BMS150 - Wk 2

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Questions and Answers

What is the primary role of HLA proteins in the immune response?

To present antigens to T-cells (correct)

To directly destroy pathogens

To produce cytokines

To generate lymphocyte receptors

Which cell types are primarily responsible for presenting antigens via HLA-2?

Cytotoxic T-cells

All body cells

Neutrophils and eosinophils

B cells and macrophages (correct)

What distinguishes the type of antigens presented by HLA-1 and HLA-2?

HLA-1 and HLA-2 both present antigens from all types of pathogens equally.

HLA-1 presents endogenous antigens, while HLA-2 presents exogenous antigens. (correct)

Both HLA types present intracellular antigens exclusively.

HLA-1 presents extracellular antigens, while HLA-2 presents intracellular antigens.

Which of the following statements about T-cell activation and HLA proteins is incorrect?

T-cells can mount a response to self antigens presented by HLA. Signup and view all the answers

What is cross-presentation in the context of antigen presentation?

The ability of certain cells to present exogenous antigens through HLA-1. Signup and view all the answers

What is the primary source of antigenic peptides in the endogenous pathway?

Cytosolic proteins Signup and view all the answers

Which step occurs after the peptide is transported into the RER?

It is loaded onto the HLA-1 protein Signup and view all the answers

What type of proteins do immunoproteosomes process for HLA-1 presentation?

Both foreign and altered proteins Signup and view all the answers

How are proteins targeted for degradation by proteasomes?

By tagging with ubiquitin Signup and view all the answers

During what condition can HLA-1 proteins bind foreign peptides?

During infection or malignancy Signup and view all the answers

What is the role of IL-2 in lymphocyte activation?

Stimulates T cell activation and proliferation. Signup and view all the answers

Which characteristic uniquely distinguishes Treg cells from other Th cells?

They have a role in suppressing immune responses. Signup and view all the answers

What distinguishes the cSMAC from the pSMAC during the APC-Th interaction?

cSMAC is involved in initial T cell activation while pSMAC stabilizes the interaction. Signup and view all the answers

Which Th cell type is primarily associated with combating intracellular pathogens?

Th1 Signup and view all the answers

How does signal 2 help in the regulation of Th cells during their activation?

It promotes T cell survival and proliferation. Signup and view all the answers

What key function do Th17 cells serve in the immune system?

Protecting against bacterial and fungal infections Signup and view all the answers

Which cytokines are essential for the polarization of naïve Th cells into Th17 cells?

IL-6, TGF-β, and IL-23 Signup and view all the answers

What is the role of ROR-γt in the polarization of Th17 cells?

It serves as the transcription factor for Th17 cell polarization. Signup and view all the answers

How do Th17 effector cells exert their major functions?

In inflamed tissues outside of SLOs Signup and view all the answers

What distinguishes Th1 and Th17 cells in terms of their impact on antibody production?

Th1 cells specifically encourage one antibody subtype while Th17 cells do not stimulate antibody production. Signup and view all the answers

Which bacteria are commonly found in the nasal cavity as part of the normal microbiome?

Staphylococcus bacteria Signup and view all the answers

What type of bacteria is characterized as gram-negative and anaerobic, and includes lactate-fermenting species?

Veillonella spp. Signup and view all the answers

What is the primary role of Haemophilus spp. in the upper respiratory microbiome?

Utilizing X factor (hemin) and V factor (NAD+) Signup and view all the answers

Which of the following statements about the microbiota of the upper and lower respiratory tracts is correct?

The upper respiratory system has a diverse microbiome, while the lower is free of resident microbiota. Signup and view all the answers

Which bacteria are identified as potent nitrate reducers in the normal microbiome of the pharynx and nasal cavity?

Veillonella spp. Signup and view all the answers

Which bacterium is identified as the causative agent of streptococcal pharyngitis?

Streptococcus pyogenes Signup and view all the answers

Which of the following is NOT a known virulence factor of Streptococcus pyogenes?

Lipopolysaccharide Signup and view all the answers

What is one of the primary benefits of the upper respiratory microbiome?

It limits the occurrence of infections. Signup and view all the answers

Which symptom is commonly associated with streptococcal pharyngitis?

Pain during swallowing Signup and view all the answers

What type of hemolysis is characteristic of Streptococcus pyogenes?

Beta-hemolysis Signup and view all the answers

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.