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.