unit 4

• Barriers to infection


  • Innate Immune System
  • How do organisms respond to pathogens
  • Unit 4 AOS1
  • Disease challenges
  • Acquiring immunity
  • Lymphatic system
  • Adaptive immune response
  • Disease strategies
  • Initiating an immune response
• Responding to antigens


  1. Responding to antigens

  2. Immunity:

  3. Types of immunity & Vaccination

  4. Responding to antigens: Introduction

  5. Responding to antigens: Innate Immune System

  6. Cellular Signals: Apoptosis
• Responding to antigens


  • physical, chemical and microbiota barriers as preventative mechanisms of pathogenic infection in animals and plants
  • the innate immune response including the steps in an inflammatory response and the characteristics and roles of macrophages, neutrophils, dendritic cells, eosinophils, natural killer cells, mast cells, complement proteins and interferons
  • initiation of an immune response, including antigen presentation, the distinction between self-antigens and non-self antigens, cellular and non-cellular pathogens and allergens
• Innate immune response


  • the innate immune response including the steps in an inflammatory response and the characteristics and roles of macrophages, neutrophils, dendritic cells, eosinophils, natural killer cells, mast cells, complement proteins and interferons
• How and when could the 1st line of defence fail?
• Protecting ourselves from pathogens: three lines of defence

  1. 1st line of defence: physical, chemical and microbiota barriers as preventative mechanisms of pathogenic infection in animals and plants

  2. 2nd line of defence is non-specific Responds the same way regardless of the pathogen or antigen that gets through the first line of defence
• Innate Immune Response


  • is not specific to a particular pathogen components respond the same way regardless of the pathogen or antigen present
  • is fast as it aims to limit the spread of the infectious agent within the body
  • depends on a group of proteins and cells that are quickly activated to help destroy invading pathogens
• Types of blood cells

  • Red Blood Cells (erythrocytes)
  • White Blood Cells (leucocytes)
• Red Blood Cells (erythrocytes)

  • Carry oxygen and have no nucleus or organelles
  • They typically last around 120 days
  • Blood contains approximately 5 million red blood cells per ml of blood
• White Blood Cells (leucocytes)

  • Contain a nucleus and organelles
  • Seek out and destroy disease causing microorganisms and substances
  • They can last from a few hours or just a few minutes as they are required to fight infections
  • Blood contains approximately 5-10,000 white blood cells per ml of blood
  • Able to move through blood vessels and move into tissues when required to fight infection
• Innate Immune Response components

  • Macrophages
  • Neutrophils
  • Dendritic cells
  • Eosinophils
  • Natural killer cells
  • Mast cells
  • Complement proteins
• Phagocytes


  Cells capable of engulfing pathogens or foreign particles to destroy them
• Phagocytosis


  1. Engulfing of microorganisms or other cells and foreign particles by phagocytes

  2. Step 1: Binding with cell receptors on phagocytes to foreign particle

  3. Step 2: Particle engulfed and enclosed in a vacuole (phagosome)

  4. Step 3: Phagosomes merge or fuse with lysosomes whose enzymes destroy the engulfed particle (lowers pH)

  5. Step 4: Once the contents have been neutralized, the waste products are discharged from the cell
• Phagocytes


  • Macrophages
  • Neutrophils
  • Dendritic cells
• Macrophages


  • Primary Role: Eat or ingest pathogens and clean up the mess of dead cells
  • Action: Use Phagocytosis to consume foreign pathogens (and cancer cells)
  • Part of the pathogen once broken up is 'presented' to the surface of the cell, acting as a signal to other immune cells, alerting them to an invading pathogen
  • Releases cytokines
  • Derived from blood stem cells in the bone marrow
  • Circulate in the blood and then migrate or travel into tissues
  • Very large and efficient phagocytes
• Neutrophils


  • Primary Role: Eat or ingest pathogens and clean up the mess of dead cells
  • Action: Rush to the site of incoming bacteria and start fighting (first to arrive as they go straight to the site of the infection or trauma)
  • Engulf bacteria and once inside the neutrophil releases antimicrobial compounds such as defensins and hydrogen peroxide that disrupt bacterial and fungal membranes. This can lead to its own death.
  • Recruit other immune cells to the site of infection by releasing cytokines (cytokines also cause inflammation)
  • High turnover rate as they are considered dispensable and are short lived, lasting only a few days
  • Generated everyday by the bone marrow – very abundant
  • Circulate in the blood and are approximately 65% of wbc
  • Phagocyte – distinctive appearance is due to thousands of tiny granules containing chemicals to kill pathogens
• Dendritic cells


  • Primary Role: Act as spies looking for invaders and sending messages
  • Action: Patrol the peripheral tissues that are in contact with the external environment
  • Contain many grooves to increase their surface area and allow them to come into contact with a large number of nearby cells
  • Once activated migrate to lymph nodes or spleen and present the antigen to B and T cells, activating them
  • Produce and release cytokines
  • Derived from blood stem cells in the bone marrow but patrol the peripheral tissues
  • Phagocyte with long projections called dendrites
• Cells of the Innate immune Response

  • Macrophages
  • Mast cells
  • Neutrophils
  • Dendritic cells
• Innate Immune Response components

  • Phagocytes
  • Neutrophils (release cytokines)
  • Macrophages*
  • Dendritic cells*
  • Mast cells (release histamine)
  • Eosinophils
  • Natural Killer Cells
• Innate Immune Response components

  • Macrophages
  • Neutrophils
  • Dendritic cells
  • Eosinophils
  • Natural killer cells
  • Mast cells
• Eosinophils


  • Primary Role: Defence against parasitic infections
  • Action: Act on large pathogens that can't be phagocytosed
  • Contain granules that contain various toxic enzymes
  • Granules allow eosinophils to target parasitic worm infections (and allergic reactions, chronic inflammation and some autoimmune diseases)
  • Derived from the blood stem cells in the bone marrow
  • Large granulated cells
• Natural killer cells


  • Primary Role: Kill cells infected by viruses or cancerous cells
  • Action: Do not harm normal body cells but reject cells that contain viruses or tumours
  • Activated by interferons (cytokines)
  • Have small granules in the cytoplasm that contain proteins (perforin) which when released create pores in the cell membrane of the target cell inducing apoptosis (ensures virus particles are not released)
  • Derived from the blood stem cells in the bone marrow
  • Large granulated cells
• Mast cells


  • Primary Role: Protective and involved in wound healing, defending tissues from disease
  • Action: Once activated release molecules to eliminate the pathogen. The molecule is histamine.
  • The release of histamine causes blood vessels to dilate and become leaky allowing phagocytes (macrophages and neutrophils) to reach the site of infection
  • The secretion of histamine leads to inflammation (and allergic reactions)
  • Derived from the blood stem cells in the bone marrow but reside in tissues
  • Cell containing huge numbers of granules in storage sacs (not a phagocyte)
• Innate Immune Response


  • the innate immune response including the steps in an inflammatory response and the characteristics and roles of macrophages, neutrophils
• Apoptosis


  Ensures virus particles are not released
• Mast cells


  Large granulated cells derived from the blood stem cells in the bone marrow
• Mast cells


  • Primary role is protective and involved in wound healing, defending tissues from disease
  • Once activated release molecules to eliminate the pathogen. The molecule is histamine.
  • The release of histamine causes blood vessels to dilate and become leaky allowing phagocytes (macrophages and neutrophils) to reach the site of infection
  • The secretion of histamine leads to inflammation (and allergic reactions)
• Supply Chain


  Mast cells are derived from the blood stem cells in the bone marrow but reside in tissues
• Type of cell


  Mast cells are cell containing huge numbers of granules in storage sacs (not a phagocyte)
• Components of the innate immune response

  • Cellular
  • Non-Cellular
• Cellular components of the innate immune response

  • Macrophages
  • Neutrophils
  • Dendritic cells
  • Eosinophils
  • Natural killer cells
  • Mast cells
• Non-cellular components of the innate immune response

  • Complement proteins
  • Interferons
• Complement proteins


  • A number of small proteins in the blood act to help or 'complement' the ability of phagocytotic cells (or antibodies) to destroy pathogens.
  • There are over 25 proteins or fragments of small proteins that form the complement system.
  • Complement proteins can act by: Covering or coating the pathogen to enhance phagocytosis (opsinisation), attracting phagocytes to the pathogen (chemotaxis), rupturing the pathogen by creating pores in the membrane (lysis).
• Complement system


  • Complement and antibodies cover the pathogen to enhance phagocytosis
  • Attraction of phagocytes to the pathogen
  • Lysis/rupturing of the pathogen
• Interferons


  • Cytokines produced by and act on a host cell infected by a virus.
  • Interferons activate infected cells causing them to produce enzymes that break down viral RNA and proteins that block translation.
  • Interferons are non-specific and will act against any virus but not all viruses are susceptible to them.
• Inflammatory response


  A protective response to pathogen invasion that can destroy the cause of infection and remove it and its products from the body
• Inflammatory response


  • The key responses enacted by the innate immune response include inflammation, fever and reduction of blood loss.
  • Inflammation is the accumulation of fluid, plasma proteins and leukocytes (wbc) that occurs when tissue is damaged or infected. Results in heat, pain, swelling, redness and loss of function.
  • Inflammation is triggered by the interaction of leucocytes (typically phagocytes) and pathogens
• Inflammatory response


  1. Initiation

  2. Vasodilation

  3. Migration
• Initiation of inflammatory response

  1. Pathogen breaches the first line of defence (barriers) such as a cut or open wound in the skin

  2. Injured cells release cytokines that attract neutrophils; mast cells release histamine which increases blood vessel dilation and permeability allowing leucocytes and proteins such as complement proteins to enter the infected tissue.

  3. Neutrophils migrate towards the cytokines and are activated, recruiting macrophages and secrete factors that degrade and kill pathogens

  4. Macrophages are activated and secrete cytokines. Phagocytosis of the pathogen and debris at the site of infection occurs – may result in pus containing leucocytes, dead pathogens and cell debris

  5. Process continues until the pathogen is removed and wound is healed
• Inflammatory response


  1. Initiation: A splinter or object pierces the skin, damaging cells and introducing bacteria into the body. Damaged cells release cytokines and mast cells degranulate (release granule contents from the cell) and release histamine

  2. Vasodilation: Histamine, released by mast cells, travels to nearby blood vessels where it causes vasodilation. Vasodilation causes the blood vessels to become bigger, and the vessel walls become more permeable through the formation of gaps. Blood flow to the injured site causes swelling, redness and warmth

  3. Migration: Vasodilation and increased leakiness of blood vessels allows components of the innate immune system to leave the bloodstream and enter the site of injury. Phagocytes are guided by cytokines secreted by damaged cells. Complement proteins are attracted to the pathogens making it easier for phagocytes to destroy them. Platelets travel to the wound and stop active bleeding