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Four types of defensive barriers in Innate immunity: 1) Anatomic 2) Physiologic 3) Phagocytic 4) Inflammatory
What do innate immune defenses have in common? 1) Present intrinsically without previous stimulation 2) Limited specificity for shared structures of microbes 3) Are not enhanced in activity by repeated exposure 4) Limited diversity of expression
What are the main components of the adaptive immune system? 1) Lymphocytes 2) APCs (Macrophages, B cells, and dendritic cells)
What do adaptive immune defenses have in common? 1) Specifity 2) Diversity 3) Enhanced with repeated exposure (memory) 4) Self/non self recognition 5) Self limiting
Antibodies and the complement system enhance: Phagocytosis
Antibodies activate: The complement system
Do cytokines stimulate adaptive or innate responses? Both
Antibodies produced by B-lymphocytes bind to pathogens and assist with phagocytosis. What is this process called? Opsonization
What are the two common progenitor cells which arise from the pluripotent stem cells in the bone marrow? 1) Lymphoid - B, T cells/NK cells 2) Myeloid
How are monocytes identified under the microscope? Kidney bean shaped nucleus
How are macrophages identified under the microscope? Ruffled membrane Cytoplasm with vacuoles and vesicles
Function of monocytes: Phagocytic Differentiate into tissue macrophages
Function of macrophages: Phagocytic Cytokine Secretion
How are dendritic cells identified? Long cytoplasmic arms
Function of dendritic cells: Antigen capture, transport, and presentation
How are neutrophils identified? Multilobed nucleus Small pink granules
What is the function of neutrophils? Phagocytosis Activation of bactericidal mechanisms
How are eosinophils identified? Bilobed nucleus Large pink granules
What is the function of eosinophils? Killing of antibody coated parasites
How are basophils identified? Bilobed nucleus Large blue granules
Function of basophils: Non phagocytic Release pharmacologic substances during allergic responses
Identification of mast cells: Small nucleus Large blue granules in cytoplasm
Function of mast cells: Release of granules containing histamine
Identification of lymphocytes: Large dark nucleus
Function of lymphocytes: B cells produce antibodies T helper cells regulate immune response Cytotoxic T cells kill foreign/ infected cells
Function of NK cells: Kill tumor/virus cell targets Kill antibody coated cells
Identification of plasma cells: Small dark/intensely staining nucleus Golgi apparatus
Function of plasma cells: Produce antibody
The naive B-cell antigen receptors are: IgM and IgD
The T-cell antigen receptor is made of: a and B chains TCR
Membrane bound immunoglobulin is composed of: Two identical heavy chains Two identical light chains
The heavy chains of immunoglobulin molecules are joined by: A hinge region
The hinge regions purpose is Flexibility of movement using disulfide bonds
The unique 3D shape of the N-terminal pocket formed by the light and heavy chains is called: The idiotype
How many idiotypes can be expressed per cell? One
The molecule of the TCR is: Rigid and cell-bound
T cells recognize what type of antigens? Cell-bound peptides
B cells recognize what type of antigens? Unprocessed antigens
The B-cell signal transduction complex is: Ig-a, Ig-B CD19 CD21
The T-cell signal transduction complex is: CD3
Number of combining sites of B-cell antigen receptor: 2
Number of combining sites of T-cell antigen receptor: 1
Which gene segments are combined to form B-cell light chain or the TCR-a chain? V and J
What is the function of the enzyme terminal deoxyribonucleotidyl transferase? Inserts bases randomly at the junctions of V,D, and J Increases variability
What process generates more diversity than the random combination of V,D, and J alone? Tdt being active during the rearrangement of all gene segments in the formation of TCR
Once a functional product has been made: The homologous chromosome is inactivated
Tdt is used as a marker for: Early stage T and B-cell development in ALL
If the cell fails to make a functional protein, it undergoes: Apoptosis
In the light chain, once a functional product has been achieved by one arrangement The cells shuts off the arrangement on the other allele- Allelic exclusion
What is the purpose of allelic exclusion? Ensures that B and T cells synthesize only one specific antigen-receptor per cell
The products of variable domain arrangements are spliced at which level? The RNA level
Somatic hypermutation occur in which type of cells? B cells only, after antigen stimulation
The variable domains code the: Antigen-combining portion of the molecule
The amino acid sequences of all the remaining domains tend to make up the: Constant domain
What are the two isotypes of light chain constant domains of B cells? Kappa and delta
Which cells mediate allergic response? Basophils and mast cells
Plasma cells are the end cells of: B cells differentiation
What are the two chains of the TCR made up of? alpha/beta or delta/sigma
What is the difference between light and heavy chain? The presence of the D region in the heavy chain
A germline B-lymphocyte possesses 200 distinct V region genes, 5 J region genes, and 2 isotypic possibilities to rearrange for its selection of light chain synthesis. How many idiotypes could be produced by combining this sequence with 1 heavy chain? (Assuming there are no recombinational inaccuracies) A) 10 B) 205 C) 400 D) 1000 E) 2000 Answer: V x J = 200 x 5 =1000 (D)
Isotype switching during B cell ontogeny dedicates mature B cells to production of a single heavy chain isotype, except in the case of IgM and IgD, which can be expressed concomitantly. How is this expression of both isotypes simultaneously possible? A) Allelic exclusion B) Allelic codominance C) Affinity maturation D) Alternative RNA splicing E) Somatic hypermutation Answer: D
A 4 year old caucasian boy is brought to his pediatrician with complaints of abnormal bruising and repeated bacterial infection. Blood work reveals thrombocytopenia, neutropenia, and numerous dense small lymphocytes with scant cytoplasm. Immunopenotyping- of the abnormal cells determines them to be extremely primitive B cells, which are CD 19+, HLA-DR+, and Tdt+. Which of the following best describes the status of IgG synthesis most likely in the cells?
A) IgM heavy chains inserted in the membrane B) IgM heavy chains inserted in the cytoplasm C) IgM monomers inserted in the membrane D) IgM monomers present in the cytoplasm E) No Ig chains synthesis present Answer: E- Acute lymphoblastic Leukemia
A woman with AML is treated with chemotherapy and undergoes remission. The prognosis for relapse is high, bone marrow transplant is undergone in the first remission. Which cytokines administered would have the result of stimulating lymphoid cell development of stem cell? A) IL-1 B) IL-2 - T cell proliferation C) IL-3 -Myeloid precursor D) IL-6 - acute phase proteins E) IL-7 Answer: E
2 year old boy with severe combined immunodeficiency disease. Normal cellularity of bone marrow Normal number of T cell precursors entering the thymus, but no normal T cells in peripheral blood Cells populating the thymus lack CD3 Which of the following capabilities would the cell lack? A) Binding cell-bound peptides B) Expresing CD4/CD8 receptors C) Producing Tdt D) Proliferation in response to antigen E) Regeneration of T cell receptor segments Answer: D
What are the primary lymphoid organs? 1) Bone marrow 2) Thymus
What are the secondary lymphoid organs? 1) Spleen 2) Lymphoid 3) MALT
Clonal anergy and deletion produce: Self-tolerance
What is clonal deletion? Deletion of cells whose idiotype has too great an affinity for normal cellular molecules Occurs in the bone marrow
What is clonal anergy? Inactivation of cells whose idiotype has too great an affinity for normal cellular molecules Occurs in the periphery
The thymus consists of two main parts: 1) Cortex -outer, full of immature T cells 2) Medulla - T cells passes it as they mature
The cortex and medulla are laced with what types of cells? Epithelial cells Dendritic cells Macrophages
Why is a selection process required to remove certain cells during maturation? TCR is designed to bind antigenic peptides and it must be confirmed that the TCR will recognize normal self antigens Prevent autoimmunity
How is the selection process for developing thymocytes done? Exposing these cells to high levels of a unique group of membrane bound molecules called MHC molecules
MHC 1 gene poducts: HLA-A HLA-B HLA-C
MHC 2 gene products: HLA-DP HLA-DQ HLA-DR
Class 1 cells are expressed in what fashion? Codominant
What makes up MHC 1 molecules? alpha chain plus beta2 microglobulin
MHC 1 molecules are present in: all the nucleated cells of the body
What is the function of beta2 microglobulin? Transport of the class 1 antigen to the cell surface
MHC 2 molecules are expressed in what fashion? Codominant
MHC 2 molecules are present in: APCs
MHC 2 molecules are made up of: alpha and beta chains
A groove that will accommodate peptides to be presented to the TCR is formed where? At the N terminal ends
Cells with good receptors capable of binding with low affinity receive: Positive selection
Cells with useless receptors which refuse to bind self-MHC recieve: No positive selection
The cells that bind too strongly to self MHC molecules will recieve: Negative selection Undergo apoptosis
What are the two accessory molecules expressed on the surface of immature thymocytes? CD4 and CD8
What is the purpose of the accessory molecules expressed on the surface of immature thymocytes? Stabilize the interaction between MHC and TCR
Cells express only CD8 if their TCR binds: MHC1
Cells express only CD4 if their TCR binds: MHC2
CD4+ cells that recognize class 2 MHC T-helper cells
CD8+ cells that recognize class 1 MHC Cytoxic T cells
What happens to 99% of all T-cells going to the thymus? They die
8-year old boy diagnosed with ALL. Flow cytometry is used to determine the immunophenotype of the malignant cells. Patients cells are evaluated with monoclonal Abs for MHC 2, CD19, and D34. High levels of flourescence with ALL of these markers What is the developmental stage of these cells? A) Immature B cell B) Lymphoid progenitor cell C) Mature B cell D) Pre B cell E) Pro B cell Answer: D
Blood from 8 year old boy analyzed by flow cytometry. these cells are treated with fluorescent-labeled Ab's to various cell surface markers before they were evaluated by flow cytometry. Which of the following markers would identify the B lymphocytes? A) CD3 - T cells B) CD4 -TH cells C) CD8- Cytotoxic cells D) CD19 E) CD56-NK cells Answer: D
Markers for identification of B lymphocytes: 1) CD19 2) CD20 3) CD21
18 year old member of soccer team seen by a physician because of chest tightness and dyspnea on exertion. 15cm mediastinal mass is detected readiographically. 80% of WBCs in peripheral blood are small, abnormal with lobulated nuclei and scant cytoplasm. Immunophenotyping of the abnormal cells shows them to be CD4 and CD8. Where would such cells normally be found in the body? A) BM B) Peripheral blood C) Thymic cortex D) Thymic medulla E) Splenic periarteriolar lymphoid sheaths Answer: C
A 12-year old child is diagnosed with a T-cell lymphoma. The phenotype of the malignant cell matches that of normal progenitor cells that leave the BM to enter the thymus What surface cell markers do you expect to find on the malignant cells? A) CD4-,CD8-,TCR- B) CD4-,CD8-,TCR+ C) CD4-,CD8+,TCR+ D) CD4+,CD8-,TCR+ E) CD4+,CD8+,TCR+ Answer: A
Herpes simplex viruses are extremely successful pathogens because they have a variety of immunologic evasion mechanisms. For example, both HSV1 and 2 depress the expression of MHC class 1 molecules on the surface of infected cells; Which coreceptors binding would be inhibited by this technique? A) CD2 B) CD4 -MHC 2 C) CD8 D) CD16 E) CD56 Answer: C
Pararteriolar lymphoid sheaths contain which cells? T cell areas
What structures make up the red pulp? Vascular sinusoids
