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Immunity. State of protection against foreign organisms or substances ('antigens') Defence against disease Defence against tumours. Figure 1. Immune responses are directed at our barriers with the environment. Innate Immunity.

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immunity
Immunity
  • State of protection against foreign organisms or substances ('antigens')
  • Defence against disease
  • Defence against tumours
figure 1

Figure 1

Immune responses are directed at our barriers with the environment

innate immunity
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.
acquired immune responses
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!
how is this achieved
How is this achieved?
  • 2 inter-related events:
  • recognition of ‘antigen’
  • response to ‘antigen’
figure 2

Figure 2

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

antigen presentation
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.
b lymphocyte receptors bcr
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)
figures 3 and 4

Figures 3 and 4

Structure of the B cell receptor

t lymphocyte receptors tcr
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
figures 5 6 and 7

Figures 5, 6 and 7

Structure of the TCR and it’s interaction with MHC/peptide complexes

how are immune responses diverse
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
function of t lymphocytes i
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….)

functions of t lymphocytes ii
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!!!)

functions of b lymphocytes
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
where do immune response take place
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
where do pathogens enter the body
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
class exercise
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?
tolerance
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
thymic education
Thymic education

Pre- T cell  into the thymus:

Positive selection: TCR binds to MHC= GROW

Negative selection: TCR has high affinity for MHC+self peptide = DIE

mature T cell

figure 9

Figure 9

Structure and function of the thymus

what happens if i vaccinate you
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

figures 10 11 and 12

Figures 10, 11 and 12

Vaccination protocols, effect on disease prevalence and immune response

what happens when you eat food
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'.
why might you have rheumatoid arthritis
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.
why might you have multiple sclerosis
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.
immune responses

fight disease

destroy self

Immune responses
healthy balancing act
Fight Disease

eradicate pathogens

response

immunity

Don’t fight your ‘natural’ environment

ignore food / commensals

non-response

tolerance

Healthy balancing act
balance vs dysregulation
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
immune regulation
Immune regulation
  • There are clearly physiological mechansims of response and non-response.
  • Can these be switched on and off to resolve disease….?