Study guide for Midterm 1
Biology 585, Spring 2003

What is innate immunity?  What is adaptive immunity?  What are the specific components of each?  How are innate and acquired immunity linked?

What are the lymphatics and lymphoid tissues?  What is the architecture of the lymphoid tissues?  How does their structure enhance their function and what is their function? What organs filter what parts of the body? Describe lymphocyte recirculation.

Describe hematopoiesis and the basic function of each cell type produced. What are neutrophils and what is their role in innate and adaptive immunity?  What are monocytes/macrophages (what is the difference?) and what is their role in innate and adaptive immunity?

The clonal selection theory is the guiding principal of the adaptive immune response.  What is the theory and why?

What are the cardinal features of adaptive immune responses? What is the sequence of events in an immune response?

What are some of the basic functions of Abs?  What are the two different kinds of T cells and how are they different?  What is immunological memory and how does it work? What are the basic features of primary and secondary immune responses that make them different?

Draw an Ab molecule.  Indicate the heavy and light chains, the variable and constant regions, where Ag binding occurs, and what part of the Ab opsonizes and/or fixes complement.  What are the five classes of Ab and what is a major function of each one?  Which chain(s) determine(s) the class?  Which chain(s) participate in Ag binding?  What is a CDR or HV region, how many are there and what do they do?

What are monoclonal Abs and how are they made?  What are they useful for and why are they often better than antisera?  What advantages do antisera have over mAbs?

What is the immunoglobulin supergene family?  What is an immunoglobulin domain?

What are the different kinds of epitopes? What Ags do T cells see? What Ags do B cells see? What is a hapten? A carrier? What is affinity, avidity, and valence?

What are the MHCs of mouse and human called? What are the Class I molecules? What are the Class II molecules? What other genes are found in the MHC? What are haplotyes and what does it mean that they have linkage disequilibrium? What part of the molecules interacts with T cells and present peptide? MHC molecules are ligands for what receptors?

Completely describe Ag presentation by Class II molecules.  What is the source of the Ag (be specific)?  What cells can do this?  What is the structure of the Class II molecule and how does it avoid presenting peptides more appropriate for Class I molecules? What are the specific functions of the different APC types?

What are the three kinds of Ag presenting cells and how do they differ from one another (in terms of Ags presented, expression of important ligands, location and Ag uptake)?

Completely describe Ag presentation by Class I molecules.  What is the source of the Ag (be specific)?  What cells can do this?  What is the structure of the Class I molecule and how does it avoid presenting peptides more appropriate for Class II molecules? What is required for a cell to express Class I?

What is the meaning of the polymorphism found in the MHC?  Where do the alleles differ from one another?  What is the consequence of this polymorphism for the immune response with respect to population viability, tissue transplantation and Ag recognition?

What is self-MHC restriction? What does it mean (at the molecular level)?

What is the structure of the T cell Ag receptor and how does it work? What are the other important cell surface molecules (accessory molecules) on T cells and what is their structure and function? Why is adhesion important?

What are the stages of B cell development?  Where does proliferation occur?  Where does recombination occur?  What events control proliferation and recombination?  Are these events Ag dependent or independent? What are the B-1 cells? How does selection work in B cells?

Diversity in Ab and BCR is caused by what 4 mechanisms and how do they work (be able to describe in detail please)?  In what one major way does TCR diversity alter from BCR or Ab diversity? Describe heany chain gene rearrangements in detail. Describe light chain gene rearrangements in detail.

Describe how membrane and secreted Ig come from the same gene.  How do IgM and IgD come from the same genetic locus?

What is allelic exclusion?  What is class exclusion and what genes does it occur in?  What are the molecular mechanisms (2) that lead to allelic and class exclusion?
 

Studyguide for Midterm 2
Biology 585, Spring 2003

IMPORTANT NOTE:  ANSWERS TO SOME OF THE FOLLOWING QUESTIONS ARE OVERLAPPING; ALSO QUESTIONS MARKED WITH AN * ARE MOST LIKELY TO APPEAR AS ESSAY QUESTIONS ON THE TEST. THE REST ARE BEING USED TO DESIGN THE REST OF THE EXAM.

Describe thymic development.  Include the involvement of the TCR, CD4, CD8, epithelial cells, dendritic cells, positive and negative selection, and what happens as T cells enter the medulla.  What determines the final phenotype of a T cell?

What is self-MHC restriction and how does thymic development assure that peripheral T cells are self-MHC restricted?

What is self-tolerance and how does thymic development assure that peripheral T cells are self-tolerant?

*A transgenic mouse line was created that expressed a Class I MHC-restricted TCR specific for a Y chromosome encoded antigen H-Y, which is expressed in male mice but not females (of course). Female mice in this line contain normal numbers of T cells in the periphery and in the thymic medulla. In contrast, male mice have few TCR-expressing, single positive thymocytes in the medulla or in the periphery?  Explain why this is in detail.

