Immunology

Blood Cells Related to the Innate Immune Response

  • The types of blood cells include:
    • Monocytes
    • Lymphocytes
    • Neutrophils
    • Red Blood Cells (Erythrocytes)
    • Platelets
  • Leukocytes (white blood cells) are crucial for the immune system.
  • Source: Boundless. "Pathogen Recognition." Boundless Microbiology, 26 May 2016.

Introduction to Immunology

  • Immunology: A branch of biology focused on host defense mechanisms against disease, encompassing various structures and processes.
  • There are three lines of defense in the immune system:
    1. Innate Immunity (Non-specific):
    • First Line of Defense: Skin, mucous membranes, normal microbiota.
    • Second Line of Defense: Specialized cells (e.g., phagocytes), antimicrobial molecules (e.g., interferons), and processes (e.g., inflammation, fever).
    1. Adaptive Immunity (Specific):
    • Third Line of Defense: Characterized by the ability to recognize and defend against non-self entities and having immune memory.
    • Major players: B-lymphocytes (antibody-mediated response) and T-lymphocytes (cell-mediated response).

Skin Structure and Function

  • Skin Composition:
    • Composed of two main layers:
    • Epidermis:
      • Multiple layers of tightly packed cells, enriched with keratin, serving as a physical barrier against pathogens.
      • Undergoes continual renewal; helps discard microorganisms through dead skin shedding.
      • Contains dendritic cells, capable of engulfing (phagocytizing) and deactivating pathogens.
    • Dermis:
      • Rich in collagen, providing strength and pliability.
      • Secretes antimicrobial peptides (AMPs) such as defensins that have a broad spectrum against Gram-positive and Gram-negative bacteria, fungi, and viruses.
      • Contains lysozyme, an enzyme that hydrolyzes sugar linkages in peptidoglycans, especially effective against Gram-positive bacteria.
      • Sebaceous (oil) glands secrete sebum, which maintains skin pliability and a low pH (~5).

Pathogen Access and Defense Mechanisms

  • For a pathogen to effectively cause disease, it must:
    1. Gain access to the body.
    2. Attach itself to host cells.
    3. Evade detection by the host's defense long enough to cause harm.

Mucous Membrane (Mucosa)

  • Covers all body cavities open to the environment (respiratory, urinary, reproductive, and digestive tracts).
  • Functions:
    • Secretes mucus (a mixture of glycoproteins, water, and electrolytes) that can inactivate microorganisms.
    • Composed of live epithelial cells with increased susceptibility to infections.
    • Ciliated epithelial cells physically displace microorganisms (e.g., in the respiratory tract).
    • Can also secrete antimicrobial peptides.

Normal Microbiota (Human Flora)

  • Protects the body from pathogens through microbial antagonism:
    • Prevents growth of harmful microorganisms by outcompeting them.
    • Maintains an environment unfavorable for most pathogens.

Established Microbiota by Body Site

  • Skin: Streptococcus, Staphylococcus, Candida
  • Gastrointestinal tract:
    • Oral cavity: Streptococcus, Candida
    • Intestine and rectum: Streptococcus, Staphylococcus, Candida, Escherichia, Lactobacillus
  • Upper respiratory tract: Similar flora to oral cavity
  • Genital tract: Streptococcus, Candida, Escherichia, Lactobacillus
  • Urinary tract: Streptococcus, Staphylococcus, Lactobacillus
  • Eye: Streptococcus, Staphylococcus
  • Ear: Staphylococcus, Candida.

Components and Functions of Blood

  • Blood Composition:

    • A liquid tissue consisting of cells (blood cells) and plasma.
    • Plasma: Contains water, electrolytes, clotting factors, acute-phase proteins, complement proteins, and cytokines.
    • Serum: Plasma devoid of clotting factors.

  • Types of Blood Cells Produced in Bone Marrow:

    • Erythrocytes (Red Blood Cells): Contain hemoglobin, responsible for oxygen transport to tissues.
    • Platelets: Cell fragments involved in clotting responses.
    • Leukocytes (White Blood Cells): Engaged in immune defense, categorized into:
    • Basophils
    • Neutrophils
    • Eosinophils
    • Monocytes
    • Lymphocytes.

Hematopoiesis

  • Origin of Blood Cells:
    • Blood cells originate from multipotent hematopoietic stem cells (hemocytoblasts).
    • Stem cells may remain as stem cells or differentiate along either myeloid or lymphoid pathways depending on received signals.

White Blood Cells (Leukocytes)

  • Diapedesis: Ability of WBCs to exit blood capillaries and reach infection sites.
  • Types of Leukocytes and their Functions:
    • Basophils: Participate in inflammation, releasing histamine (degranulation) which contributes to allergies.
    • Neutrophils: Phagocytize pathogens and release antimicrobial substances (degranulation).
    • Eosinophils: Combat parasitic infections, involved in allergy and asthma, possessing phagocytic properties.
    • Monocytes: Differentiate into macrophages or dendritic cells, both specialized phagocytes.
    • Lymphocytes:
    • Natural Killer (NK) Cells: Part of innate immunity; they induce apoptosis in virus-infected cells.
    • T cells: Involved in cell-mediated adaptive immunity.
    • B cells: Involved in humoral (antibody-mediated) adaptive immunity.

