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97 Cards in this Set
- Front
- Back
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How do having differing serotypes promote immune invasion by Streptococcus pneumoniae?
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They differ in their capsular polysaccharides. Antibodies recognize only one polysaccharide coat. Different serotypes (or strains) have different coats. Won't prevent primary reinfection with another serotype because they have different coats.
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What is antigenic drift? Give an example.
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Due to original antigenic sin, pathogens that differ in only a few epitopes will prevent the formation of a new primary immune response. The old response is used. Causes relatively mild and limited disease epidemics.
Viral genomes are constantly mutating, producing new forms of these antigens. If one of these new forms of an antigen is sufficiently different from the old antigen, it will no longer bind to the receptors and viruses with these new antigens can evade immunity to the original strain of the virus. When such a change occurs, people who have had the illness in the past will lose their immunity to the new strain and vaccines against the original virus will also become less effective. Example is the constant mutation of some parts of the flu virus. |
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What is antigenic shift? Give an example.
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A new pathogen (usually virus) emerges that is so different from its predecessors it's able to infect almost everyone. They inflict severe disease and mortality (pandemic).
Example. Influenza strains that cause pandemics are recombinants from human and avian viruses. They're antigenically very different and NO ONE has protective immunity. |
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Which is more serious: antigenic drift or shift?
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SHIFT. In antigenic drift there will be SOME, but not complete immunity.
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What is the best way to clear a virus by Ig?
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Neutralization. This means the binding of Ig to the portion of the virus that would bind to host cells (the virus' receptor).
Ig binding to other parts of the virus is useful, but this is the best way. |
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Which part of the flu virus is more likely to no longer react with antibodies from previous infections?
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Hemagglutinin.
It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected. |
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How do gene rearrangements promote immune invasion by Trypanosoma brucei (T brucei), the sleeping sickness protozoan?
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Certain protozoans regularly change their surface antigens by a process of gene rearrangement. Leads to multiple primary immune responses that produce a dramatic cycling in parasite load in infected person.
Trypanosome's surface is a glycoprotein of which there are numerous variants encoded by different genes. The dominant surface protein is constantly changing. |
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How does herpes virus hide from immune system?
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Has a latent state that is primarily in neurons (because neurons have little MHC Class I) where replication and generation is NOT occurring. Can reactivate if immune response gets weaker.
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How does Epstein-Barr Virus (EBV) hide from immune system?
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EBV infects cells by binding to CR2 component of BCell coreceptor complex. This causes stimulation and proliferation of EBV-specific T cells. The result is a large number of mononucleocytes. CD8 T cells kill infected B cells after a certain amount of time.
After disease (mono in adulthood, less serious disease in childhood), some B cells are latently infected and synthesis of viral proteins is shut down except one that maintains replication. Reactivation is unusual unless immunosuppression occurs. There is a possible malignancy link to the virus. |
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How do pathogens exploit immune system by using phagocytic cells as protected haven?
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The prevent fusion of the vesicle they're in with the lysosome so they go into the cytoplasm (sometimes not in vesicles anymore) or just stay in special vesicle.
They prevent the activation of the macrophage, basically. |
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How does listeria exploit the immune system?
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It lives in macrophages and moves around with it and replicates. Another macrophage will pinch off a little of the infected macrophage and get infected itself. This is how it spreads.
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Of the four classes of human pathogens which are the best as subverting the immune response and why?
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Viruses, because they can hide out inside cells.
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How does blocking TAP lead to evasion of IS?
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In order to make new MHC Class I with antigenic proteins, the cell endocytoses the antigen and breaks it down in the proteasome, which then sends it to TAP for insertion into the nascent MHC Class I.
Some pathogens prevent peptides from being loaded into nascent MHC Class I molecules, leading to decreased expression of peptide-loaded MHC, resulting in the cell not being recognized by CD8 T cells. |
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How does CMV evade immune system?
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It has many genes targeting varying aspects of immune response, one of which is prevention of TAP activity/function.
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What are superantigens?
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They're bacterial toxins that stimulate a massive but ineffective polyclonal T cell response.
They do this by simultaneously binding MHC Class II molecules and TCRs in the absence of a specific peptide antigen, mimicking antigen binding and causing massive T cell activation. This causes massive cytokine release leading to systemic shock. |
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How is respiratory syncytial virus (RSV) an example of how the immune response alone causing sickness?
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RSV causes a Th2 response which causes wheezy bronchitis in infants.
Vaccine failure was because Th2 were sufficiently induced but no Ig was produced, resulting in increased inflammation and damage. |
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T/F Excessive Th2 activation and inflammation can cause disease
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T
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Anti IL-4 antibody would inhibit a _______ response
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Th2
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What are the main cytokines secreted by Th1 cells? What do they do?
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IL-2 and IFN-γ.