Naive lymphocytes enter the lymph nodes and leave the blood from the: High endothelial venules
This migration of naive lymphocytes to the lymph nodes involves a multistep sequence of: interactions between the lymphocytes and adhesion molecules on the endothelium
The initial low-affinity interaction between lymphocytes and adhesion molecules is mediated by: Homing receptors, called L-receptors
L-selectins bind to: Adressins present on the HEVs
Lymph node biopsy of 6 year old boy shows markedly decreased numbers of lymphocytes in the paracortical areas. Analysis of his peripheral blood leukocytes is likely to show normal to elevated number of cells expressing surface: A) CD2 B) CD3 C) CD4 D) CD8 E) CD19 Answer: E
65 year old woman involved in an automobile accident that necessitated the removal of her spleen To which of the following pathogens would she have the most susceptibility? A) Babesia microti B) Bordatella pertussis C) Corynebacterium diphteria D) Enteroaggressive E.coli E) HPV Answer: Blood borne antigen (A)
4 year old boy reffered to a specialist for the diagnosis of a possible immunologic problem. Child has extremely electaed WBC counts with profound lymphocytosis. A biopsy performed on the cervical lymph nodes shows extreme hypocellularity in both cortical and paracortical areas. Absence of which of the following of leukocyte surface molecules could result in this clinical picture? A) Adressins B Chemokines C) Ig family cell adhesion molecules D) Integrins E) L-selectins Answer: E
6 year old child taken to his pediatrician because of an indurated fluctuant mass on the posterior aspect of his neck. the mass is nontender and shows no signs of inflammation. No other masses are found. Biopsy submitted to pathologist. Pathologists reports back that the mass is a lymph node with increases cells of the cortical area. Flourescent antisera to which of the cell surface markers is most likely to bind to these cells? A) CD2 B) CD3 C) CD4 D) CD16 E) CD19 Answer: E
A radioactive tracer dye is injected SC into the forearm of an experimental subject. What is the first area of the first draining lymph node that would develop significant radioactivity? A) Cortex B) Medulla C) Paracortex D) Primary follicle E) Subscapular sinus (after afferents --> this --> cortex --> paracortex-->medulla) Answer: E
For a molecule to be an immunogen, it needs to fit three basic criteria: 1) Foreign 2) Chemical complexity 3) MW of 5000-10000 K
Antigen and immunogens can both initiate: an immune response
The portion of the immunogen that has 3D complementarity with the idiotype is: Epitope or antigenic determinant
B lymphocytes can only be activated when their antigen receptors are cross-linked by the accommodation of: More than one identical epitope
Molecules that possess only one epitope are called: Haptens
T lymphocytes recognize: 1) Peptides 2) 10-20 aas 3) ONLY when presented to them in MHC
Drugs allergies can be induced with small doses of the drug because: They act as haptens and can become conjugated to body proteins, serving as the immunogen
What is the first response to antigen invasion? Acute inflammatory response
What is the first step of acute inflammatory response? Vascular endothelium in the breached epithelial barrier activation Cytokines and inflammatory mediators released in the area
Cytokines increase expression of: Selectin-type adhesion molecules
The first cell to bind to the inflamed endothelium: Neutrophils Peak within 6 hours
In response to neutrophil-released mediators, what cells arrive? Monocytes Macrophages Eosinophils
The extravasation of phagocytes into the area requires four, sequential overlapping steps: 1) Rolling 2) Activation of chemoattractants 3) Arrest and adhesion 4) Transendothelial migration
Details of the first Rolling step: Phagocytes attach loosely to endothelium by selectin -carbohydrate interactions E-selectin molecules on endothelium bind to mucin-like adhesion molecules Blood flow causes the cell to detach and reattach- rolling to find stronger forces
Details of the step involving activation by chemoattractants: Chemokines released in the area during inflammation- IL-8 Complement split product C5a and N-formyl peptides produced by bacteria bind to phagocyte surface Trigger G mediated activating signal Conformational change integrin> increased affinity for Ig
Details of arrest and adhesion: Interaction between integrins and Ig superfamily cellular adhesion molecules (Ig-CAMs) stabilizes adhesion of the phagocytes to the endothelial cell
Transendothelial migration: The phagocyte extends pseudopodia through the vessel wall and extravasates into the tissue
Leukocytes ahdesion deficiency: *Rare autosomal recessive disease *Absence of CD18 --> common B2 chain of a number of integrin molecules *Inability of the leukocytes to undergo adhesion dependent migration into sites of inflammation *Abcess and pus fomation do not occur
Substances chemoattractive to neutrophils are: 1) IL-8 2) C5a 3) Fibrenopeptides 4) Leukotriene B4 5) Formyl methionyl peptides
Origin of chemokines: Tissue mast cells Platelets Neutrophils Monocytes Macrophages Eosinophils Basophils Lymphocytes
Origin of C5a: Endothelial damage --> acitvation of Hageman factor --> plasmin activation
Origin of Fibrinopeptides: Endothelial damage --> acitvation of Hageman factor --> thrombin --> fibrin clot degradation
Origin of Leukotriene: Membrane phospholipids of marophages, monocytes, neutrophils, mast cells --> arachadonic acid cascade --> lipoxygenase pathway
Origin of formyl methionyl peptides: Released from microorganisms
Phagocytosis involves: 1) Extension of pseudopodia 2) Formation of phagosome 3) Fusion with lysosome to form phagolysosome 4) Digestion 5) Exocytosis
Opsonins are: 1) IgG 2) C3b
The respiratory burst activates a: Membrane-bound oxidase that generates oxygen metbolites, which are toxic to ingested microorganisms
Two oxygen dependent mechanisms of intracellular digestion are activated as a result of this process. What ae they? 1) NADPH oxidase 2) Myeloperoxidase
Function of NADPH oxidase: reduces oxygen to superoxide anion, which generates hydroxyl radical and hydrogen peroxide which are microbicidal
Function of Myeloperoxidase: Act on hydrogen peroxide and chloride ions to produce hypochlorite, which is microbicidal
Lysosomal contents of phagocytes contain oxygen-independent degradative materials: 1) Lysozyme --> digests bacterial cell walls by cleaving peptidoglycan 2) Defensins 3) Lactoferrin - chelates iron 4) Hydrolytic enzymes
Chronic granulomatous disease: Inherited deficiency in production of one of the subunits of NADPH oxidase Eliminates the phagocyte's ability to produce critical oxygen dependent intracellular metabolites Recurrent infections with catalase positive organisms Detected by NBT or NOI
Rabbit hunter in Arkansas diagnosed with ulceroglandular tularemia and treated with streptomycin. Within a week, he returns to the hospital. The tularemic papule, lymphadenopathy, and bacteremia have resolved-> developed a raised, itching skin rash, fever The drug was discontinued, and the symptoms subsided. What was the role of streptomycin in this case? A) Acted as a B-cell mitogen B) As a hapten C) Acted as a provider of costimulatory signals D) As a superantigen E) As an immunogen Answer: B
During WW2, when quinine was used as a prophylactic against malaria in soldiers, a small portion of soldiers developed blackwater fever (KD from the autoimmune effects of complement hemolysis). In this case, quinine played the role of: A) Auotantigen B) Carrier C) Hapten D) Immunogen E) Reagin Answer: C
2 year old child has suffered recurrent bacterial infections and is evaluated for immunologic deficiency. The child has age normal numbers of CD19 and CD3 in the peripheral blood, and extreme neutrophilia. The nitroblue tetrazolium dye reduction test is normal. What is the most likely defect in this child? A) Absence of CCR4 B) Absence of CD18 C) Absence of IL-1 D) Absence of IL-4 E) Absence of TNF-a Answer: B - LAD
Absence of CCR4 would cause: Difficulty in extravasation and migration of activated T cells and monocytes Not found on neutrophils - no effect on them
Absence of CD18 would cause: Leukocyte Adhesion Deficiency Inability of WBCs to migrate to sites of inflammation
Absence of IL-1 would cause: Difficulties in producing the acute and chronic inflammatory response Similar to TNF and IL-6 so might not show side effects
Absence of IL-4 would cause: Defects in the ability to mount a normal IgE Ab response Development of TH2 from naive TH cells
Absence of TNF-a would cause: Difficulty in acute and chronic response Same as IL-1
2 year old boy is admitted to the hospital for workup of a possible immunological disorder. History is remarkable for the occurrence of multiple skin infections. On examination, the child has cervical lymphadenopathy and mild hepatosplenomegaly. Blood tests reveal an elevated erythrocyte sedimentation rate and neutrophilia. NBT dye reduction test and NOI are negative. Most likely defect in A) C3 B) CD18 C) Myeloperoxidase D) NADPH oxidase E) Phagocyte granule structural defect Answer: D
Catalase positive bacteria: 1) Staph 2) Pseudomonas 3) Candida
in animal experiments there are advantages to eliciting non-specific inflammation at the site of inoculation of antigen toward the ultimate development of protective immune response to that immunogen. Which of the following substances if introduced with a vaccine would serve the purpose of attrating a neutrophilic infiltrate into the area? A) C3b B) IgG C) IL-8 D) Myeloperoxidase E) TNF-a Answer: IL-8
What is the function of APCs? Load partially degraded peptides they have ingested into the groove of the class 2 MHC molecules, so that they can be presented to T cells Endosomal (exogenous) pathway
When MHC2 molecules are produced in the ER of an APC what chains are produced? a and B chains Invariant chain
What is the function of the invariant chain? Blocks the peptide binding groove so no normal peptides are accidentally attracted there
MHC 1 molecules are loaded with peptides via which pathway? Endogenous pathway
MHC 1 molecules present small peptides in the groove at its: N-terminal These pepcytes are from the endogenous oathway
Proteins synthesized in the cell cytosol are routinely degraded in proteosomes and these are transported to into the ER by: A peptide transporter known as the TAP complex
Does MHC 1 have an invariant chain? No
Does MHC1 have B2 microglobulin? Yes, but MHC2 doesn't
APCs with MHC2 molecules travel to: Secondary lymphoid organs
Dendritics cells are: Long, finger-like processes The most efficient APC
What is the first signal for the naive T cell to begin its activation? Binding of TCR to the MHC 2-peptide complex
What is the second signal? Co-stimulatory molecules on the APC secrete cytokine and induce the clonal expansion of T cells into effector and memory cells
What are the second signal costimulatory molecules? CD4 --> which binds MHC2 CD8 --> MHC1 LFA-1 (Integrins) --> IgCAM-1 IgCAM (CD2) --> LFA-3 CD28 --> B7
What is the most important growth factor for T cells? IL-2
What are the third signal cytokines involved in T cell activation? IL-2 IL-1 IL-6 TNF-a
What are superantigens? Viral or bacterial proteins that cross-link the variable B domain of a TCR to an a-chain of a MHC 2 molecule
What function does the cross-linkage made by superantigens serve? Provides an activating signal that induces T cell activation and proliferation. in the absence of antigen-specific recognition peptides
Which substances are over-produced by superantigen activation of T cells? IFN-y --> macrophages --> IL-1, IL-6, and TNF-a These excess amounts cause systemic toxicity
Which molecules tend to act as superantigens? Staph enterotoxins Toxic shock syndrome toxin-1 Streptococcal pyrogenic exotoxins
What are the effector mechanisms controlled by the TH cells? 1) Antibody synthesis 2) Macrophage acitivation 3) Cytotoxic T-cell killing 4) NK cells killing
What is Bare Lymphocyte syndrome? MHC class 2 molecule deficiency *Inherited autosomal recessive *Increased susceptibility to infections * CD4 deficiency
