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Week 7
Adaptive Immunity
76
Biology
Graduate
09/22/2008

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Term
Antibodies are the excreted proteins more generally known as __________?
Definition
Immunoglobins
Term
What are the 5 isotypes of constant region heavy chain and the 2 isotypes of light chain?
Definition
IgA, IgD, IgE, IgG, IgM; kappa and lambda.
Term
True or False: Since the immunoglobin genes are inherited through germ line configurations, they are also expressed in those same configurations.
Definition
False, they are not expressed that way.
Term
Which region of the immunoglobin chain is made first?
Definition
Variable region of both light and heavy chains
Term
In regards to gene arrangement in Ig’s, a light chain joins a V and J segment and the heavy chain joins the J and D to the V segment, is this correct?
Definition
Yes
Term
What is somatic recombination and the enzymes it uses?
Definition
It is the process that splices genes various regions of immunoglobin genes together utilizing Rag 1&2 enzymes to enhance genetic variety.
Term
What are the first Ig’s that naïve B cells can express on their surfaces and are the only ones that can be produced simultaneously by a B cell?
Definition
IgM and IgD
Term
Since Ig molecules on the surface of B cells can't communicate to the cell interior what additional proteins make the process fully functional?
Definition
Surrounding the Ig with Ig-alpha and Ig-beta proteins with long cytoplasmic tails
Term
Describe what happens to the following immature B-cells when: it expresses receptors for multi-valent self-antigens, expresses weaker self-antigen receptors, or has no self reaction.
Definition
1- They are deleted from immune system via apoptosis, 2- it forms a anergic B-cell capable of producing auto-antibodies in peripheral tissues, 3- forms a marture B-cell in peripheral tissues.
Term
What is allelic exclusion?
Definition
Despite the B-cell having two copies of the each gene, this process allows the production of monoclonal antibodies.
Term
What type of antibodies are used in serological assays, diagnostic probes, therapeutic agents?
Definition
Monoclonal antibodies
Term
What initiates the process of a naïve B cell proliferating and differentiating and the synthesis of IgA, IgG, IgE?
Definition
Binding of antigen for the first time.
Term
Once the appropriate signals are given to the B-cell for antibodies to be made what 3 important things occur?
Definition
Secreted antibodies, somatic hypermutation, and isotype swithching.
Term
How are somatic hypermutation and affinity maturation related?
Definition
Somatic hypermutation described how mutations accumulate in the variable regions of the antibody molecule, while the process that selects those mutants that bind the antigens with the greatest affinity are allowed to proliferate is called affinity maturation.
Term
What is the necessity for isotype switching in antibody creation?
Definition
Because it allows the variable regions of antibodies to utilize the different effector functions of the other isotypes.
Term
What is an epitope?
Definition
The part of the macromolecule that an antibody binds to.
Term
The presence of what immunoglobin is effective in diagnosing recent infections?
Definition
IgM, which is present for approx. 6 weeks
Term
List the main features of IgM and IgD.
Definition
IgM- first antibody produced, activates complement cascade, present on naïve B-cells; IgD- main role as a membrane receptor on B-cell, also active in naïve B-cells
Term
List the main features of IgA, IgG, and IgE.
Definition
IgA- most made of any isotype despite not reaching serum, important in mucosal immunity in the GI/nose/lung, crossing epithelium; IgG- inactivates toxins, opsonize bacteria, activate complement, neutralize viruses/bacteria, crosses the placenta, most abundant antibody in internal fluids; IgE- fight parasites and worms, cause allergic responses by activating mast cells.
Term
What is the key difference in antigen binding in T-cell receptors versus Ig receptors?
Definition
T-cell receptors only recognize peptide antigens that are bound to MHC molecules and doesn’t have class switching/somatic hypermutation, whereas Ig receptors can bind to many epitopes and can do those things.
Term
True or False: T cell receptors are rarely membrane bound, have somatic mutations after stimulation, can become soluble once stimulated.
Definition
False, always membrane bound, no mutations once antigen has bound, never soluble.
Term
What is the process called where antigen is degraded to a peptide:MHC complex for recognition outside the cell?
Definition
Antigen presentation.
Term
What are the 3 antigen presenting cells?
Definition
Dendritic cells, Macrophages, B-cells.
Term
Briefly describe the T-cell response to antigen from extracellular pathogens.
Definition
Extracellular pathogen, APC (antigen presenting cells) present MHC-II, induce Helper T Cells CD4-Th2, antibody creation
Term
Briefly describe the T-cell response to antigen from intracellular bacteria or fungus.
Definition
Pathogen’s antigen presented by APC’s as MHC-II, induce T-cell CD4-Th1, activate macrophages and upregulate lysosomes
Term
Briefly describe the T-cell response to antigen from viral infected cells.
