MLS immunology practice questions test 1

What are the major differences between innate and adaptive immunity?

Innate: responds immediately with effector cells and molecules that are always present, uses a limited number of receptors which recognize patterns, responses are identical in quality and magnitude upon repeated exposure.

Adaptive: require activation of clones to lymphs. To expand and differentiate, which takes days. Uses two types of highly specific antigen receptors, each with millions of variations. Generates long-lived memory that responds more rapidly in a specialized manner

What are the two types of adaptive immunity and what type of microbes do these adaptive immune responses combat?

Cell mediated immunity: mediated by T cells, essential for protection against pathogens that infect tissue cells or phagocytes.

Humoral immunity: mediated by antibodies, provide protection primarily against extracellular pathogens.

• many pathogens have extra and intracellular life cycles (viruses) so they are defended against both cell mediated and humoral immunity

What are the principal classes of lymphocytes and how do they differ in function?

B lymphs express surface Ig, which is their antigen receptors and mediate humoral immunity. After activation, B lymphs differentiate into antibody-secreting plasma cells. T lymphs express TCR and either CD4 or CD8 and mediate cell-mediated immune responses. After activation by peptide antigens on MHC, CD4+ T cells secrete cytokines and express membrane-bound activating ligands → inflammation, enhance phagocytosis, promote B cell antibody responses. After activation, CD8+ T cells release cytotoxic proteins that kill cells.

What are the important differences among naive, effector, and memory T and B lymphocytes?

Naive: mature B or T cells that have not yet encountered a foreign antigen. After activation by antigen, naive lymphs differentiate into →

Effector cells: can protect against or eliminate pathogens, but most die after the antigen is eliminated besides the subset→

Memory cells: live for extended periods of time and respond more rapidly and vigorously than do naive lymphs when challenged w/antigen

Where are T and B lymphocytes located in lymph nodes, and how is their anatomic separation maintained?

B lymphs: reside in follicles in secondary (peripheral) lymphoid organs

T lymphs: reside in the parafollicular cortex of lymph nodes and the periarteriolar lymphoid sheaths of spleen

• maintained in these locations by the action of specific cytokines called chemokines, secreted by stromal cells in the lymphoid organ and bind to different chemokine receptors expressed on B and T cells

How do naive and effector T lymphocytes differ in their patterns of migration?

Naive: home from the blood into the secondary lymphoid organs, then, via lymphatics exiting lymph nodes or through blood vessels in spleen, they migrate back into the blood and recirculate through other secondary lymphoid organs

Effector: generated in secondary lymphoid organs, and most migrate into blood then home to tissue site where the activating antigen is located

How does the specificity of innate immunity differ from that of adaptive immunity?

Innate: directed against common molecular patterns shared by different microbes and the products of damaged cells and is mediated by cellular receptors located in the plasma membrane, where they recognize extracellular microbes, endosomal vesicles, and cytosol

Adaptive; uses an extremely diverse set of antigen receptors (TCRs) to recognize a wide range of microbial and nonmicrobial antigens

What are examples of microbial substances recognized by the innate immune system, and what are the receptors for these substances?

lipopolysaccharides recognized by TLR-4, peptidoglycan recognized by TLR-5, microbial DNA recognized by TLR-9 and cytoplasmic DNA sensors, viral RNA recognized by endosomal TLR-3, -7, and -8 and by cytosolic RIG-like receptors; bacterial peptidoglycans recognized by the cytoplasmic NOD-like receptors; and mannans recognized by the cell surface mannose receptors.

What is the inflammasome and how is it stimulated?

Multiprotein complexes found in the cytoplasm of phagocytes, dendritic cells, and other cell types that respond to pathogens or cell stress by inflammatory cytokine secretion or cel death. Several type of inflammasomes generate an enzyme that proteolytically cleaves a precursor of the cytokine IL-1b, producing an active proinflammatory form that is released from the cell.

• example: NLRP3 (NOD family) responds to stimuli → activation of capase-1→ cleaves IL-1b precursor

What are the mechanisms by which the epithelia of the skin and gastrointestinal tract prevent the entry of microbes?