What are the two major classes of TH cells which rise from TH0? TH1 TH2
Microbes that stimulate a strong innate immune response with resultant production of IL-12 by macropages or IFN by Nk cells stimulate which TH cell? TH1
Absense of such an innate immune stimuli stimulates production of: TH2
In response to allergens which TH cell is stimulated? TH2
Which cytokines do TH1 cells produce? IFN-y TNF-B IL-2
Which cytokines do TH2 cells produce? IL-2 IL-4 IL-5 IL-6 IL-10
Which cytokines inhibit TH2? IFN-y
Which cytokines inhibit TH1? IL-4 and IL-10
Difference between tuberculoid and leptromatous leprosy: Tuberculoid --> stimulates TH2 Lepramatous --> TH2
Human infections with Mucobacterium leprae express many clinical presentations depending on the immune response of the IC organism. Patients with tuberculoid leprosy produce an effective cell-mediated immune response, which kills the IC organisms but produce tissue damage. These patients have granulomas with elevated IL-2, IFN-y, and TNF-B. Which immune cells is responsible for this? A) Cytotoxic T B) Epitheloid C) Macrophage D) TH-1 E) TH2 Answer: D
Immunologic pathway that distinguishes the selection between the two forms of leprosy depends on the initial means of antigen presentation and different immune response. If these events elicit production of IL-4. IL-5, IL-6, and IL-10,lepromatous leprosy Will result in failure to mount protective delated hypersensitivity. What characteristic is predicted based on the cytokines produced? A) Autoimmunity B) Granuloma formed C) Hyper-y-emia D) Immediate hypersensitivty E) Inflammation Answer: C
10 year old infant girl with signs of Pneumocystis carinii pneumonia. Peripheral blood tests demonstare age normal counts of CD 19+, but CD and CD4 depressed. Immunoelectrophoresis shows moderate hypogammaglobulinemia. Lymphocytes proliferate normally with phytohemagglutinin and MHC 1. Allogenic T lymphocytes do not proliferate. Which describes the molecule lacking? A) Binds endogenous peptides B) Binds exogenous peptides C) Posess B2 D) Two unequal chains E) On all nucleated cells Answer: B
Elderly man with diabetes develop a blister on his foot,which becomes infected. Wound is cleaned and treated with topical antibiotic ointment, but he develops a fever and hypotension and desquamating rash spreads from the site of the original blister How does the toxin responsible cause these signs? A) Activates IL-1 homologue B) Activates B cell polyclonally C) Activates complement D) Cross links MHC class 2 to TCRs E) Stimulates neutrophils Answer: D
Proliferation and differentiation of T-lymphocytes in response to tumor cells is low because tumor cells lack co-stimulatory molecules. If melanoma cells were induced to express these molecules, antitumor response might occur. Which of the following molecules would be the best choice for transfection of these tumor cells? A) B7 B) CD2 C) CD4 D) CD28 E) LFA-1 Answer: A
What is the main component of humoral immunity? Antibodies
B-lymphocytes are attracted to which organs? Follicular areas of secondary lymphoid organs
Most pathogens are what type of antigens? Thymus-dependent antigens Response to these molecules requires the direct contact of B cells with TH cells and their cytokines
What are the requirements of B cell contact with TH cells? 1) MHC 1 2) Costimulatory molecules (B7) 3) CD 40/40L binding
What are the characteristics of thymus independent antigens? 1) Contain no peptides- lipolysaccharides and polysaccarides 2) Only stimulate IgM 3) Create no memory
How is the response for these antigens stimulated without TH cells? By directly stimulating B cells May act as B-cell mitogens (which activate clones of B cells and are used to assess lymphocytes function)
Idiotypes determine antigen specificity and isotypes: dictate the effector function
Isotype switching is directed by which cells? TH2
If an AB is digested with papain, where does cleavage occur? Above the disulfide bonds that hold the heavy chains together
What three fragments are formed after digestion with papain? 2 Fab fragments 1 Fc fragment
Cleavage of the Ab with pepsin generates what fragments? One large F(ab2 fragment Digested Fc frafments
What is the function of Fab? Binding
What is the function of F(ab)2? Binding and bridging
Which is bridging of antigens by Abs important? It is required for agglutination of particulate antigens or the precipitation of soluble antigens
What is the first isotype of Ig that can be produced by a B cell? IgM
IgM exists as what type of structure? Pentamer
The monomer units of the IgM molecule are held together by: A J chain
How many epitopes can be bound by IgM simultaneously? 10
What is the function of IgM? Trapping free antigens - Most effective Ig
IgM provides the highest avidity, but low: Affinity
What is the most effective isotype in activating complement? IgM
At what point can a cell never produce IgM again? Once it undergoes isotype switching by TH2 cells Because excised DNA is degraded
IgM is used as a measure of: Primary response
Convalescent serum will contain mostly, which immunoglobulin? IgG
What are germinal centers? Clones of proliferating antigen-specific B cells
What does somatic hypermutation cause? Single point mutations in the antibody idiotype If these mutations give them higher affinity, these cells are at an advantage Clones with higher affinity will predominate
Predominance of clones with increased affinity for an antigen is called: Clonal selection
The process of increasing affinity for the antigen is called: Affinity maturation
In these cells, affinity increase, but avidity: decreases
Antibodies in order of abundance: GAMDE
What is X-linked Hyper-IgM syndrome? Deficiency of IgA, G, and E and ellevated M X-linked recessive Fail to make germinal centers Susceptible to Pneumocystis carinii infection Defect in gene coding CD40 L
What is the major antibody after IgM? IgG
How many subtypes does IgG have? 4
What is the function of IgG? Activates complement Opsonization Mediates ADCC
Which immunoglobulin is actively transported across the placenta? IgG
Where is most IgA produced? In the submucosa rather than in the lymph and spleen
What is the structure of IgA? Dimer with a J chain
What is the function of IgA? Inhibits binding of adhesive substances to mucosal surface Important component of breast milk
IgE is bound to which types of cells? Mast cells Basophils
What reactions does IgE mediate? Immediate type 1 allergic reactions
IgE protects against which foreign bodies? Parasites
Clinical manifestation of immunodeficiencies involving B lymphocytes: *Recurrent pyogenic infections with extracellular pathogens *Absence of Igs for opsonization and complement activation *T-cell immune system in-tact
Which antibodies act in complement activation? IgM and Ig
Which antibodies are on the naive B-cell antigen receptor? IgM and IgD
What Abs are on the memory B-cell antigen receptor? IgG, IgA, and IgE
What are the functions of the complement system? *Enhances inflammation *Enhances phagocytosis *Causes lysis
What is the more primitive pathway of the two complement system activation pathways? Alternative pathway
The alternative pathway is initiated by: surfaces of pathogens C3b + Bb (C3 convertase) --> C3bBb3b(C5 convertase) --> C5b *MAC)
The classical pathway is activated by: Ag/Ab complexes Ab --> C4b, C2a, C3b, C5b --> MAC
Physiologic controls on complement activation act at the level of: C1, C3, and C5
Clinical manifestations of complement deficiencies: *Uncontrolled activation of the complement cascade *In hereditary angioedema, uncontrolled complement causes edema and pain In paroxysmal nocturnal hemoglobinuria, the absence of regulatory proteins --> hemolysis of RBCs
Ab preparation is being used in lab protocol to study B lymphocytes. Preparation does not activate the cells or cause capping, does not cause precipitation of its purified ligand, or cause agglutination of latex beads covalently coupled to its ligand. Which of the following is the most likely Ab preparation? A) Monoclonal anti-CD-19 IgG B) MC anti-CD56 IgG C) Papain treated anti-CD19 IgG D) Papain anti CD56 IgG E) Pepsin treated anti-CD19 IgG F) Pepsin anti-CD56 IgG Answer: C
IgM isohemaglutinins from an individual of blood group A are treated with pepsin. When the product of this reaction is added to group B erythrocytes, they will be: A) Agglutinated B) Lysed C) Phagocytosed D) Precipitated E) Unaffected - if papain is used Answer: A
A 26 year old obstretic patient becomes ill during the first trimester of pregnancy with fever and lymphadenopathy. Rising titer of anti-Toxoplasma gondii Abs. Full term baby delivered with no apparent signs of utero infection. The best test to diagnose acute infection in the neonate would be a parasite specific ELISA for which isotype? A) IgA B) IgD C) IgE D) IgG E) IgM Answer: E
4 year old boy is evaluated for possible immunologic deficiency. He has suffered repeated infections of mucosal surface pathogens. Delayed development of protective responses to the standard childhood vaccination. Immunoelectrophoresis of his serum shows absence of macroglobulin. Sputum devoid of secretory IgA. Normal IgM, IgA, IgEm and IgG. Which deficiencies account for these findings? A) CD40 B) J chains C) Il-4 D) Tdt E) TH2 Answer: B
56 year old homeless, alcoholic, febrile man. Brought to ER after coughing all night. On arrival his pulse is rapid, breathing is labored, Endotracheal aspirates produce a mucopurulent discharge containing gram +ve cocci in chains. Serum high in IgM Abs Strep pneumonia. Effector mechanism lost likely to act in concert with early IgM production to clear infection is: A) ADCC B) Complement mediated opsonization C) Cytotoxic T lymphocytes D) LAK cells E) NK cells Answer: B
3 year old boy has several bouts of pneumonia. Strep pneumonia was isolated and identified in each of the cases. Child treated with penicllin and the condition resolved. Now being evaluated for deficiency. Normal values for Ig isotypes Serum levels of some components of complement are depressed. Which of the following deficiencies could explain his problem? A) C1 B) C2 C) C3 D) C4 E) C5 Answer: C
the cell mediated arm of the immune response (CMI) are designed to kill what pathogens? INTRACELLULAR
TH1 cells stimulate which cells? 1) Macrophages 2) CTLs 3) NK cells Killing is enhanced by IFN-y, TNF-a, and TNF-B
How is TH1 function measured? DTH skin test Delayed type hypersensitivity
Clinical manifestations of MHC class 1 deficiency: Deficiency of CD8 Ab responses may be higher than usual because of absence of inhibitory responses (IFN-y)
CTL stimulation requires: Class 1 MHC CD28-B7 IL-2
Steps of cytoxic T cells killing cells: 1) Attachment by TCR, CD8, and LFA-1 2) Activation 3) Exocytosis 4) Detachment
CTLs kill with what substances? 1) Perforins 2) Cytokines 3) Granzymes 4) Fas/FasL
Function of NK cells: 1) Kill tumor cells and virus-infected cells 2) Kill by granzymes and perforin
NK cells are enhanced by: IFN-a, IFN-B, and IL-12
NK cells are inhibited by: MHC class 1
NK cells are counted with which other cells? CD16 and CD56
Cells included in antibody dependent cell-mediated cytotoxicity: 1) NK cells 2) Macrophages and monocytes 3) Neutrophils 4) Eosinophils
NK cells recognize their targets via which Ab? IgG
ADCC cells kill by: Lytic enzymes TNF Perforin
CD markers of CTL cells: TCR CD3 CD8 CD2
CD markers of NK cells: CD16 CD56 CD2
CD markers of macrophages: CD14
Effector molecules of CTL and NK cells: Perforin Granzymes Cytokine (TNF-B. IFN-y)
Effecotr molecules of macrophages: TNF-a Enzymes NO Oxygen radicals
How do viruses evade CMI? Block host cell protein synthesis, specifically MHC class 1 synthesis, transport, and expression However the second CMI response is NK kiling Exception to this rule is CMV
62 year old accountant develops a solid tumor that is unresponsive to chemotherapy. Participates in experiment to stimulate his own immune effector cells to recognize and kill the malignant cells. Tumor cells have no expession of MHC class 1 antigens. Which of the following in vitro treatments stimulates the most effective immune response when reinfused into the patient? A) IFN y B) IL2 C) IL8 D) IL10 E) TNF-B Answer: A
