Immunology

• Introduction to the Immune System in Animals

  • All organisms are targets for diseases from pathogens, disease-causing organisms

  • The pathogens include bacteria, parasites, viruses, fungi, and protists

  • If an animal contracts a bacterial or viral illness, it may recover and even become immune to the disease

  • Immunity is a resistance to or protection against a disease-causing pathogen

  • The immune system of the animal is responsible for defending animals against pathogens
• Introduction to the Immune System in Animals

  • The immune system success depends on three key processes:

  1. Preventing the entry of potential pathogens

  2. Detecting the presence of a pathogen by

  distinguishing it from the animal’s own body

  3. Eliminating the pathogen
• Introduction to the Immune System in Animals

  • Immune system cells that are ready to respond to foreign invaders at all times confer innate immunity to an organism

  • Cells that must first be selectively activated to tailor their response to a specific pathogen confer adaptive immunity to an organism
• The Immune System Has Two Arms:

  Innate Immune System and Adaptive Immune System
• Innate Immunity

  • Innate immunity is inherent in all animals and is ready to go from birth

  • Only 1% of animals have adaptive immunity, and it has a delayed development

  • The innate immune system on its own has succeeded in protecting a diverse array of animals

  • It is the first line of defense and includes exterior anatomical structures that protect animals from invading pathogens
• Barriers to Entry

  • Innate immunity is very successful on its own

  • The most effective way for animals to avoid getting an infection is to prevent pathogens from entering their bodies in the first place

  • Insects are covered with a tough layer called cuticle

  • Soft-bodied invertebrates are covered with a protective layer of mucus—a slimy mix of glycoproteins and water that traps pathogens and then sloughs off

  • Human skin has a layer of dead cells that are reinforced with tough fibers of the protein keratin
• Barriers to Entry

  • These outer surfaces also ensure a restrictive chemical environment

  • Example: In humans, the oil secreted by your skin cells is converted to fatty acids by bacteria that live harmlessly on your body

  • The fatty acids lower the pH of the surface to 5, creating a dry, acidic environment that prevents the growth of most pathogens
• How Are Openings in the Body Protected?

  • The places in animal’s bodies that are most vulnerable to pathogens are the gaps in the surface

  • Wherever the digestive and reproductive tracts, gas- exchange surfaces, and sensory organs contact the environment

  • Gaps have a protective physical barrier in the form of mucus and other chemicals that discourage pathogen entry

  • Pathogens get stuck in the mucus layer and cannot come in contact with the plasma membrane
• How Are Openings in the Body Protected?

  • Gaps in the body that are not covered with mucous layers are often protected by other types of secretions

  • Examples: Waxy secretions in the ears; lysozyme, an antibiotic that occurs in tears

  • Despite preventative measures, however, pathogens are still able to gain entry to tissues beneath the skin
• How Do Pathogens Gain Entry?

  • Flu viruses have an enzyme on their surface that disrupts the mucous lining of the respiratory tract

  • When the outer surface of the virus contacts a host cell beneath the mucous layer, the virus can enter the cell and begin an infection

  • Wounds provide another important mode of entry

  • When the skin is broken, bacteria and other pathogens gain direct access to the tissues inside
• The Innate Immune Response

  • The innate immune response—the body’s first response to pathogens—involves leukocytes (white cells)

  • Leukocytes provide an immediate, generic response against broad groups of pathogens

  • Innate response is nonspecific, but will respond to groups of pathogens such as bacteria and fungi

  • They are alerted to the presence of foreign invaders by antigens that are found on the surfaces of pathogens, but not on host cells
• How Are Pathogens Recognized by the Innate Immune System?

  • A link between Toll protein and immune function in fruit flies was found when fungal infections were more severe in flies lacking Toll protein

  • It was surprisingly specific to fungi

  • Toll protein were identified in humans and mice by exposing them to antigens—foreign molecules that initiate an immune system response

  • Toll-like proteins act as a receptor that receives the signal that a pathogen is present
• How Are Pathogens Recognized by the Innate Immune System?

