Edits to the study guide are in red, and the retrieved questions are in blue at the end. I will have office hours on Tuesday Dec 13th, and Wednesday, Dec 14th at 4pm. If you need to meet with me at other times, please e-mail me and I’ll find more time. You can also e-mail me or your TA with questions, but your best study approach would be to try to understand each of these issues first on your own.

Subfamily: (1 Genus) Subfamily: (6 Genera) Genus: (9 Species) Genus: (5 Species) Genus: (4 Species) Genus: (3 Species) Genus: (17 Species) Genus: (9 Species) To which genus does HIV belong? Naturally occurring in these genus(es): always, never, sometimes result in immunodeficiency? Can these viruses cause other disorders? What conditions are required for HIV to infect a cell? For example, from what species, and what cell surface receptors have to be present. What types of cells are infected? Infection and death of which cells causes AIDS? What is the surface glycoprotein on HIV called, and how does it initiate viral infection? Which part of the (which protein) initiates fusion? What stages of the viral life cycle have been targets for anti-retroviral (ARV)drug therapy? The time from infection to low CD4 counts is how long? Answer: highly variable. Average from 5-10 years, but some people progress almost immediately and some never progress. When is an HIV+ individual most infectious? Early-phase acute infection with HIV causes what? How does APOBEC3G work to restrict lentivirus infection? Why doesn’t it work in humans to prevent infection or disease? How do genetics affect an individual’s susceptibility to HIV infection? Do these genetics correlate with the concept of human races? How do we routinely determine whether someone is infected with HIV? What other possibilities exist to screen for HIV infection? Who developed the first commercialized HIV test? What did it measure? What is being measured in an Elisa or in a Western blot assay? Know how this works. Why did it take three or four years to develop an assay? Is the assay perfect in diagnosing HIV infection? Why or Why not? Why didn’t the blood banking industry screen out HIV+ donors in the early 1980’s? Which groups were in favor of screening donors, which groups were against (from ATBPO)? How do we know that HIV1 came from chimpanzee’s? What do we call the major Group of HIV world-wide? Which subtype is predominantly found in North America? UK? How did this subtype get from Africa to the United States? How did the virus get to the UK? If there was an intermediate step (from Africa to the US), when did it occur? Where did chimpanzees get SIV? Does SIV cause disease in chimps? Does it cause AIDS? Are human SIV infections rare in Central Africa? Do we have a probable first-hand account of the original HIV1 outbreak causing immunodeficiency in Central Africa? If so, what was the approximate date of this account? How else have we been able to date the origin of the HIV1 epidemic? Where in the world is the highest diversity of HIV1? From where did HIV2 originate? Did we get it from chimps? How did each of these factors contribute to the HIV epidemic? Movement of people to cities in Africa Changing status of women Large African gay population Sex for compensation IV recreational drug use Ulcerative venereal diseases Concurrent relationships Violence against women, especially young women Gay sex-partner networks in N. America

How often is someone infected with HIV in the United States? Can you define the populations most highly affected (infected) by HIV? Explain Is there a racial bias in HIV prevalence in the US? Do we know why? What are some of the explanations? What are the factors that DO NOT account for the ‘racial’ bias? In the very last lecture, before Heather Arculeo spoke, I briefly discussed the societal factor most clearly associated with HIV infection: poverty. We don’t know why but if you account for poverty, there is no difference in race for urban populations. What are all the ways that HIV can be transmitted from person to person? How did Heather Arculeo’s husband contract HIV? What do we know about this means of HIV transmission? How do these means of transmission differ in terms of frequency, that is probability of infection per encounter? What is the role of dendritic cells in HIV infection? Macrophages? T cells? How does HIV infection affect the integrity of the gut epithelium? That is, as virus infection peaks which cells die, and how does that affect the gut epithelium? What are the consequences of breaching the integrity of the gut epithelium? As patients progress to AIDS, what are the consequences? What types of infections result? What were the symptoms of AIDS that were first reported in the literature? What was the very visible change that seemed to affect gay men, but not i.v. drug users? What genetic mutation makes people resistant to HIV infection? How frequent is it? Has anyone ever been completely cured? How?