Toxoplasma gondii is an IC parasite that lives inside phagocytic and non phagocytic cells by generating its own IC vesicle. This may allow it to avoid recognition and killing by CD8 lymphocytes, which require the presentation of foreign peptides transported into the ER and loaded onto MHC molecules that have: A) a B2 domain instead of a B2 microglobulin B) Invariant chains C) Peptide-binding groove D) Single transmembrane domain E) Two similar chains Answer: D (MHC 1)
Children with enlarged thymus glands were frequently irradiated to functionally ablate this organ. Over the lifetime of such individuals which of the following conditions was likely to develop? A) Depressed immune surveillance of tumors B) Depressed oxygen dependent killing by neutrophils C) Depressed primary response to soluble antigens D) Increased cellularity of lymph node paracortical areas E) Increased tendency to atopy Answer:A
42 year old Nigerian man in the US comes into the hospital clinic. Complains of several months of weight loss, night sweats, mild sputum production, and hemoptysis. You run a PPD skin test and the rests are +ve What can you conclude from this result? A) CMI response has occured B) Humoral immune response has occured C) B-cell system is functional D) B and T-cell systems are functional E) Neutrophilic phagocyte system is functional Answer: A
Immunologic memory is generated when? As pathogens are eliminated
Memory B cells have what Abs on their surface? IgG, IgA, or IgE
Function of Activation induced cell death: Removal of activated T cells after the primary response Mediated through the Pas pathway
Memory cells return to the tissue where: they first ecountered antigen
Effector cells tend to return to areas of: Areas of active inflammation because of their expression of cell adhesion molecules such as LFA-1
Time lag after immunizations of primary and secondary responses? Primary - 5-10 days Secondary-1-3 days
Antibody isotype of primary and secondary responses: Primary- IgM, then IgG Secondary - IgG, IgA, or IgE
Antibody affinity of responses: Primary: Variable to low Secondary - High
Inducing agent of responses - Primary- All immunogens Secondary- proteins antigens
Immunization protocol of responses: Primary- high dose of antigen with adjuvant Secondary - low dose of antigen without adjuvant
What are the MALT? Mucosal associated lymphoid tissues The tonsils and Peyer patches
What is the function of the secretory component of secretory IgA? Transepithelial transport Protection from proteolytic cleavage
What is the secretory component? Polyimmunoglobulin receptor
A patient is suffering from lymphadenopathy and splenomegaly. He has increased lymphocytes, less platelets, and autoimmune anemia. When his peripheral blood leukocytes are exposed to T cell mitogens, they proliferate wildly for weeks. Which of the following is most likely to be the genetic defect? A) Absence of complement B) Absence of Fas C) Absence of IFN-Y D) Absence of perforin E) Absence of TNF Answer: B
Tonsillectomies were routinely performed on children with swollen tonsils. This procedure has lost its appeal as MALTs are important in the protective immune response. What is the major immunoglobulin produced by the MALT? A) Dimeric Ig with secretory component B) Monomeric Ig crosses the placenta C) Monomeric Ig bound by mast cells D) Monomeric Ig that opsonizes E) Pentameric Ig activates complement Answer: A
In a lifetime, a person may recieve a dozen or more tetanus toxoid inoculations. When boosters are administered at 10 year intervals, which of the following would be true of the B lymphocytes that respond? A) Their receptors would have high avidity B) They would be large and highly metabolic C) Would have low levels of adhesion molecules D) Surface IgG, IgA, or IgE E) Surface IgM Answer: D
64 year old man undergoes surgery to excise 18 inches of bowel with adenocarcinoma. When the tissue is examined, the Peyer patches are noted to be hyperplastic with IgA-secreting plasma cell, but there is no secretory IgA in the lumen of the colon. Which of the following changes in the bowel epithelium would explain this? A) Failed isotype switching B) Failed variable domain gene-segment rearrangement C) Loss of J chain synth. D) Loss of poly-IgG receptor E) Loss of TH2 cells Answer: D
Immunologic lab is studying migration patterns of different lymphocytes subpopulations. One population of small nondividing lymphocytes which are CD3 and CD4 and express low IL-2 levels, but high levels of LFA-1, labeled with radioactive marker. What type of cell has been labeled? A) A blast cell B) Memory T cell C) Activated T cell D) A naive T cell E) An effector T cell Answer: B
Natural immunity is acquired through: Passive means - Placental IgG transport/colostrum Active means- Recovery from infection
What are the risks of passive immunotherapy? 1) IgE production causing systemic anaphylaxis 2) IgM or IgG anti-isotype Abs which an lead to type 3 hypersensitivity reaction 3) Anti-allotype Abs
Live viral vaccine should not be given to immunocompromised patients because: Even attenuated live viruses could cause significant pathology in these individuals
Clinical importance of natural and passive immunity: 1) Presence of maternal Abs affects vaccinations 2) Infant has 20% adult IgA at 12 months so colostrum is imp 3) IgM only isotype useful for diagnosing neonate infections 4) Normal infants have few infections 5) Immune-def infants don't show
Haemophilus influenza type B vaccine is dependent on: T-cells
Living viral vaccines elicit which immune responses? Cell mediated Humoral Mediated
Killed viral vaccines elicit which immune response? Antibodies
Hepatitis B vaccine is what type of vaccine? Recombinant Antigen Vaccines
Experimental vaccine strategies: 1) DNA vaccines 2) Recombinant vaccine
Artificial immunity is acquired through: Passive means - Horse antivenin against black widow spider and snake bite Horse antitoxin against botulism, diptheria Pooled humman Ig versus Hep A and B, measles, rabies, or tetanus Active means -Vaccines
What are adjuvants? Substances that increase the immunogenicity of an antigen when administered with it
What effects do adjuvants exert? 1) Prolonging antigen persistance AlKSO4 2) Enhancing costimulatory signals-muramyl dipeptide 3) Inducing granuloma formation - alum 4) Inducing nonspecific lymphocyte proliferation -LPS
A 10 year old child was bitten by a stray dog. The child is started on a course of inoculations of pooled human antirabies IgG. Repeated inoculation of this Ig preparation is likely to induce? A) Anti-allotype Abs B) Anti-epitope Abs C) Anti- idiotype Abs D) Anti-isotype Abs E) Anti-rabies Abs Answer: A
All residents of a nursing home are inoculated IM with an H3N2 influenza A preparation. The goal of this protocol is to stimulate which of the following types of immunity? A) Adaptive B) Artificial active C) Artificial passive D) Natural active E) Natural passive Answer: B
A sanitation worker is struck by a car and his leg is crushed against his sanitation truck. The trauma necessitates amputation above the knee. Although the man took a tetanus booster 6 years ago, he was revaccinated. Human pooled , anti-tetanus Ig injected around the macerated tissue. Administration of Ig is an example of which type of immunization? A) Adaptive B) Artificial active C) Artificial passive D) Natural active E) Natural passive Answer: C
28 year old man brought into court for not paying child support. 20 year old insists he is the father. the court suggests before the hearing that genetic tests are performed on the mother, father and child. One of the tests was for genetic Ig Which immunoglobulin marker would be useful in this case? A) Allotype B) Idiotype C) IgA2 D) IgM E) Isotype Answer: A
In 1988, a new childhood vaccine was developed to protect against epidemic meningitis by mixing HIB polysaccharide with whole, killed Bordatella Pertussis bacteria. The function of the whole killed bacteria is as a(n): A) Carrier B) Hapten C) Mitogen D) Adjuvant E) Immunogen Answer: D
Molecular defects and symptoms of Chronic granulomatous disease: Defect - Deficiency of NADPH oxidase/failure to generate O2 radicals Symptoms - Recurrent infections with catalase positive bacteria and fungi
Molecular defects and symptoms of Chediak Higashi syndrome: Defect- Granule structural defect Symptoms- Recurrent infection with bacteria Chemotactic and degranulation defects Absent NK activity Partial albinism
Molecular defects and symptoms of G6PD deficiency: Defects: Deficiency of essential enzyme in hexose monophosphate shunt Symptoms-Same as CGD, with associated anemia
Molecular defects and symptoms of Myeloperoxidase deficiency: Defects- granule enzyme defects Symptoms: Mild or none
Molecular defects and symptoms of Leukocyte adhesion deficiency: Defect- Absence of CD18 Symptoms- Recurrent and chronic infections Fail to form pus Do not reject umbilical cord stump
What are the defects of phagocytic cells? 1) CGD 2) Chediak Higashi syndrome 3) G6PD deficiency 4) Myeloperoxidase deficiency 5) Leukocyte adhesion deficienct
What are the defects of humoral immunity? 1) Bruton X-linked hypogammaglobulinemia 2) Transient hypogammaglobulinemia of infancy 3) Common variable hypogammaglobulinemia 4) Selective IgA deficiency 5) X-linked hyper IgM syndrome
Molecular defect of Bruton X-linked hyogammaglobulinemia: Deficiency of tyrosine kinase blocks B-cell maturation
Signs and symptoms of Bruton X-linked hyogammaglobulinemia: Low Igs of all classes No circulating B cells Pre-B cells in bone marrow
Treatment of Bruton X-linked hyogammaglobulinemia: Monthly gamma-globulin replacement Abs for infection
Molecular defect of transient hyogammaglobulinemia of infancy: Delayed onset of normal IgG synthesis
Symptoms/signs of transient hyogammaglobulinemia of infancy: Detected in 5th to 6th month of life Resolves by 16-30 months Susceptibility to pyogenic bacteria
Treatment of transient hyogammaglobulinemia of infancy : Antibiotics Gamma-globulin replacement
Molecular defect of common variable hyogammaglobulinemia: Unknown
Symptoms/signs of common variable hyogammaglobulinemia: Onset in late teens and early twenties B cells present in peripheral blood Ig levels decrease with time Increased auto-immunity
Treatment of common variable hyogammaglobulinemia: Antibiotics
Molecular defect of selective IgA deficiency: Deficiency of IgA
Symptoms/signs of selective IgA deficiency: Repeated sinopulmonary and GI infection
Treatment of selective IgA deficiency: Antibiotics, not Igs
Molecular defect of X-linked hyper IgM syndrome: Deficiency of CD40L on activated T cells
Symptoms/signs of X-linked hyper IgM syndrome: High serum titers of IgM without other isotypes Normal B and T cell numbers Susceptibility to EC bacteria and opportunists
Treatment of X-linked hyper IgM syndrome: Antibiotics Gammaglobulins
Deficiencies in the classical pathway occur where? C1q, C1r, C1s, C4, C2
Signs/diagnosis of classic pathway deficiency: Marked increase in immune complex diseases Increased infections with pyogenic bacteria
Deficiencies in the alternative pathway occur where? Factor B, properdin
Signs/diagnosis of alternative pathway deficiency: Increased Neisseria infections
Deficiencies in both pathways occur where? C3 C5, C6, C7, and C8
Signs/diagnosis of C3 deficiency: Reccurent bacterial infections Immune complex disease
Signs/diagnosis of C5, C6, C7, or C8: Reccurent meningococcal and gonococcal infections
Deficiencies in complement regulatory proteins occur where? C1-INH (Hereditary angioedema) Decay activating factor or homologous restriction factor
Signs/diagnosis of C1-INH: Overuse of C1, C4, or C2 Edema at mucosal surfaces
Signs/diagnosis of Decay activating factor or homologous restriction factor: Paroxysmal nocturnal hemoglobinuria
Diseases of selective T cell deficiency: 1) DiGeorge syndrome 2) MHC class 1 deficiency
