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pszurnicki
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What are the 3 effects of Interferon Alpha, Beta and Gamma have?
- 1. Interferon Alpha and Beta--stop viral protein synthesis via upregulating ribonuclease
- 2. Interferon gamma--upregulation of MHC I and II and increased Antigen presentation
- 3. Activates NK cells to kill virus infected cells
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What are the different types of MHC class I?
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What are the different types of MHC class II?
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Thymus is embryologically derived from?
3rd branchial arch
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Transmembrane and secreted IgM are both derived from the same mRNA thru what process?
alternative splicing
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What is the enzyme involved in somatic hypermutation, gene conversion and class switching?
activation induced cytidine deaminase (AID)
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Which MHC receptor has the beta 2 microglobulin?
MHC I
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Leukocyte adhesion deficiency Type I is caused by what?
deficiency of CD18 integrin on leukocyte membrane
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Leukocyte adhesion Deficiency Type II is caused by a defect in what?
Fucosyl transferase---which synthesizes a ligand for a selectin molecule
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Chediak-Higashi syndrome is caused by a defect in what?
defect in microtubular function
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Chronic Granulomatous Disease is caused by what?
deficiency of NADPH
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Myeloperoxidase deficiency is caused by what?
absent MPO-H202
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Gram positive or negative bacteria have LPS on their surface?
Gram-negative
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Toll Like receptors (TLR) are located where in the cell?
- - cell membrane
- - endosomes
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Signaling thru TLR or NOD receptors induces the expression of what?
NFkappaB
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Deficiency of C1 esterase inhibitor leads to what condition?
angioedema
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Membrane attack complex defends against what type of bacteria?
gram-negative bacteria
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C5B, C6,C7,C8,C9 make up what?
membrane attack complex
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What are the derivates of common lymphoid progenitor?
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Deficiency of C5-C8 causes what?
Neisseria bacteremia
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Deficiency of DAF (Decay-accelelrating factor) leads to what?
paroxysmal nocturnal hemoglobinuria
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An increased susceptibility to Type III hypersensitive rxn's and recurrent pyogenic sinus and respiratory tract infection are due to a deficiency of what complement factor?
C3
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C1 thru C4 are involved in what ?
viral neutralization
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C3b is involved in what?
opsonization of bacteria
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C3a and C5a are involved in what?
anaphylaxis and neutrophil chemotaxis
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What interleukin induces the liver to express acute phase proteins?
IL-6
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Which portion of the Antibody molecule, Fab or Fc determines the isotype?
Fc
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Which part of the antibody determines the idotype?
Fab
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To which part of the antibody does the complement bind to?
Fab
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Which part of the antibody is the amino terminal?
Fab
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What are the 3 functions of antibodies?
- -Opsonization
- -Neutralization
- -Complement activation
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Antibody diversity is generated in 4 ways, what are they?
- 1. Random recombination of VJ (light chain) and VDJ (heavy chain)
- 2. Random combination of heavy and light chains
- 3. Somatic hypermutation after Ag stimulation
- 4. Addition of nucleotides DNA during recombination by terminal deoxynucleotidyl transferase
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B cell is able to detect complement via CD21
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Co receptor on a B cell recognizes what?
complement
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Cyclosporin is an inhibitor of what?
calcineurin
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Protein tyrosine kinases and other signalling molecules are located in what portion of the lipid membrane?
lipid rafts
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In an immunological synapse, which part, the inner or the outer portion functions to anchor the Antigen presenting cell to the T cell?
The outer portion via LFA-1 (integrin)
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What ion is often used to amplify the original signal?
Ca 2+
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Upon binding of the antigen, what part of the T or BCR gets phosphorylated?
ITAM
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Signal # 2 for B cell is what?
Binding of CD 40 from a T helper cell
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Co receptors like CD 19, 20, 21 perform what function on a B cell??
Complement component binding
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MAPK kinase cascade activates what in response to signals?
Transcription factors
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ITIM attract ____________while ITAM attract ____________?
- ITIM attract protein tyrosine Phosphatase
- ITAM attract protein tyrosine kinases
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What type of receptors activate NFkappaB?
Toll like receptors
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Deficiency of RAG1/2 causes what syndrome?
Omenn Syndrome
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What does H. Pylori release that neutralizes the acidic environment in the stomach?
ureaase---breaks down urea to NH4
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What are the 2 forms of Leprosy?
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What enzymes are used for VDJ recombination?
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Omenn Syndrome is caused by what?
RAG1/2 missense mutation
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Bruton's agammaglobulemia is caused by a deficiency of what?
BTK (Tyrosine kinase)
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Hyper IgM is caused by a deficiency of what?