Key Cytokines and Their Roles

  • Cytokines: Small proteins released by one cell affecting the behavior of another cell.
    • Functions include:
    • Production of inflammatory mediators (e.g., histamine, prostaglandins).
    • Examples:
      • Interferon gamma (IFN-γ): Blocks viral replication, activates macrophages, enhances antigen presentation, promotes NK cell activity.
      • Interleukins (IL-4, IL-12): Activate B-cells and T-cells, respectively, in adaptive responses.
      • Tumor Necrosis Factor alpha (TNF-α): Inflammatory mediator, can induce fever and apoptosis.

The Complement System

  • Comprises over 30 proteins circulating in blood that achieve:
    • Opsonization: Coating pathogens to enhance phagocytosis.
    • Cell Lysis: Forming pores in pathogen membranes.
    • Induction of inflammation and fever responses.

Inflammation

  • A non-specific response to tissue damage characterized by:
    • Symptoms: Swelling, redness, heat, pain.
    • Initiated by the production of cytokines by leukocytes.
    • Involves vasodilation and increased permeability of vessels allowing more immune cells to reach the site.
    • Can be acute (beneficial) or chronic (harmful).

Fever

  • A rise in body temperature above normal (>37 °C / 98.6 °F).
  • Pyrogens: Substances (exogenous like pathogens and endogenous like cytokines) that induce fever.
  • Fever boosts the effects of interferons and inhibits some pathogens but too high can damage body proteins and nerves.

Phagocytosis Stages

  1. Engulfment of pathogens.
  2. Formation of a phagosome.
  3. Digestion in the phagolysosome.
  4. Expulsion of undigested materials.

Pathogen-Associated Molecular Patterns (PAMPs)

  • PAMPs: Conserved molecules on pathogens recognized by the immune system; examples include LPS, peptidoglycans, and viral nucleic acids.
  • Pattern Recognition Receptors (PRRs): Found on phagocytes, communicate with the nucleus upon recognizing PAMPs to activate immune responses (e.g., initiate phagocytosis, produce cytokines).
  • Toll-like Receptors (TLRs): A type of PRR that plays a critical role in recognizing PAMPs.

Characteristics of Adaptive Immunity

  • Ability to recognize specific invaders: Tailored responses to distinct pathogens.
  • Immunological Memory: Faster responses upon subsequent infections.
  • Clonability: Clonal expansion of lymphocytes upon antigen detection.

Lymphatic System

  • A system of vessels and tissues involved in transporting lymph—a fluid similar to blood plasma but lacking erythrocytes.
  • Facilitates immune cell circulation and maturation.
  • Includes structures like lymph nodes and the thymus.
  • Key for adaptive immunity processes.

Antigens and Immune Response

  • Antigens: Molecules recognized as foreign; specific immune responses are directed against them.
  • Immunogens: Antigens that actively elicit an immune response.
  • Epitopes: Small portions of antigens recognized by the immune system.

Major Histocompatibility Complex (MHC)

  • Set of proteins on cell surfaces: MHC class I (on all nucleated cells) and MHC class II (on antigen-presenting cells).
  • Identifies self from non-self, significant for immune responses.

Antigen-Presenting Cells (APCs)

  • Including macrophages, dendritic cells, and B cells.
  • Present foreign epitopes with MHC class II to activate T-cells.

T Cell Activation and Differentiation

  • T cells can differentiate into:
    • Cytotoxic T Cells (CTL)
    • T Helper Cells (Th)
    • Memory T Cells
    • Regulatory T Cells
  • CTLs target and kill infected cells via cytotoxins.

Superantigens

  • A type of exotoxin causing an excessive, non-specific immune response.
  • Can lead to systemic reactions like shock syndrome, requiring careful management.

Antibody-Mediated Adaptive Immunity

  • Involves interaction between T-helper cells and B cells, leading to B cell activation and proliferation.
  • Immunoglobulins (Antibodies): Produced by B cells, which recognize and bind to specific epitopes with high specificity, aiding in pathogen neutralization and opsonization.

Types of Immunoglobulins

  • IgG: ~80%; crosses the placenta.
  • IgA: ~10%; found in secretions.
  • IgM: ~5%; first antibody produced.
  • IgE: <0.5%; involved in allergic responses.
  • IgD: <0.5%; function not fully understood.

Mechanisms of Antibody Action

  • Antibodies function in:
    • Activation of the complement system.
    • Neutralizing toxins.
    • Opsonizing pathogens for phagocytosis.
    • Facilitating antibody-dependent cell-mediated cytotoxicity (ADCC).

Acquired Adaptive Immunity

  • Natural Immunity: General immune protection from natural exposure to pathogens.
  • Artificial Immunity: Induced by medical interventions like vaccinations.
  • Active Immunity: Body generates its immune response.
  • Passive Immunity: Antibodies transferred from another organism; protective only while antibodies are present.