What is the defect of DiGeorge syndrome? Failure of formation of the 3rd and 4th pharyngeal pouches Thymic aplasia
Clinical manifestations of DiGeorge syndrome: Facial abnormalities Hypoparathyroidism Cardiac malformations Depression of T cell numbers Absence of T cell responses
What is the defect in MHC class 1 deficiency? Failure of TAP 1 molecules to transport peptides to ER
Clinical manifestations of MHC 1 deficiency: CD8 T cells deficient CD4 cells normal Recurring viral infections Normal DTH and Ab
What are the diseases of combined partial B and T cell deficiency? 1) Wiskott-Aldrich syndrome 2) Ataxia telangiectasia
Defect in Wiskott Aldrich syndrome: Defect in cytoskeletal glyoprotein X-linked
Clinical manifestations of Wiskott-Aldrich syndrome: Defective responses to bacterial polysaccharides Depressed IgM Gradual loss of CMI and HMI Thrombocytopenia Eczema
Defect in Ataxia telangiectasia: Defect in kinase involved in the cell cycle
Clinical manifestations of Ataxia telangiectasia: Gait abnormalities Capillary distortions in the eye Deficiency of IgA and IgE
What are the diseases of complete functional B- and T-cell deficiency? Severe combined immunodeficiency SCID
Which defects cause SCID? 1) Defects in common y chain of IL-2 receptors (present in receptors for il-4,-7,-9,-15) -- X linked 2) Adenosine deaminase deficiency 3) Defect in signal transduction from T-cell IL-2 receptors 4) Bare lymphocytes syndrome
Clinical manifestations of the first 3 defects in SCID" Chronic Diarrhea Skin, mouth, and throat lesions Opportunistic fungal infections Low levels of irculating lymphocytes Cells unresponsive to mitogens
Clinical manifestations of Bare lymphocytes syndrome: T cells present and responsive to non-specific mitogens No GVHD Deficient in CD4 Hypogammaglobulinemia
New born is evaluated for immunologic function. He has distortion in the shape of his mouth, low set malformed ears, and widely spaces eyes. Evidence of cardiac malformation and absence of a thymic shadow, radiographically. Which parameters are normal? A) Antibody dependent cell mediated cytotoxicity of parasite agents B) Cellularity of splenic PALS C) Cytotoxic killing of virus infected targets D) Generation of oxygen metabolites E) Proliferative response to concavalin A Answer: D
14 month old male infant is reffered to a specilaist for diagnosis of an immunologic deficiency. For 4 months the child has suffered repeat bacterial infections and pneumoncoccal vaccine has failed. Absence of cells responsive to pokeweed mitogen. Hypercellularity of pro-B cells in bone marrow. Most likely diagnosis? A) Bruton agammaglobulinemia B) Common variable hypogammaglobulinemia C) DiGeorge syndrome D) Selective immunoglobulin deficiency E) Wiskott-Aldrich syndrome Answer: A
31 year old man treated for 4th episode of disseminated Neisseria gonnorhea infection in the last 5 years. He had no previous history of unusual or recurrent infection. If he has an immunologic defect, which of the following is most likely? A) Common variable immunodeficiency B) C8 deficiency C) DiGeorge syndrome D) Selective IgA deficiency E) SCID Answer:B
A patient has been hospitalized 3 times for painful abdominal edema and is now complaining of swollen lips. What will lab findings in this patients most likely include? A) Abnormal superoxide production by neutrophils B) Abnormal T cell function C) Abnormal T-cell numbers D) Defective neutrophil chemotaxis E) Reduced C4 levels Answer: E
4 year old girl presents with sever Staph aureus abcess. Her history is significant for a previous Serratia marcasens infection. If she has an enzyme deficiency, which of the following is most likely? A) Adenosine deaminase B) c1 inhibitor C) Myeloperoxidase D) NADPH oxidase E) Superoxide dismutase Answer:D
4 year old boy with several boil-like lesions on his arm, which appear on several different occasions. Antibiotics caused resolution of the lesions and the child has had all of his immunizations. In all lab tests, the result are normal and NBT is negative No eczema or bleeding problems. Which disease is indicated by these findings? A) Bruton X-linked agammablobilunemia B) CGD C) DiGeorge syndrome D) SCID E) Wiskott-Aldrich syndrome Answer: B (Negative NBT --> no oxygen radicals)
Acutely ill 2 year old boy hospitalized with Staph aureus pneumonia, which is treated appropriately. Recovered from measles 6 months ago. Scant tonsillar tissue and no palpable lymphadenopathy. Electrophoresis reveals subnormal levels of y-globulins. NBT and chemiluminiscense assays indicate normal phagocytic activity. Which disorder is responsible for this condition? A) Adenosine deaminase deficiency B) Defect of Btk gene *** C) Defect of SAP gene D) Defect of WAS gene E) ICAM1 deficiency
2 year old boy suffers from repeated painful bouts of inflammation of mucosal surfaces, especially the lips. The mother remembers similiar symptoms in previous generations of the family and fears a heritable tendency toward food allergy. What lab finding would support this suspicion? A) Depressed C3 B) Depressed C4 C) Depressed C5 D) Elevated C1 E) Elevated C1,4, and 2 Answer: B
HIV infects which cells? CD4 cells
The HIV virus uses which chemokine receptors as coreceptors? CCR5 -- Macrophage tropic receptor CXCR4 --> T-cell tropic
Mechanisms by which HIV destroys the Immune system: 1) Multiplication in cells 2) Cytopathic effect on lymphocytes and macrophages 3) Nef gene product downregulates MHC 1 4) Tat gene product 5) Destroy TH cells 6) Immune deviation to TH2 7) Antigenic drift of gp120 8) Heavy glycosylation gp120
How does multiplication in lymphovytes and macrophages affect the immune system? 1) Reproduces the virus 2) Increases the viral load
What cytopathic effect does HIV have on lymphocytes and macrophages? Eliminates cell and antibody mediated immunity
What effect does down regulation of MHC 1 by HIV have? Makes infected cells less susceptible to CTL killing
What result does production of the Tat gene by HIV have on the immune system? Inhibits cytokine synthesis in both infected and uninfected cells
Destruction of TH cells by HIV leads to: Elimination of immune enhancement
What is the immunologic result of deviation towards the TH2 response? Inhibits protective CMI repsonses Produces Abs that can mediate ADCC
What effect does antigenic drift and heavy glycosylation of gp120 have on the immune system? 1) Evades Ab mediated effector mechanisms and exhausts an individual's immune capacity 2) Hides potentially protective epitopes from immune recognition
Which cells serve as the reservoirs for HIV infection? Macrophages and dendritic cells
How does the immune system respond to the inital infection? There is an initial, massive response by CD8 cells which controls the viremia and transition into clinical latency, but these leads to the death of many CD4 cells (which amplify the cytoxic response), so the amplification loop for CTL stimulation will end
How can HIV be diagnosed? Many Abs are generated within 6-9 weeks of infection These Abs are identified using ELISA and Western blot
27 year old woman who's 5 months pregnant presents for prenatal care. The patient is negative for RPR, but positive for HIV Ab by the EIA assay.The HIV western blot only demonstrated the presence of an Ab to HIV p24 antigens. How should this patient be counseled? A) She and her baby are both infected with HIV B) She is -ve for HIV because RPR is more specific C) She is positive for HIV D) She should have a PCR performed E) False-positive HIV result Answer: D
A neonate born to an HIV-positive mother is evaluated for HIV. What would be the assay of choice? A) CD4 cell count B) EIA for detecting te HIV Ab C) PCR D) p120 antigen assay E) Western blot Answer: C
Attachment of HIV to TH is initiated by binding of HIV gp120 to CDR receptor. Then gp120 undergoes a conformational change and binds to a second molecule. What is the second molecule on the surface of CD4 that acts as coreceptor & binds lymphotropic HIV? A) CCR5 expressed on dendritic cells B) CXCR4 expressed on T cells C) CXCR5 expressed on T cells D) Complement receptor CR2 (CD21) on B cells E) CC5 on T cells Answer: B
Male exotic dancer has been HIV positive for 10 years. Because of his low income, he can only irregularly afford the anti-retroviral drugs prescribed to him. When he goes for a checkup, his CD count is 390/mm^3, Which immunologic parameter is most depressed at this stage of infection? A) Cell proliferation in response to pokeweed mitogen B) Delayed type hypersensitivity to Candida antigens C) IgA production D) IC killing of bacteria E) Rejection of allogenic skin grafts Answer: B
Patients with HIV display an immunologic deviation toward TH2 response relatively early in the course of their disease. Which of the following cytokines would be increased in a patient with a CD4 count of 500/mm^3? A) IFN-y B) IL-1 C) Il-2 D) IL-10 E)TNF-B Answer: D
What are the two main categories of hypersensitivity diseases? 1) Excessive responses to foreign antigens 2) Autoimmunity (failure of self tolerance)
What are the types of hypersensitivity? 1) Immediate (type 1) 2) Antiibody mediated (type 2) 3) Immune-complex mediated (type 3) 4) T cell mediated (Type 4)
What is the immune mechanism of Immediate/Type 1 hypersensitivity? IgE
What is the mechanism of tissue injury in Type 1 hypersensitivity? Mast cells and their mediators
What is the immune mechanism in Antibody mediated/ Type 2 hypersensitivity? IgM, IgG Abs against cell or tissue Ags
What is the mechanism of tissue injury in type 2 hypersensitivity? Opsonization and phagocytosis of cells Complement and Fc receptor mediated recruitment and activation of neutrophils and macrophages Abnormality in cellular functions (hormone/receptor signalling)
What is the immune mechanism in Immune-complex mediated/Type 3 hypersensitivity? Immune complexes of circulating Ags IgM orIgG Abs
What is the mechanism of tissue injury in type 3 hypersensitivity? Complement and Fc-receptor mediated recruitment and activation of leukocytes
What are the immune mechanisms in T-cell mediated/Type 4 hypersensitivity? 1) CD4 T cells (delayed type) 2) CD CTLs (T-cell mediated cytolysis)
What is the mechanism of tissue injury in Type 4 delayed hypersensitivity? Macriophage activation Cytokine mediated inflammation
What is the mechanism of tissue injury in Type 4 hypersensitivity T-cell mediated cytolysis? Direct target cell killing Cytokine mediated inflammation
What do all hypersensitivity reactions have in common? 1) The fist exposure to the antigen sensitizes lymphocytes 2) Subsequent exposure elicit damage 3) Response is Ag-specific
Characteristics of Type 1 hypersensitivity: 1) IgE mediated 2) Protective response to Helminths 3) Atopic/allergic individuals develop this response to innapropriate stimuli Example-pollen/pet dander allergies
What are the type 1 effector cells? Mast cells Basophils Eosinophils
Two to four hours after the immediate response to release of these mediators, what reaction begins? A late-phase reaction mediated by the products of the arichodonic acid cascade
What are the stored mast cell mediators and their effects? 1) Histamine -Smooth muscle contraction 2) Heparin - anticoagulant 3) Eosinophils -chemotaxis
What are the mast cell mediators newly synthesized from arachadonic acidand their effects? 1) PE2- Increased pain and vascular permability 2) PD2- Smooth muscle contraction and VP 3) Leukotrienes C4,D4,E4- Smooth muscle contraction and VP 4)Leukotriene B4- chemotactic for neutrophils
What are the different types of allergic diseases? 1) Allergic rhinits (hay fever) 2) Food allergies 3) Wheal and flare 4) Asthma 5) Systemic anaphylaxis
What are the possible allergens in Allergic rhinitis? Trees, grass, dust, cats, dogs, mites
What are the possible allergens in food allergies? Milk, eggs, fish, cereals, grain
What are the possible allergens in Wheal and flare? Insect stings Used in vivo skin testing for allergies
What are the possible allergens in Asthma? Inhaled materials