The skin provides a relatively impermeable multilayered physical epithelial barrier by virtue of a surface layer of keratin produced by the skin epithelial cells called keratinocytes and by tight junctions between the keratinocytes. The intestinal tract is lined by a single layer of epithelial cells, held together by tight junctions. Some of the intestinal epithelial cells secrete a layer of mucus thats a microbial barrier. Both skin and intestinal cells secrete antimicrobial peptide antibiotics, and both contain intraepithelial lymphocytes

How do phagocytes ingest and kill microbes?

They express a variety of receptors that recognize microbial carbohydrates, Fc receptors that bind microbes opsonized by antibodies, and complement receptors that bind microbes opsonized by complement proteins. Microbes that bind to these receptors are internalized into phagosomes, which fuse with lysosomes, where the microbes are destroyed by reactive oxygen and nitrogen species and lysosomal enzymes

What is the role of MHC molecules in the recognition of infected cells by NK cells, and what is the physiologic significance of this recognition?

NK cells express inhibitory receptors that recognize MHC class I molecules of healthy host cells and can then inhibit NK cell activation. In virally infected cells, MHC class I molecules may be down regulated and fail to engage inhibitory receptors, and ligands for activating NK cell receptors are expressed. As a result, NK cells are activated to kill these infected cells

What are the roles of the cytokines TNF, IL-1 in defense against infections?

Tumor necrosis factor (TNF) and IL-1 stimulate inflammation in part by activating endothelial cells that line blood vessels to express molecules that recruit neutrophils and monocytes out of the blood vessels and into sites of infection

What are the roles of the cytokines IL-12 in defense against infections?

IL-12 made by macrophages and dendritic cells contributes to NK cell and T cell activation

What are the roles of the cytokines IL-12 in defense against infections?

IL-12 made by macrophages and dendritic cells contributes to NK cell and T cell activation

How do innate immune responses enhance adaptive immunity?

Innate immune responses induce the expression of costimulators on dendritic cells that can provide signals for T cell activation that work together with signals produced by antigen recognition. Also make cytokines that promote the adaptive immune responses. Complement activation as part of this response can lead to the generation of complement fragments that enhance B lymphocytes activation

When antigens enter through epithelial barriers, such as the skin or intestinal mucosa, in what organs are they concentrated? What cell types play an important role in this process of antigen capture?

Antigens that enter are captured by dendritic cells that reside in or below the epithelium, and the dendritic cells transport the antigens to the draining lymph nodes, where the antigens are displayed to lymphocytes. Cell-free antigens also may enter secondary lymphoid organs and be captured by resident dendritic cells

What are MHC molecules? What are human MHC molecules called?

Major histocompatibility complex molecules are cell surface proteins that bind peptides derived from protein antigens and display them for recognition by T cells. Human MHC proteins are called human leukocyte antigen (HLA) molecules

How were MHC molecules discovered and what is their function?

They were initially discovered as products of polymorphic genes that mediate transplant rejection or induce antileukocyte antibody responses in multiparous women. They bind peptides derived from protein antigens and display them for recognition by T cells

What are the differences between the antigens that are displayed by class I and class II MHC molecules?

Proteins that are produced in the cytosol or are internalized from outside the cell into endosomes and are then transported to the cytosol are digested by cytosolic organelles called proteasomes, and the peptides generated by the proteasomes are presented by class I MHC molecules. Proteins from outside the cell that are internalized into endocytic vesicles may be processed by lysosomal proteases, and the peptides generated in this way are presented by class II MHC molecules

Describe the sequence of events by which class I MHC molecules acquire antigens for display

Protein antigens in the cytosol are cleaved into peptides by proteasomes, and the peptides are transported into the endoplasmic reticulum (ER) by the TAP molecules. Once inside the ER, these peptides bind to newly produced class I MHC molecules. The peptides- class I MHC complex is transported to and displayed on the cell surface

Describe the sequence of events by which class II MHC molecules acquire antigens for display

MHC class II a and b chains are produced in the ER, where they assemble w/each other and with an invariant chain that occludes the antigens binding cleft. The MHC class II invariant chain complex is transported to a late endosomal/lysosomal compartment, where the invariant chain complex is degraded, leaving CLIP in the cleft. Proteins internalized by the endocytic pathway may be degraded into peptides, then displace CLIP and bind tightly to the cleft of the class II HC molecules→ transported and displayed on cell surface

Which subsets of T cells recognize antigens presented by class I and class II MHC molecules?

