LO: Discuss how immunology is covered across the MBBS

Evolution of the immune system

• We are surrounded by infectious agents - pathogens
• This includes worms, protozoa, fungi, bacteria, viruses which enter the body and cause disease
• Primary function is to eliminate pathogens and minimise the damage they cause
• Most infections are short-lived and leave little damage

Humoural immunity

• Serum from animals vaccinated against diphtheria protects unvaccinated animals
• Gamma globulin, immunoglobulin, antibody contained in body fluids (humours)
• Transfer of antibodies = Passive immunisation
• Vaccination - production of own antibodies = Active immunisation

Cellular immunity

• White blood cells (phagocytes) ingest microorganisms
• Phagocytes more active in immunised animals
• Immunity against tuberculosis conferred by transfer of white blood cells between guinea pigs
• T lymphocytes - Thymus
• B Lymphocytes - Bursa fabricius (Bone marrow)

Antigen

• Antibody generator
• Molecule is recognised by immune receptors
• injection of animals with almost any non-self organic compound induces an immune response against the specific antigen
• 1900 Paul Ehrlich: Selective side-chain theory - cells have multiple receptors for multiple antigens (not true)
• 1950 Burnet, Jerne and Talmadge: Clonal selection theory 0 cells have one type of antigen receptor and undergo clonal expansion and differentiate

Immune response

• Needs to be tailored to the type and environment of assault
• Viruses/intracellular bacteria - identification and killing of infected cells by cytotoxic T cells (perforin)
• Extracellular fungi, parasites, bacteria - detection of surface structures by antibodies and destruction by phagocytes
• Large parasites - deposition of toxic substances or killing by mast cells/eosinophils
• No immune response in immunoprivileged areas (CNS, eyes, placenta)
• Tolerance of commensual bacteria in the gut (microbiota)

Three levels of defence against invaders

External defence

• Physically prevent exposure to outside
• Skin - impervious to pathogens
• Trachea/bronchi - mucus to trap microorganisms
• Eyes - tears which cleanses eyes and contain chemicals to inhibit bacterial growth

Innate immune system

• "Primitive"
• Non-specific
• Fast response (minutes)
• No Memory

• Epithelial barriers
• Phagocytes
• Dendritic cells

Adaptive immune system

• Highly specific
• Slow response (days)
• Memory
• B lymphocytes
• Antibodies
• T lymphocytes
• Effector T cells

Immune dysregulation

• Balance between activation and suppression
• Hypersensitivity - Overreaction to benign antigens
• Autoimmunity - Attack against self-proteins or tissues
• Immunodeficiency - Failure to protect against foreign antigens

Hypersensitivity

• Anaphylactic shock - Severe, life-threatening allergic response
• Hypersensitivity type I-IV (1-4)
• Type I - allergy (hay fever, asthma, hives, ezcema)

Autoimmunity

• Immune system must distinguish between "self" and "non-self" - tolerance
• Self-reactive immune cells usually eliminated by the immune system
• Breakdown of tolerance - autoimmunity
• Genetic and environmental factors
• Hypothesis: Increase in allergies, autoimmune diseases in developed countries.
• Early and regular exposure to certain bacteria/parasites promotes immune homeostasis

Immunodeficiency

• Component of innate/adaptive immune system absent or defective
• Inherited - primary immunodeficiency
• Severe combined immunodeficiency (SCID) - no functional adaptive immunity
• Damage by external agents - secondary immunodeficiency (e.g. AIDS from HIV)
• Opportunistic infections

Challenges

Transplantation

• Immune system attacks/rejects foreign transplanted organ
• Need immunosuppressive drugs
• ABO blood groups - blood transfusion
• Major histocompatibility complex (MHC) tissue antigens - organ transplants

Cancer

• Unrestricted cell division and spread
• Display self-antigens and tumour-specific antigens
• Evade immune response by rapid change (mutations) and active inhibition
• Immunotherapies against cancer
• Boost body's natural defences
• Antibodies marking cancer cells to deliver radiation or drugs