What are the possible allergens in Systemic anaphylaxis? Insect stings, snake venoms, drug reactions
Clinical finding in allergic rhinitis: Edema Irritation Mucus in nasal mucosa
Clinical finding in food allergies: Hives Gi problems
Clinical finding in Wheal and flare: Local skin Edema Reddening Vasodilation
Clinical finding in Asthma: Bronchial and tracheal constriction Edema Mucus production Massive inflammation
Clinical finding in Systemic anaphylaxis: Bronchial and tracheal constriction Complete vasodilation and death
In type 2 hypersensitivity, the Abs produced cause damage by: 1) Opsonization or activating the complement 2) Recruit inflammatory cells 3) Binds to receptors and interfere will cellular function
Diseases of type 2 hypersensitivity; 1) Autoimmune hemolytic anemia 2) Autoimmune thrombocytopenic purpura 3) Goodpasture 4) Acute rheumatic fever 5) Myasthenia gravis 6) Graves 7) Type 2 diabates 8) Pernicious anemia
Target antigen of autoimmune hemolytic anemia: RBC membrane proteins (Rh, Ags)
Target antigen of autoimmune thrombocytopenia purpura: Platelet membrane proteins
Target antigen of Goodpasture antigen: Noncollagenus protein in basement membranes of kidney glomeruli and lung alveoli
Target antigen of acute rheumatic fever: Streptococcal cell-wall Ag Ab cross-reacts with myocardial Ag
Target antigen of myasthenia gravis: Acethylcholine
Targert antigens of graves disease: TSH receptor
Target antigens of type 2 diabetes: Insulin receptors
Target antigens of pernicious anemia: Intrinsic factor of gastric parietal cells
What is the mechanism of pathogenesis of autoimmune hemolytic anemia? Opsonization, phagocytosis, and complement mediated destruction of RBCs
What is the mechanism of pathogenesis of autoimmune thrombocytopenic purpura? Ab mediated platelet destruction through opsonization and complement activation
What is the mechanism of pathogenesis of goodpasture syndrome? Complement and Fc receptor mediated inflammation
What is the mechanism of pathogenesis of acute rheumatic fever? Inflammation Macrophage activation
What is the mechanism of pathogenesis of myasthenia gravis? Ab inhibits Ach binding Down modulates receptors
What is the mechanism of pathogenesis of Graves disease? Ab mediated stimulation of TSH receptors
What is the mechanism of pathogenesis of Type 2 diabetes? Ab inhibits binding of insulin
What is the mechanism of pathogenesis of pernicious anemia? Neutralization of intrinsic factor Decreased absorption of vitamin B12
Clinical manifestations of autoimmune hemolytic anemia: Hemolysis Anemia
Clinical manifestation of autoimmune thrombocytopenic purpura: Bleeding
Clinical manifestations of Goodpasture syndrome: Nephritis Lung Hemmorhage
Clinical manifestations of acute rheumatic fever: Myocarditis Arthritis
Clinical manifestations of myasthenia gravis: Muscle weakness Paralysis
Clinical manifestations of Graves disease: Hyperthyroidism followed by hypothyroidism
Clinical manifestation of Type 2 diabetes: Hyperglycemia Ketoacidosis
Clinical manifestations of pernicious anemia: Abnormal erythropoiesis Anemia
Hemolytic disease of the newborn is also known as: Erythroblastosis fetalis
Erythroblastosis fetalis is what type of hypersensitivity? Type 2 Due to IgG transport for Rh protein antigens (RhD)
If a mother is Rh-, and the father is Rh+, what will happen? The fetus may be Rh+ No problem in the first pregnancy In later pregnancies , there may be HDNB because during the first pregnancy the Rh+ fetal blood entered the mother's blood
Hemolytic disease od the newborn can be prevented with: Treating the mother with RhoGam (a preparation of human anti-RhD igD Ab) at 28 weeks of gestation and within 72 hours after birth
Characteristics of Type 3 hypersensitivities: 1) Systemic damage 2) Immune complex activates complement 3) Self or foreign Ags
Examples of diseases of Type 3 hypersensitivity: 1) Systemic lupus erythematosus 2) Rheumatoid arthritis 3) Post strep. glomerulonephritis 4) Serum sickness 5) Arthus reaction
Antigens involved in SLE: dsDNA, Sm, other nucleoproteins
Antigens involved in rheumatoid arthritis: IgM versus IgG Fc region
Antigens involved in poststreptococcal glomerulonephritis: Streptococcal cell wall Ags
Antigens involved in serum sickness: Various proteins
Antigens involved in arthus reaction: Any injected protein
Clinical manifestations of SLE: Nephritis Arhtitis Vasculitis Rash
Clinical manifestations of Rheumatoid arthritis: Joint pain Erosions
Clinical manifestations of postsreptococcal glomerulonephritis: Nephritis
Clinical manifestations of serum sickness: Arthritis Vasculitis Nephritis
Clinical manifestations of arthus reaction: Local pain Edema
Characteristics of Type 4/T-cell mediated hypersensitivites: *Delayed type (48-72 hours) CD4 TH cells mediate it Activate macrophages Cause inflammation Common in chronic intracellular infections
Diseases of type 4 hypersensitivity reaction: 1) Type 1 diabetes 2) Multiple sclerosis 3) Contact dermatitis 4) Peripheral neuritis 5) Guillain Barre syndrome 6) Hashimotos thyroiditis
Specificity of pathogenic T cells in Type 1 DM: Islet cell Ags Insulin Glutamic acid decarboxylase
Specificity of pathogenic T cells in Multiple sclerosis: Myelin basic protein Proteolipid protein
Specificity of pathogenic T cells in contact dermatitis: Nickel Poison Ivy/oak catechols Hapten/carrier
Specificity of pathogenic T cells in Peripheral neuritis: P2 protein of peripheral nerve myelin
Specificity of pathogenic T cells in Guillain-Bare syndrome: Peripheral nerve myelin or gangliosides
Specificity of pathogenic T cells in Hashimoto's thyroiditis: Unknown Ag in thyroid
Clinical manifestations of Type 1 DM: Polydipsia Polyuria Polyphagia Ketoacidosis
Clinical manifestations of Multiple sclerosis: Progressive demyelination Blurred vision Paralysis
Clinical manifestations of contact dermatitis: Vesicular skin lesions Pruritis
Clinical manifestations of peripheral neuritis: Ascending paralysis
Clinical manifestation of Guillan Barre syndrome: Ascending paralysis Peripheral nerve Demyelination
Clinical manifestation of Hashimoto's thyroidits: Hypothyroidism
Effector cells of each hypersensitivity reaction: Type 1- Basophils, mast cells Type 2- PMN, macrophages, NK cells Type 2 noncytotoxic - None Type 3 - PMN, macrophages Type 4- CTL, TH1, macrophages
Which type 2 disease are noncytotoxic? Myasthenia gravis Graves disease Type 2 DM
Tuberculin test is an example of which hypersensitivity? Type 4
Which hypersensitivity reactions involve the complement? Type 2 cytotoxic Type 3
Which hypersensitivity reaction involves no Abs? Type 4
Characteristics of autoimmunity: Failure of self tolerance The strongest genetic associations with the development of autoimmune diseases are the class 2 MHC genes Environment associations -infections Hormones
Infections can trigger autoimmunity through: 1) Activating bystanders 2) Molecular mimicry 3) Inflammatory damage
Therapies for immune diseases: 1) Inhibit proliferation -cyclosporine 2) Inhibit function - corticosteroids 3) Kill T cells - cyclopshsphamide 4) Antiagnosts to proinflammatory cytokines or costimulatory molecules - monoclonals or binding proteins
Other therapeutic regimens used to inhibit pathologic responses: 1) Desensitization by injecting small doses od allergens 2) Plasmapheresis 3) High doses of IV IgG- may bind to Fc receptors and inibit synthesis 4) Tolerance induction - high dose administration of antigens
43 year old woman is seen by her physician with complaints of painful, swollen joints. Her hands appear to be disfigured by the joints with SC nodule formation. Left knee is grossly enlarged and 100 mL of fluid is withdrawn. An examination of the fluid should reveal what? A) Activated L lymphocytes B) Abs against type 4 collagen C) Abs against double stranded DNA D) Abs against microsomal Ags E) IgM Abs reactive with the Fc region of IgG Answer:E
36 year old farmer exposed to poison ivy. Very severe skin lesions. Which of the following cytokines administered topically could inhibit the severity of this reaction? A) y-INF B) IL-2 C) IL-3 D) IL-8 E) IL-10 Answer:E
In individuals exposed to massive doses of cercariae, IgG Abs developed in response to the developing worms and when the adults release eggs, the patients suffer acute and life threatening symptoms of fever, edema, arthralgia, and rash Which of the following is another condition that arises by a similiar immunologic mechanism? A) Arthus reaction B) Atopic allergy C) Goodpasture syndrome D) Tuberculin reaction E) Transfusion reaction Answer: A
Young women goes to doctor about hereditary problem concern. She was born blue covered with splotches and bruises, although an earlier sibling was born normal. Two further pregnancies ended in stillbirths. How should he advise the patients? A) Her husband should be tested for Rh incompatibility B) She is RhD- and should be treated with Rhogam C) She is RhD-, no risk to a fetus D) She is RhD+ and should be treated with Rhogam E) She is RhD+, no risk to the fetus Answer: E
On first ecposre, cercariae penetrate the skin and become schistomula, which enter the circulation and eventually mature in the mesentric veins. On subsequent exposure, schistosomula are frequently killed within minutes by an immune response in the skin. This response is manifestated by intense itching, stinging, and urticaria. What is this protective immune response a manifestation of? A) Arthus reaction B) Contact dermatitis C) Cutaneous anaphylaxis D) Serum sickness E) Type 1 ***
What is transplantation? Tissues taken from donor given to the host
What is the most common transplantation? Transfusion
Types of grafts: 1) Autografts - same individual 2) Syngeneic grafts - genetic individuals 3) Allogenis grafts- genetically different members of same species 4) Xenogeneic grafts- different species
MHC alleles are expressed: Co-Dominantly
What are the effectors of Graft rejection? CTLs Macrophages Ab-mediated *Interferons and TN-a and -B all increase the expression of class 1 MHC molecules in the graft *IFN-y increases class 2 MHC expression
What are the types of graft rejection? 1) Hyperacute 2) Accelerated 3) Acute 4) Chronic
How long does each type of rejection take? Hyperacute - minutes to hours Accelerated - days Acute - days to weeks Chronic-months to years
Cause of hyperacute graft rejection: Preformed anti-donor Abs and complement
Cause of accelerated graft rejection: Reactivation of sensitized T cells
Causes of acute graft rejection: Primary activation of T cells
Causes of chronic graft rejection: Causes are unclear Abs, immune complexes, slow cellular reaction, recurrence of disease
Characteristics of Graft-Versus-Host disease: *Special case of rejection *Many mature T cells remaining in the bone marrow inoculum can attack allogenic MHC bearing cells of the recipient *Rash, jaundice, diarrhea, GI hemorrhage
What lab tests are done to test for tissue compatability? ABO blood typing HLA matching Screening for Abs Crossmatching Mixed Lymphocyte reaction -type 2 Microcytotoxicity test- class 1
How is ABO blood typing used to test tissue compatibility? If a persons RBC react with another persons RBCs, agglutination occurs
What is the purpose of tissue typing? match the HLA antigens of recipient and donor The larger number of matched MHC allele, the better the graft survival
HLA typing focuses on: HLA-A, HLA-B, and HLA-DR
To test class 1 compatibility: Use microcytotoxicity test
To test class 2 compatibility: Use mixed lymphocyte reaction (MLR) Lymphocytes are irradiated so they can't proliferate, but act as stimulator cells for presenting MHC antigens If the antigens are the same, no proliferation will occur
Characteristics of immunosupression: *Necessary for all transplants except autografts *Inhibits T-cell mitosis *Inhibits T-cell function *Kills T cells *Blocks cytokine or costimulatory molecules
What does generalized immunosupression do? Leaves the host susceptible to increased risk of infection
What therapies are used to prevent graft rejection? 1) Mitotic inhibitors 2) Corticosteroids 3) Fungal metabolites 4) Experimental monoclonals