CD4+ (both naive and helper) recognize peptide antigens bound to class II molecules. CD8+ (both naive and cytotoxic) recognize MHC class I

What molecules on T cells contribute to their specificity for either class I or class II MHC- associated peptide antigens?

The CD4 coreceptor on the T cells binds to class II MHC molecules on antigen-presenting cells, and the CD8 coreceptor on T cellsbind to class I MHC molecules on antigen-presenting cells and infected target cells.

What are the functionally distinct domains (regions) of antibody and TCR molecules? What features of the amino acid sequences in these regions are important for their functions?

They contain variable domains that are involved in antigen recognition and constant domains that, in the case of antibodies, mediate effector functions. Variable domains contain hypervariable regions (sequences that differ among different antibodies or TCRs) that form the binding sites for antigens

What are the differences in the types of antigens recognized by antibodies and TCRs?

Antibodies can recognize many types of molecules including small chemicals, proteins, carbohydrates, lipids, and nucleic acids. In proteins, antibodies can recognize conformational or linear features, called epitopes. TCRs can recognize only linear peptides ranging from 8 to 20 amino acid residues, that are proteolytically generated from proteins and bound to the clefts of MHC molecules

What are some of the checkpoints during lymphocyte maturation that ensure survival of the useful cells?

Diversity of antibodies and TCRs is generated by V-D-J recombination, which is the joining of individual V, D, and J DNa segments in developing lymphs from a choice of many such segments that are spatially separated in the inherited DNA of antibody and TCR gene loci. Variations in nucleotide sequences introduced by the use of different combinations, and loss or enzymatic introduction of uninherited sequence variations between the segments during VdJ joinging (junctional diversity) contribute to diversity.

What are some of the checkpoints during lymphocyte maturation that ensure survival of the useful cells?

The first checkpoint in B and T cell maturation involves the selection of pre-B and pre-T cells that have productively arranged the u heavy-chain gene in the case of B lineage cells and the TCR b hain gene in T cells. The second one is after the production of complete antigen receptors and ensures that only cells w/the proper VDJ recombination maure.

What is the phenomenon of negative selections, and what is its importance?

Negative selection results in the deletion or editing of strongly self-reactive lymphocytes, in the thymus for T cells and in the bone marrow for B cells. This process eliminates many self antigen- reactive lymphocytes

What is positive selection

Positive selection is a process in which T cells that can recognize self MHC molecules weakly are allowed to survive and express the type of coreceptor (CD4 or CD8) that matches the type of MHC molecule recognized

What are the components of the TCR complex? Which of these components are responsible for antigen recognition and which for signal transduction

The TCR complex is made up of the TCR a and B chains, which are responsible for antigen recognition, and the CD3 and zeta protein, which are required for signal transduction

What are some of the molecules in addition to the TCR that T cells use to initiate their responses to antigens, and what are the functions of these molecules?

Include the CD4 and CD8 coreceptors, which bind to class II and class I MHC molecules, respectively; costimulatory receptors such as CD28 which bind to costimulators expressed on activated antigen-presenting cell (APCs) and adhesion molecules such as the integrin LFA-1, which mediates T cells activate responses adhesion to APC

What is costimulation?

Costimulation refers to signals delivered to a lymphocyte that are required for activation in addition to but independent of antigen receptor signaling

What is the physiologic significance of costimulation?

Costimulatory signals are commonly referred to as a “second signal” (antigen being “signal 1”) and provide lymphocytes with the information that the antigen they are recognizing may be of microbial origin.

What are some of the ligand-receptor pairs involved in costimulation?

B7-1 (CD80) and B7-2 (CD86) are the major costimulators on APCs, which bind to CD28 on T cells

Summarize the links among antigen recognition, the major biochemical signaling pathways in T cells, and the production of transcription factors

Antigen recognition results in the CD4 or CD8 coreceptors in T cells bringing the LCK tyrosine kinase bound to their cytosolic tails in proximity to CD3 and zeta chain ITAMs. Phosphorylation of the ITAMs by LCK results in the recruitment and activation of ZAP-70→ phosphorylates other adaptor protein and enzymes, initiating signaling pathways by activating different downstream enzymes.