Definition
Viral infection, MHC-I presentation, induce T-cells to CD8 Cytotoxic, identification and killing of viral infected cells
Term
If the T-cells that bind to MHC-I or II with self-antigen are quickly deleted, how do T-cells still contribute to autoimmunity?
Definition
Sometimes the MHC is not bound avidly enough to present the antigen and therefore those T-cells may not be eliminated. Later these T-cells may be activated to cause disease.
Term
True or False: Staph endotoxins and the toxic shock syndrome toxin function as antigens.
Definition
False, they are superantigens which stimulate a massive generalized immune response which are systemically toxic and suppress the adaptive response.
Term
What are the two signal required to induce a B-cell to a plasma cell?
Definition
Two complexes on the CD4-Th2 cell induce it, TCR-MHC-II and B7-CD28.
Term
What is the site for T-cell maturation?
Definition
Thymus and thymic stroma, some can develop in intestine
Term
True or False: The major histocompatibility complex is completely different from the HLA, human leukocyte antigen.
Definition
False, the HLA is the variable component of the MHC.
Term
True or False: The genes that encode the MHC-I/II molecules rearrange and undergo developmental changes just like Ig’s.
Definition
False, they do not rearrange or undergo changes, diversity is obtained because of unique expression
Term
Name the MHC Class I genes and recite how many class I genes a given individual might express.
Definition
HLA-A,B,C and a person expresses 6 genes, two from each type
Term
Name the MHC Class II genes and recite how many genes are expressed on a cell surface.
Definition
HLA-DP,DQ,DR, with varying alpha and beta chain alleles, but a person normally expresses 6 genes, two from each group
Term
True or False: The MHC is both polygenic AND polymorphic.
Definition
True
Term
If the association of antigenic peptides and MHC molecules is a low affinity interaction then how can the complex work?
Definition
The low affinity indicates a slow on rate and off rate, so once the complex forms it stays bound for weeks to be recognized by T-cell receptors
Term
Can multiple different peptides bind to the same MHC molecule?
Definition
Yes, but one at a time, this is unlike highly specific antibodies
Term
What types of cells express MHC-I and MHC-II?
Definition
MHC-I are expressed on almost all cells with a nucleus, MHC-II are expressed on professional antigen presenting cells macros/B-cells/dendtritic
Term
What is MHC restriction?
Definition
Each TCR is specific to not just the antigen but the MHC component, so each TCR recognizes 1 out of 12 MHC proteins
Term
Why are transplant patients given cyclosporine?
Definition
To prevent the upregulation of IL-2 and inhibit T-cell production.
Term
True or False: Mature B-cells can respond to bacteria polysaccharides without the need for T-cell antigen.
Definition
True, they are called thymus-indepent 2 antigens.
Term
What is a conjugate vaccine?
Definition
Antigen is bound to a carrier protein that is ingested by a naïve B-cell, the components are presented to T-cells via MHC-II, the T-cells then activate the B-cell to become mature and provide protection against the antigen.
Term
What is hypersensitivity, autoimmunity, immunodeficiency?
Definition
Too much immunity to foreign antigen; too much for self; to little for foreign
Term
What are the 4 types of immune responses/hypersensitivity reaction?
Definition
I- Allergy and Anaphlyaxis, II- antibody mediated, III- antibody-antigen complex mediated, IV- Cell mediated(T-lymphocytes)
Term
What are the different body reactions to Type I Hypersensitivity of subcutaneous allergens, intravenous allergens, inhaled allergens?
Definition
Local release of histamine with wheal and flare; general release of histamine, anaphlyaxis; allergic rhinitis and asthma due to contraction of bronchial smooth muscle
Term
What is the proposed hypothetical benefit to the release of IgE in hypersensitivity I reactions?
Definition
Possible parasite fighter
Term
Briefly describe the process of a hypersensitivity I reaction.
Definition
Allergy antigen induces CD4-Th2 to signal B-cells via IL-4 to create antibodies IgE, IgE binds to mast cells and basophils, second exposure to allergen, mast/basophil cells release inflammatory granules
Term
Briefly describe the process of a hypersensitivity II reaction.
Definition
IgG or IgM antibody coats cell surfaces or ECM, induces complement system for either opsonization or C5-C9 cell lysis
Term
True or False: An ABO blood type mismatch can cause a type 2 hypersensitivity reaction inducing red blood cell destruction.
Definition
True.
Term
Briefly describe the process of hypersensitivity III reaction.
Definition
IgG antibody forms complex with antigen(endo/exogenous), induces complement C3a/4a/5a inflammatory mediators and mast cell degranulation, local inflammation occurs with phagocytosis and blood vessel occlusion
Term
True or False: Since Type III hypersensitivity gives rise to local or systemic disease the following diseases are all associated with type III - glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, serum sickness.
Definition
True.