Which drugs are mitotic inhibitors? Cyclophosphamide Methotrexate
Which drugs are corticosteroids? Prednisone Dexamethasone
What drugs are fungal metabolites? Cyclosporin A
What drugs are experimental monoclonals? Anti-CD3 Anti-IL2 receptor Anti-CD40L
Action and use of mitotic inhibitors? Block proliferation Prevent acute graft rejection
Action and use of corticosteroids? Broad spectrum antiinflammatories During episodes of acute graft rejection
Action and use of fungal metabolites? Block proliferatio of TH cells and production of their cytokines Prevent acute graft rejection
Actions and use of experimental monoclonals? Anti-CD3- Binds to and depletes T cells Anti-IL2 receptor- Inhibits T-cell proliferation Anti-CD40 ligand- Blocks T-cell proliferation *Prevents acute graft rejection
42 year old mechanic diagnosed with end stage renal disease. His twin brother is HLA identical at all MHC loci and volunteers to donate a kidney. What type of graft transplant terminology is correct in this situation? A) Allograft B) Autograft C) Heterograft D) Syngeneic graft E) Xenograft Answer:D
Patient with AML undergoes irradiation and chemotherapy for his malignancy while awaiting bone marrow transplantation from a closely matched sibling. Six months after the transplant, the immune response is fine. 9 months later-rash desquamation, jaundice and bloody diarrhea appear.10 months after- the patient dies. Which effector mechanism is most closely associated with this rejection reaction? A) Macrophages B) Abs and complement C) CD8 D) LAK cells E) NK cells Answer: C
45 year old welder develops a sever corneal ulcer, which requires treatment with transplantation. A suitable cadaver cornea is succcesfully grafter. What is the appropriate postsurgical treatment? A) Corticosteroids, such as prednisone for life B) Fungal metabolites, such as cyclosporin A, for life C) Mitotic inhibitors, such as cyclophosphamide for life D) Monoclonal anti-IL2 receptor for life E) No treatment required Answer: E
What are the immunopriveledged areas in the human being? Cornea Testes Uterus Brain Thymus Placenta
In heart lung transplants, where the critical illness of the recipient and his inability to preserve tissue from brain dead donor often precludes tissue typing. In one immunosupressive experiment, patients are treated with anti-CD28Ab Fab fragments at the time of transplantation and montly after. What is the goal of such therapy? A) To destroy T cells B) To induce anergy to transplanted tissues C) To inhibit mitosis in B cells D) To inhibit mitosis in T cells E) To stop inflammation Ans: B
Tumor antigens: *Products of oncogenes Ras or tumor supressor genes -p53 *Products of genes are silent in most normal tissues *Products of overexpressed genes *Products of oncogenic viruses (E6,7) *Oncofetal antigens *Atopic Differentation antigens
Antitumor effectors include: CTLs Antibodies (with complement of ADCC) Macrophages NK cells
How do tumors evade the immune system? 1) Downregulate MHC 2) Antigen-loss variants 3) TGF-B inhibits effector functions 4) Tumors may not stimulate CTLs if they lack costimulators 5) Fasl induces apoptosis of lymphocytes 6) Antigens of tumors masked by Polysaccarides
What is the immunotherapy for tumors? 1) Vaccination 2) Increase costimulatory moleciles 3) Stimulate T cell proliferation and differentiation 4) Antitumor Abs 5) Immunotoxins 6) Administrate tumor reactive T and NK cells from culture
What was the first antitumor vaccine to be placed on the market? HIB
What are the functions of INFs? Induce increases in MHC 1 and 2 expression Increase the efficiency of APCs to CTL and TH cells
Therapeutic uses of INFs: Treatment of hepatitis B and C Treatment of hairy B-cell leukemia, CML, and Kaposi sarcoma Multiple sclerosis CGD
Stages of Rrecipitation of Ag-Ab complexes Ag excess: early infection Equivalence: window period Ab excess: late
What is the difference between Direct and indirect Coombs test? Direct-Abs bound to RBC Indirect- production of anti RBC antibodies
The direct flourescent Ab test is used to: Detect and localize Ags in tissue via binding of flourescent Abs Used to diagnose RSV, Herpes simplex 1 and 2, and pneumocystis infections
Indirect flourecent Ab test is used to detect: pathogen specific Abs Anti-Ig is added, if binding occur Used to detect antinuclear Abs, Anti-ds DNA ab, anti-thyroid Abs, antiglomerular Abs, and anti-EBV Ag Abs
RIA and ELISA: Extremely sensitive tests Used to detect the presence of hormones, drugs, Anti-biotics, serum proteins, Ags, and tumor markers. RIA- uses radiolabeled product ELISA- presence of enzyme mediated color change
In the screening fro HIV, which test is used? ELISA
What test is used as a confirmation of HIV? Western blot
How is the western blot done? Viral organism--> proteins Proteins seperated SDS PAGE Proteins transferred onto nitrocellulose sheet Reacted with patient serum Antihuman y globulin labeled and reacted for color development/identifation Cells with high flourescne--> top right
When do we use flow cytometry to analyze cell populations? In complex mixture
Acts at three sites: antigen recognition site, proliferation step, and differentiation/synthesis steps: anti-lymphocyte globulin & monoclonal anti-T cell antibodies
Tacrlimus acts on which sites in the lymphocytes cycle proliferation; differentiation/synthesis sites
Which agents act to diminish tissue injury? prednisone (Deltasone)
Which agents reduce proliferation of B cells? prednisone (Deltasone) Tacrolimus Azathioprine (Imuran) dactinomycin (Cosmegen) methotrexate cyclophosphamide (Cytoxan)
dactinomycin (Cosmegen) also inhibits which steP/ differentiation/synthesis step
Which agents have an Anti-profilerative site of action: Antilymphocyte globulin & monoclonal anti-T cell antibodies dactinomycin (Cosmegen) methotrexate azathioprine (Imuran)
RHo(D) immune globulin acts on antigen recognition site
Example of first-class of hormonal agents noted to have lipolytic properties: Prednisone(Deltasone)
Glucocorticoid effects: inhibition of leukotriene production inhibition of prostaglandins
Effective in lowering incidents of rejection in infectious complications in transplant patients: azathioprine (Imuran) prednisone (Deltasone) antilymphocyte antibodies cyclosporine (Sandimmune, Neoral)
Tests of immunocompetency:-- measurements in vitro IL-2 stimulation of lymphokine activated killer cell production in vitro lymphocyte profilerative responses to mitogens
About two-thirds of children with early diabetic symptoms can discontinue or reduce insulin treatment within about six weeks after starting treatment with this drug: cyclosporine (Sandimmune, Neoral)
This immunosuppressant antibiotic commonly approved for use in liver transplantation, is 10 to 100 times more potent than cyclosporine in inhibiting immune responses: tacrolimus (FK 506)
Implicated in initiation of hypersensitivity vasculitis; a Type III vasculitic reaction: sulfonamides penicillin thiouracil anticonvulsants
Blockade of mediator release following exposure of sensitized tissue mast cells or blood basophils to drugs that initiate Type I drug allergic reactions: isoproterenol (Isuprel) theophylline
Example of immunostimulatory cytokine that may be useful in cancer immunotherapy IFN-a
What is levamisole? Immunomodulator
For synthesized for treating parasitic infections, this drug is now FDA approved for clinical use in the treatment of Dukes class C colorectal cancer after surgery: levamisole combined with flouracil
Alkylating agent; destroys proliferating lymphoid cells; in low doses -- for effective against autoimmune disorders including systemic lupus erythematosus cyclophosphamide (Cytoxan)
beneficial in maintaining renal allografts azathioprine (Imuran)
Anti-folate agent; used extensively, in addition to anticancer applications, in management of rheumatoid arthritis Methotrexate
Cytotoxic agents with immunosuppressive properties: Cyclophosphamide (Cytoxan) vincristine (Oncovin) methotrexate cytarabine (ARA-C)
Congenitally-acquired immunodeficiency disease DiGeorge's syndrome
adenosine deaminase deficiency severe combined immunodeficiency disease (SCID)
strong tropism for CD4+ helper T cells human immunodeficiency virus
reaction effective in eliminating infections caused by intracellular pathogens (e.g. Leishmania) delayed hypersensitivity
cell type associated with cell-mediated immunity activated cytotoxic T cell
activated lymphocytes effectors of cell-mediated immunity
antibodies effectors of humoral immunity
IL-4, IL-5, IL-6 produced by this subset of T cells TH2
present mainly fragments of cellular antigens (e.g. virus or tumor antigens) process through Golgi apparatus Class I MHC molecules
present antigen fragments from internalized and enzymatically digested foreign antigens Class II MHC molecules
Immediate hypersensitivity type associated with hemolytic disease in the newborn Type II immediate hypersensitivity
Immediate hypersensitivity reaction associated with asthma, hay fever, hives -- following blood basophil or tissue mast cell degranulation Type I hypersensitivity
Roferon interferon alpha-2a
HypRho-D Rho(D) immune globulin micro-dose
Atgam lymphocyte immune globulin
Most important anatomical sites for mast cells distribution and IgE sensitization: skin, lung, gastrointestinal tract
Acute glomerulonephritis: drug choice prednisone; alternatives -- mercaptopurine, cyclophosphamide
Immunosuppressive agents used in management of acquired factor XIII antibodies: cyclophosphamide plus factor XIII
Idiopathic thrombocytopenic purpura: treatment drug of choice Prednisone; Other drugs include vincristine, occasionally mercaptopurine or azathioprine, high-dose gamma globulin; Other Treatment: plasma immunoadsorption
Isoimmune disease -- hemolytic anemia of the newborn immunosuppressive agent of choice: Rho D immune globulin
Mediators released following binding of allergen to specific IgE antibody on sensitized mast cell surfaces: histamine, leukotrienes, kinins, prostaglandins, serotonin, platelet-activating factor
Examples of drugs which may partially block degranulation and mediator release from IgE-sensitized mast cells subsequent to allergen exposure: isoproterenol, theophylline, epinephrine, cromolyn
Immunomodulator -- FDA approved for use in combination with flurouracil in treatment of Dukes class C colorectal cancer after surgery levamisole
When you want to take a sample of the bone marrow, from where do you take it? Either from the Sternum or The iliac crest
Structural analog/antimetabolite: cytotoxic immunosuppressive drug azathioprine
Immunomodulatory sedative drugs used in the management of some forms of leprosy; also effective in managing skin manifestations of lupus erythematosus thalidomide
Drug of choice in treating autoimmune hemolytic anemia: prednisone
Interferes with cell cycle of activated lymphoid cells;example of first-class hormonal agents recognized have lympholytic properties: dexamethasone
Useful in management of idiopathic thrombocytopenic purpura refractory to prednisone vincristine
Drug of choice in treating hemolytic anemia of the newborn: Rho(D) immune globulin
Clinical uses of interferon: A) cancer treatment B) multiple sclerosis
immunomodulating agents: A) thymosin B) interferon beta C) interferon-gamma D) TNF alpha
Inhibits antigen recognition of B-cell Rho(D) immune globulin
Mannose sugar, LPS, bacterial DNA, RNA fragments, peptidoglycans and flagella PRR (Pattern Recognition Receptors) or what's known as Toll like receptors (TLR), they all are molecules present on bacteria
Acute phase proteins: C-reactive protein, mannose-binding protein, complement factors
when the cell is damaged by bacteria or by other means it starts expressing special molecules on their surface such as Heat shock proteins and MIC (MICA and MICB)
How many domains are there in different Igs? IgM & IgE: have 5 domains "so the total is (5), (1) Variable domain & (4) constant domains.” IgG, IgA & IgD: have 4 domains "so the total is (4), (1) Variable domain & (3) constant domains.”
