Animal Immune Systems Vocabulary

Animal Immune Systems

Chapter 48 Opening Roadmap

• This chapter will cover how animals use their immune systems to fight infectious diseases.
• It will start by comparing:
  • Innate immunity
  • Adaptive immunity
  • The use of B-cell and T-cell receptors
• Then looking closer at:
  • Antigen presentation
• Finally asking:
  • What happens when the immune system doesn't work correctly?
  • Response and memory

Innate vs. Adaptive Immune System

• Pathogens: Bacteria, fungi, protists, and viruses.
• Innate Immunity (all animals):
  • Recognition of a broad range of pathogens.
  • Doesn't vary with reoccurrence.
  • Rapid response.
  • Barrier defenses:
    • Skin
    • Mucous membranes
    • Secretions
  • Internal defenses:
    • Phagocytic cells
    • Natural killer cells
    • Antimicrobial proteins
    • Inflammatory response
• Adaptive Immunity (vertebrates only):
  • Recognition of specific pathogens.
  • Broad set of receptors.
  • Slower response.
  • Humoral response: Antibodies defend against infection in body fluids.
  • Cell-mediated response: Cytotoxic cells defend against infection in body cells.

Barrier Defenses: Invertebrates

• Insects:
  • Waxy cuticle.
• Soft-bodied invertebrates:
  • Protective mucus.
• Insect Integument:
  • Epicuticle:
    • Cement
    • Wax layer
    • Outer epicuticle
    • Inner epicuticle
  • Procuticle:
    • Exocuticle
    • Endocuticle
  • Epidermal epithelium
  • Basement membrane
  • Epidermal cell
    • Pore Canal

Barrier Defenses: Humans

• Skin with keratinized dead cell layer.
• Mucous-lined passages (respiratory and GI).
• Wax secretions (ears).
• Lysozyme secretions (tears).
• Microbiota.

How Pathogens Gain Entry

• Disruption of barrier defenses (e.g., wounds).
• Adaptations of pathogen to defeat barriers (e.g., influenza viruses have enzyme to break down respiratory mucus).

Antigens

• Molecules found in pathogens that the immune system recognizes as non-self.
• Cause immune responses.
• Molecules common in pathogens but not host cells:
  • Lipopolysaccharides (bacteria).
  • Flagellin (bacteria).
  • Double-stranded RNA (viruses).
  • Zymosan (polysaccharide in fungi).
  • Surface antigens of influenza A virus

Innate Immune Response

• Present from birth and before any exposure to pathogens.
• Involves:
  • Special cells: leukocytes (white blood cells) that are phagocytic.
  • TLRs—Toll-like receptors and other pattern recognition receptors.
  • Signaling molecules that recognize pathogens.

Phagocytosis

• Process:
  1. Phagocytic cell surrounds microbe with pseudopodia.
  2. Forms vacuole containing microbes.
  3. Vacuole and lysosome fuse.
  4. Microbes destroyed, toxins detoxified.
  5. Debris released.

Types of Leukocytes in Innate Immune System

• Mast cells:
  • Release histamines (local regulator) involved in inflammatory response.
• Neutrophils:
  • Phagocytes that kill pathogens.
• Macrophages:
  • Phagocytes that kill pathogens and chemically signal other immune response cells.

Toll Proteins and TLRs

• Named after 1st discovered (Toll proteins in insects).
• Analogous proteins in other eukaryotes are called TLR (Toll-like receptor).
• Receive signals that pathogens are present, alert immune cells.

Pattern Recognition Receptors Recognize Antigens

• Includes Toll-Like Receptors (TLRs).
• TLRs present in most eukaryotes (animals, plants, fungi), probably ancestral.
• Humans have 11 TLRs that recognize and bind to antigens.
• TLRs signal other cells in immune system in various ways.

Innate Immune System Signaling Molecules

Inflammatory Response

1. Bacteria and other pathogens enter wound.
2. Platelets from blood release blood-clotting proteins at wound site.
3. Injured tissues and macrophages at the site release chemokines, which recruit immune system cells to site.
4. Mast cells at the site secrete histamine and other factors that dilate surrounding blood vessels, making them more permeable.
5. Neutrophils are recruited to remove pathogens by phagocytosis.
6. Other recruited leukocytes mature into macrophages that phagocytize pathogens and secrete key signaling molecules (that may recruit the adaptive immune system, if necessary).

The Adaptive Immune Response

• Allows the body to generate a specific attack on a new invader.
• Involves special cells = lymphocytes.
• Involves antibodies = proteins produced and secreted by certain lymphocytes and that bind a specific antigen. Flags the pathogen for attack by other cells.

Characteristics of Adaptive Immune Response

• Specificity: recognize/attack specific sites on specific antigens.
• Diversity: can recognize almost limitless # of antigens.
• Memory: can be reactivated quickly if attacked by pathogen 2nd time.
• Self-nonself recognition: molecules that are produced by the organism do not act as antigens.

