Exam 11: Integrated Dynamics of Innate and Adaptive Immunity

Studies in mice have shown that resident memory cells (T_RM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (T_CM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (T_EM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of T_EM cells provides an important component of protective immunity to re-infection by the same pathogen because:

Allergic airway inflammation can be induced in mice by immunizing them with an allergen that produces a T_H2 effector response, and then challenging the immunized mice with an inhaled form of that allergen. In this disease model, the T_H2 effector cells present in the lung respond to the inhaled allergen challenge by producing type 2 cytokines that recruit eosinophils and induce airway inflammation. In addition, a component of this T_H2 response is antigen-independent, as shown by the effects of administering a neutralizing antibody along with the allergen challenge. This neutralizing antibody (anti-'X' IgG) has the effects shown in Figure Q14). antibody was shown to inhibit the response of the T_H2 cells, and therefore is likely to be:

Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, virus-specific memory CD8 T cells cannot be maintained, and disappear over time as shown in Figure. The most likely identity of the cytokine that is missing in these knockout mice is:

The immune response to helminthic worm infections in the gastrointestinal tract requires specialized mechanisms due to the fact that helminths are too large to be ingested and destroyed by phagocytes. For example, cytokines made by T_H2 cells elicit responses from multiple non-hematopoietic cell types that aid in parasite expulsion. Name two of these cell types and for each of them, their response to T_H2-produced cytokines.

Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because:

Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection provokes a type 3 response, including the development of T_H17 cells, in the GI tract. However, this type 3 response in the GI tract does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the T_H17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that:

A set of mice are each immunized with one of the following as shown in Figure. Mouse A is immunized with tetanus toxoid protein. Mouse B is immunized with the Haemophilus influenzae type b polysaccharide antigen. Mouse C is immunized with a conjugate of the diphtheria toxoid protein linked to H. influenzae type b polysaccharide. Mouse D is left unimmunized (naive). Four weeks later the spleen cells from each mouse are isolated, and B lymphocytes and T lymphocytes from each spleen cell population are purified. When mixed together in culture together with a conjugate antigen of the tetanus toxoid protein linked to the to H. influenzae type b polysaccharide, which combination of spleen cells would generate a memory B cell response?

Toxoplasma gondii is a single-celled parasitic protozoan that infects and replicates in macrophages. It is common in the environment, and is transmitted to humans by the ingestion of undercooked meat or by accidental ingestion of the parasite's oocytes from contaminated water or cat litter. Infected individuals with healthy immune systems are generally asymptomatic, and rapidly clear the infection. However, in AIDS patients, infections of Toxoplasma gondii can lead to severe disease and even death. To investigate the immune mechanisms important in controlling Toxoplasma gondii, a mouse model of the infection was developed. Mice were infected with the protozoa at a dose where the majority of the mice survive the infection, and at the same time, were injected with a neutralizing antibody to a cytokine made by T cells (anti-'X' IgG). A second group of mice received the protozoa plus a control IgG antibody, as shown in Figure Q10). Figure Q10) The most likely candidate for cytokine 'X' is: