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109 Cards in this Set
- Front
- Back
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Define Sensitivity.
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The probability that a test will be positive if a patient actually has the disease.
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The more sensitivity you have, the _____ false negatives you have.
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Less
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Why may a false negative happen?
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1. It may be too early in the infection for the patient to have antibodies to it
2. People may be immunosuppressed 3. You may be looking for an antibody that hasn't developed yet (IgG when you are in the IgM phase) |
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Define Specificity.
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The probability that a test will be negative if a patient actually doesn't have the disease.
The antibody won't bind anything that isn't the antigen although it may not always bind to the antigen. |
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The more sensitivity you have, the _____ false positives you have.
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less = more false positive
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Is an ELISA very specific?
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No
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What would you do if you had a positive ELISA test?
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You would follow it up with a western blot.
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How are ELISA's in terms of cost and speed?
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They are fast and cheap.
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What are the two ways in which ELISA's can be run?
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1. Start off with an anchored antobody and use it to detect antigen.
2. Start off with an antigen and use it to detect existing antibodies. |
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What is the unique critical component of ELISA tests?
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Secondary antibodies that have their Fc region bount to some sort of indicator
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Define cross reactivity
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When an antibody binds to something that looks like the antigen it is specific to, but it is something different.
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What is an example of an autoimmune disease that can arise from cross reactivity.
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Rheumatic fever. You develop antibodies to strep pyrogenes, but this also looks like myosin in heart so you end up attacking your own heart.
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Describe indirect vs direct immunoflorescence.
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Direct - the primary antibod is bound to a flourescent molecule
Indirect - the secondary antibody is bound to a flourescent molecule and will bind to a primary antibody. |
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Why is it preferable to use an indirect immunoflorescence technique?
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Cheaper - You can just buy one secondary, labeled antibody that will bind all Fc regions of promary antibodies.
More Visualization - several labeled secondary antibody can bind to one primary one and provide more immunoflourescence. |
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What are the types of immunoflorescence?
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Rhodamine/Flourescein
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Describe agglutination
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You put the sample onto a plate and add antibodies to see if the antibodies will attach to them and cause them to clump together.
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Which antibody works the best for agglutination?
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IgM
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Why?
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It is large and able to overcome the zeta potential through cross linking and attracting each other's Fc regions. All other antibodies are too small for direct cross linking.
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What is zeta potential?
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The electrical force that prevents two molecules from coming together
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When may you need to do indirect agglutination?
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Adding a secondary antibody to cross link non IgM antibodies to bring them together.
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What antibody can cross the placenta?
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IgG
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When may you use agglutination on fetal testing?
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If you want to find out if the second child that the mother is carrying is having IgG molecules attack it's rhd units on it's RBC's.
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When may you have lots of monoclonal antibodies?
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Multiple myeloma where you basically have a tumor of a B cell.
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What is a monoclonal antibody?
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An antibody that comes from the same plasma cell.
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What is the concept of herd immunity?
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You are less likely to get a disease if more people around you are immune to it.
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What is the advantage of live attenuated viruses?
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It will confer more immunity because the virus can actually get into the cell and induce both humoral and cell mediated immunity. (CD8 cells will differentiate and provide effector cells in the future)
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What type of immune protection is lacking in killed vaccine? How many doses do you need to give?
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cytotoxic immunity
needs multiple doses |
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What is a component vaccine?
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A vaccine composed of antigenic molecules that are extracted from the original pathogen. (components of the pathogen)
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What do component vaccines need to be administered with? Why?
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An adjuvant to keep it alive and stable in the host long enough for the immunogen to elicit an immune response.
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WHat else do adjuvants do?
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They act as a nonspecific immunogen stimulating macrophages.
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What is a toxoid vaccine?
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A component vaccine that is a chemically altered toxin.
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What is DTaP?
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Vaccine against diphtheria, tetanus, and petussis - they are all component vaccines
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What is a conjugate type of vaccine?
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A vaccine that injects polysaccharide-protein conjugates to induce linked recognition in B cells.
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What is a polysaccharide-protein conjugate?
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A protein of interest attached to a polysaccharide. The B cell will bind easily with the polysaccharide, but process and present the protein on it's MHC II.
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Do polysacharides get processed onto MHC?
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NO
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What is the definition of autoimmunity?
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it is an adaptive immune response to self antigens
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What does autoimmunity result because of?
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breakdown of either central or peripheral tolerance.
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What are the two types of peripheral tolerace?
