Give three advantageous features that distinguish vertebrate adaptive immune responses from the innate immune responses made by both vertebrates and invertebrates.
i. Unique differences distinguishing particular pathogens from other pathogens and from the vertebrate host are targeted specifically.
ii. Pathogen-specific memory cells generated during first exposure are available during a secondary encounter and mediate a more rapid and effective clearance during a recall response.
iii. Even as pathogens mutate at a rapid rate, adaptive immune responses retain the capacity to recognize molecular changes in evolving pathogens.
The process by which a pathogen stimulates only those lymphocytes with receptors specific for that pathogen is called
Explain why a pathogen is most capable of causing disease the first time it is encountered
Because it takes several days for the immune system to generate adequate numbers of pathogen-specific lymphocytes after clonal selection, the host is most vulnerable to disease during this time.
Which of the following statements characterizing B-cell receptors and T-cell receptors is incorrect?
The process of _____ results in the recombination of gene segments of the T-cell receptor and immunoglobulin genes giving rise to lymphocytes with unique specificities for antigens:
During a typical infection, dendritic cells first encounter pathogen in _____ and then transport the pathogen to _____ where pathogen-derived peptide fragments are presented to _____:
Explain the fundamental differences between CD4 and CD8 T cells in terms of (A) their effector function and (B) their interaction with MHC molecules.
A) CD4 T cells, also known as helper T cells, function by secreting cytokines that instruct other cells to acquire effector function. CD8 T cells differentiate into cytotoxic effector cells and kill the target cells that they recognize. (B) CD4 T cells recognize only antigens presented by MHC class II molecules. CD8 T cells recognize only antigens presented by MHC class I molecules.
A. Identify the two major sources of the pathogen-derived antigens recognized by T cells
A. CD8 T cells recognize antigen that was derived from intracellular sites in the host such as viruses and some bacteria that live and replicate within cells. CD4 T cells recognize antigen derived from extracellular fluid and interstitial spaces between cells and tissues where all types of pathogen can be found, and where some toxins secreted by pathogens are located.
B. Explain why it is advantageous to the host to use different effector mechanisms to combat antigens encountered in these two distinct locations.
B. The host’s immune response needs to be able to identify all types of pathogen in the various anatomical locations in which they exist. This is essential so that effective clearance mechanisms can be tailored to combat infections regardless of which strategy the pathogen has evolved for its survival and dissemination in the host.
Describe how (A) MHC class I molecules and (B) MHC class II molecules encounter the peptides to which they will bind and ultimately present to T cells.
A) MHC class I molecules do not bind to peptides derived from pathogen-derived proteins until the peptides have been transported into the endoplasmic reticulum. Transport to the endoplasmic reticulum does not occur until after proteolytic cleavage of the pathogen proteins has occurred in the cytoplasm. Once the peptide has bound to an MHC class I molecule, the peptide:MHC class I complex is transported to the cell surface for presentation to CD8 T cells. (B) MHC class II molecules bind pathogen-derived peptides in a location distinct from MHC class I molecules inside endocytic vesicles, the same location where proteolytic cleavage of pathogen proteins occurs after engulfment of pathogen-laden material from infected tissue. Once the peptide has bound to an MHC class II molecule, the peptide:MHC class II complex is transported to the cell surface for presentation to CD4 T cells.
Which of the following is paired correctly?
Discuss why a vaccine based solely on carbohydrate moieties (for example capsular polysaccharides) of a pathogen would be ill conceived if the goal was to stimulate not only antibody responses but also strong helper T-cell responses.
In fact there are vaccines made solely of polysaccharide constituents of encapsulated bacteria that stimulate antibody responses (for example, Pneumovax is used in humans older than 2 years of age). The most successful vaccines of this nature, however, are conjugated; this means that the bacterial polysaccharide is covalently linked to an antigenic protein by a chemical process (for example, the Hib vaccine is a conjugate of Haemophilus influenzae polysaccharide and tetanus toxoid and is administered to infants). For CD4 T helper cells to participate in B cell activation, protein sequences must be included in the vaccine; CD4 T cells are activated only when pathogen peptides are presented on the surface of antigen-presenting cells together with MHC class II molecules. Vaccines devoid of protein constituents will therefore not provoke T cell responses, and may be limited to weaker T-independent B-cell responses.
