Introduction to Immunology

Introduction to Immunology

• Immunology studies the body's defense mechanisms against injuries, infectious organisms, or foreign substances.
• Two main types of immune systems: innate and adaptive.

Innate Immune System

• Low specificity, recognizing molecules shared by groups of microbes and molecules produced by damaged host cells.
• Low diversity, molecules encoded by inherited genes.
• Limited memory.
• Barriers include skin, mucosal epithelia, antimicrobial molecules, and secreted proteins like complement.
• Cells include phagocytes (macrophages, neutrophils), dendritic cells, NK cells, mast cells, and innate lymphoid cells.

Adaptive Immune System

• High specificity, targeting many different microbial and non-microbial antigens.
• High diversity, antigen receptors generated by somatic recombination of gene segments in lymphocytes.
• Possesses memory.
• Cells include lymphocytes: B cells and T cells.

Immune Response Phases

• Phase 1: Neighbouring cells enter an antiviral state, preparing for potential infection.
• Phase 2: C-type lectin receptors (CLRs) recognize carbohydrate structures on pathogens (mannose, glucans, fucose).
• Phase 3: NOD-like receptors (NLRs) sense intracellular PAMPs and DAMPs, playing a vital role in inflammation and immune homeostasis.
• Phase 4: Dendritic cells (DCs) capture protein antigens and present them to T cells.

C-Type Lectin Receptors (CLRs)

• Membrane-bound receptors, mainly on macrophages and dendritic cells.
• Recognize carbohydrate structures on pathogens, promoting phagocytosis and initiating immune signaling.
• Examples: Dectin-1 (β-glucans), Mannose receptor (mannose and fucose).
• Signaling pathway: Syk kinase/CARD9, NF-κB, AP-1, leading to pro-inflammatory cytokines and immune cell recruitment.

NOD-Like Receptors (NLRs)

• Cytoplasmic receptors detecting microbial components and stress signals.
• Located on endothelial cells, macrophages, dendritic cells, but not neutrophils.
• Examples: NOD1 (DAP), NOD2 (muramyl dipeptide).
• Signaling pathway: NF-κB or inflammasome formation, leading to pyroptosis and the release of pro-inflammatory cytokines.
• NOD2 also influences type I interferon production.
• NLRP3 forms inflammasomes, activating caspase-1, leading to IL-1β and IL-18 maturation.

Dendritic Cells (DCs)

• Major types: Classical/Conventional DCs (cDCs), Plasmacytoid DCs, Monocyte-derived DCs (moDCs), Langerhans cells.
• cDCs: Most numerous DC subset, involved in presenting protein antigens to T cells.
  • cDC1: Specializes in cross-presentation of antigens to CD8+ T cells, critical for anti-viral and anti-tumor immunity.
  • cDC2: Activates CD4+ T cells (helper T cells) and orchestrates the broader immune response.
• Plasmacytoid DCs: resemble plasma cells, main producers of IFN I, involved in antiviral immunity.
• moDCs: Differentiate from monocytes in inflammatory conditions, play a role in inflammation and infection.
• Langerhans cells: Found in epidermis, present antigens to CD4+ T cells, inducing tolerance or activating immune responses.
• DC Maturation: Upon exposure to pathogens or inflammatory cytokines, DCs undergo a maturation process characterized by:
  • Upregulation of MHC class I & II molecules for antigen presentation.
  • Upregulation of costimulatory molecules (CD80, CD86, CD40) for efficient T cell priming.
  • Secretion of cytokines (IL-12, IL-6, IFN-alpha) to shape the adaptive immune response.
• DC Migration: DCs lose their phagocytic ability and gain migratory properties, expressing chemokine receptors like CCR7, enabling them to migrate to lymph nodes.

Major Histocompatibility Complex (MHC) Molecules

• Proteins on cell surfaces, crucial for the immune system's antigen recognition and response.
• Functions:
  • Bind and present peptide antigens to T cells.
  • Distinguish self from non-self.
• Types:
  • MHC Class I: Presents intracellular antigens to CD8+ cytotoxic T cells, found on most nucleated cells.
  • MHC Class II: Presents extracellular antigens to CD4+ helper T cells, found on antigen-presenting cells (APCs).
  • MHC Class III: Encodes immune-related proteins like complement proteins and cytokines.

MHC Genes

• Located in the human leukocyte antigen (HLA) complex on chromosome 6.
  • MHC-I genes (HLA-A, HLA-B, HLA-C): Highly polymorphic, contributing to genetic diversity.
  • MHC-II genes (HLA-DP, HLA-DQ, HLA-DR): Significant polymorphism, allowing for various combinations.
• Characteristics:
  • Highly polymorphic, allowing individual variation in antigen presentation.
  • Multiple MHC genes expressed in each individual, inherited as haplotypes.
  • Maternal and paternal alleles expressed, further enhancing diversity.
  • Heterozygosity (having two different alleles) is beneficial, providing broader antigen-presenting capabilities.
• Disease Association: Specific MHC alleles can be associated with particular diseases, like HLA-B27 with ankylosing spondylitis.

This quiz covers the fundamental concepts of immunology, focusing on the body's defense mechanisms against infections and foreign substances. It distinguishes between the innate and adaptive immune systems, detailing their characteristics and components. Test your understanding of immune responses and the cellular actors involved!