CD40L on a Helper T cell----> impaired class swithcing
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IgG, IgM, IgA are all different what?
idiotypes
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What determines the different idiotypes?
antigenic binding site
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What determines the different isotypes?
Heavy chain
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What causes Ataxia-telangiectasia?
DNA enzyme repair defect
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What is the triad of Ataxia-telangiectasia?
- ataxia
- angiomas -spider
- IgA deficiency
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B class switching requires two signals, what are they?
- Signal 1--IL-4, IL-5, IL-6
- Signal CD40L from a Th cell
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What are the 3 function of antibodies?
- Opsonization
- Neutralization
- Complement activation---via IgG and IgM
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To what toxins are antibodies given to patients? (Passive immunity)
- Tetanus
- Botulism
- HBV
- Rabies
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Membrane attack complex is activated by what?
- IgG and IgM
- molecules on the surface of microbes
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What happens in Wiskott-Aldrich syndrome?
progressive deletion of T and B cells
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What 2 antibodies are common in Hashimotos Thyroditis?
- Thyroglobulin
- Thyroid peroxidase enzyme
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What is amyloidosis?
deposition of protein in tissues
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A condition in which fragments of immunoglobulins are deposited in the tissues is called?
Amyloidosis
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Presence of a large amount of protein in plasma cells is called?
Russell Bodies
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What are the two most important action of the innate immune system?
- inflammation--recruitment of leukocytes
- anti-viral response--via dendritic and NK cells
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What are the Innate immunity receptors that recognize molecular patterns of microbes?
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TLRs and NLRs activate what common transcription factor?
NF-kappa B
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What are defensis?
anti-microbial molecules produced by the epithelial cells of the skin, respiratory and digestive tracts
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What 3 factors trigger activation of the complement system?
- 1. Antigen-antibody complex
- 2. Microbial surface antigens
- 3. Mannose binding lectin
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What are the 2 ways of activating complement system in the innate immunity?
- 1-Mannose binding lectin
- 2- Microbial surface markers/antigens
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What are the 2 divisions of the adaptive immunity?
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The enzyme which mediates the rearrangement of antigen receptor genes in developing lymphocytes is called?
RAG 1 and 2
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What can be used as a T cell marker?
Rearranged
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How can lymphoid tumors be identified?
by analyzing antigen receptor gene rearrangements
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Gamma and Sigma T cells which are specialized T cells are found where in the body?
Epithelial surfaces
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What is the antigen binding component of the B cell receptor?
IgM and IgD antibodies
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What receptor on the B cell is used by the Epstein Barr Virus for infection?
CD21
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What is the complement receptor on the B cells?
CD21
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What are the two types of dendritic cells?
- Follicular Dendritic cells
- Interdigitating dendritic cells
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Follicular dendritic cells are located in what two locations?
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Follicular dendritic cells in the spleen and L.node have what type of receptor?
Fc receptor
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Fc receptor is for what two entities?
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Balance of what two signals determines whether a NK cell with kill a cell?
activating and inhibitory signals
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What are the inhibitory cell signals that prevent NK cells from killing normal healthy cells?
MHCI molecules
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Pathogens that penetrate the epithelium end up in lymph nodes how?
Dendritic cells (langherans) cells ingest them and take them to l. nodes
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Th1 cells play a role in defense against what microbes?
intracellular microbes
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Th2 cells play a role in defense against what ?
- helminthic parasites
- allergy
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Which Th cell is implicated in allergy?
Th2
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Th17 cells play a role in defense against what microbes?
extracellular bacteria and fungi
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Which interleukin stimulates the proliferation of T cells?
IL-2
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What molecules on a T helper cell activates macrophages and stimulates class switch on B cells?
CD40L
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Which Ig is transported across the placental barrier?
IgG
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What receptor on the phagocytes binds to antibodies?
Fc receptor--Fc for the Fc region of the antibody molecule
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Which Types of Hypersensitivity disorders are mediated by antibodies?
Types I thru III
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Anti-Glutamate decarboxylase antibodies present in what disorder?
DM I
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Antihistone antibodies present in what disorder?
Drug induced SLE
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Anti-smooth muscle in what disorder?
Autoimmune hepatitis
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Synovia cysts are associated with what disorder?
Rheumatoid arthritis
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Anti-IgG antibodies are present in what disorder?
RA
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What are epitheloid cells?
epithelium like transformed macrophages
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What is a granuloma?
aggregation of Epithelioid cells surrounded by lymphocytes
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What are the specific lysosomal enzymes?
- histaminase
- lysozyme
- collagenase
- gelatinase
- lactoferrin
- plasminogen activator
- alkaline phosphatase
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What are the azurophilic enzymes?
