defect found in X-linked agammaglobulinemia (Bruton's)?
Lack of the gene for Btk (Bruton's tyrosine kinase). This is involved in maturation of the pre-B cell to a B cell.
What are the major immunologic defects found in Bruton's agammaglobulinemia and why do they occur?
Low to no detectible immunoglobulin - all classes. No B cells in the peripheral blood and lymphoid tissues. Lack of the Btk enzyme: Inhibits B cell development.
What is the molecular defect responsible for common variable immunodeficiency?
Probably many different defects are responsible - Exact genes not known at this time.
What clinical and laboratory findings help discriminate between Bruton's agammaglobulinemia and common variable immunodeficiency?
Age of presentation of CVA, which is usually not until late teens. Presence of B cells in the blood of CVA patients. Slightly more immunoglobulin in the serum of CVA patients.
What is the most common form of dysgammaglobulinemia?
Selective IgA deficiency.
If you have a patient who does not have IgA in their serum and also does not have repeated infections, what should you do?
No treatment now. Monitor for increased infection - this may never happen. Check IgG subclass levels - decrease in IgG2 associated with immunodeficiency.
What is the defect that results in the DiGeorge Syndrome?
Failure of development of the third and fourth pharyngeal pouches. Due to deletion of genes on chromosome 22.
What anomalies occur in the DiGeorge Syndrome?
Hypoplastic thymus. Hypoplastic parathyroid glands. Facies. Cardiac anomalies.
What is the major immunologic defect of the DiGeorge Syndrome?
No T cells, therefore no cell-mediated immunity.
What is the major immunological defect in chronic mucocutaneous candidiasis?
Lack of T cell response to antigens of Candida albicans.
What is the major molecular defect in the X-linked form of severe combined immunodeficiency disease (SCID)?
Lack of the common gamma chain shared by several different cytokine receptors - IL-2R, IL-4R, IL-7R, IL-9R, IL-15R.
Why does a deficiency of JAK3 result in severe combined immunodeficiency disease?
JAK3 transmits intracellular signals from the gamma chain that is shared by the receptors for several different cytokines therefore signaling does not occur.
Besides problems with cytokine receptors, name six other defects that result in severe combined immunodeficiency.
Deficiency of the alpha chain of the IL-7R ADA deficiency No MHC class II molecules. RAG-1 and/or RAG-2 deficiency No ZAP70 Deficiency of a nuclear factor needed for lymphocyte signaling. Artemis mutation (defective DNA repair after VDJ and TcR recombination).
Why does a deficiency of adenosine deaminase (ADA) affect the immune system?
Metabolites accumulate that are toxic for T cells and their precursors.
What immunologic defects in purine nucleoside phosphorylase (PNP) deficiency may be different from ADA deficiency?
PNP may lead to an immunodeficiency that affects cell-mediated immunity more than B cell immunity.
What triad of features is characteristic of Wiscott-Aldrich syndrome?
Thrombocytopenia - from birth. Eczema. Immunodeficiency.
What immunologic defects are characteristic of Wiskott-Aldrich syndrome?
Deficiency of IgM with elevated IgA and IgE. Failure to respond to polysaccharide antigens.
What is the genetic defect in Wiskott Aldrich syndrome?
A defect in the gene that makes WASp (Wiskott Aldrich protein). May be involved in polymerization of actin and in other processes.
What disease occurs in children who develop ataxia, have dilated vessels in the sclera of the eyes and have immunodeficiency?
Ataxia telangiectasia
What is the primary immunologic defect in patients who have ataxia telangiectasia?
Selective IgA deficiency.
What is the primary genetic defect in ataxia telangiectasia?
A mutated gene that produces ATM (ataxia telangiectasia mutated protein). ATM is important for protection from ionizing radiation.
If a patient has repeated sinopulmonary infection and/or intestinal infections, what type of immunodeficiency would you suspect?
IgA deficiency or secretory IgA deficiency.
What are the primary immunologic findings in a patient with AIDS?
Elevated immunoglobulin levels. Low CD4+ lymphocyte count. Low CD4/CD8 ratio.
Which anatomic sites of the body contain sequestered antigens?
Eye Cartilage Testes (i.e. spermatozoa)
Name three methods whereby microbial infections could contribute to the initiation of autoimmune disease?
