Questions and Answers
What is the primary role of HLA proteins in the immune response?
Which cell types are primarily responsible for presenting antigens via HLA-2?
What distinguishes the type of antigens presented by HLA-1 and HLA-2?
Which of the following statements about T-cell activation and HLA proteins is incorrect?
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What is cross-presentation in the context of antigen presentation?
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What is the primary source of antigenic peptides in the endogenous pathway?
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Which step occurs after the peptide is transported into the RER?
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What type of proteins do immunoproteosomes process for HLA-1 presentation?
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How are proteins targeted for degradation by proteasomes?
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During what condition can HLA-1 proteins bind foreign peptides?
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What is the role of IL-2 in lymphocyte activation?
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Which characteristic uniquely distinguishes Treg cells from other Th cells?
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What distinguishes the cSMAC from the pSMAC during the APC-Th interaction?
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Which Th cell type is primarily associated with combating intracellular pathogens?
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How does signal 2 help in the regulation of Th cells during their activation?
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What key function do Th17 cells serve in the immune system?
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Which cytokines are essential for the polarization of naïve Th cells into Th17 cells?
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What is the role of ROR-γt in the polarization of Th17 cells?
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How do Th17 effector cells exert their major functions?
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What distinguishes Th1 and Th17 cells in terms of their impact on antibody production?
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Which bacteria are commonly found in the nasal cavity as part of the normal microbiome?
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What type of bacteria is characterized as gram-negative and anaerobic, and includes lactate-fermenting species?
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What is the primary role of Haemophilus spp. in the upper respiratory microbiome?
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Which of the following statements about the microbiota of the upper and lower respiratory tracts is correct?
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Which bacteria are identified as potent nitrate reducers in the normal microbiome of the pharynx and nasal cavity?
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Which bacterium is identified as the causative agent of streptococcal pharyngitis?
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Which of the following is NOT a known virulence factor of Streptococcus pyogenes?
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What is one of the primary benefits of the upper respiratory microbiome?
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Which symptom is commonly associated with streptococcal pharyngitis?
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What type of hemolysis is characteristic of Streptococcus pyogenes?
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Study Notes
Antigen Presentation Overview
- HLA (Human Leukocyte Antigen) complexes play critical roles in the immune system's recognition of antigens.
- HLA-1 is primarily involved in presenting intracellular antigens; HLA-2 presents extracellular antigens.
Learning Objectives
- Understand functions of HLA proteins in antigen presentation.
- Identify basic structures of HLA-1 and HLA-2.
- Recognize which cell types present antigens via HLA-1 and HLA-2.
- Describe endogenous (intracellular) and exogenous (extracellular) pathways for antigen processing.
- Distinguish between the types of antigens for each HLA type.
- Explore cross-presentation and identify capable cell types.
- Relate antigen presentation to T-cell activation and the necessary interactions for CD8+ (cytotoxic) and CD4+ (helper) T-cell activation.
Importance of HLA in T-cell Recognition
- T-cells require antigens to be presented in order to recognize and respond to them.
- Antigens are presented bound to HLA proteins on various cells, helping distinguish between foreign and self-antigens.
- MHC (Major Histocompatibility Complex) proteins in mice are analogous to HLA proteins in humans.
HLA-1 Expression and Function
- HLA-1 proteins bind primarily to intracellular antigens through the endogenous pathway.
- Endogenous antigens are often self-antigens; however, foreign peptides can occur during infection.
- Viral infections may lead to HLA-1 presenting both viral and host peptides.
HLA-1 Antigen Processing
- The source of antigenic peptides for HLA-1 is from the cytosol, often from proteasomal degradation of proteins.
- Peptides are transported to the Rough Endoplasmic Reticulum (RER) to bind with HLA-1 proteins before being expressed on the cell surface.
- Specialized proteasomes, termed immunoproteasomes, enhance peptide processing for HLA-1 presentation.
Regulation of HLA-1 Expression
- Intracellular invaders trigger an increase in HLA-1 protein transcription through NOD-like Receptors (NLRs), activating the NFκB pathway.
- Cytokines (e.g., Type 1 and Type 2 interferons, and TNFα) can upregulate HLA-1 expression following infection or cell activation.
T-cell Activation by HLA-1
- Peptide-bound HLA-1 on the cell surface engages CD8+ T-cells, leading to cytotoxic T-cell activation.
- Activated cytotoxic T-cells induce apoptosis in infected cells.
HLA-2 Expression
- HLA-2 binds extracellular antigens via the exogenous pathway, requiring the upregulation of HLA-2 protein.
- Interferon-gamma (IFN-γ) is a key cytokine that enhances HLA-2 expression, though it down-regulates HLA-2 in B-cells.
- IL-4 promotes HLA-2 expression specifically in B-cells.
HLA-2 Antigen Processing
- The exogenous pathway involves phagocytosis, where extracellular antigens are engulfed and processed within phagosomes before loading onto HLA-2 proteins.
- B-cell-mediated phagocytosis occurs through receptor-mediated endocytosis, allowing antibody-bound antigens to be processed in endosomes.
Summary of HLA Types
- HLA-1 and HLA-2 differ in the types of antigens they present, their pathways, and the specific T-cell types they activate.
- HLA-1 focuses on intracellular and endogenous pathways; HLA-2 addresses extracellular sources through exogenous pathways.
T-lymphocyte Biology Objectives
- Understand the activation process of helper T cells (Th) and T-lymphocyte class restriction.
