Immunology Ch 1

T cells expressing the co-receptor CD8 are generally cytotoxic cells, with an important function in eliminating virus infections that can occur in many different cell types and tissues. In contrast, CD4 T cells directly interact with a very restricted set of cells, such as dendritic cells, macrophages, and B cells. Describe one important mechanism that accounts for this division of labor between CD8 and CD4 T cells.

CD8 T cells recognize antigenic peptides bound to MHC class I molecules, which are expressed on nearly all cells of the body. Therefore, any cell type that becomes virus- infected would be able to present viral peptides on MHC class I molecules for recognition by CD8 T cells. In contrast, CD4 T cells recognize antigenic peptides bound to MHC class II molecules. MHC class II proteins are expressed only on other cells of the immune system, such as dendritic cells, macrophages, and B cells. Due to the restricted expression of MHC class II proteins, CD4 T cells are restricted to interacting with these cells of the immune system.

The clonal selection theory was first proposed in the 1950s, decades before the molecular details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that:

Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor.

Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node:

From the blood by crossing the high endothelial venules

When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to:

Increase their permeability, allowing fluid and proteins to leak into the tissue

Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to:

Interactions with other cells, such as virus-infected cells or other immune cells

The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by:

Intracellular pathogens, such as viruses and some protozoa

Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because:

It concentrates antigens in centralized locations for rare lymphocytes to encounter

The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because:

Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes.

The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is:

Mucus production

The effector activities important in eliminating infectious organisms from our bodies can be categorized into four different groups: cytotoxicity, intracellular immunity, mucosal and barrier immunity, and extracellular immunity. Briefly describe why the immune system requires four different effector modules for maximum protection.

Pathogenic microorganisms can be divided into groups based on their lifestyle in the host. Each of these lifestyles requires a different set of effector mechanisms for pathogen eradication. Cytotoxic activity is required to eliminate virus infections, which can take place in many different cell types in the body. Intracellular immunity is required for pathogens that have evolved to live inside phagocytes. Mucosal and barrier immunity is required for large parasites that generally enter the body through mucosal sites and cannot be engulfed by phagocytes. Extracellular immunity is required for most smaller extracellular pathogens that can be engulfed and eliminated by phagocytes.

When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by:

Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium

The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that:

Some antigen receptors might recognize the individuals on cells or antigens BECAUSE: The random process that generates lymphocyte antigen receptors can create antigen receptors that are self-reactive. Many of these potentially self-reactive lymphocytes are eliminated during lymphocyte development, a process known as clonal deletion. Other self-reactive lymphocytes are functionally inactivated or inhibited from responding to their self-antigen. Altogether, these mechanisms ensure that the individual's lymphocytes remain tolerant to self.

In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues

TRUE

Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body.

TRUE Innate lymphoid cells are tissue-resident cells found primarily in the lung epithelium, the skin, and the intestinal epithelium. Since most pathogens enter the body through one of these sites, it is important to post innate immune cells in these locations where they will readily encounter a pathogen that has breached one of the body's barriers.

An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because:

The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.

Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because:

The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection.

Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate:

The essential immune mechanism required for resistance to each category of pathogen

One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is:

The extensive polymorphism of MHC genes in the human population

Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to:

The important role of T follicular helper cells in generating protective antibody responses

The best evidence supporting the concept of immunological memory is:

The increased rapidity and magnitude of the secondary response to the same antigen

Dendritic cells, also called 'antigen-presenting-cells' are considered the bridge between the innate and the adaptive immune responses. Describe two key features of dendritic cells that are essential for them to provide this bridging function

The most relevant features of dendritic cells in this context are: 1. Dendritic cells respond to infections using innate pattern recognition receptors (PRRs) that recognize PAMPs. 2. Once triggered by PRR stimulation, dendritic cells are induced to migrate from the infected tissue to the regional draining lymph node. 3. Following stimulation of the PRRs on a dendritic cell, dendritic cells up-regulate co-stimulatory molecules that are required to activate T lymphocytes. 4. Following pathogen uptake by the dendritic cell, the pathogen is degraded and peptides of the pathogen are displayed on the dendritic cell surface for recognition by the antigen receptors on T lymphocytes.

Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT:

The presence of adenosine residues in viral RNA *IN CH 3

The immune system evolved to protect us against infections from pathogenic microorganisms. However, immune responses can also cause, rather than prevent disease. Give two examples of situations in which an immune response causes a disease, whereas the absence of a response has no consequences.

There are several cases in which immune responses can cause diseases, whereas their absence is a neutral event. One example is allergic responses to non-threatening antigens, such as food items, antibiotics, metal ions, or inhaled substances. Another example is autoimmune diseases, in which individuals make destructive immune responses to their own cells or tissues. Graft rejection in transplant patients is another possible example, although it doesn't quite fit the criterion of being 'an immune response that causes disease,' since in this case, the immune response is prevented 'the cure' rather than causing the disease.

The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because:

They neutralize the virus or toxin, preventing it from attaching to and entering our cells.

For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.

True. Cells of the innate immune system generally express multiple pattern recognition receptors. Each of these receptors recognizes a conserved feature of a class of pathogens. Therefore, a single innate immune cell can respond to a multitude of different pathogens. In contrast, the antigen receptor on B and T lymphocytes is clonally distributed; each single cell expresses only one version of this receptor, and has a single binding specificity.

Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must:

Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis

Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of:

Vaccines

Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because:

Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses.

A common characteristic of a site of infection, such as a pimple on the skin, is pus. What is responsible for the white color of pus?

White blood cells, primarily neutrophils. Pus is an inflammatory response to a bacterial infection of the skin. The inflammatory response recruits neutrophils from the blood into the site of infection, along with some monocytes.

One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.

true

TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.

true

The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.

true

Most B and T lymphocytes in the circulation appear as small, inactive cells, with little cytoplasm, few cytoplasmic organelles, and nuclei containing condensed inactive chromatin. Yet these cells comprise the adaptive immune response, without which individuals die in infancy. What is the explanation for this apparent dichotomy?

B and T lymphocytes are a heterogeneous population, comprised of cells that each express a unique antigen receptor. As a consequence, only a small number of B and T lymphocytes will respond to any particular pathogenic infection. The vast majority of the circulating cells will never encounter the pathogen that binds to their antigen receptor; hence these cells remain in a naive, inactive state.

Dendritic cells are phagocytic, but also capable of ingesting large amounts of extracellular fluid and its contents, a process known as macropinocytosis. What specialized function do dendritic cells have in immunity that might account for their need to perform macropinocytosis?

Dendritic cells are essential in activating T lymphocytes. Therefore, it is important that dendritic cells acquire all possible categories of threats. While many intact microorganisms can be taken up by phagocytosis, small toxins produced by pathogens are more efficiently ingested by macropinocytosis.

In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT:

Endothelial cells

Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies

FALSE