Term
Of the 5-year survival rates for organ transplant which of these is different from all the others in that it is lower than 70%: kidney, liver, heart, bone marrow, lung, cornea?
Definition
Lung has the lowest survival rate of organ transplants.
Term
In organ transplant, you can never get a complete HLA match from the donor except in which case?
Definition
Identical twins
Term
Which types of hypersensitivity are involved in organ transplant rejection?
Definition
Type II, III, IV (CD4 and CD8)
Term
Briefly describe the process of type IV hypersensitivity in both the delayed type and cell mediated type.
Definition
Delayed - CD4-Th1 cells see MHC-II, release cytokines causing vasodilation/inflammation and recruit monocytes, and may form a granuloma; Cell-mediated - CD8 cells see MHC-I on virus-infected cells, tumors, transplants and induce apoptosis.
Term
What is the difference between central and peripheral tolerance in immunity?
Definition
Central is the development of tolerance during development and peripheral occurs out in tissues after antigen encounter.
Term
What are the 4 mechanisms of tolerance and what do they involve?
Definition
Clonal deletion- removes autoreactive B/T cells by apoptosis during maturation and in the periphery following immune response; Clonal Anergy- cell are alive but turned off, T-cells see Ag without B7/CD28, B-cells lose surface immunoglobin expression; Peripheral suppression- dendritic/CD4/CD8 cells suppress immune response by contact or cytokines; Immunologic ignorance- low antigen density so threshold for response not achieved
Term
True or False: Autoimmune diseases occur in every organ but it is rarely due to a failure of tolerance mechanisms.
Definition
False, occurs in most organs and it is due to usually do to failure of tolerance.
Term
What is the most common cause of immunologic disease in regards to tolerance mechanisms?
Definition
Failure in immune ignorance
Term
Describe the four mechanisms causing immune ignorance to fail- creation of new epitopes, molecular mimicry, polyclonal lymphocyte activation, exposure to immune privileged sequestered antigen.
Definition
1-drugs/microbes attach to self-antigens(haptens) or molecular degradation exposes cryptic self-antigens; 2- infectious agent has antigen that resembles self, so cross-reacting antibodies now recognize self-antigen; 3- occurs when APCs or bacterial LPS or virus overcomes anergic cell with stimulation causing proliferation; 4- since these antigens were not seen by lymphocytes during development they will be recognized as foreign(antigen from brain, lens, testes, inside of cell)
Term
What perturbs an immune system to trigger development of autoimmune disease?
Definition
Trauma, infection, puberty
Term
What is the difference between primary and secondary immunodeficiency?
Definition
Primary is the result of a specific genetic deficiency affecting the development/function of immunity versus secondary which is the result of an acquired condition that suppresses or destroys the immune system.
Term
True or False: The following agents can cause primary immunodeficiency - infections, malnutrition, aging, side effect of chemo, aids.
Definition
False, secondary
Term
True or False: The phenotype for T-cell defects are viral/fungal infections and no granuloma formation.
Definition
True
Term
True or False: the phenotype for B-cell defects are recurrent bacterial infections due to inability to oposonize and susceptibility to some parasites.
Definition
True.
Term
What percentage of immunity is needed for herd immunity?
Definition
95%
Term
What are the top 3 targets for vaccination?
Definition
Tb, malaria, HIV
Term
Regardless of the mechanism of HIV, loss of which cell type is the cause of immune failure and eventually AIDS?
Definition
CD4+ T-cells
Term
Elaborate on the concept of “set point” for viremia.
Definition
There is a correlation between CD8 Tcells onset/decline with viremia reduction/rise over time; in the asymptomatic phase, while CD8 and virus equilibriate, there is a set point maintaining the level of viral load at a certain amount in the blood. The higher the setpoint the quicker the onset of disease progression at the end of the asymptomatic phase.
Term
What are the 4 different factors of HIV infection that cause the failure of the CD8 Tcells?
Definition
Loss of CD4 help because HIV kills active CD4’s, viral Nef protein downregs MHC class I expression on cells, ability of HIV-I to mutate changing its epitope, clonal exhaustion of CD8 progenitors
Term
True or False: The key reasons that antibody responses fail in HIV-1 is because of conformational masking and extensive glycosylation of the virus membrane making antibody binding difficult.
Definition
True, it is also due to viral escape mutation in the epitope and the general dysfunction of B cells due to the lack of CD4-Th2’s to induce them.
Term
Elaborate on the structure of an antibody.
Definition
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Term
Elaborate on the process of antibody cleavage considering that fragments are still antigen binding.
Definition
[image]
Term
Elaborate on the difference between antibody and T cell receptor structure.
Definition
[image]
Term
Elaborate on the structure of the T cell receptor complex.
Definition
[image]
Term
These are the most important IL molecules, their source, and their target.
Definition
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