Immunology Dr Swapnil Pawar
In this podcast, Maddi & I talk about innate immunity, MHC proteins, the role of T & B lymphocytes along with hypersensitivity reactions.
Outline the components involved in innate immunity
Innate immunity is the first line of defence of the body. It is non-specific and consists of life-long immune mechanisms that do not require prior exposure to antigens and are not modified by repeated exposure to a pathogen. The innate immune system consists of physiochemical barriers, soluble proteins and cellular defence mechanisms.
Cellular defence mechanisms: consist of leukocytes, mast cells and natural killer cells.
What is the major histocompatibility complex?
When antigens are engulfed by human cells they transported to the surface of the cells and are attached to proteins to be presented to the bodies defence mechanisms. These proteins are called major histocompatibility complex proteins. Major histocompatibility complex is a group of genes located on chromosome 6 that code for these cell surface proteins which help the immune system distinguish foreign proteins from its own. The MHC is polygenic and polymorphic, thus making it difficult for pathogens to evade the host immune response. There are two important classes of MHC, class 1 and class 2. Class 1 proteins are expressed on all nucleated cells and present antigens to cytotoxic T lymphocytes which then kill the infected cell. Class 2 proteins are only found on B lymphocytes, macrophages and other professional antigen presenting cells and present antigens to helper T cells. Class 1 MHC proteins are especially important for the detection of intracellular pathogens such as viruses while class 2 MHC proteins are particularly important for extracellular antigens such as bacteria. There is also a class 3 MHC which encode for components of the complement system and other inflammatory molecules.
MHC is also called human leukocyte antigens and is a crucial part of organ transplantation. There are three major MHC class 1 genes known as HLA-A, B and C and three major MHC class 2 genes, as well as several minor genes. These closer the match between the donor recipient HLA complex, the lower the risk of organ rejection.
Briefly describe the functions of T and B cells
Both T and B cells are lymphocytes that are derived from multipotent haematopoietic stem cells in the bone marrow and are a vital component of the acquired immune system.
T progenitor cells migrate from the bone marrow to the thymus where they mature. They cannot bind to antigens directly but need to have broken down peptides of the antigen presented to them by antigen presenting cells. T cells are involved in cell mediated immunity. There are four main types of T cells; helper, cytotoxic and regulatory
B cells are involved in the humoral immune response.
B cells can be activated directly by an antigen, unlike T cells. They can also be activated by T cells. When a B cell encounters its matching antigen, it engulfs it and displays fragments on MHC class 2 molecules. This attracts helper T cells which secrete cytokines and helps the B cell clone proliferate producing plasma cells. Plasma cells secrete antibodies to specific antigens which directly attack antigens and also activate the complement system. Some B cells also differentiate into memory B cells which become activated if there is a reinfection by the same antigen. This helps to launch a rapid response against the pathogen in the future.
What are immunoglobulins
Immunoglobulins, also known as antibodies, are large Y shaped proteins produced by plasma cells and are a vital part of the immune system. They can directly attack invaders by agglutination and lysis or can indirectly attackvia activation of the complement system. Immunoglobulins consist of two heavy chains and two light chains joined to form a Y shaped protein. Both the heavy and the light chains have constant and variable regions. The constant regions determine some of the biological properties of the antibody and they are divided into five major classes, IgG, IgM, IgA, IgD and IgE depending on the constant region of the heavy chain.
The variable region contains the antigen binding site and mediates antigen recognition. It gives the antibody its specificity for an antigen and provides diversity, allowing the immune system to recognise a wide variety of antigens. Immunoglobulins occur in two main forms, soluble antibodies which are in the blood and membrane bound antibodies which are attached to the surface of B cells and otherwise known as B cell receptors. The membrane bound immunoglobulins detect antigens and facilitates the activation of B cells and subsequent differentiation into plasma or memory B cells.
Classify the hypersensitivity reactions. Briefly describe the pathophysiological processes underlying each reaction and give an example of each.
Hypersensitivity is an exaggerated or inappropriate immune response that results in tissue damage. There are four types of hypersensitivity reactions; type 1 immediate, type 2 cytotoxic, type 3 immune complex and type 4 delayed.
Type 1: Immediate or ‘classic’:
Type 2: cytotoxic
Type 3: immune complex
Type 4: delayed