Immunological Danger Notes PDF

**What is an immunological danger?** Damage - anything that can damage or potentially damage us. Various sources, including viruses, bacteria and parasites. **Defences** The body's first line of defence are **external epithelia** like the skin and **mucosal surfaces** like the airway, gastrointe...

**What is an immunological danger?** Damage - anything that can damage or potentially damage us. Various sources, including viruses, bacteria and parasites. **Defences** The body's first line of defence are **external epithelia** like the skin and **mucosal surfaces** like the airway, gastrointestinal tract and reproductive tract. These barriers employ defences such as **mucus, cilia and defensins** (molecules that are secreted). **Inflammation** When these barriers are breached, the body mounts an inflammatory response. This response starts with the activation of **pattern recognition receptors** which are found both inside and outside many cells. They recognise patterns of possible dangers. Inflammation leads to the release of signalling molecules such as **histamine, peptides, cytokines and chemokines**. Classic signs of inflammation: - **pain** - **heat** - **redness** - **swelling** **The Lymphatic System** **Lymphatic vessels**: these vessels connect the system and transport lymph **Lymph nodes**: points in the network where lymphatic vessels intersect or branch, serving as hubs for immune cell interaction and activation **Lymph**: a colourless fluid containing white blood cells that drains through the lymphatic system into the bloodstream The lymphatic system often mirrors the blood vessels, and lymphnodes often sit at the convergence of these systems. **Thymus**: the organ responsible for the development and maturation of T cells **Spleen**: organ that filters blood, removes old or damaged red blood cells and stores white blood cells **Immune Cells** **Blood** contains various cells, including **red blood cells** (responsible for carrying oxygen) and **white blood cells** (responsible for immune defence). **Red blood cells** - Carry oxygen - 5-6 million per ul blood - \~2 x\$10\^{6}\$ made / second - Lifespan \~ 110 days - Transport \$O\_{2}, CO\_{2}\$ **White blood cells** - Immune cells - Many different types, e.g. neutrophils, macrophages, monocytes, eosinophils, mast cells, basophils, T cells, B cells, dendritic cells - Classified as innate or adaptive **Innate immunity** = what happens in the first 12 hours after a barrier breach, danger signal has been recognised and immune cells activated **Adaptive immunity** = takes time to kick in, days following barrier breach The key players in the innate immune response are: **Neutrophils** - **most abundant** type of white blood cell - active **phagocytic** cells - **engulf and kill pathogens** - employ neutrophil extracellular traps (NETs) to trap and kill pathogens - recruited by inflammation into tissues - **short lived** **Macrophages** - develop in tissues from precursors - active **phagocytic** cells - **consume and kill pathogens** - activated by inflammation - **long lived** **Dendritic Cells** - develop in tissues from precursors - active **phagocytic** cells - migrate out of peripheral tissues - carry antigens (from pathogens) to lymph nodes - in lymph nodes, they present these antigens to T cells - bridge innate and adaptive immunity by activating adaptive immune response **Complement** - the complement system is a cascade of proteins in serum (blood) that can sense danger - boosts/amplifies immune response - activated by antibodies or molecules from pathogens - can directly kill pathogens or attract immune cells to infection site Typically, the immune system is divided up into the innate and adaptive responses. **Innate responses** - limited specificity - found in all tissues, esp at barrier sites - acts quickly following infection - limited memory **Adaptive responses** - specific to particular proteins/antigens - mainly found in lymphoid organs - take 5-10 days to get going - long lived immune memory - B and T cells are adaptive immune cells that recognise antigens via specialised surface receptors - there are millions of different T and B cells, each with a specific receptor **Stages of adaptive immune response** Adaptive immune response is triggered by the innate immune response. Innate immune cells, such as dendritic cells, macrophages and neutrophils, sense pathogens and pass down information to adaptive immune cells. For mild infection, innate immune cells may be able to clear the pathogen themselves. If not, they alert the adaptive immune cells. 1. **T cell activation** - finding the right T and B cells 2. **T cell differentiation** - deciding how to respond 3. **T cell effector stage** - immune response **B Cells** - B cell receptors (BCRs) can bind to native proteins or antigens without accessory cells (i.e. no processing of proteins necessary) - up to \$10\^{12}\$ different BCRs - B cells can protect the host by making antibodies which come in different classes, including: - IgM = low affinity, high avidity - IgG = the most abundant antibody in serum - IgA = found at mucosal sites - IgE = involved in allergy and anti-helminth worm (parasitic worm infection) responses - antibodies are made by plasma cells, which are differentiated B cells - antibodies can work in various ways: - neutralising the pathogen to stop it infecting host cells - activating complement to enhance immune response - enhancing phagocytosis (opsonisation) by binding to receptors on phagocytes **T Cells** - around \$10\^{8}\$ different T cell receptors (TCRs) - T cells recognise processed antigens presented on MHC molecules on the surface of antigen-presenting cells (i.e. T cells will require accessory cells called antigen presenting cells) - CD4 T cells (helper T cells) - recognise longer peptides on MHC class II molecules, which are mainly expressed by professional antigen-presenting cells like B cells, macrophages and dendritic cells - support other immune cells by: - enhancing CD8 T cell responses - aiding B cells in producing high-affinity antibodies - activating macrophages for more effective pathogen destruction - CD8 T cells (cytotoxic T cells) - recognise shorter peptides on MHC class I molecules, which are expressed by all nucleated cells like B cells, macrophages, dendritic cells and epithelial cells - kill infected cells and tumour cells at the site of infection by releasing toxic granules - trick to remember which T cell goes with which MHC: 4x2=8, so CD4 T goes with MHC class II. 8x1=8, so CD8 goes with MHC class I **Specificity** Spike protein - the spike protein is an example of an antigen found on the surface of certain viruses - protein antigens can be processed and broken down to form smaller peptide chains, known as epitopes - epitopes are the specific parts of the antigen recognised by immune receptors (BCRs and TCRs) **Where are adaptive immune cells located?** Generation of adaptive immune cells: - primary lymphoid organs (thymus and bone marrow) Activation of adaptive immune cells: - secondary lymphoid organs (lymph nodes and spleen) **Timings of the immune response** - innate = 0-5 days (dendritic cells, neutrophils, macrophages and monocytes) - adaptive = 3-15 days (B cells, CD4 T cells, CD8 T cells) - long-lived = months to years (long-lived plasma cells, memory B and T cells) **Immunological memory** - allows for rapid control of previously encountered pathogens - memory T and B cells can act quickly upon reinfection by remembering the training they received during the first immune response - memory cells act at different sites in the body to protect the host \ Key Points - B and T cells make up the adaptive immune system - They have specialised proteins on their plasma membrane that enable them to recognise antigens - these are called B and T cell receptors - B cells can protect the host by making pathogen specific antibodies - CD4 T cells can protect the host by coordinating the actions of other immune cells - CD8 T cells can protect the host by killing infected cells or tumour cells - Memory T and B cells act rapidly to prevent or control a previously met pathogen (or one the host has been vaccinated against) \