*If a transgenic a,b TCR with known MHC restriction is expressed in a mouse strain that also expresses the MHC allele for which the TCR is specific, T cells will mature and populate peripheral lymphoid tissue. If the mouse is of another MHC haplotype and does not express the specific MHC molecule that the transgenic TCR recognizes, there are normal numbers of double positive thymocytes in the cortex, but few mature TCR-expressing T cells in the medulla or periphery. Explain why this is in detail.

What are the 10 T cell molecules discussed in chapter 6 and what is the major function(s) of each? (REPEAT since the last exam didn't go so well)

How do T cells recognize where they are in the body?  What molecules are used and, picking a specific example, describe how they work?

*What are the basic signal transduction pathways activated by the TCR and other important surface receptors that lead to the production of IL-2? Start with the earliest events and include the Ras/Rac and PLC dependent pathways and the transcription factors that result in transcription of IL-2. Know the individual pathways and what TF they activate because the exam may ask a question about specific pathways leading to activation of a specific TF.

What is anergy and how does it occur? What cell surface molecules (on T cells and APCs) block anergy? What is the purpose of anergy (theoretically)?

What are the three phases of T cell responses and what are the events that occur at each stage?

*What are the major differences between T-independent and -dependent Ags (be all inclusive)?  What is the protective role of Abs made to T-independent Ags?

What are the signaling molecules associated with the BCR? What must happen to the BCR for B cell activation?  What facilitates this?  How do B cells receive T cell help?

*What are the events in the lymph node that allow for T cell dependent responses to take place?

What are the various functions of CD40?

What events (or processes) in humoral immunity are absolutely dependent on T cells and why?

Where does somatic hypermutation take place and what is required?  What are the results of somatic hypermutation?  How does isotype or class switching occur and what is required?

What is a plasma cell and what are the major differences between them and B cells?  How do B cells change from making a membrane bound BcR to making secreted Abs?

*What are the functional categories of cytokines?  What is the JAK/STAT pathway, how does it work, and what do STAT proteins do?

What are the 10 specific cytokines (or groups of cytokines in two instances) that we have discussed in class and what are their major functions?  (Wouldn't this make a great matching question?)

What are Th1 and Th2 subsets and what influences their development and activity (be complete)?

*A neonatal mouse expressing a specific MHC haplotype (strain A) is injected with white blood cells from a mouse of a different haplotype (strain B). The neonatal mouse becomes a chimera (has cells from two individuals). 8 weeks later, the mouse is given a skin graft from strain B and accepts the graft but rejects skin from strain C. Provide explanations for the 4 different mechanisms (negative selection, anergy, suppressors, ignorance) that could contribute to tolerance induction in the neonatal mouse.

What is AICD? What is its role in normal immune responses versus persistant infections?

*What is apoptosis? What can cause apoptosis? List and briefly describe four different situations where apoptosis will occur in T cells (including developing cells).

How does B cell tolerance work?  How do normal immune responses terminate and what is the role of CTLA-4?

*How does innate immunity distinguish self from nonself (be specific)? Why are microbes often unable to change these targets? What are the components (cells and molecules) of innate Immunity?

What are the major ways that epithlia protect us from infection (be specific)?

What are the major phagocytes? What are their jobs and how do they differ from one another? What receptors do they use in innate immune function and what responses do the receptors cause? How does phagocytosis occur and what are the killing mechanisms of phagocytes?

How do NK cells participate in innate immunity and what is their function?  How do they recognize their targets and what important cytokines do they secrete?

*How is the endothelium important to inflammation? What are the three features of inflammation that the vascular is involved in?

List and define 6 ways that innate immune responses enhance adaptive immunity.

Describe the events that occur in the lymph node that result in a humoral immune response (be complete).  Once effector T cells are produced in the lymph node, how do they reach the site of infection?  What is different about them from naïve cells that allows them to avoid homing to the lymph node where they were produced?  What is one cell-surface molecule that can be used to distinguish memory from naïve T cells and how?
 
 

Studyguide for FINAL
Biology 585, Spring 2003

*What is the function of the CD4+ T cell (use the Th0 cell as your paradigm and include all functions of helper T cells)?  How do these cells accomplish their functions, including what cytokines and cell surface molecules do they use to promote certain responses by other cells?

Describe an immune response mediated solely by CD4+ T cells (as opposed to including Ab and CTLs).  Include the cells, cytokines, and molecules involved and finish your description with a resolution of the response.  What kind of Ag could elicit an immune response that includes no Ab or CTL involvement?

*What are the five steps in CTL killing?  Describe fully the two mechanisms CTLs most commonly use to kill target cells (do NOT include osmotic lysis which is probably very uncommon).

*Describe fully three paradigms that lead to the activation of CD8+ T cells, their proliferation and differention to CTLs.  Which paradigm is likely the most common in immune responses?

*What are the three major functions of Ab molecules?  Describe these functions in detail, including how they work, what cells and molecules are important if applicable, and the downstream effects of each of the functions.  How does IgA work and how does it get into secretions?  What is the neonatal Fc receptor and what does it do?