What is the principal growth factor for T cellss?

Interleukin-2 (IL-2), it is produced by T cells in response to antigen receptor signals and costimulation

Why do antigen-specific T cells expand more than other (bystander) T cells on exposure to antigen?

T cells that have recognized antigens express increased levels of receptors for IL-2 and thus respond to the growth factor during immune responses to the antigens. Regulatory T cells (Tregs) also need IL-2 for their survival and function

What are the mechanisms by which CD4+ effector T cells activate other leukocytes?

CD4+ helper T cells activate other cells (B lymphs, macrophages) by the surface molecules CD40-ligand engaging CD40 on the other cells and by the actions of secreted cytokines

What are the major properties of memory T lymphocytes?

Memory cells survive after the antigen is cleared, slowly proliferate to maintain their numbers for months to years, and respond more rapidly and strongly to antigen exposure than do naive cells.

What proteins of the CD28 family function to inhibit T cells activate responses, and how do they work?

2 proteins in the CD28 family that are expressed on T cells and act to inhibit T cell responses are CTLA-4 and PD-1. CTLA-4 is expressed on activated T cells and is always expressed on regulator T cells. It binds to B7-1 and B7-2 with higher affinity than CD28, and therefore prevents the B7 proteins from costimulating T cells. PD-1 is expressed on activated T cells, and upon binding PD-LI/PD-L2 on antigen-presenting cell, delivers inhibitory signals that block the activating signals generated by TCR and CD28

Why do naive T cells migrate preferentially to lymphoid organs and differentiated effector T cells (which have been activated by antigen) migrate preferentially to tissues that are sites of infection?

Naive T cells express the adhesion molecule L-selectin and the chemokine receptor CCr7, which mediate homing to secondary lymphoid organs, like lymph nodes. Differentiated effector cells lose expression of these molecules and instead express adhesion molecules that bind to molecules on endothelium exposed to inflammatory cytokines. The effector cells also express receptors for chemokines produced at sites of inflammation→ migrating to these sites

What are the types of T lymphocyte-medated immune reactions that eliminate microbes and are sequestered in the vesicles of phagocytes and microbes that live in the cytoplasm of infected host cells?

Intracellular microbes that reside in phagosomes of macrophages (bacteria and fungi) are eliminated by Th cells, specifically Th1 subsrt that activate the phagocytes to destroy ingested microbes. Microbes whose life cycles in the cytosol (viruses) are eliminated by CD8+ T cell-mediated killing of the infected cells, eliminating the reservoir of infection

What are the major subsets of CD4+ effector T cells?

Th1, Th2, Th17

How does each major subsets of CD4+ effector T cells differ?

Th1: secrete IFN-y

Th2: secrete IL-4, IL-13, IL-5

Th17: secrete IL-17, IL-22

What are the major subsets of CD4+ effector T cells roles in defense against different types of infectious pathogens

Th1: secrete IFN-y → activates macrophages to kill phagocytosed microbes

Th2: secrete IL-4, IL-13,→ stimulate mucus production and gut peristalsis (induce B cell IgE production) , IL-5 → activates eosinophils

Th17: secrete IL-17→ enhance neutrophil responses, IL-22 → promotes repair of epithelial barriers injured by microbes

What are the mechanisms by which T cells activate macrophages?

In addition to activating macrophages by secreting IFN-y, Th1 cels also express CD40 ligand, which activates macrophages. Macrophages activated by Th1 cells make increased nitric oxide and reactive oxygen species. These free radicals destroy ingested micobes.

What are the responses of macrophages that result in the killing of ingested microbes?

Activated macrophages also produce increased amount of lysosomal enzymes, which help to destroy microbes and cytokines like IL-1, TNF, IL-6 and chemokines→ inflammation

How do CD8+ CTLs kill cells infected with viruses/

CD8+ cytotoxic T lymphocytes that recognize microbial peptide antigen displayed by class I MHC on an infected tissue cell release granules that contain perforin and granzymes, which enter the infected cells and induce their death by apoptosis

What are some of the mechanisms by which intracellular microbes resist the effector mechanisms of cell-mediated immunity?

Some intracellular microbes evade immunity by preventing phagolysosomal fusion. Many viruses inhibit antigen presentation and some may inactivate effector T cells