- Compare the roles and locations of costimulator, co-receptor, and adhesion molecules during APC-Th interaction, emphasizing cSMAC vs. pSMAC.
- Define the function of interleukin-2 (IL-2) in lymphocyte activation and its release mechanism.
- Differentiate the activation signals, polarizing cytokines, transcription factors, effector cytokines, and immune response contributions of Th1, Th2, Th17, Tfh, and Treg cells.
- Recognize the unique characteristics of Treg and Tfh cells compared to other Th cells.
- Describe cross-regulation among Th cells and the underlying mechanisms.
- Detail CD8+ cytotoxic T-cell activation, antigen recognition, and foreign cell destruction.
T-cell Activation
- All CD8+ T cells are Class I MHC-restricted, while all CD4+ T cells are Class II MHC-restricted.
- Signal 1 involves the T-cell receptor (TCR) interacting with MHC-II (HLA-2) and CD4 co-receptor presence.
- Signal 1b indicates rare conversion of Th1 cells to Th2, with Tfh cells potentially undergoing re-polarization after antibody response completion.
- Cross-regulation is when polarized Th cells generate signals that inhibit polarization of local Th cells into different types.
Th17 - Innate Activating T Cells
- Th17 cells identified recently, primarily engaged in defense against bacterial and fungal infections, and implicated in several autoimmune conditions (e.g. rheumatoid arthritis, MS).
- Th17 polarization occurs in secondary lymphoid organs (SLOs) via pro-inflammatory cytokines (IL-6, IL-23) and TGF-β.
- Activated Th17 cells secrete IL-22 and IL-17, promoting recruitment of neutrophils/macrophages and antimicrobial protein secretion in inflamed tissues.
- ROR-γt is the critical transcription factor driving Th17 polarization, inhibiting secretion of other cytokines.
Follicular Th Cells - Key Role in Antibody Production
- Tfh cells remain in SLOs, promoting B-cell development and germinal center formation.
- Facilitate two rounds of antibody production: initial lower-affinity and subsequent higher-affinity antibodies through affinity maturation.
- Lack of Tfh activity results in reduced B-cell functionality and antibody refinement.
T-regulatory Cells
- T-regulatory cells (Tregs) down-regulate other immune cell activities, particularly in anti-inflammatory environments driven by TGF-β.
- TGF-β acts as the polarizing cytokine with minimal inflammatory cytokines present.
- FoxP3 is the essential transcription factor for Treg differentiation.
- Effector functions include anti-inflammatory cytokine secretion (IL-10, TGF-β), down-regulation of CD80/CD86 signaling via CTLA-4 binding, and IL-2 consumption from other effector T-cells.
Cross-Regulation Among Th Cells
- Expression of the determining transcription factor signals polarization of naive Th cells.
- Each Th type’s transcription factor prevents production of alternative transcription factors and cytokines.
- Cytokines produced by one Th type can inhibit survival and proliferation of other Th types.
Upper Respiratory Tract Microbiology
- Upper respiratory system hosts a diverse microbiome, unlike the lower respiratory system, which is free of resident microbiota.
- Key microorganisms in the upper respiratory tract include:
- Nose: Haemophilus, Veillonella, diphtheroids
- Nasal Cavity: Staphylococcus, diphtheroids
- Pharynx: Staphylococcus, Streptococcus, diphtheroids
Normal Microbiome Components
- Haemophilus spp.: Requires X Factor (Hemin) and V Factor (NAD+) for growth; notable species includes H. influenzae.
- Veillonella spp.: Gram-negative, anaerobic bacteria; effective lactate fermenters and nitrate reducers; example species is V. parvula.
- Staphylococcus spp.: Staphylococcus aureus is a major pathogen linked to pneumonia, meningitis, toxic shock syndrome, and more.
- Diphtheroids: Include Corynebacterium diptheriae and Propionibacterium acnes.
- Alpha-hemolytic Streptococci: Capable of varying levels of hemolysis; includes Streptococcus pneumoniae and Streptococcus pyogenes.
Microbiome Benefits and Risks
- Positive Aspects: The microbiome limits the potential for infections.
- Negative Aspects: Opportunistic pathogens can become problematic under certain conditions.
Bacterial Pharyngitis Overview
- Commonly referred to as "strep throat," characterized by painful swallowing, bad breath, fever, malaise, and headache.
Causative Agent
-
Streptococcus pyogenes:
- Gram-positive, facultative anaerobe; Lancefield Group A Streptococcus; exhibits beta-hemolytic activity.
Virulence Factors of Streptococcus pyogenes
- M protein inhibits C3b activity, aiding in evasion of the immune response.
- Possesses a hyaluronic acid capsule for protection.
- Produces enzymes like streptokinases and C5a peptidase to enhance pathogenicity.
- Can secrete pyrogenic toxins and streptolysin O, contributing to its infectious potential.
Epidemiology of Streptococcal Pharyngitis
- Understanding of epidemiology links to transmission patterns, risk factors, and demographic considerations, although specific details were not provided.
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Description
This quiz provides an in-depth look at the roles of HLA (Human Leukocyte Antigen) complexes in the immune system, focusing on HLA-1 and HLA-2. Explore their functions, structures, and the pathways for antigen processing crucial for T-cell activation. Test your knowledge on the distinctions between intracellular and extracellular antigens along with cross-presentation.