These regions (26/53/96 amino acids) are called HYPERVARIABLE REGIONS
There are 3 CDRs on each variable domain. What are they? CDR1…..[a.a #26] CDR2…..[a.a#53] CDR3[a.a#96] Most variable one is CDR3
The light chain can be of two classes : Kappa and Lambda, in humans, 60% of lg contain kappa and 40% contain lambda chains
Which subclass of IgG doesn't cross the placenta? Which subclass doesn't activate the complement? IgG2 IgG4
Gene of heavy chain is present on chromosome 14
Genes of kappa chain are on chromosome 2
lambda chain is on 22
Combinatorial diversity is calcultaed as Kappa chain: 100 V's and 4 J'S; 4*100=400 different kappa chains -heavy chain: number of V* number of J * number of D -Then we add the possibilities
Mannose binding protein [mannan lectin ] pathway: Acts like c1 Associated with this protein, you will find proteins known as masp( masp 1,2,3) they are serene proteases, they do the work of c1s and c1r and activates the classical pathway
 If we measure the transmitted light and scattered light in precipitations: Turbidimetry Nephalometry These 2 tests are quantitative & qualitative
Single radial immunodiffusion This test is qualitative
Characteristics of rocket electrophoresis: Quantitative Expose the reactants to an electrical current Start at neutral pH Assign standards Apply the current, the current will affect the Ags Make them migrate toward the cathode Measure the distance travelled by Ags
Widal test: looking for Abs against Salmonella Typhi Ags in the serum of the patient ͞Rising Titer: a titer should be increased 4 folds or more to be considered significant Other infections like Brucellosis
Flow Cytometry: Mix the cells in a liqui-put them through this system They come out one after the other,hit them with a laser Scattering of light at (an angle) The bigger the cell, the less it will scatter light forward The scattered light indicates granularity
FACS (fluorescence-activated cell sorting): Bring Abs against relevant antigen Before we mix these Abs we label them 1st one with fluorescein, 2nd one with rhodamine etc Mix these labeled different Abs with cells in the mixture wash excess and pass these cells in line like in flow cytometer
Follicular B-cells "FO-B cells": This type is the one that get activated by encountering Ags which are made of proteins, producing first IgM and then other isotypes of the immunoglobulins, then, giving rise to memory cells and plasma cells
Marginal Zone B-cells "MZ-B cells": Undergo some transitional processes; designated as T1- and T2- B cells Responsible for encountering the Ags which are made of polysaccharids, expressing only IgM on their surface -No Memory Cells They can give rise to naïve memoryB-cells
There is another, third, type of B-cells called: B1-cells or CD5 B-cells, because it expresses the CD5 molecule on their surfaces. These cells are apparently produced in the fetus , propagate themselves and continue dividing there Only IgM
The Fate of the Immature B-cells if it encounter an antigen 1) Apoptosis 2) Anergy 3) Receptor Editing: the B-cells, here, is given a chance to reactivate RAG-1 & RAG-2 and try to assemble a different light chain 4) Immunological Ignorance
Pokeweed mitogen Acts upon both T and B cells Mainly works on memory cells
Concanavalin & Phytohaemagglutinin is a plant mitogen, and is known for its ability to stimulate T-cell subsets ACTs upon T.cells
Linkage disequilibrium is the non-random association of alleles at different loci
Mutation in AIRE gene results in APS (Autoimmune polyendocrinopathy Syndrome )
Mutation in FOXP3 results in: IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome)
Suggested mechanism by which natural autoantibodies “ fight ” bacteria is blocking bacterial epitopes
These PATHOLOGIC autoantibodies are of the IgG variety
Best example of molecular mimicry: rheumatic fever
The conversion of H antigen to A or B antigen is dependent on transferase enzymes : 1- A transferase enzyme : which adds N-acetylgalactosamine t the H chain forming A blood type . 2- B transferase enzyme : which adds galactose to the H chain forming B blood type
mutation in fucose transferase because of that they can't add fucose to the terminal part of the H-chain consequently they can't add neither NAGA nor galactose this phenotype is called Bombay blood group
The rhesus antigen has how many antigenic determinants? 5 D, C, E, c and e
There is no d antigen. Lowercase "d" indicates absence of the D antigen
Rhesus antigens are proteins and the antibodies that are produced against them are IgG antibodies
ABO antigens are Carbohydrates (sugars), and the antibodies that are produced against them are IgM antibodies
There are two possible mechanisms of action, in case of Rh immunization: 1) ANTI D Abs will collect and clear all the Ags in the mothers blood quickly preventing an immune response 2) Abs will bind to the Ag -form immune complexes - bind with B-cell that is reactive to D Ag -undergo Ab feedback - inactivation B-cell
What is febrile reaction? A type of transfusion reaction that is associated with fever. Arises because the donor WBCs will release IL-1 and IL6 that work on the hypothalamus of the recipient Not serious because antipyretics can relieve the effects of the ELs
What are the symptoms of a faulty transfusion {cross match ABO incompatibility}? 1. Hemolysis and complement activation 2. Fever, nausea, sweating, and vomiting. 3. Shivering 4. Kidney failure and other organs failure 5. DIC 6. Shock and death
ACUTE LUNG INJURY REACTIONS: will only happen if the recipient has anti HLA Abs, if there are a high number of these anti HLA antibodies, they might activate the complement system in the lungs and lead to pulmonary EDEMA
The Natural mechanisms for avoiding “FETUS GRAFT REJECTION” are : Most MHC 1 class (A) Ags are lacking on the surface of fetally derived trophoblasts- can’t be rejected by CTLs Trophoblastic tissue expresses the human leukocyte antigen-G which gives a non-classical MHC class I on their surface- -ve signal to NK cells
Factors that can be deficient are: Factor B, Factor H, Factor I
C1 inhibitor "C1-INH" Angioneurotic Edema,
Complement Receptor 1 (CR1) deficiency: CR1 is present on RBC to remove immune complexes from blood to spleen, so patients are more susceptible to immune complex diseases like SLE
B-cell problems Bruton’s Agammaglobulinemia. Transient Hypogammaglobulinemia of Infancy. Selective IgA - Selective IgG - X-linked Hyper-IgM Common variable Good syndrome Selective IgM:
T-cell problems DiGeorge Chronic mucocutaneous candidiasis
SCID: 50% are X-linked (no γ chain of IL receptor) - 10% are JAK3 kinase (JAK3 kinase transmits signal from IL receptor) - 30% Omenn syndrome (RAG1 and RAG2)
- Selective IgM Deficiency These people do not have IgM, yet they still have the other Igs normally. This is contradictory, since we know that all B cells initially express IgM then may switch to another class of Igs.
Selective IgG Deficiency Involves a certain subclass, the most common being the ones affecting IgG2 and IgG3 IgG1 is very rare IgG4 deficiency is not actually a problem- no symptoms of immunodeficiency
Cancer antigens: CEA or carcinoembryonic antigen-colon Alpha fetoprotein-liver PSA (prostate specific antigen) & Prostatic acid phosphatase CA-125 -ovarian cancers CA19 - pancreatic cancer CA15 - breast cancer
Carcinogenic viruses: HTLV1 (human T- lymphotropic virus)- T cell leukemia Hepatitis B virus-liver cancer HPV- cervical cancer
X-linked: 1-properdin deficiency 2-2/3 chronic granulomatous disease (the rest 1/3 are recessive) 3-Brutonagammaglobulinemia (x-linked recessive) 4-X-linkged hyper IgM syndrome 5-x-linked SCID 6-Wiskott-Aldrich syndrome
Recessive: 1-1/3 CGD 2-Chediak Higashi 3-Job syndrome 4-Jak3 kinase deficiency 5-Omenn syndrome 6-Ataxia Telangiectasia
dominant C1 inhibitor deficiency
drug used for coronary artery disease sirolimus
not a humanized type of mono clonal AB abcimixab
monoclonal AB against CD3 Muromonab
-IL-2 receptor monoclonal anti-bodies Daclizumab, basiliximab
Functions of corticosteroids: 1- Decrease the expression of transcription factors (IL-1, IL-2, IL-3, IL-4) 2- Increase transcription of lipocortin, which is an important component in anti-inflammatory
Clinical uses for steroids: 1) Graft versus host disease 2) useful in treatment of diseases like: asthma, psoriasis الصدفية, and atopic dermatitis 3) rheumatoid arthritis and idiopathic thrombocytopenic purpura (ITP)
Side effects of steroids: 1) Immunodeficiency 2) Adrenal gland supression 3) Hyperglycemia 4) Fat redistribution 5) Growth failure/delayed puberty 6) Effects on CNS 7)Cataracts 8) Osteoporosis 9) Gastric ulcer
Calcineurine inhibitors: Cyclosporines , Tacrolimus
Function of Cyclosporines , Tacrolimus They bind to calcineurine and reduce their activity toward the activation of IL-2
Uses of calcieurine inhibitors: 1- human organ transplantation 2- in Graf-versus-host disease after Hematopoietic stem transplantation 3- in selective autoimmune diseases (psoriasis, rheumatoid arthritis, and SLE)
Side effects of Clacineurine inhibitors: 1- liver toxicity 2- nephrotoxicity 3-hypertension 4-hyperkakemia 5-hyperglycemia 6- viral infection 7- lymphoma, hirsutism, gum hyperplasia 8- anaphylaxis after IV administration
both calcineurine inhibitors cause 1- nephrotoxicity 2- neurotoxicity ( mostly tremor ) 3- hypertension 4- hyperglycemia
The predominant enzyme responsible for metabolism of tacrolimus and cyclosporine is CYP3A5
Function of Sirolimus : Inhibits the CELLULAR IMMUNITY throw inhibiting kinase activity of mammalian target of rapamycin (mTOR)and decrease the IL activity
When is sirolimus used? instead of calcineurine inhibitors (tacrolimus and cyclosporines): when the patient can't tolerate the side effects especially if the patient develops nephrotoxicity If the patient can't take glucocorticosteroides
Antimebolites of drugs: 1) Methotrexate 2) Azathioprine-Micropbenolate is better Glucocorticoid + Cyclosporine/tacrolimus + Azathioprine
kidney transplantation surgery, what do you have to do? 1) High doses of corticosteroids Methyl Prednisolone(500mg, IV)1-2h prior the transplantation- after 24h 2) Then we give - cyclosporine -Tac. triple therapy ( tacrolimus + prednisolone + Azathioprin) 1st 6 months high doses monitor next 1/2 dose
Uses for Anti-CD3(muromonab-CD3) treatment of acute rejection of renal allograft as well as for corticosteroid-resistant acute allograft rejection in cardiac and hepatic transplant patients also used to deplete T cells from donor bone marrow prior to transplantation
Anti IL-2 Basiliximab
Uses of Basiliximab anti-IL-2 which is given as a prophylactic (20mg prior and 20mg on day 4) for acute rejection in renal transplantation in combination with cyclosporine/tacrolimus and corticosteroid.
Joint disease Infliximab
Bone marrow rejection: Retuximab
Atopic asthma: Omalizumab
Created by: Ulaisl