- acid hydrolase
- myeloperoxidase
- defensins
- acid hydrolases
- elastase
- cathepsin G
- non specific collagenase
- proteinase=
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Which organism causes Lyme disease?
borrelia burgorderi
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c-ANCA antibodies found in what condition?
Wegener's granulomatosis
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p-ANCA in what disorder?
other vasculitis
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Anti-smooth muscle
immune hepatitis
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3 drugs for Gout?
- Allopurinol--xanthine oxidase inhibitor
- Colchicine--microtubule
- Propenecid--inhibits uric acid reabsorption in PCT and inhibits secretion of penacillin
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Self-reactive T cells that become nonreactive without co-stimulatory molecules are called?
anergic
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Stem cells express what marker?
CD34
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When does CD19 become expressed on the developing B cell?
After heavy chain has been rearranged
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The heavy chain is rearranged by which stage in the developing B cell?
Large Pre-B cell
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The light chain is rearranged by which stage in the developing B cell?
Immature B cell
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By which stage in the developing B cell is the intracellular IgM expressed?
Large Pre-B cell
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What are Reed-Sternberg cells?
B cells without specific cell markers
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Positive selection of T cells occurs where in the thymus?
Cortex
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Negative selection of T cells in the thymus occurs where?
medulla
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How is positive and negative selection of T cells different in the thymus?
- Positive selection---T cells that recognize self antigen are selected for
- Negative selection--T cells that recognize self antigens are selected against
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B cells are found in what area of the spleen?
white pulp white for Bleach....B cells
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T cells are found in what area of the spleen?
Red pulp
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A Superantigen binds to a site other than Ag binding site and elicits what type of syndrome?
Toxic shock syndrome
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Clostridium Difficile causes diarhea usually secondary to an exposure to what agent?
antibiotics --clindamyocin or ampicillin
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Polysaccharides or proteins are sufficient to activate B cells?
polysaccharides
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Abnormal proliferation of plasma cells in the bone marrow leads to what kind of cancer?
Multiple Myeloma
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What enzyme induces somatic hypermutation, gene conversion and isotype switch?
AID
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Hyperacute organ rejection is mediated by what?
B cell---antibody
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Acute, GVHD and chronic organ rejection is mediated by what?
T cell
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What two superantigens cause toxis shock syndrome?
- streptococcus pyogens
- staphylococcus aureus
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What activates macrophages?
INF-gamma
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What induces the Truncus Arteriousus to become ascending aorta and pulmonary trunk?
Neural crest cell migration
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Humoral rejection of cell mediated rejection is characterized by vasculitis?
humoral
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Humoral or cell mediated rejection is characterized by monocyte infiltration?
cell mediated rejection
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Primary immunodeficiencies are caused by what?
genetic factors
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Secondary immunodeficiencies are caused ?
- infections
- immunosupression
- malnutrition
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Neutrophilia, Omphalitis and recurrent bacterial infections are indicative of what?
Leukocyte deficiency type I
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LAD
Integrin CD18 defect beta chain
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What kinds of organisms cause recurrent infections in a person with Chronic Granulomatous Disease?
- C
- A
- T
- Aspergillus
- L
- Aureus
- S
- E. coli
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Infections with catalase positive organisms occur in people with what disease?
Chronic Granulomatous disease
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Hyper Ig-E or Job syndrome is caused by what?
deficient production of IFN-gamma from Th cell
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What Immunoglobulin is overproduced in Job syndrome?
IgE
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Hyper IgM syndrome is caused by what?
- deficient CD40 on Th cell
- failed class switching
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What is the only B cell immunodeficiency where there is no production of B cells?
Bruton's agammaglobulinemia
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What is the etiology of rheumatic heart disease?
antibodies produced to group A streptococcus cross react with heart
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What is the fluorescent pattern of glomeruli in good pasture?
ribbon like--continuos
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What is the flourescent pattern of staining of glomeruli in SLE or Post streptococcal glomerulonephritis?
Bumpy Lumpy--interrupted vs ribbon like in good pasture
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Cyclophosphamide and isofamide function how?
covalently linking DNA at guanine N-7
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What are the VDRL false positives?
- viruses (mono, hepatitis0
- Drugs
- Rheumatic fever
- Lupus and Leprosy
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What CD markers are present on Reed-Sternberg cells?
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What condition is accompanied by secondary antiphospholipid syndrome?
Systemic Lupus Erythromatouses
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Libman-Sacks endocarditis is a condition caused by what disorder?
Systemic Lupus Erythromatosus
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Which syndrome is characterized by Xeropthalmia, Xerostomia and arthritis along with destruction of lacrimal and salivary glands?
Sjogren syndrome
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What is the only lipid that is an antigen?
