Immune system Disorders

• Immune System


  • Serves as protection for pathogens abound in the environment
  • Capable of causing tissue injury and disease
• Immune disorders


  • Allergies
  • Autoimmune disorders
• Innate Immunity


  • Also called Natural or Native Immunity
  • A mechanism that is ready to react to infections even before they occur
  • It has evolved to specifically recognize and combat microbes
• Innate Immunity functions


  1. Recognition of the microbes or damaged cells

  2. Activation of various mechanisms

  3. Elimination of unwanted substances
• Components of the Innate Immunity

  • Epithelial Barriers
  • Phagocytic Cells
  • Dendritic Cells
  • Natural Killer Cells
  • Mast Cells
  • Innate Lymphoid Cells
  • Soluble Proteins
• Epithelial Barriers


  • The skin and the lining of the GIT and Respiratory tract provide mechanical barriers to the entry of microbes
  • It also produces antimicrobial molecules such as defensins
  • Lymphocytes located in the epithelia also combat microbes
• Phagocytic Cells


  • Monocytes and neutrophils are phagocytes present in the blood
  • Monocytes that enter tissues & mature are called macrophages
  • These cells not only sense the presence of offending agents but they also ingest (phagocytose) these invaders and destroy them
• Dendritic Cells


  • Specialized cell population present in the epithelia, lymphoid organs, and most tissues
  • They capture proteins and display peptides for T Cell recognition
  • They have rich collection of receptors that sense microbes and cell damage
  • They also stimulate the secretion of cytokines and mediators that play critical roles in inflammation and anti-viral defense
  • Dendritic cells are involved in the initiation of the innate immune response but they are not part of destruction of offending agent
• Natural Killer Cells (NK Cells)

  Provide early protection against viruses and intracellular bacteria
• Mast Cells


  Capable of producing mediators of inflammation
• Innate Lymphoid Cells


  • Cells with the appearance of Lymphocytes but with the features more like the cells of innate immunity
  • Contributes early defense against microbes
• Soluble Proteins


  • Complement System
  • Mannose-Binding Protein
  • C-reactive protein
  • Lung surfactant
• Classic Pathway (Complement System)


  Activated by Ag-Ab complex
• Lectin Pathway (Complement System)


  Activated by mannose on bacterial surface
• Alternative Pathway (Complement System)


  Activated by microbial surface
• The innate immune response is mediated by alternative and lectin pathways, while the adaptive immune response is mediated by the classical pathway
• Pathogen-Associated Molecular Pattern (PAMPs)


  Molecules associated with groups of pathogens that are recognized by the cells of the innate immunity
• Damage-associated Molecular Pattern (DAMPs)

  Molecules released by injured and necrotic cells recognized by leukocytes
• Pattern Recognition Receptors


  • Cell receptors that recognize PAMPs and DAMPs
  • These receptors are located in all the cellular compartments
• Toll-Like Receptors (TLR)


  • Discovered in Drosophila
  • There are 10 TLRs in mammals; each recognizes a different set of microbial molecules
  • Present in the Plasma Membrane & in Endosomal Membrane
  • All receptors signal by a common pathway that culminates in the activation of NF-kB and Interferon Regulating Factors (IRF)
• NF-kB


  • Stimulates the synthesis and release of cytokines
  • Expression of adhesion molecules
  • Both of which are critical for the recruitment and activation of leukocytes
• Interferon Regulating Factors (IRF)


  Stimulates the production of the anti-viral cytokines (Type 1 IFN)
• Germline loss-of-function mutations affecting TLRs and their signaling pathways are associated with rare but serious immunodeficiency syndromes
• NOD-Like Receptors (NLRs)


  • Cytosolic receptors that recognize a wide variety of substances, including products of necrotic cells, ion disturbances, and some microbial products
  • The NLR signal a multiprotein complex called the Inflammasome
  • The inflammasome activates caspase-1 that cleaves a precursor of IL-1 to generate a biologically active form of IL-1
  • IL-1 is a mediator of inflammation that recruits leukocytes and induces fever
• • Gain-of-function mutations in one of the NLRs result in periodic fever symptoms called autoinflammatory syndromes
  • This syndrome responds very well to treatment with IL-1 antagonists
• Roles of NLR-Inflammasome pathway

  • Recognition of urate crystals in gout
  • Detection of lipids and cholesterol crystals that are abnormally deposited in the tissues that may result in inflammation in obesity-associated DM type 2 and Atherosclerosis
• Other Receptors for Microbial Products

  • C-type Lectin Receptors (CLRs)
  • Rig-Like Receptors (RLR)
  • G-Protein Coupled Receptors
  • Mannose Receptors
• 1. type Lectin Receptors (CLRs)


  Expressed on the plasma membrane of dendritic cells that detect fungal glycans and elicit inflammatory reaction against fungi
• Rig-Like Receptors (RLR)


  • Located in the cytosol
  • Detect nucleic acids of viruses that replicate in the cytoplasm of the infected cells
  • These receptors stimulate the production of anti-viral cytokines
• 1. Protein Coupled Receptors


  • Those found in most leukocytes can recognize short bacterial peptides containing N-formylmethionyl residues
  • These receptors enable the neutrophils to detect bacterial proteins and stimulate chemotactic response of the cells
• Mannose Receptors


  Recognize microbial sugars which often contain mannose residues and induce phagocytosis of the microbes
• Reactions of the Innate Immunity

  • Inflammation – cytokines and products of the complement activation triggers the vascular and cellular components of the inflammatory process
  • Anti-viral defense – Type 1 Interferons produced in response to viruses act on infected and uninfected cells, and activates enzymes that degrade viral nucleic acid
• Innate immunity does not have memory or fine antigen specificity, it uses 100 different receptors to recognize 1,000 molecular patterns. In contrast, the adaptive immunity uses two types of receptors (Antibodies and T-Cell Receptors), each with millions of variations that recognize millions of antigens
• Adaptive Immunity


  • Also called Acquired or Specific immunity
  • Mechanisms that are stimulated by or adapt to microbes and are capable of recognizing microbial and non-microbial substances
  • Usually develops later after exposure to the agents
  • The term Immune Response refers to the adaptive immunity
  • Consist of lymphocytes and their products (including Antibodies)
• Types of Adaptive Immunity

  • Humoral
  • Cell-Mediated
• Humoral Immunity


  • Mediated by B-lymphocytes (from Bone marrow)
  • Function against extracellular microbes and toxins
  • These secrete antibodies (also known as Immunoglobulins)
• Cell-Mediated Immunity


  • Mediated by T-lymphocytes (from Thymus)
  • Function against intracellular microbes
• Both classes of adaptive immunity have highly specific receptors for a wide variety of substances called Antigens
• Lymphocytes


  • B and T lymphocytes are morphologically unimpressive, but they are actually remarkably heterogeneous and specialized in molecular properties and functions
  • Lymphocytes and other cells involved in the immune system are not fixed in a particular tissue but constantly circulate among lymphoid and other tissues via the lymphatic circulation
  • This allows immune surveillance of the lymphocytes
  • In lymphoid organs, the different classes of lymphocytes are arranged in such way that they interact with one another only when stimulated
• Types of Lymphocytes


  • Naïve Lymphocytes
  • Effector Cells
  • Memory Cells