What three pathways lead to the activation of complement?  What is the importance of C3b and two major functions of this protein (describe in detail please)?  What is the importance of C5-C9 complexes and what do they accomplish in vivo?  What is the importance of C3a and C5a and what are their functions (describe in detail please)?  What are the C3 and C5 convertases and how are they formed?  (Wouldn't this be a great basis for a matching question?)

*What is the role of IFN a and b in the protection against viruses?  How are NK cells involved in protection against viruses, what 2 major mechanisms do they use to identify virally infected targets, and how do they kill?

*What innate and adaptive immune responses are important in the erradication of each type of microorganism: bacteria, viruses, fungi and parasites.  Be able to describe the different ways these pathogens avoid immune responses and/or ways immune responses can fail to irradicate these organisms.  (Wouldn't this also be a great basis for a matching question?)

Why are live vaccines more successful than killed vaccines?  Why are the most successful anti-bacterial vaccines against toxins rather than organisms?  Why is it easier to make a successful vaccine against viruses than bacteria?

*How do corticosteroids work to suppress the immune response and inflammation (include molecules and cytokines involved)?  Specifically how does cyclosporin A/FK506 suppress the immune response (include molecules and cytokines involved)?

Why are bone marrow transplants more difficult than others?  Why are MHC and blood group Ag compatibilities important in transplantion?  What are minor histocompatibility Ags?  What is an MLR and how is it used in transplantation?  What causes hyperacute rejection, why, and how is this avoided in the clinic?  What are the other types of rejection, what mediates them, and how do they lead to death of the graft?

What is the association between HLA molecules and autoimmunity (what are some specific examples)?  Speculate on what role MHC molecules might have on the development of autoimmunity.  What other genes are involved in the development of autoimmunity?  What other factors contribute to the breaking of tolerance?

*How do Abs molecules cause autoimmune diseases?  What types of hypersensitivities involve Ab molecules?  Give an example of each of the types of hypersensitivities using human diseases, including the molecules, cell types and cytokines involved in the destruction of tissue or the development of disease.

How do immune complexes (IC) form and what is responsible for the different sizes?  How are they normally cleared from the body?  What is responsible for the lack of removal of IC in many autoimmune individuals?  Where are the most common sites of inflammation caused by IC and what mechanisms are involved in the inflammation?

Describe a classic type IV hypersensitivity to an environmental allergen.  What cells, molecules and cytokines are involved?  Describe a classic example of type IV autoimmune disease, including the molecules, cell types and cytokines involved in the destruction of tissue or the development of disease.

*How do mast cells cause the immediate and late-phase responses to allergens?  What are the important mediators and what do they do?  What are the five types of allergic reactions that IgE can be responsible for and what are the unique events that occur at each of the five sites?  What are the characteristics of antigens that induce IgE production?

What are some of the major genetic deficiencies that lead to immunodeficiencies?  What infectious organisms are difficult to control in individuals missing humoral responses?  missing T-cell mediated immunity?  with defects in phagocytic cells?  missing Complement?

*What are the M and T tropic strains of HIV and what is the difference?  Which is responsible for transmission?  What is the course of viral infection with respect to virus in the blood from the time of infection until death (without treatment)?  What happens to HIV specific Ab and CD8+ T cells and to total CD4+ T cells during this time?  Name 3 ways HIV can lead to the destruction of CD4+ T cells.  What is the "viral load" or "viral set point" and what does it mean?  What is HAART and how does it work?

*Questions marked in this way may appear more or less verbatim on the final exam.  All questions contain material that will be tested in the multiple choice and other formats.
 
 

QUESTIONS THAT ARE CUMMULATIVE IN NATURE THAT MIGHT APPEAR ON THE EXAM  (10-15 pts each)

What are the three characteristics of inflammation?  What molecules that have we studied cause or are involved in the various aspects of the inflammatory response and, if appropriate, what cell types do they come from?  Please include cell products, complement and cytokines in your description of mediators and include cell types and adhesion molecules involved where appropriate.

An A strain mouse is irradiated to destroy its bone marrow derived cells and transplanted with bone marrow from an AxB F1 mouse.  No GVH occurs; why?  Describe fully the immune system that will develop in this mouse, with respect to MHC-restriction and self-tolerance, and how it will develop the way that it will.  If the opposite experiment is done; i.e. A strain mouse bone marrow is transplanted into an irradiated AxB strain mouse; will GVH occur?  Why or why not?  If GVH is avoided, will a functional immune system develop in this mouse?

In an immune response, effector CD4+ T cells are generated in the lymph node.  Describe the events (molecules and cell types) that lead these effector T cells to leave the lymph node and accumulate at the site of infection.  Describe also how they erradicate the infection process including molecules and cell types involved.

Describe a primary immune response.  Use a bacterial infection as your model.  Include 1) how inflammation is started and what molecules and cell types are involved, 2) how inflammation contributes to the activation of an adaptive immune response, 3) what components of the adaptive immune response will be involved in the response, 4) important cytokines and receptors will participate in the development of the response, 5) what products of adaptive immunity will go to the site of infection and 6) how they will eradicate the infectious organism.  Be specific and complete.