The Animal Immune System

Question 1

What are Pathogens?

Answer 1

Pathogen = bacteria, fungus, virus, or other disease-causing agent

Question 2

Why do pathogens like to be inside animals?

Answer 2

• For pathogens, internal environment of animals is an ideal habitat
  » Ready source of nutrients
  » Protected setting
  » Transport to a new environment
• Infection not so ideal for the animal (the host)
  → immune system has evolved as protection against many pathogens

Question 3

What is the immune system?

Answer 3

Immune system = combined body defences against “foreign” molecules (incl. pathogens)
» Enables animal to avoid (or limit) invasions

Question 4

How many sub systems of the immune system are there and what are they called?

Answer 4

• 2 main sub systems
• Innate Immunity (all animals)
• Adaptive Immunity (Vertebrates only)

Question 5

What are the External defences of the immune system?

Answer 5

• Outer covering of animals = barrier to pathogen entry
• Physical barriers
  » Skin (prevents entry)
  » Mucus (traps microbes)
• Chemical barriers
  » Acidic secretions (sweat, stomach acids)
  » Antimicrobial proteins (saliva, tears, mucus)

Question 6

What happens is a pathogen enters the body?

Answer 6

• Once pathogen breaches barrier defences and enters body, the problem changes dramatically: body must now be able to distinguish “self” from “nonself”

Question 7

How does the body distinguish “self” from “non-self”?

Answer 7

Immune cells have receptors that specifically bind foreign molecules (ie, molecular recognition system)
» Innate immunity recognition system
» Adaptive immunity recognition system

Question 8

What is the Innate Immune system?

Answer 8

• sub-system of immune system
• (Innate immunity includes barrier defences)
• Present in all animals (inverts + verts)
• Molecular recognition based on small set of receptor proteins that bind molecules / structures common to groups of pathogens (but absent in animals)
  » ≈ PAMP-triggered immunity in plants

Question 9

How does Innate Immunity work in insects?

Answer 9

• Chitin exoskeleton provides physical barrier
• Lysozyme secreted in digestive tract breaks down bacterial cell wall
• Haemocytes (special immune cells) present in haemolymph
  » Can ingest and break down bacteria and other large foreign substances (phagocytosis)
  » Have receptors that bind alien molecules (eg, polysaccharides on fungal cell wall, unique polymers of sugars and amino acids present only in bacteria)
  » Binding release antimicrobial peptides that kill or entrap pathogens, which circulate throughout haemolymph

Question 10

How does Innate Immunity work in Vertebrates?

Answer 10

• Vertebrate immune system more developed than invertebrates
  » Innate immunity is more complex
  » (Note vertebrates also have an additional type called adaptive immunity)
• Have various immune cells in blood and tissues called “leukocytes” or “white blood cells” (WBC)
• Pathogen detection triggers production and release of a variety of peptides and proteins that attack pathogens (eg, “complement system”), impede their reproduction and spread (“interferon”) and signal to other immune cells (“cytokines”)

Question 11

What are Phagocytes?

Answer 11

• a type of white blood cell
• Destroys pathogens by phagocytosis
  » Neutrophils (≈ 60% of all white blood cells)
  » Monocytes (≈ 5%), mature into macrophages

Question 12

What is another type of white blood cell after Phagocytes?

Answer 12

• Some release destructive enzymes that destroy target cells (enzymes stored in granules → “granulocytes”)
  » Eosinophils (≈ 2%), can also phagocytose
  » Natural killer (NK) cells, which detect abnormal protein on cell surface characteristic of virus infected or cancerous cells

Question 13

What is another type of white blood cell?

Answer 13

• Some release histamine, which makes blood capillaries become more permeable → white blood cells can more easily cross
  » Basophils (≈ 0.5%), including mast cells

Question 14

What is the Lymphatic system?

Answer 14

• Lymphatic system drains and cleans interstitial fluid
• Important role in immune system:
  » Lymph nodes filter foreign particles and contain macrophages (≈ pathogen detection device)

Question 15

What is the Inflammatory response?

Answer 15

• Localised
  » Mast cells produce histamine (↑ capillary permeability; ↑ blood flow) → swelling, redness and heat
  » Macrophages produce cytokines (signal neutrophils)

Question 16

How does the inflammatory response work if there is severe damage or infection?

Answer 16

• If damage or infection is severe → systemic (widespread) inflammatory response
• Massive release of cytokines (and neutrophils) lead to:
  » Rapid increase in leukocytes
  » Increased body temperature (fever)
• Inflammatory response that is out of hand can cause “septic shock”
  » Very high fever, low blood pressure, poor blood flow through capillaries
  » Kills over 20 million people worldwide every year

Question 17

What is the Adaptive Immune System?