These lead to macrophage activation, production of opsonizing antibodies like IgG. |
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What are the main cytokines secreted by Th2 cells? What do they do?
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IL-4 and IL-5.
They lead mainly to B cell differentiation and production of neutralizing antibodies, like IgE, which can be effective against parasitic worms. |
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Which Helper T cell is associated with:
A) IFN-γ B) IL-4 C) Fox P3 |
A) Th1
B) Th2 C) Treg |
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If leprosy infection activates a Th1 response, what happens?
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The disease is highly localized and a good prognosis is expected.
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If leprosy infection activates a Th2 response, what happens?
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The disease is systemic, and correlates with poor prognosis.
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What is a potential treatment for a Th2 leprosy response? Why?
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IFN-γ. This is what the more effective Th1 cells secrete.
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What is a potential downfall of too much Treg?
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While Treg is important to prevent autoimmunity, high Treg activity increases cancer risk because it blocks self-recognition.
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What cytokines do Th17 T cells produce?
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IL-17 (this is what they're named for), and IL-22.
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What is a high amount of Th17 T cells correlated with a susceptibility to?
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MS and arthritis
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What is the animal model of ms?
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Experimental Autoimmune Encephalomyelitis
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What is the importance of IL-23?
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In conjunction with IL-6 and TGF-β1, IL-23 stimulates naive CD4+ T cells to differentiate into a novel subset of cells called Th17 cells, which are distinct from the classical Th1 and Th2 cells. Th17 cells produce IL-17, a proinflammatory cytokine that enhances T cell priming and stimulates the production of proinflammatory molecules such as IL-1, IL-6, TNF-alpha, NOS-2, and chemokines resulting in inflammation. Knockout mice deficient in either p40 or p19, or in either subunit of the IL-23 receptor (IL-23R and IL12R-β1) develop less severe symptoms of multiple sclerosis and inflammatory bowel disease highlighting the importance of IL-23 in the inflammatory pathway
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What does IL-23 stimulate CD4 t cells to become?
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Th17 cells
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Why was there a delay in finding Th17 cells?
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IL-12 (induces differentiation of T cells into either Th1 or Th2) and IL-23 (the one that causes expansion of Th17 cells) share some chains. Original studies were knockouts of the common chain, leading to no Th17.
The transcription factor induction of IL-12 and IL-23 is differnt. |
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What cells do Tregs block activation of?
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Th1, Th2, and Th17
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What causes the differentiation of the different T helper cells?
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The cytokine environment
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What is
A) the protective role of Th1 B) The harmful role of Th1 |
A) protective against intracellular pathogens
B) systemic pathology (??) |
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What is
A) the protective role of Th2 B) The harmful role of Th2 |
A) Protective against parasitic worms
B) Allergy and asthma |
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What is
A) the protective role of Th17 B) The harmful role of Th17 |
A) protective against extracellular bacteria by activating neutrophils
B) Can cause autoimmunity, inflammation, and cancer |
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What is
A) the protective role of Treg B) The harmful role of Treg |
A) Counter regulation, prevent self-recognition by other T helper cells
B) increased cancer susceptibility by prevention of recognition of tumor cells |
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Infection with <i>Pnemocystis carinaii</i> in children can indicate what?
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immunodeficiency. It is characteristic of children with genetic immune deficiency.
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What is IFN-γ needed for?
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Needed to effectively activate macrophages. Mutations of this causes diseases of varying severity.
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What cell types make IFN-γ and when?
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1) NK cells during innate immune response
2) Th1 CD4 T cells and CD8 T cells during adaptive response |
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Antibody deficiency leads to an inability to clear ___________ bacteria.
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extracellular (primary pyogenic infection that is characterized by severe local inflammation, usually with pus formation, generally caused by one of the pyogenic bacteria.)
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What does a defect in Bruton's Tyrosine Kinase (BTK) cause?
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X-linked agammaglobulinemia. (XLA)
Btk signaling contributes to growth and differentiation of pre-B cells. Without it, no Ig can be formed because no mature B cells are formed. |
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What will the pattern of X-inactivation be on women who are carriers of XLA?
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Because only B cells with BtK functioning can be produced, a carrier female's B cells will all have the SAME x chromosomes. It will be non-random (usually it's random).
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What is the treatment for Ab deficiency (other than antibiotics)?
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Periodic infusions of pooled IgG from human serum.
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What is bronchiectasis and what is it a complication of?
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It happens due to chronic inflammation in the airways when there is an insufficient immune response. It leads to bronchi losing elasticity.
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Other than a B cell development problem, what else could be a cause of diminished antibody production?
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Inherited defects in T-cell help.
Lack of CD40L (no isotype switching --> hyper IgM syndrome) Lack of germinal centers The same treatment (infusion of Ig) is given. |
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What is neutropenia?
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A deficiency of neutrophils.
