Immunity

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Immunity

• State of protection against foreign organisms or
  substances ('antigens')
• Defence against disease
• Defence against tumours

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Figure 1

• Immune responses are directed at our barriers
  with the environment

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Innate Immunity

• Non specific immune responses which include
  anatomic, physiologic, phagocytic and
  inflammatory barriers that help prevent the
  entrance and establishment of infectious agents.
• These keep the invading pathogen at bay until a
  specific response can be made.

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Acquired Immune responses

• Specific response made against a particular
  pathogen or agent
• Diverse - responses can potentially be made
  against any pathogen etc.
• Memory - the immune system can remember a
  pathogen that has previously infected the body
• Escalating response - and generates a faster more
  effective response next time!

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How is this achieved?

• 2 inter-related events
• recognition of antigen
• response to antigen

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Figure 2

• The immune system is compartmentalised to enable
  lymphocytes to come into contact with
  pathogens/antigens.

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Antigen Presentation

• Antigen presenting cells (dendritic cells,
  macrophages), B lymphocytes and T lymphocytes are
  involved in the generation of immune responses.
• Both B and T lymphocytes possess antigen
  receptors in their cell membrane.

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B lymphocyte receptors (BCR)

• Antibody molecules bound to the cell membrane
  form the B cell receptor (BCR)
• BCR can recognise and internalise intact
  'antigen'. (antigen here can be a 3-dimensional
  structure)

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Figures 3 and 4

• Structure of the B cell receptor

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T lymphocyte receptors (TCR)

• T lymphocytes only recognise 'antigen' associated
  with MHC class I and class II molecules
• antigen here is a short linear peptide - primary
  structure

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Figures 5, 6 and 7

• Structure of the TCR and its interaction with
  MHC/peptide complexes

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How are immune responses DIVERSE?

• Each T and B lymphocyte has a DIFFERENT antigen
  receptor
• Clonal expansion of a single cell results when
  the lymphocyte receptor meets its specific
  antigen.
• Expanded lymphocytes then develop different
  effector and memory functions

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Function of T lymphocytes I

• There are 2 major sub-populations. Helper T
  cells (Th) and cytotoxic T cells (Tc).
• Th cells express CD4 and recognise 'antigen'
  class II MHC (on antigen presenting cells).
• 'Antigen' is a peptide of 18-22 amino acids, and
  is derived from proteins from outside the cell.
• ? fight extracellular pathogens. (can produce
  soluble mediators cytokines.)

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Helper CD4 T lymphocytes
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Functions of T lymphocytes II

• Tc cells express CD8 and recognise 'antigen'
  class I MHC (on all body cells).
• 'Antigen' is a peptide of 9 amino acids, and is
  derived from proteins synthesised inside the
  cell.
• ?Normally self peptides are expressed in class I
  MHC.
• ? fight intracellular pathogens. (can lyse body
  cells!!!)

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Cytotoxic CD8 T lymphocytes
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Functions of B lymphocytes

• B cell antigen receptor - membrane bound antibody
  molecule
• Activated B cells become plasma cells and secrete
  antibody - potent soluble effector molecues
  (IgM, IgG, IgA, IgE, IgD)
• Need T cell help to become activated
• Express class II MHC and can ?activate CD4 T
  cells

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Functions of B lymphocytes
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Where do immune response take place?

• Specific lymphocytes need to come into contact
  with specific pathogen/antigen to make an immune
  response
• This occurs in the specialised micro-environment
  of the lymph node
• Figure 8. Structure of a lymph node

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Where do pathogens enter the body?

• Barriers - skin, nasopharynx, gut, lungs (mucosa)
• a) recognise pathogen
• b) make an immune response
• The mucosa contains organised lymphoid tissue (eg
  peyers patches in the gut) and many lymphocytes

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Class exercise

• What happens if I vaccinate you?
• Why do I do this?
• How does it work?
• Why is it effective
• What happens when you eat food?
• What happens to food?
• Where does it go?
• Do you make an immune response to food?
• Why might you have rheumatoid arthritis or
  multiple sclerosis
• what are the symptoms?
• what is happening?
• what is the cause?

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So why don't you respond to self antigen?
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? Tolerance ?

• T and B lymphocytes have unique antigen receptors
• The T cell receptor (TCR) is produced by the
  genetic organisation germ-line DNA
• There are approximately 10 17 different TCRs!!!!
• ?During development, TCRs go through 2 selection
  procedures

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Thymic education

• Pre- T cell ? into the thymus
• Positive selection TCR binds to MHC GROW
• ?
• Negative selection TCR has high affinity for
  MHCself peptide DIE
• ?mature T cell

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Figure 9

• Structure and function of the thymus

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What happens if I vaccinate you?

• Intentional administration of a harmless or less
  harmful form of a pathogen to induce a specific
  immune response that protects the individual
  against later exposure to the same pathogen.
• ?Stimulate specific adaptive immune response
  (antibodies T cells)
• ?Memory

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Figures 10, 11 and 12

• Vaccination protocols, effect on disease
  prevalence and immune response

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What happens when you eat food?

• Ingest kilogram quantities of foreign 'antigen'
• Digest and absorb nutrients etc
• Do not make an immune response against food
  (except in disease eg)
• coeliac disease - respond to gluten
• The mucosal immune system functions to switch off
  responses to ingested / inhaled 'antigens'.

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?THIS IS ORAL TOLERANCE
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Why might you have rheumatoid arthritis?

• Immune mediated destruction of joints.
• Inflammatory disease, and it is thought that T
  cells are recognising self-antigens.
• THIS IS AN AUTO-IMMUNE DISEASE
• Current theories suggest that 'molecular mimicry'
  may be responsible for the disease.

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Why might you have multiple sclerosis

• MS is an auto-immune disease affecting the
  central nervous system.
• Auto-reactive T cells participate in the
  formation of inflammatory lesions along the
  myelin sheaths of the nerve fibres.
• Myelin is destroyed, nerve fibres lose insulation
  and this results in numerous neurological
  dysfunctions.

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Immune responses

• ?
• fight disease

• ?
• destroy self

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Healthy balancing act

• Fight Disease
• eradicate pathogens
• response
• immunity

• Dont fight your natural environment
• ignore food / commensals
• non-response
• tolerance

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Balance vs Dysregulation

• Both requires a functional immune system
• Auto-immunity is caused by T cell responses to
  self antigen (egs)
• Pathogenic T cell responses vs Benign T cell
  responses

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Immune regulation

• There are clearly physiological mechansims of
  response and non-response.
• Can these be switched on and off to resolve
  disease.?