Answer 17

• Main sub-system of the immune system
• Also called “acquired” or “specific” immunity
• Unique to vertebrates
• Relies on:
  » A special type of white blood cell called “lymphocyte”
  » The presence of almost infinitely varied number of pathogen specific antigen receptors on lymphocyte cell surface
• Recognition of traits specific to particular pathogens, using a vast array of receptors
• slower response
• Humoral Response: Antibodies defend against infection in body fluids.
• Cell-mediated response: Cytotoxic cells defend against infection in body cells.

Question 18

How do Lymphocytes work?

Answer 18

• Lymphocytes have surface receptors to detect specific pathogen molecules
  » “Antigen” = pathogen molecule
  » “Antigen receptor” = receptor for that antigen
  » Lymphocytes can have up to 100,000 receptors on surface of a single cell!

Question 19

What is the “Self-reactivity test”?

Answer 19

• Body produces a huge variety of antigen receptors (≈ 10 million!)
• Randomly assembled from different gene fragments
  » This creates a problem … random assortment can create antigen receptors that react with “self”!
  » During lymphocyte maturation, they undergo a “self reactivity” test → failing this test triggers programmed cell death

Question 20

What are the different types of Lymphocytes?

Answer 20

• There are two types of lymphocytes:
  » B lymphocytes: produced and educated in bone marrow
  » T lymphocytes: produced in bone marrow, but then educated in thymus

Question 21

How are Lymphocytes activated?

Answer 21

• When an antigen receptor is on the surface of a lymphocyte, it binds to an antigen which activates that lymphocyte → clonal proliferation, with some of the clones becoming:
  » Short-lived effector cells
  » Long-lived memory cells

Question 22

What are Effector cells?

Answer 22

• Short-lived cells organise and effect (conduct) the current immune response, which takes 2 forms:
  » Cell-mediated immune response (T cells)
  » Humoral immune response (B cells)

Question 23

What is Cell-mediated immune response?

Answer 23

• Cell-mediated immune response: activated T cells become
  » Cytotoxic T cells: release toxic proteins to kill infected cells
  » Helper T cells: release cytokines to activate other lymphocytes

Question 24

What is the Humoral (antibody-mediated) immune response?

Answer 24

• Humoral immune response: activated B cells produce soluble version of antigen receptor (“antibody”) in extracellular fluid (eg plasma, lymph, interstitial fluid)
• Antibodies can:
  » Bind pathogen and neutralise it
  » Promote phagocytosis
  » Activate proteins (“complement system”) → “membrane attack complex” (lyses foreign cells)
• Antibodies passed from mother to foetus, also present in breast milk

Question 25

What are memory cells?

Answer 25

• “acquired immunity” → long-term protection (years!), forms the basis for immunological memory
• Make future response to the same antigen faster and stronger (fast-track clonal proliferation)
  » 1st response (primary) ≈ 10-17 days
  » 2nd response (secondary) ≈ 2-7 days

Question 26

What are immunisations

Answer 26

• Introduction of a milder form of the antigen in the body to produce memory cells, eg,
  » Mild disease cowpox provides immunity to the very similar but deadly smallpox
  » Exposure to inactivated or weakened pathogens
• Much misinformation about the risks of immunisation → resurgence in diseases we could easily eradicate
  » Also pose a risk to greater population, as disease remains “in the pool”

Question 27

What are the Implications for organ transplants

Answer 27

• Immune cells can recognise transplanted organ as nonself
• For a successful transplant, need to:
  » Ensure that the two patients have similar ID proteins on cell surface (MHC = “major histocompatibility complex”)
  » Suppress immune system of recipient

Question 28

What are Immune system Malfuctions?

Answer 28

• Allergies
  » Exaggerated response to antigens called “allergens”
• Autoimmune diseases
  » Immune system targets some molecules of the self (eg lupus, type 1 diabetes, MS, rheumatoid arthritis)
• Exertion and stress
  » Immune system downregulated by excess exercise and stress
• Immunodeficiency
  » Genetic or developmental defect → incomplete immune system, eg severe combined immunodeficiency (SCID), where no functional lymphocytes present

Question 29

What is HIV?

Answer 29

• Attack on the immune system
• Human immunodeficiency virus (HIV)
  » HIV infects helper T cells
  • HIV RNA genome is then reverse transcribed, and product DNA integrated into host’s genome → production of new viruses
  » HIV mutates quickly → immune system is trying to fight it, but it cannot develop antigen recognition
  » Eventually HIV kills all helper T cells (“acquired immunodeficiency syndrome”, AIDS), leaving patient prone to other opportunistic disease (eg pneumonia)