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Why should patients with immunodeficiencies not be given live viral vaccines (e.g., polio)?
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They won't develop immunity, and even though they're not given the virulent form of the disease, if the immune system can't neutralize/clear the lesser form or respond to it, it can hang out and possibly backmutate to more virulent form.
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What is the phenotype like in defects in complement components?
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extracellular pyogenic bacterial infections, similar to Ab deficiencies.
Accumulation of immune complexes due to inability to phagocytose. |
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What is the phenotype like in defects in complement control components?
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Will see overactivation of complement, and therefore autoimmune problems
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What is C1 inhibitor (C1INH) deficiency?
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Autosomal dominant disease caused by deficiency in complement regulator C1. Causes hereditary angioedema.
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What is hereditary angioedema?
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Subepithelial swelling of face, larynx, abdoman caused by deficiency in complement regulator C1 inhibitor. No C1 inhibitor means no inactivation of parts of complement.
C1 inhibitors are part of a large class of serine and cysteine protease inhibitors called serpins. |
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What are serpins?
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A large class of serine and cysteine protease inhibitors. They act as pseudosubstrates and inactivate proteases.
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What do defects in phagocytes result in?
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enhanced susceptibility to bacterial infection. Problems in BOTH innate and adaptive immunity.
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What is leukocyte adhesion deficiency (type I and type II) ?
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Cause: defective cell adhesion molecules (type I:CD18, an integrin; type II:selectin deficiency) results in inability for phagocytes to stick to walls and migrate to site of infection
phenotype: persistent infection with encapsulated bacteria that can't be cleared. Likely needs bone marrow reconstitution. |
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Which cell adhesion molecule mediates weak attachment that slows down cells? Which mediates stronger attachment?
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Selectins; Integrins
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Which are usually more serious - T cell or B cell deficiencies?
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T cell, because they function in all aspects of adaptive immunity. (B cells only function in antibody response)
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What is the common γ chain?
What is the phenotype if lacking this? |
A protein subunit of several cytokine receptors. It interacts with protein Jak3 to induce signaling from the receptor when the cytokine binds.
Patients defective in this have SCID. |
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A deficiency in JAK3 leads to what phenotype?
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SCID
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What is Wiskott-Aldritch syndrome?
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Impairment of platelets and lymphocytes.
They don't make good Ig responses even though normal levels of T and B cells. IR signaling defect but can be treated with γglobulin. |
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What is adenosine deaminase deficiency? (ADA?)
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Lack of adenosine deaminase, an enzyme in purine degradation, causes buildup of toxic metabolites in all cells.
Developing T cells (and B cells to a lesser degree) are particularly susceptible to poisoning with excessive nucleotide analogs. Phenotype of SCID. |
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What is bare lymphocyte syndrome?
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Lack of MHC Class II. CD4 cells fail to develop by failure of thymus to positively select.
Phenotype of SCID. |
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What is bare lymphocyte syndrome MHC Class I?
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Lack of MHC Class I. Lack of CD8 T cells resulting in increased viral infection susceptibility.
Less severe phenotype than MHC Class II deficiency. |
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What is IL-12 receptor deficiency?
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Receptor for IL-12 is nonfunctional producing a susceptibility to intracellular bacterial infections.
IL-12 is normally secreted by macrophages that binds to IL-12 receptors on T cells. Helps induce differentiation to Th1 cells. Normally the activated Th1 cell would stimulate the macrophage to strengthen its activation. When there is no IL-12 receptor, the cycle of mutual activation can't happen. |
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How is bone marrow transplant accomplished?
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Patient's own bone marrow is destroyed. Then healthy donor's bone marrow is transfused which then reconstitutes the entire hematopoietic system.
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What is graft-vs-host-disease?
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Mature T cells in the transplant respond to allogeneic MHC Class I and II molecules of the recipient. (Mature T cells attack host/recipient).
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What must the donor and recipient of bone marrow transplant share in order to restart T cell function in recipient?
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HLA Class I and II
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Why is there a necessity for (at least) partial HLA matching in bone marrow transplant?
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The recipient/host's total immune system is destroyed and bone marrow from donor/graft is what will make up the new immune system.
Immature T cells leave bone marrow for thymus. To get out of thymus they must be <b>positively selected by the HOST/RECIPIENT's thymic epithelial cells</b>. But once they're out in the periphery, they will respond to antigen presented by <b>GRAFT/DONOR's APCs</b>. If they don't have HLA in common they won't be able to respond to pathogen-derived antigens presented by APCs. |
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What type of infections will the following deficiencies be MOST susceptible to?
A) Antibody B) T cell or Combined C) Complement D) Phagocytic |
A) Bacterial
B) Bacterial, Viral, Fungal, Protozoan (ALL) C) Bacterial D) Bacterial and fungal |
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What is the treatment of antibody deficiency?