Why is there a difference in the frequency of transmission comparing anal and vaginal intercourse? What countries have the highest incidence of HIV in the world? Why? new Which component of the immune system is able to directly kill HIV-infected cells? What form of antigen stimulates CD8 T cells? What form of antigen stimulates CD4 T cells? In an uninfected person, would you expect the HIV-specific T cells to be: 1/10 1/1000 or < 1/1,000,000? How about B cells, what would be the frequency of B cells able to make antibodies able to bind HIV? How many different antibody receptors are expressed on the surface of a B cell? How many different MHC class II molecules are expressed on the surface of a B cell? Do B cell express both MHC class I and MHC class II molecules? How about dendritic cells? Do CD4 T cells recognize antigen peptide bound to MHC class I or class II molecules? Describe for yourself how peptides from HIV GP120 could be found bound to MHC class I, and then separately MHC class II. Hint: think about cells infected with HIV vs. cells, such as macrophages and dendritic cells that take up viral particles via phagocytosis. What aspects of HIV make it difficult to generate an effective antibody response? How does the CMV vaccine developed by Louis Picker’s lab work to control SIV infection in monkey’s (T cells, B cells, etc)? How effective has it been? How frequently do people make bNAb? Are they all Long-term non-progressors? Other than the CCR5-delta32 allele, what genes are associated with Long-term non-progression? What does that tell you about the immune mechanism involved? Third version

What was the first ARV, and how did it work? How do the other ARVs work? How is Ritonavir used in ARV therapy? Know the Basis for ARV drug resistance—slide 13 in the ARV lecture. What is salvage therapy? What is PreP?

Why? Think of the types of epithelia, and the evolutionarily selected function. The vagina not only accommodates a penis, but it can expand to allow passage of a newborn. Anus, well, it has another functions. What countries have the highest incidence of HIV in the world? Sexual promiscuity in Sub-saharan Africa is a strong factor in the incidence of HIV, T/F What is the probability of HIV transmission between discordant couples? What about other examples of intercourse, e. g., sex workers and their clients? Why do you suppose they are different? In far-east Asian countries, such as China, order the frequency of cause for new HIV infections: heterosexual, homosexual, i.v. drug use, infected blood supply. The proportion of HIV prevalence in women is same around the world. If not how does it differ? What is the concurrency rate in American college students? What is the prevalence of HIV? We don’t know. [in one study students had negative attitudes towards concurrency (M=2.33, SD =1.07) and perceived the behavior to not be the norm among their peers (M=2.35, SD=1.05). Students also strongly indicated that they would end relationships with a partner who had other partners (M=4.55, SD=.60)] For your own thoughts, not for public consumption, what is your sense of concurrency at UCSD? What is the acceptance of concurrency as a practice among your peer-group? How many of your friends practice it at least sometimes? According to Burton, up to 20% of individuals eventually develop broadly neutralizing antibodies bNAb, and yet these people do not control disease, why? Where do bNAb bind? What are the requirements for bNAb? Do they all bind to the same epitope (part of the viral glycoprotein)? What are the difficulties to be overcome in making a vaccine that will induce bNAb? What are the 3 phases of HIV infection? How are they different? What role do CD8+ T cells play in the course of an HIV infection? (cytotoxic, killing virus-infected cells) What role do CD4+ T cells play? (they are the target, they activate macrophages, they help B cells make Ab, they maintain gut integrity) How about dendritic cells. What are all the roles they play? How does the MHC affect the course of an HIV infection? What factors affect the nature of an obligate parasite (bacteria, virus, protozoa, fungus, etc)? What is the cause understood to explain the fact that vector-transmitted infectious agents are often much more virulent than agents spread by proximity and respiratory droplets? Incidence, prevalence, epidemic, pandemic, endemic, academic, vector, zoonosis, and such Understand innate vs. adaptive (aka acquired) immunity What are the principle cell types of the immune system, and in broad terms, what do they do? Examples of innate immunity covered in class? What are the principles types of Adaptive immunity we discussed? What does the term “antigen- presenting cell” refer to? What are toll-like receptors? PAMPs? PRRs? What does clonal selection refer to? Why do plasmacytes have such a massive golgi complex? How is it possible for vertebrates, such as yourselves, to produce billions of different antibody molecules? What is somatic hypermutation and how does it affect the antibody response? Where are the different antibody isotype found in the body. What is the unique characteristic of each antibody isotype? What are the complementarity determining regions of Ab? What genes give rise to each? What are the similarities and differences between T and B cells? (receptors, ways they recognize viruses, localization in the body). What is meant by the Ins and Outs of antigen presentation? How do MHC molecules function in the induction of an immune response?