Discuss (A) the similarities and (B) the differences between neutralization and opsonization.
(A) Neutralization and opsonization are similar in that once antibody is bound to antigen it is targeted for destruction by phagocytes after ingestion. This process is mediated by receptors for antibodies. (B) Neutralization differs from opsonization in that by binding to antigen (such as a toxin or a virus), the host cell receptor is unable to bind to native antigen, uptake is blocked, and the antigen is thus inhibited from damaging the host cell.
If there are no receptors on macrophages for the constant region of IgM, then how does IgM coating a pathogen promote its phagocytosis?
When bound to the surface of a pathogen, IgM induces the classical pathway of complement activation. This in turn leads to the deposition of C3b on the pathogen’s surface. Phagocytes contain complement receptor CR1, which binds to C3b fixed on the pathogen’s surface; receptor-mediated endocytosis—that is, opsonization—ensues.
Describe briefly the two mutational mechanisms that drive the enhancement of antibody quality in activated B cells.
(i) Somatic hypermutation is a mutational mechanism that results in nucleotide substitutions affecting coding regions of the variable loci of heavy- and light-chain genes in immunoglobulins. Three possible consequences arise as a result of a nucleotide substitution in the variable region: (1) no change to the affected amino acid; (2) a change reducing the affinity of antibody:antigen interaction; and (3) a change increasing the affinity of antibody:antigen interaction. The last of these interacts with antigen most effectively, and cells bearing them will be selected for clonal expansion and differentiation into plasma and memory cells. (ii) Isotype switching is the second mutational mechanism affecting antibody quality and memory B cells. Here the constant region is involved; the variable region, which binds to antigen, is preserved. By switching the constant region from IgM to IgG, IgA, or IgE, the secreted antibodies are more effectively transported to the appropriate anatomical locations where antigen is located, and subsequent elimination of the antigen by antibody-receptor-bearing leukocytes occurs.
Describe three types of unwanted and potentially harmful immune response
(i) Allergy. IgE antibodies made against normally innocuous environmental antigens trigger widespread mast-cell activation. This can lead to allergic diseases such as asthma or to a potentially fatal anaphylactic reaction. (ii) Autoimmune disease. Chronic immune responses by B cells or T cells to self antigens can cause tissue damage and chronic illnesses such as diabetes, multiple sclerosis, and myasthenia gravis. Autoimmunity is sometimes provoked as a consequence of an immune response to pathogen-derived antigen that cross-reacts on healthy host cells or tissue. (iii) Transplant rejection. A person’s immune system will make an immune response against the foreign MHC molecules on transplanted tissue that is MHC-incompatible.
At 42 years old, Stephanie Goldstein developed occasional blurred and double vision, numbness and “pins and needles” in her arms and legs (paresthesia), and bladder incontinence. After a month of these symptoms she went to her doctor, who sent her to the neurology specialist. An MRI scan revealed areas of demyelination in the central nervous system (CNS) and Stephanie was diagnosed with the autoimmune disease multiple sclerosis (MS). Which of the following best explains why some people are susceptible to the development of MS?
a. Negative selection of autoreactive T cells occurs during T-cell development.
b. Apoptosis of autoreactive B cells occurs in the bone marrow during B-cell development.
c. An inability to produce immunological tolerance toward CNS-derived constituents results in the generation of self-reactive lymphocytes.
d. An immunodeficiency inhibiting somatic recombination of immunoglobulins and T-cell receptors results in impaired lymphocyte development.
e. Regulatory T cells fail to activate autoreactive T cells in secondary lymphoid organs.
Rationale: The correct answer is c. One mechanism for achieving immunological tolerance to self proteins is negative selection in the thymus. Developing T cells bearing T-cell receptors that bind too strongly to self-MHC or to self-MHC:self-peptide complexes are signaled to die by apoptosis, which eliminates self-reactive T cells. Self proteins not presented to developing T cells in the thymus, such as proteins sequestered in the central nervous system, would not be scrutinized during negative selection, and self-reactive T cells would result.