Block C

• Immune response


  Comprised of innate immunity and adaptive/acquired immunity
• Innate immunity


  • First responders in case of an infection (~2-6 hours, can remain until ~18 hours)
  • Nonspecific as it protects against foreign cells or entities without having to recognise their specific identity
  • No lasting immunity as it doesn't require a prior exposure to infection or memory cells
• Innate immunity - body surface as the initial line of defence

  1. Mucus - sticky to trap invaders, and with antimicrobial properties

  2. Stomach acid - has a pH of 1.5-2 to destroy invaders

  3. Skin glands - secrete antimicrobial molecules such as mild acids and enzymes to destroy microorganisms
• Subtypes of innate immune cells

  • Granulocytes
  • Monocytes
• Granulocytes


  • Neutrophils - phagocytose and kill bacteria; mediate inflammation
  • Basophils - enters tissues at side of injury and secretes heparin and histamine
  • Eosinophil - phagocytose and release chemicals that will kill parasites; participates in allergic responses
• Monocyte


  • Monocyte (blood) - develops into macrophages and some cases dendritic cells
  • Macrophage (tissue) - phagocytose microbes; mediate inflammation; present antigens to adaptive immune cells
  • Dendritic cells - properties similar to macrophages; main antigen presenting cells for B cells
• NK cells


  • Participate in the early recognition and elimination of virus-infected and malignant-transformed cells, limiting their spread and subsequent tissue damage, by secreting toxic chemicals
• Inflammation


  The innate local response to infection/injury (causing disruption). It allows the elimination of foreign invaders, clears area of dead cells and sets stage for tissue repair
• Inflammation process


  1. Injury introduces bacteria beneath the skin

  2. Inflammatory signals produced by injured tissue, mast cells, neutrophils and endothelial cells induce vascular changes

  3. Capillaries dilate and become leaky

  4. Fluid and neutrophils exit the capillaries and enter the site of the wound

  5. Neutrophils and macrophages engulf and destroy bacteria

  6. The remaining phagocytes die, capillaries return to normal, infection is brought under control

  7. Imperfect tissue repair = scar tissue
• PAMPs


  Pathogen associated molecular patterns - conserved molecular features that are vital to the survival of the pathogen
• TLRs


  Toll like receptors - recognise and bind to pathogens with PAMPs
• Adaptive immunity


  Specific immunity as it only responds to a specific strain of disease. If the same strain is acquired, the immune response is fast and the symptoms are contained (short)
• Lymphocytes


  • Helper CD4 T cell
  • Cytotoxic CD8 T cell
  • B cell
  • NK cells
• Adaptive immunity - lymphatic system


  • Primary lymphatic organs - where the T and B cells mature and develop
  • Secondary lymphatic organs - where lymphocytes activate and replicate
• T cell activation


  1. Immature dendritic cells phagocytose bacteria

  2. Dendritic cells migrate via lymphatic vessels to regional lymph nodes

  3. Mature dendritic cells (APC) activate naive T cells in the lymphoid organs

  4. T cells undergo differentiation and are activated
• MHC


  • Cellular "identify tags" and are genetic markers of "self"
  • MHC II class II is found only on APCs
  • MHC class I is found on all cells in the body except erythrocytes
• Antigen-presenting cells roles


  1. Microbe is phagocytised and digested into fragments or epitopes

  2. Epitope-MHC complex is transported to the cell surface

  3. Specific helper T cell binds to complex with CD4 protein helping link

  4. APC also secretes cytokines-IL-1 and Tumour Necrosis Factor (TNF) to stimulate attached helper T cells
• Cytotoxic T cells


  1. Bind to virus infected cells and secrete proteases and perforin, which inserts into the plasma membrane of the virus infected cell to form channels

  2. The cell takes up water and proteases and lyses, in this process the host cell is killed
• B cell activation


  1. Antigen binds to B cells displaying a specific immunoglobulin

  2. Multiple cell divisions result in a clone of this specific type of B cells

  3. Cloned B cells undergo clonal differentiation into plasma cells, which secrete antibodies
• Antibodies


  Inactivate pathogens by opsonisation, forming complexes to be destroyed by phagocytes, and blocking binding sites so viruses can't invade
• Antibody structure


  • 2 light chains
  • 2 heavy chains
  • Fab - fragment binding region
• Clonal selection


  Binding of antigen stimulates only one specific B cell to divide
• Clonal differentiation


  1. Multiple cell divisions result in a clone of this specific type of B cells

  2. Progeny of this lymphocyte/B cell all express the same receptor

  3. Cloned B cells undergo clonal differentiation into plasma cells, which secrete antibodies; recognising the original antigen
• Antibodies


  • Inactivate pathogens by opsonisation - antibody marks pathogen for phagocytosis by immune cell
  • Forms complexes to be destroyed by phagocytes
  • Block binding sites so viruses can't invade
• Effector plasma cells and cytotoxic cells

  • Die by apoptosis to prevent excessive immune response
  • Some T and B cells persist as memory cells, awaiting future infection by the same pathogen
• Antibodies


  Globular glycoproteins (quaternary), forming the group of plasma proteins (immunoglobulins)
• Components of antibodies


  • 2 light chains
  • 2 heavy chains
  • Fab - fragment binding region (variable region); contains antigen-binding site and varies amongst different B cells
  • Fc - fragment crystallisable region (constant region); the tail region of antibody that reacts with the csm, allowing it to activate the immune system. This domain is identical for any given class
• Classes of immunoglobulins


  • IgM
  • IgG
  • IgE
  • IgA
  • IgD
• IgG


  • 𝜸-chains (monomer)
  • Most abundant in mammals, provides bulk of specific immunity against viruses in extracellular fluid
• IgM


  • µ-chains (pentamer)
  • Same as IgG
• IgA


  • 𝛂-chains (Dimer)
  • Secreted by plasma cells in gut, respiratory and genitourinary tract linings; acts locally; major Ab in milk
• IgE


  • 𝛆-chains (epsilon; monomer)
  • Defences against multicellular parasites and allergic responses (overactive stimulation)
• IgD


  • 𝛅-chains (monomer)
  • Function unclear
• IgG functional activity and distribution

  • IgG1 - high; neutralisation, opsonization, sensitisation for killing by NK cells and activates complement system; low for sensitisation of mast cells
  • IgG2 - high for neutralisation; low for activating the complement system
  • IgG3 - highest for activation of complement system; high for neutralisation, opsonization, sensitisation for killing by NK cells; lowest for sensitisation of mast cells
  • IgG4 - high for neutralisation; low for opsonization
• IgE functional activity and distribution

  • IgE - high for sensitisation of mast cells
  • Low distribution for diffusion into extravascular sites
• Botulinum toxin inhibits neurotransmission at neuromuscular synapses and causes spastic paralysis
• The immune system must work together to eliminate the threat - neutralisation, opsonization, complement activation
• The variation in heavy chain polypeptides allows each class to function in a different type of immune response or during a different stage of the body's defence
• Main jobs of antibodies

  • Prevent virus from uncoating (polio)
  • Prevent virus from transcribing its genome (influenza)
  • Stop pathogen attaching to its specific receptor to enter host cell (reovirus)
  • Stop essential function of pathogen (Ab attaching to specific site of phage T4)
• Complement system


  • Part of the innate immune system but can be brought to action by antibodies of the adaptive immune response (antibody + antigen)
  • Microbes are killed without phagocytosis, rather the membranes of the host cell is attacked by creating channels in the plasma membrane (membrane attack complex) and the infected host cell will lyse
  • Complement tagged pathogens are ingested by phagocytes and mediated by receptors that bind complement proteins