  • Toll-like receptors (TLRs) are a subset of a larger group known as pattern-recognition receptors

  • They serve as sentinels that signal the presence of molecules associated with pathogens

  • TLRs have been observed in fungi and plants as well
• Pathogens found in humans

  • TLR2
  • TLR4
  • TLR5
  • TLR7
• TLR2


  Binds to zymosan, a molecule from fungi
• TLR4


  Captures the lipopolysaccharide (LPS) from the Gram-negative bacteria
• TLR5


  Binds to the flagella of motile bacteria
• TLR7


  Binds to the single-stranded RNA virus
• All of these antigens are ubiquitous within the broad group identified, yet they do not occur in the host animal
• They act as reliable signals of attack
• Pattern-Recognition Receptors Transduce Signals

  1. Detection of pathogen

  2. Signal cascade activation

  3. Production and secretion of antimicrobial peptides

  4. Destruction of pathogen
• Pattern-Recognition Receptors Transduce Signals

  1. TLR4 activation by LPS

  2. Signal cascade promotes the secretion of cytokines
• Cytokines


  A class of diverse molecules that attract other immune cells to the site of infection or stimulate other immune cells into action
• Pattern-Recognition Receptors Transduce Signals

  1. TLR7 on a human leukocyte detects a virus

  2. Cell produces and secretes a specific cytokine called an interferon

  3. Interferon stimulates cells to produce proteins that interfere with viral replication
• The full engagement of the immune system depends on the reception of a signal and an action cascade
• Inflammatory response


  A multistep innate immune response that occurs at the site of an injury
• Steps of the inflammatory response

  1. Break in the skin allows pathogens to enter the body

  2. Platelets release proteins that form clots and lessen bleeding

  3. Clotting proteins form cross-linked structures that help wall off the wound and reduce blood loss

  4. Wounded tissues and macrophages secrete chemokines that recruit immune cells

  5. Mast cells secrete histamine and other signaling molecules that dilate blood vessels

  6. Neutrophils move out of the dilated blood vessels and migrate to the site to remove pathogens by phagocytosis

  7. Other leukocytes arrive at the wound, mature into macrophages, and secrete chemokines and cytokines that stimulate bone marrow, induce fever, and activate cells involved in tissue repair and wound healing
• The inflammatory response continues until the foreign material is eliminated and the wound is repaired
• Natural Killer Cells

  NK cells are large granular lymphoid-like cells with important functions in innate immunity, especially against intracellular infections, being able to kill other cells.
• Adaptive Immunity: Recognition


  The adaptive immune response is based on interactions between specific immune system cells and a specific antigen
• Adaptive Immunity: Recognition


  • Uses antibodies, which are secreted proteins that bind to a specific part of a specific antigen
  • Can respond to a seemingly limitless array of antigens
• Adaptive Immunity: Recognition


  • Specificity - Antibodies and other components of the adaptive immune system bind only to specific sites on specific antigens
  • Diversity - The adaptive response recognizes virtually any type of antigen
  • Memory - The adaptive immune responses are stronger and quicker when an individual is exposed to antigens from previous infections
  • Self-nonself recognition - Molecules that are produced by an individual do not normally trigger a response, meaning that the adaptive immune system can distinguish between self and nonself
• Lymphocytes


  The cells involved in the adaptive immune response
• Lymphocytes


  • Leukocytes of the innate immune system are diverse, but those of the adaptive immune system are primarily divided into two distinct cell types that differ in their role and their site of maturation
• B cells


  Discovered when researchers were working with an antigen that attacked Salmonella from chickens
• B cells in chickens

  • Produced in the bursa, an organ found in chickens
  • Bursa-dependent B cells produce antibodies
• B cells in humans and other species

  Mature in bone marrow
• T cells


  Identified in mice while researchers were exploring the function of the thymus—an organ in the upper part of the chest of vertebrates
• T cells


  • Thymus-dependent
  • Involved in recognizing and killing host cells that are infected with a virus
• Where lymphocytes are found

  • Lymphocyte origin - Bone marrow
  • Lymphocyte maturation - B cells in bone marrow, T cells in thymus
  • Lymphocyte activation - Spleen and lymph nodes
  • Lymphocyte transport - Blood and lymphatic system