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Infusion of immunoglobulins by IV
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What is the treatment of SCID?
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Bone marrow transplant; Enzyme therapy; Interleukin-2 infusion; Gene therapy (in future)
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What is the treatment of WASP? (Wiscott-Aldritch Syndrome)
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γglobulin (sometimes BMT)
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What is the treatment of Chronic Granulomatous disease?
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Interferon gamma to activate macrophages better
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What is the treatment of LAD (leukocyte adhesion deficiency)?
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Bone marrow transplant
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Which cells are vulnerable to HIV Infection because they express CD4?
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Macrophages, Dendritic Cells, and CD4 T cells
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What does HIV use as a receptor? Co-receptor?
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CD4 cell surface markers; Other chemokine receptors that determine what variant of HIV it is such as CXCR3 or CCR5
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What are macrophage-tropic HIV variants?
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Requires only modest levels of cell-surface CD4. These are the ones that spread infection preferentially. They use CCR5 as the chemokine receptor
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How do DC cells play a role in HIV transmission?
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DC specific surface C-lectin (DC-SIGN) bind HIV and don't allow infection of the DC itself but instead enhance its presentation to and infection of CD4+ T cells.
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How can follicular dendritic cells (FDCs) come into play in HIV?
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They can bind infectious HIV and protect it from antibody and be in close contact to CD4+ T cells
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What does the production of infectious virions from the HIV provirus require?
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Activation of the CD4 T cell to induce synthesis of NFκB to bind to promoters in provirus
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When would post-exposure prophylaxis be most effective?
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36-48 hours after exposure
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What is seroconversion?
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When an infected person first exhibits detectable levels of anti-HIV antibodies in serum
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When is the virus taken to the lymph node?
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Between day 0-2
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Which response is more important : cellular or humoral?
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Cellular CD8 T cell response is more effective
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When does massive depletion of GALT occur? What are implications?
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within weeks; massive total body CD4 t cell depletion. About 50% gone in 4 weeks.
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What leads to microbial translocation? What happens after that?
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Reduced GALT T cells and IL-17 along with mucosal breaches; Excessive T cell activation and inflammation follow
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What are the implications of plasma LPS (bacterial endotoxin) being increased?
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they correlate directly with HIV related T cell activation which is characteristic of HIV 1
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Other than opportunistic infection risk, what are other causes of problems in HIV? Ie., what are the implications of chronic CD8 T cell activation?
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Accelerated T cell activation and senescence. Result is aged population of T cells (telomere depletion). Can lead to systemic inflammation that puts people at risk for CVD etc.
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What are the most important players in reducing viral load?
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CD8 T cells
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Why has there not been a vaccine?
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Vaccine would induce antibody production/humoral IS which doesn't help that much with HIV.
Most antibody is non-neutralizing and doesn't help clear HIV. Most HIV neutralizing Ig formed is to a specific region of a viral surface glycoprotein which is generally hidden/silent. The main surface glycoprotein gp120 is a tough antibody target because it's so variable. There is lots of mutation all the time. |
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Which domain would an antibody bind that is MOST effective?
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The gp120 CD4 binding domain.
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how does HIV persist despite an effective CTL response?
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Amazing HIV mutational capability results in CTL and humoral immune “escape”
Selective elimination of anti-HIV CD4+ T-cells Downregulation of MHC and CD4 molecules Immune “sanctuaries” (eg. gut, brain, testes) Ability of HIV to integrate into host cell genome |
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What are the implications of HIV inducing a Th1 to Th2 cytokine shift?
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It drives a more humoral (less effective) Th2 response instead of the cellular (more effective) Th1 response.
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What is HIV NEF? What does it downregulate?
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The expression of Nef early in the viral life cycle ensures T cell activation and the establishment of a persistent state of infection, two basic attributes of HIV infection. Nef also promotes the survival of infected cells by downmodulating the expression of several surface molecules important in host immune function. These include major histocompatibility complex-I (MHC I) and MHC II present on antigen presenting cells (APCs) and target cells, CD4 and CD28 present on CD4+ T cells.
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Why does B cell dysregulation and autoimmunity happen in HIV?
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Because of loss of CD4.
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What do inflammatory or coagulatory biomarkers have to do with HIV?
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Their levels can be predictive/associated with mortality
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What are the effects of long term antiretroviral therapy?
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Initially, improved CD4+ T-cell survival and expansion of the “memory” CD4 T-cell pool
Peripheral recruitment & proliferation of lymphoid tissue sequestered cells (during first several months) Reconstitution of naïve T-cells due to increased thymic output (over several years) Reduced T-cell activation (often remains above “normal”) ?Reduced gut leak and systemic inflammation (often remains above “normal”) Less morbidity and improved survival (remains below “normal”) Increased lymphoproliferative response to recall antigens are observed as well…except to HIV. |