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Anergy and suppression
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What is responsible for suppression?
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T regulatory cells
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What marker does a T regulatory cell have?
Mnemonic? |
CD25.
These regulatory cells are super AnaL. |
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When does autoimmunity usually get triggered by?
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Infection- during or after
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What genes are associated with inherited autoimmunity?
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Genes associated with MHC II
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What normal body molecules can influence autoimmunity? What does this mean for predisposition to autoimmunity?
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Hormones. This means that women are more prone to autoimmunity.
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What are six mechanisms for loss of self tolerance?
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1. Escape of autoreactive B or T cells
2. Bystander effect 3. Molecular mimicry 4. Anitgen spreading 5. Release of new antigens 6. Supression loss |
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Explain molecular mimicry
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Molecular mimicry - cross reactivity from an infection from a pathogen that looks very much like a self protein
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Explain the Bystander effect
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Bystander effect - an autoreactive lymphocyte just happens to be around during a massive infection or around an active superantigen and receives signals to become active.
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What is a classic example of molecular mimicry?
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Rheumatic fever with S. pyogenes and cardiac myosin
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What is a more recent example of molecular mimcry?
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Diabetes caused by infection with Coxackie virus and CMV that cross reacts with glutamate decarboxylase on pancreatic islet cells.
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Explain antigen spreading.
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This happens when you have tissue damage that results in conformational change/degradation of proteins. This leads to new parts of the protein being exposed that you haven't developed tolerance to.
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How does loss of supression occur? (we think)
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loss of T regulatory cells as we age
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What are the three classes of autoimmune diseases?
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1. Type II hypersensitivty
2. Type III hypersensitivty 3. Mix of antibody and T cell causes |
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What is the cause of myasthenia gravis?
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there is an antibody that binds to the ACh receptor, blocking the function.
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What happens to the ACh receptors in myasthenia gravis?
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the post synaptic neuron is endocytosed and degraded
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What is the clinical presentation of myasthenia gravis?
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progressively worsening muscle weakness
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Who is predisposed to myasthenia gravis?
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women under 40
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What is the treatment for myasthenia gravis? What is it's mechanism?
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acetylcholine esterase inhibitors to keep the ACh in the cleft longer so that it has increased chance of binding with the reduced amount of receptors.
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How can you stop the progression of this disease? What is the downside?
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Give azathioprine, which is a generalized immunosuppressant. We can't just shut off that antibody production. The downside is increased infection.
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What is the level of autoreactive lymphocytes in the normal person?
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They exist, but are in very low levels.
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What causes Graves disease?
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Your body produces antibodies that are an agonist to TSH receptor on the thyroid cells.
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What is autoimmune hemolytic anemia?
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antibodies created against antigens on the surface of our RBC's
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What is the warm Ab type of autoimmune hemolytic anemia?
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When you develop IgG to RhD antigens.
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How do RBC's marked with antibody in warm Ab type get destroyed?
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Opsonization
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WHy don't the RBC's in warm type get destroyed by complement?
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They have complement regulating proteins like DAF on their surface that overcome complement activation because there isn't so much of the Rh antigen on their surface.
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What is the Cold Ab type of autoimmune hemolytic anemia?
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Creation of IgM to glycophorin
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How would you test for warm ab type?
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Use the Coomb's test and add a secondary Ab to visualize agglutination.
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What would happen to RBC's in cold Ab type? Why?
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They would get lysed by complement because glycophorin is prevalent enough on the cell surface to overcome the complement regulating factors.
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Why is it called cold type?
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The binding tends to occur in colder regions so you will see the lysis more in the hands and feet.
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What is the protein involved in rheumatic fever?
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M protein
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Why doesn't everyone get rheumatic fever when they get strep pyogenes?
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M protein is huge with very many epitopes. Only a few of those will cross react with heart myosin and it is just random chance who develops immunity using those epitopes.
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What is Goodpasture's syndrome?
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The development of antibodies to Type IV collagen, which is present mostly in the basement membrane of glomeruli.
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What is rheumatoid arthritis caused by?
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IgM develops against IgG Fc region.
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Why does rheumatoid arthritis start happening?
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We don't really know, but we have a theory. When an unusual IgG is bound to an epitope and undergoes conformational change to facilitate opsonization, it exposes a new epitope on it's Fc region. IgM is created against this.
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How can we test if someone has rheumatoid arthritis? What is the mechanism behind their prevalence?