Providing stimulation with cross-reactive antigens. Simulation of T cells with microbial superantigens. Mitogenic and activation effects of microbial products.
If the concept of immunological ignorance is valid as a contributing factor for the development of autoimmunity, what level of antigen presentation would you expect to find in the susceptible individual?
Just below the level where effective immune responses are induced.
During an autoimmune disease, complement levels are sometimes decreased. When would you expect this to happen?
During the time that the disease process is active.
What is rheumatoid factor? In what disease(s) is it found?
RA factor is an IgM antibody that is directed at the Fc region of IgG molecules. It is found in rheumatoid arthritis and in many other autoimmune diseases.
What is the pathogenesis of rheumatoid arthritis?
Macrophages and fibroblasts release cytokines (TNFa, IFN, IL-1, IL-8) that cause damage to the joint. TNFa is the most important.
Which autoantibody is found exclusively in patients with systemic lupus erythematosus?
What autoantibody test is used as a screening test for autoimmune conditions, especially for the collagen vascular diseases?
Anti-nuclear antibodies (ANA)
What organ system(s) is (are) affected in patients with systemic lupus erythematosus?
Many different organs. Most important are brain and kidneys.
What changes can be seen in the kidney of the Lupus patient?
Deposition of immune complexes along the glomerular basement membrane. This occurs in a lumpy, bumpy pattern when viewed by fluorescent microscopy.
Which autoimmune disease results in chronic inflammation of the lacrimal and salivary glands?
Sjogren's syndrome
What types of autoantibodies are specifically associated with Sjogren's syndrome?
Antibodies directed at salivary duct epithelium.
Which autoimmune disease is usually self-limiting, occurs after vaccination and characterized by an immune response to myelin basic protein?
Acute disseminated encephalomyelitis
What are the clinical characteristics associated with Guillain-Barre syndrome?
Progressive weakness of the lower extremities which progressively move up the body. Weakness is greater in the proximal than in the distal limbs.
What is the target for immune attack in multiple sclerosis?
Myelin basic protein (MBP). Proteolipid protein. Oligodendrocyte glycoprotein.
What are significant findings in the spinal fluid of MS patients?
Increased IgG levels, antibodies to measles virus.
What is the immunologic basis for symptoms that occur in myasthenia gravis?
IgG antibodies to acetylcholine receptor block the interaction of acetylcholine with its receptors at myoneuronal junctions.
What type of abnormality in T3 and T4 levels are found in patients with chronic thyroditis (Hashimoto's thyroditis)?
Both are low
What autoantibodies are used to aid in the diagnosis of chronic thyroiditis?
Anti-thyroglobulin - usually with the highest titer. Anti-microsomal.
What is significant about the T3 and T4 levels in patients with Grave's disease?
Both are elevated.
What autoantibodies are used to aid in the diagnosis of Grave's disease?
Anti-thyroglobulin. Anti-microsomal - usually with the highest titer.
What are the target organs in Goodpasture's syndrome?
Lungs and kidneys.
What is the immunological finding in the kidneys of patients with Goodpasture's syndrome?
Antibodies directed at type IV collagen. When studied by fluorescent microscopy, a smooth linear pattern along the glomerular basement membrane is seen in kidney sections stained with fluorescently labeled anti-human IgG.
What is the cause of the RBC defect that occurs in pernicious anemia?
Defective RBC maturation due to malabsorption of vitamin B12 in the gut.
Why is there a deficiency of B12 in patients with pernicious anemia?
Parietal cells in the gut are lost due to immune destruction. These cells produce intrinsic factor which is needed to transport B12 across the small intestine.
What is the immunological basis for the most common form of autoimmune hemolytic disease?
IgG antibodies to RBC membrane proteins cause lysis and/or phagocytosis of RBCs.
Which of anti-RBC antibodies are found in patients who develop hemolytic anemia in association with mycoplasma infections?
IgM, cold agglutinins.
Some patients develop symptoms of RBC hemolysis after coming out of a cold environment into a warm environment. What is the reason for this?
Antibodies attach to RBC in the cold. Interaction of the RBC-antibody complex with complement in the warm environment causes lysis of the RBC.
What is the immunological basis for the disease idiopathic thrombocytopenic purpura?
Antibodies directed at platelets lead to platelet removal by the RES (primarily by the spleen).