Innate Immunity: Rapid, Non-Specific Response

Innate Immunity (EGGO 1)

• Innate immunity is a rapid, non-specific immune response that lacks immunological memory.

Videos for review

• INSERM videos explain the inflammatory reaction and adaptive immunity

Differences between innate versis acquired immunity

• Innate immunity acts rapidly (in minutes), with non-specific responses and no memory.
• Acquired/adaptive immunity takes longer (7-10 days), is specific and evokes immunological memory (years).
• Inductions of innate immune responses are local or at the site of infection
• Adaptive immunity inductions occur in lymphoid organs, lymph nodes, the spleen, tonsils, and mucosa-associated lymphoid tissue (MALT).
• Innate immunity involves macrophages, natural killer cells (NK), dendritic cells and mast cells, and recognizes pathogens/antigens using receptors.
• Adaptive immunity relies on T cells (via T cell receptors) and B cells (via B cell receptors).
• Key non-cellular components of the innate immune response are complement proteins C3b (opsonins), C3a/C5a (anaphylatoxins), and cytokines.
• Antibodies (Igs) are key to the acquired immune response.

Infectious process

• Disruption of the skin barrier
• Phagocytosis of bacteria by macrophages or dendritic cells.
• The release of pro-inflammatory cytokines/chemokines to attract other immune cells
• Migration of dendritic cells to lymph nodes
• Antigen presentation by dendritic cells to T cells activates B cells
• B cell activation leads to antibody secretion (adaptive response)
• The recognition of antigen-antibody complexes by C1q activates the classical complement pathway (innate response).

Steps in Innate Immunity

• Initial engagement involves detection of pathogens by internal defense systems.
• Bacteria are phagocytosed by macrophages, leading to intracellular digestion.
• Natural killer (NK) cells induce cytotoxicity when encountering infected cells.
• Circulating proteins, such as complement, induce extracellular digestion (lysis).
• The processes involve recruitment of other actors of the immune system.

Lymphoid System Organs

• Primary lymphoid organs: Bone marrow (B cell development) and thymus (T cell maturation).
• Secondary lymphoid organs: Spleen, lymph nodes and mucosal/epidermal tissues.
• Lymphocytes migrate to secondary organs (lymph nodes) after maturation.
• Lymphocytes encounter antigens in secondary organs, triggering specific immune responses.

Immune Cells

• Endothelial cells and exclusive tissue cells include platelets and plasmocytes respectively.
• Peripheral blood includes monocytes, T CD4/T CD8 lymphocytes, NK cells, immature dendritic cells.
• Dendritic cells can capture antigens and present.
• Macrophages act via phagocytosis.
• Neutrophils, eosinophils, and basophils are involved in the immune response.
• T cells act to help B cells or induce cell death.

Innate vs Adaptive Immunity Contact With Microorganisms

• If successful, innate immunity leads to no infection and no disease.
• If the innate immune response fails to eliminate pathogens
• Adaptive immunity is activated, leading to recovery, acquired protection, and memory.
• Failure of both innate/adaptive immunity results in chronic infections, relapses, and recurring infections.

Agent Pathogene

• Innate immunity (multicellular organisms): non-specific, rapid, no memory
• Adaptive immunity (vertebrates): specific to the pathogen, takes days, induces memory
• Innate barriers, complement, interferons, macrophages, neutrophils, eosinophils and NK lymphocytes
• Adaptive humoral immunity via B cells/antibodies; cellular immunity via T cells

Innate and Adaptive Immunity Receptors

• Innate: "Pattern Recognition Receptor" (PRR):
  • Recognizes molecular patterns associated with pathogens
  • Expressed on cells of the same type allowing for danger signals
• Adaptive:Immunoglobulin or TCR
  • Clonal expression: each cell expresses one receptor with specific recognition.
• Macrophages are fully activated/rapid
• Only a small fraction of B cells (less than 1 in 100,000) are activated.

PAMPs (Pathogen-Associated Molecular Patterns

• Molecules associated with pathogens that are recognized by the immune system.
• Bacteria: LPS, LTA, Flagellin, PGN
• Viruses: dsRNA, ssRNA, dsDNA
• Parasites: GPI, CpG motifs, Profilin.
• Yeasts: Zymosan, Fungal mannans, CpG motifs

Acute Phase Proteins

• Several acute phase proteins recognize pathogens
• Bacteria induce macrophages to produce IL-6
  • IL-6 acts on hepatocytes to induce synthesis of acute-phase proteins (SP-A/SP-D, mannose-binding lectin, fibrinogen, C-reactive protein)
• C-reactive protein binds phosphocholine/acts as an opsonin activating complements
• Mannose-binding lectin: binds mannose resides, acts as an opson and activates complements

TLR Signalling

• TLR-membrane: recognize surface patterns of pathogens
• TLR-intracellular: recognize genetic material from pathogen breakdown
• Not all innate immune effectors have all existing PRRs

Innate Immune Cells Function

• Natural killer (NK) cells mediate cytolysis of infected or altered cells (tumor cells)
• Eosinophils, basophils, and mast cells are involved in inflammation and allergic responses
• Neutrophils mediate degranulation and phagocytosis against bacteria
• Macrophages mediate phagocytosis, inflammation, tissue repair, and antigen presentation
• Dendritic cells mediate phagocytosis, inflammation, and antigen presentation.
  • Dendritic cells education of the lymphocytes.

Phygocytosis

• Key mechanisms used by myeloid innate effectors
• They include phagocytosis (internalization and degradation), degranulation (toxic granule release; cell death), and NET formation (toxic trap expulsion).

Innate effectors inflammatory process

• Histamine, prostaglandins, and leukotrienes modulate inflammation.

Complement Protein Functions

• Lysis of pathogens via the formation of a membrane attack complex (MAC).
• Enhancement of phagocytosis (opsonization) by C3b.
• Inflammation triggered by anaphylatoxins (C3a/C5a)
  • Recruits cells via C5a
  • Increases vascular permeability and migration of innate effectors.
  • Enhances microbial activity of macrophages.