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People with rheumatoid arthritis have elevated antibodies to cyclic citrullinated peptides (anti-CCPs) and elevated CD17 T cells. We don't know why these things are raised.
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Why does rheumatoid arthritis happen in the joints and where does it start?
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Because that's where the immune complexes are deposited. It starts in the small joints and progresses to the larger ones.
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How prevalent is rheumatoid arthritis and how much more likely are women to get it than men?
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It is present in 1-3% of the US population and is 3 times more prevalent in women.
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What is the etiology of systemic lupus erythematosus?
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You develop antibodies to ANA (anti nuclear antigens), which are in high levels throughout the body.
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What will the antibody to ANA activate?
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complement
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So what is the level of complement in SLE?
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Very low because they are used up.
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What are the nuclear antigens that we can develop antibodies to in SLE?
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DS DNA (diagnostic), histones, ribonuclear proteins aka Smith nuclear antigen (diagnostic), and phospholipids.
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Where do the immune complexes in SLE-1 deposit?
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blood vessels, kidneys, CT, and skin
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What is the clinical manifestation of SLE?
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whole body inflammation
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How common is lupus and how much more common is it in women?
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1 in 500 people have it and women are 4 times more likely to have it
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What kind of rash is associated with lupus?
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the butterfly rash
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What happens in multiple sclerosis? (a brief overview) What type is it?
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This is a T cell dependent autoimmunity where T cells will start attacking myelin and their cytokines will mediate destruction and progressive demyelination.
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What happens in Hashimoto's thyroiditis? (a brief overview) What type is it?
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There is destruction of the thyroid due to T cells (CD4) and antibodies.
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What happens in celiac's disease? (a brief overview) What type is it?
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It is a T cell mediated disease that destroys enterocytes as well as creating antibody to gliadin in wheat gluten.
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What is the HLA complex? What does it code for an what chromosome is it on?
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It is the complex of genes that code for both MHC I and MHC II on humans. It is always located on chromosome 6.
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What does it mean that MHC is polygenic?
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There are multiple alleles for each protein involved in MHC.
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What are the three loci of MHC I?
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A, B, and C
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What are the three loci of MHC II?
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DP, DQ, and DR
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How many subunits are there in MHC I?
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1, the alpha
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How many subunits are there in MHC II?
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2, alpha and beta
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How many MHC I variants can one person have?
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6
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How many MHC II variants can one person have?
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12
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Why is it 12?
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Because you can mix alpha and beta within a loci (2 x 2 = 4), but you cannot mix between loci so it is (3 x 4)
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What is an adjuvant? What are some ways that they work?
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Something that enhances the immune response to a vaccine either by increasing uptake or making the antigen last longer.
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What is the most common adjuvant? How does it work?
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Aluminum hydroxide. It works by creating a pocket for the vaccine so it can be released slowly and steadily.
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How can you remember that Type II and III are the ones that cause autoimmunity.
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Process of elimination.
Autoimmune is an adaptive immune response so it can't be IV. We also don't have self proteins that are like parasites so no Type I. (unsure about mechanisms) |
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What is the difference between a component vaccine and a killed vaccine?
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The killed vaccine is still the whole organism.
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WHen you immunize with just a polysaccharide, what kind of immunity do you get?
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You get the independent B cell response so only IgM is produced.
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Why do polysaccharides only induce IgM immunity?
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because it is proteins that bind to MHC to induce T cell activation.
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Why is polysaccharide immunization (even for bacteria with polysaccharide capsules) not good for intestinal or inhaled pathogens?
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Because you need IgA at the mucosal surface.
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How do you fix this problem?
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Make a polsaccharide/protein conjugate to induce T cell activation and subsequent class switching.
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Can a bacteria cell act as an adjuvant?
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Yes! It will ellicit an immune response so it counts.
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What does the DTaP vaccine contain? How is it different than DTP?
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one Diptheria protein, one Tetanus protein, and two pertussis proteins.
DTP used to contain the whole killed pertussis, but it induced too much of a response. Now DTap needs to be administered more often. |
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If you give a conjugate vaccine of S. pyogenes polysaccharide capsule with diptheria protein toxin, what antibodies will you get?
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IgG, IgA, adn IgE to Both the carbohydrate and protein.
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How powerful is the bystander effect?
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It can be so powerful that it overrides the need to have the B7-CD28 binding signal.
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Which allele is associated wit autoimmune?
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The DR3 allele for MHCII.
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Where is collagen type IV for goodpasture reaction exposed?
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Kidney glomeruli basement membrane and alveoli
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