Cardiolipin
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What is a hapten?
too small to start an immune response
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How does penicillin elicit an immune response/?
penicillin is a hapten and binds to host proteins at which point is taken up by a B cell which is activated to produce antibodies by T helper 2 cells
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What is the function of an adjuvant?
enhances immunogenicity of the antigen
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The TLRs located in the endosomes of the cells tend to detect what kind of foreign antigens?
nucleic acids
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What is the best way of introducing antigens to induce immunity?
subcutaneous because the antigen is take up by the Langerhan cells which migrates to the Lymph node and activatees T cells
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How are viruses attenuated?
they are grown and selected for in non-human cells?
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Phosphatases are found where
ITIMs?
ITAM?
ITIMS
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Kinases are found where?
ITIMs?
ITAMs?
ITAMs
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What is the function of Th17?
activates neutrophils
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Defect in AIRE causes what?
APECED--Autoimmune polyendcrinopathy candidiasis ectodermal dystrophy
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Defect in FAS causes what?
- ALPS
- Autoimmune lymphoproliferative syndrome
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What antigen is highly expressed in the anti-microsomal antigen in Hashimotos?
Thyroid Peroxidase
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What is the mutated protein involved in the pathogenesis of Familial Mediterranean Fever?
pyrin
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In all of the autoinflammatory conditions what protein is mutated?
pyrin or cryopyrin
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Staphylocci cold absecesses and eczema with High IgE levels is indicative of what condition?
Jobs, or Hyper IgE syndrome
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What is responsible for the bone resorption in RA?
MMP --metaloproteinases secreted by fibroblasts activated by cytokines
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What is the only known environmental/behavioral trigger of RA?
smoking
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What condition produces sausage fingers?
psoriatic arthritis
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Cant see, cant pee, cant climb describes what condition?
- Reactive arthritis---Reiter's syndrome
- acquired post GI or chlamydia infection
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Large vessels vasculitides have what pahological morphology?
granulomatosis disease
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Medium vessel vasculitides have what patthological morphology?
they are either immune complex fibrinoid inflammation or antibody mediated
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What does ANCA stand for?
antineutrophil cytoplasmic antibody
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How does Large vessels vasculitis present typically?
loss of pulse
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How does medium vessel vasculitis present typically?
thrombi
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How does small vessel vasculitis present typically?
hemorrhages--purpura
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Drug allergic reactions are what type of hypersensitivity?
TYPE III
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c-ANCA antibodies are produced against what protein?
proteinase-3
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p-ANCA antibodies are produced against what protein?
meyloperoxidase
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p- ANCA and c-ANCA antibodies bind to proteins found in what 3 types of cells?
- neutrophils
- macrophages
- endothelial cells
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What vasculitis is not associated with ANCA?
Polyarteritis nodosa
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Hemorrhagic mediastinitis is associated with what bacterial infection?
anthrax
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Reynolds system is associated with what vasculitis?
Buergers
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Which vasculitis has antigen antibody complexes of Hep B?
PAN
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What are 2 autoimmune disorders that affect the pulmonary and renal systems?
- Good Pasture
- Wegener's Granulomatosis
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What is the difference between Wegener's granulomatosis and Polyangitis?
- Wegener's---c-ANCA
- Polyangitis--p-ANCA
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What is the vasculitis that affects children?
Henoch-Shonlein Purpura
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What malignancy is associated with cryglobuleniemai?
multiple myeloma
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What cells amplify the response in SLE?
basophils
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The immune complexes deposit where in the kidney in a SLE pt?
between endothelium and basement membrane
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What antibody is more specific for SLE?
C1q and anti-dsDNA, Anti-SMith
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Cell mediated granulomas are responsible for crohn disease or ulcerative colitis?
CD
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Hypersensitivity is responsible for crohn's disease or ulcerative colitis?
ulcerative colitis
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Autoreactive T cells in the lamina propria cause what condition?
Inflammatory bowel disease
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Which of the IBD involves the colon only
?
Ulcerative colitis
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What is the gene mutated in Crohn's disease?
NOD2
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Increased size of the crypts is characteristic of what condition?
Celiac sprue disease
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Dermatatic Herpetiforms is associated with what disease?
Celiac Disease
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Whats deposited in the dermis in Dermatatic Herpetiforms?
IgA
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BLS-Bare lymphocyte syndrome is due to deficiency of what MHC?
MHC II
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Immunoelectrophoresis is used to demonstrate what imuunodeficiency?
Bruton's agammaglobulinemia
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What do coreceptors on B cells bind?
complement molecules
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BTK signalling deficiency prevents the the B cell from acquiring what?
Pre-B cell receptor
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Wiskot-Aldrich Syndrome results in defective what?
microtubule
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Autoimmune lymphoproliferative syndrome results from what?
absent FAS killing
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