Innate Immunity Overview

Innate Immunity

• Innate responses are generally non-specific and generic.
• Innate immune cells lack immunological memory.
• Innate defenses include humoral factors, cells, anatomical barriers, resident flora, and secretions.

Host Defenses in Innate Immunity

• Humoral factors and Acute-Phase Reactants: Complement proteins, C-reactive protein (CRP), lactoferrin, lysozyme, pepsin (stomach acidity).
• Anatomical barriers: Cilia, mucus, skin.
• Resident flora: Many non-pathogenic bacteria.
• Cells: Antigen-presenting cells (APCs), basophils, eosinophils, mast cells, natural killer cells, phagocytes.

Types of Acute-Phase Reactants

• C-reactive protein (CRP): Response time: 4-6 hours; Normal concentration: 0.5 mg/dL; Increase: 1000x; Function: Opsonization, complement activation.
• Serum Amyloid A: Response time: 24 hours; Normal concentration: 5 mg/dL; Increase: 1000x; Function: Activates monocytes and macrophages.
• Alpha1-antitrypsin: Response time: 24 hours; Normal concentration: 200-400 mg/dL; Increase: 2-5x; Function: Protease inhibitor.
• Fibrinogen: Response time: 24 hours; Normal concentration: 200-400 mg/dL; Increase: 2-5x; Function: Clot formation.
• Haptoglobin: Response time: 24 hours; Normal concentration: 40-290 mg/dL; Increase: 2-10x; Function: Binds hemoglobin.
• Ceruloplasmin: Response time: 48-72 hours; Normal concentration: 20-40 mg/dL; Increase: 2x; Function: Binds copper and oxidizes iron.
• Complement C3: Response time: 48-72 hours; Normal concentration: 60-140 mg/dL; Increase: 2x; Function: Opsonization, lysis.

Cells of Innate Immunity

• Phagocytes: Engulf extracellular antigens into vacuoles, destroying them. Monocytes in blood are phagocytic. Including but not limited to:
  • Monocytes: Circulate in the blood, have some phagocytic capability but not as effective as macrophages, can migrate to tissues but are short-lived.
  • Macrophages: Develop from blood monocytes in tissues, long-lived;
  • Neutrophils: Phagocytic; over 90% of circulating granulocytes.
• Basophils: Least common granulocyte; release histamine and heparin.
• Eosinophils: Granulocyte found mostly in tissues; Parasite fighter, release toxic proteins for helminths.
• Mast cells and Basophils: Increase vascular permeability; reside in connective tissue and mucous membranes, regulate inflammatory response.
• Natural killer (NK) cells: Destroy infected cells (e.g., viral, transformed). Found without exposure to antigens.

Receptors: PRRs and PAMPS

• Pathogen-Recognition Receptors (PRRs): On immune cells, recognize molecules (PAMPs) unique to infectious organisms.
• PRRs are found on: Macrophages, dendritic cells, neutrophils, eosinophils, monocytes, mast cells, and epithelial cells.
• Activation: PRRs bind to PAMPS, triggering phagocytic cell activation.
• Example: Toll-like receptors (TLRs).

Adaptive Immunity

• Adaptive immunity adapts to the encountered antigens.
• Key players: Phagocytes (innate), B cells (lymphocytes), antibodies (adaptive) when the antigen is extracellular.
• B cell activation requires specific CD4+ T cells (TH2) and their cytokines.
• Characterized by a more rapid, stronger memory response.

Lymphocytes

• Two types: T cells and B cells.
• T cells: Differentiate in the thymus.
• B cells: Differentiate in mammals (fetal liver, spleen, and adult bone marrow); in avians differentiate in the bursa of Fabricius.

Cells of Adaptive Immunity

• B cells and Plasma cells: Produce antibodies (anamnestic or secondary immune response).
• CD4+ T cells: Produce cytokines that enhance cytotoxic molecule production in phagocytes (TH1), regulate antigen-presenting cell activation (innate), and induce NK cell proliferation (innate).
• Cytotoxic T cells: Lyse infected cells (virally infected cells).

B Cells

• B cell antigen-specific receptor is an antibody molecule on the B cell surface.
• Recognizes whole antigens without antigen processing.
• Membrane immunoglobulin.

T Cell Thymocyte

• Progenitor T cells migrate to the thymus to become mature T cells, called thymocytes.
• Some seed secondary lymphoid tissue, while others recirculate between blood and lymphoid tissue until they encounter antigens.
• Leave the thymus as CD4+ T or CD8+ T cells.

T Cells

• Take part in cell-mediated and humoral immunity.
• In humoral immunity, antibodies play a subordinate role.
• Important for all other aspects of immunity.

T Cells Classification

• CD4+ T cells: Main function: secreting cytokines needed for regulating all immune responses and combating extracellular pathogens (Helper T cells).
• CD8+ T cells: Main role: destroying infected (intracellular pathogens) cells (Killer T cells or Cytotoxic T cells).

T Cells and MHC

• T cells recognize ("non-self") pathogens by detecting processed antigens presented in conjunction with "self" MHC (major histocompatibility complex) molecules.
• Antigen-presenting cells:
  • Dendritic cells
  • Macrophages
  • B cells
• CD8+ T cells: Recognize antigens coupled to Class I MHC molecules (self).
• CD4+ T cells: Recognize antigens coupled to Class II MHC molecules (self).
• Class I MHC: found on variety of cell types.
• Class II MHC: primarily found on antigen-presenting cells.

CD8+ T Cell

• Kill cells infected with intracellular pathogens or those that are otherwise damaged or dysfunctional.

CD4+ T Cell

• Release cytokines that influence the activities of various cell types.
• Cytokines produced enhance macrophage's microbicidal function and killer T cell activity.

Adaptive Immunity: Humoral and Cellular Responses

• T cell receptors only recognize antigens presented on MHC molecules.
• Cellular immunity involves killing infected cells.
• Humoral immunity involves antibody production.

Regulatory T Cells (Tregs)

• Suppressor T cells produce chemicals (cytokines) to "turn off" other immune system cells when an infection is brought under control.

Normal IR: Process of Inflammation

• Body's overall response to tissue injury (physical, chemical, or infectious).
• Cardinal signs:
  • Rubor (redness): vasodilation.
  • Calor (heat): increased blood flow.
  • Tumor (swelling): increased fluid/exudate.
  • Dolor (pain): stimulation of nerve endings.

Initiation of Local Inflammatory Response

• Tissue damage and bacteria activate resident sentinel cells to release chemoattractants and vasoactive factors.
• This triggers increased blood flow and capillary permeability.
• Permeable capillaries allow fluid (exudate) and cells to flow into the affected area.
• Phagocytes and antibacterial substances destroy bacteria.
• Neutrophils and other phagocytes migrate to the site of inflammation.

Hypersensitivity

• Four types, all involving initial sensitization.
• Type I (Allergy): IgE-mediated; immediate response.
• Type II (Cytotoxic): IgG or IgM-mediated cell destruction.
• Type III (Immune Complex): Immune complexes depositing, triggering complement activation.
• Type IV (Delayed): Cell-mediated; T-cells activated, leading to inflammatory response.

Diseases Manifesting Delayed Type Hypersensitivity

• Chronic diseases in humans linked to infectious agents (e.g., tuberculosis, leprosy, leishmaniasis).
• Also linked to Deep fungal infections and helminthic infections.
• Activate T cells and macrophages.