Lymphocytes: the cells of the Adaptive Immune System

• B cells produce antibodies
• T cells involved in an array of functions, including recognizing and killing infected host cells that have been “flagged”
• Also lymphocytes in mucosal-associated lymphoid tissue (MALT) of skin, digestive & respiratory tracts

Components of the immune system

• Lymphocyte origin: Bone marrow
• Lymphocyte maturation:
  • Bone marrow (B cells)
  • Thymus (T cells)
• Lymphocyte activation:
  • Spleen
  • Lymph nodes
• Lymphocyte transport:
  • Lymphatic ducts
  • Blood vessels
• Inactive lymphocytes get activated when they encounter and recognize an antigen

Lymphocytes recognize antigens via protein receptors on cell surface

• B-cell receptor (BCR)
• T-cell receptor (TCR)

Epitopes are Recognition/Binding sites on Antigens

• Epitopes for B-Cell Receptors & antibodies.
• Epitopes for T-Cell Receptors.

B-cell receptors (BCRs)

• B-cells secrete antibodies that are identical to top part of B-cell receptor.
• (more on antibodies later)
• B-cell receptors and antibodies belong to special group of proteins called Immunoglobulins (Ig).

Five Classes of Immunoglobulins

• Both B- and T-cell receptors have variable regions that arise through controlled genetic scrambling.
• Results in almost limitless BCRs.
• When a new pathogen attacks, there will be at least few B cells with matching BCRs and antibodies

Adaptive Immune System Targeted Attack

• Controlled genetic scrambling takes place within immunoglobulin (Ig) gene segments in maturing lymphocytes
• Happens differently in every cell, thus endless variants of receptor proteins. (Anti-self get weeded out)
• THIS IS HOW THE ADAPTIVE IMMUNE SYSTEM MOUNTS A TARGETED ATTACK ON SPECIFIC PATHOGENS!!!

How Adaptive Immune System Works

• Pathogen recognition by adaptive immune system is driven by variable B-cell and T-cell receptor proteins
• But only a few B-cells will bind any one strain of pathogen--How do these few cells mount an attack?
• And what do T-cells do?

The Clonal-Selection Theory

1. Antigens are recognized by receptors on lymphocytes.
2. Lymphocytes are activated when their receptor binds an antigen. (Requires help from innate immune system)
3. Activated lymphocytes are cloned.
4. Activated lymphocytes endure.

Activation of T Cells

• Dendritic cells (type of leukocyte) must present antigen bound to MHC protein.
• Then, a “matching” T Cell can bind, become activated.

1. Dendritic cell ingests antigen via phagocytosis.
2. Enzymes break antigen proteins into peptide fragments.
3. Peptide fragments are loaded onto class II MHC proteins in endosomes.
4. MHC–peptide complex is transported to cell surface.
5. MHC protein presents peptide fragment on cell surface.

T-cell activation

1. T-cell receptor binds to peptide presented on MHC protein on surface of dendritic cell. Complex activation process begins, involving interactions among many proteins on the surfaces of both cells.
2. Activated CD4+ and CD8+ T cells multiply and differentiate. Effector T cells that result leave lymph node and enter blood.

• Clonal expansion
  • Cytotoxic T cells
  • Helper T cells

Cell-mediated response: activated CD8+ T-cells (cytotoxic cells) destroy infected cells

1. Cytotoxic T cell recognizes and binds infected cell.
2. T-cell secretes pore-forming proteins and other proteins that are transported into the infected cell.
3. Infected cell breaks up into fragments. Phagocytic cells consume the fragments.

B cell activation

• B cells and helper T cells help each other
• Antibodies released to circulate in blood and lymph

Humoral response: Antibodies from activated B-cells mark extracellular pathogens for neutralization and destruction

Adaptive immunity has memory: activated B-cells and T-cells also produce memory B-cells and memory T-cells

Vaccines: creating immunological memory without infection

• Weakened or inactive pathogens (or mRNA for antigens) introduced to body
• Activates adaptive immunity
• Antibodies, memory B- and T- cells protect against future exposure

Immune Responses

• Humoral (antibody-mediated) immune response
  • Antigen (1st exposure)
  • Engulfed by antigen-presenting cell
  • Stimulates helper T cell and B cell
  • Helper T cell -
    • Memory helper T cells
    • B cell =
      • Plasma cells (secrete antibodies to defend against extracellular pathogens)
      • Memory B cells
• Cell-mediated immune response
  • Antigen (1st exposure)
  • Engulfed by antigen-presenting cell
  • Stimulates helper T cell and Cytotoxic T cell
  • Helper T cell =
    • Memory helper T cells
    • Cytotoxic T cell =
      • Active cytotoxic T cells(defend against intracellular pathogens and cancer)
      • Memory cytotoxic T cells

Immune System Malfunctions

• Allergies – IgE antibodies should fight parasitic worms, but in some people they fight harmless allergens: pet dander, nuts, pollen, etc.
• Autoimmune diseases: immune system attacks certain self cells/tissues:
  • MS – T-cells attack myelin sheath of nerves
  • RA – self-attack/inflammation of joints
  • Type I Diabetes: T-cells destroy insulin-producing cells in pancreas
• HIV: specifically attacks T-cells, eventually causes AIDS (immune system fails)

Learning Objectives

• Lots of vocabulary in this chapter! Learn first.
• Understand the components of the innate immune system
  • Main leukocyte types and their roles
  • Inflammatory response
• Understand the components and characteristics of the adaptive immune system
  • Lymphocytes (B vs T cells) in adaptive immune response
  • Humoral (antibody) vs. cell mediated response
  • Diversification of B and T cell antigen receptors
• Understand clonal selection theory, immunological memory & how vaccinations work
• Understand autoimmune disorders and allergies as disorders of the immune system and self-recognition. ### Important Equations (a^2 + b^2 = c^2)