18) Infectious diseases summary 9744 2019

Raffles Institution Infectious Diseases 2019 Prepared by: Mrs Selvamani Nair, Ms Michelle Nah, Mr Ngan Wei Yeong 1 Infectious diseases * Infection: process where a pathogen invades and multiplies in a host and causes ill health in the host * Pathogens: 1. microorganisms that cause disease (impair normal function) by invading and multiplying in the host 2. e.g. bacteria, viruses, fungi, worms and protozoa 3. can be intracellular (i.e. in cells) or extracellular (i.e. in blood, tissue fluid and lymph i.e. in the humour) 4. have antigens on their surface * Antigens: 1. many different types can be found on one pathogen 2. triggers an immune response when specific parts of the antigen called epitopes are recognised by immune cells or antibodies * Epitopes: 1. parts of a single antigen 2. each have a specific conformation complementary in shape and charge to a specific antigen-binding site of an antibody or T cell receptor or B cell receptor * Cells of the Immune System: 1. Phagocytes a) macrophages  an antigen presenting cell (APC) which resides in tissues  are produced when monocytes in the blood enter tissues and differentiate b) dendritic cells  an antigen presenting cell (APC) which resides in tissues c) neutrophils  found in blood Immune System Innate Immune System (1st line of defense) Adaptive Immune System (2nd line of defense) Cellular Components Cell-mediated Response Humoral Response 1. Skin  Acidic pH and inhibits microbial growth 2. Mucous membranes  contain antimicrobial proteins, e.g. lysozyme, which break down bacterial cell walls  release fluids e.g. saliva, tears to wash away pathogens and prevent their attachment Phagocytes 1.Macrophages 2.Dendritic cells 3.Neutrophils Antigen presenting cells (APCs) Properties of the innate (non-specific) immune response: 1. is non-specific  attacks anything that is foreign or non-self 2. is rapid  responds as soon as pathogen is encountered 3. has no memory  responds the same way to repeat encounters with the same pathogen Properties of the adaptive (specific) immune response: 1. is specific  recognises only a specific antigen on a pathogen 2. takes time to develop  this applies to first exposure to pathogen (i.e. primary immune response) 3. shows memory  responds quickly to repeat encounters to the same pathogen (i.e. secondary immune response occurs rapidly) Mediated by cytotoxic T cells that kill cells infected with intracellular pathogens Mediated by antibodies (secreted by plasma cells) which target extracellular pathogens Barriers pathogen encounter 1 breach inflammation antigen presentation removal of pathogen and generation of immunological memory 2 3 4 5 antibody A antibody B epitopes antigen- binding sites antigen

Raffles Institution Infectious Diseases 2019 Prepared by: Mrs Selvamani Nair, Ms Michelle Nah, Mr Ngan Wei Yeong 2 2. Lymphocytes T lymphocytes/cells B lymphocytes/cells Originate from haematopoietic stem cells in bone marrow but differentiate in the thymus to form naïve T cells Originate from haematopoietic stem cells in the bone marrow and differentiate in the bone marrow to form naïve B cells Each T cell has a specific T cell receptor (TCR) on its surface Each B cell has a specific B cell receptor (BCR) on its surface A TCR can only recognise and bind to a specific, complementary processed peptide of a peptide-MHC complex on an antigen-presenting cell (APC) A BCR can recognise and bind to a specific complementary unprocessed antigen of a pathogen. Antigen binding site of the BCR and the specific antibody produced in response to the antigen are the same. When a specific naïve T cell is activated by a specific antigen presenting cell , it undergoes clonal expansion and differentiation to form effector T cells (i.e. helper T and cytotoxic T cells) and memory T cells Helper T cell: activates naïve B cell so that it can undergo clonal expansion and differentiation Cytotoxic T cell : involved in cell-mediated response and hence protects against intracellular pathogens by killing cells that contain pathogens Memory T cell : When re -exposed to the same pathogen, memory T cells will recognise it and undergo faster clonal expansion & differentiation into effector T cells, mounting a faster and stronger secondary immune response (compared to the primary immune response) . Memory cells also confers long term immunity to a specific pathogen. When a specific naïve B cell is activated by a specific helper T cell, it undergoes clonal expansion and differentiation to form effector B cells (i.e. plasma B cells) and memory B cells Plasma B cell : produces antibodies which are involved in the humoral response and protect against extracellular pathogens and toxins secreted by pathogens . Plasma B cells have an extensive network of rough endoplasmic reticulum needed for synthesis of large amounts of antibodies (globular proteins) which are secreted by exocytosis. Memory B cell : When re -exposed to the same pathogen, memory B cells will recognise it and undergo faster clonal expansion & differentiation into antibody -secreting plasma B cells, mounting a faster and stronger secondary immune response (compared to the primary immune response). Memory cells also confers long term immunity to a specific pathogen. * 5 steps in immune response: Pathogen encounterInnate immune response Antigen presentationAdaptive immune responseRemoval of pathogen and immunological memory * Physical and chemical barriers of the innate immune system prevent entry of pathogens When these barriers are breached  the pathogen enters the body tissues This will cause phagocytes such as macrophages in the body tissues (A) to engulf the pathogens by phagocytosis and (B) to induce inflammation  aim: to recruit more phagocytes * (A) Phagocytosis by macrophage: 1. Bacterium becomes attached to membrane evaginations called pseudopodia 2. Bacterium is ingested, forming phagosome which then fuses with lysosome forming phagolysosome 3. Lysosomal enzymes digest the captured material and digested products are released from the cell by exocytosis * (B) How are more phagocytes recruited during inflammation? Pathogen triggers macrophages at site of infection (i.e. infected tissues) to release signalling molecules, chemokines and cytokines which (see table) Phagocytes that are recruited to site of infection during inflammation are (1) macrophages  carry out phagocytosis and clear pathogen or function as an antigen presenting cell (APC) (2) neutrophils found in bloodmigrate to site of infectioncarry out phagocytosis and then die and form pus * If a pathogen evades the innate immune system (i.e. the barriers and cellular components of the innate immune system are breached)  the adaptive immune system is activated by antigen presentation. Effect of chemokines and cytokines on blood vessels Effects Vasodilatio