Immune System, Innate Immunity

Immune System - - - - Innate Immunity: The “first line of defense” Tolerance refers to the non-reactivity of the immune system to self particles Antigens are anything that cause an immune response Cytokines are molecules that are used for cell signaling, or cell-to-cell communication (can be used to communicate with neighboring/distant cells about initiating an immune response) Chemokines are a type of cytokine that are released by infected cells in order to initiate an immune response and to warn neighboring cells of the incoming threat Innate immune system is essentially made up of barrier that aim to keep viruses, bacteria, parasites, and other foreign particles out of your body or even limit their ability to spread/move throughout the body; this includes: Physical barriers such as the skin, GI tract, respiratory tract, nasopharynx, cilia, eyelashes and other body hair Defense mechanisms such as secretions, mucous, bile, gastric acid, saliva, tears, and sweat General immune responses such as inflammation, complement, and non-specific cellular responses White blood cells (WBCs) or leukocytes work to defend and protect the body; patrols the entire body via the circulatory system Phagocytes are cells that circulate throughout the body, looking for potential threats to engulf and destroy Macrophages are efficient phagocytic cells that can leave the circulatory system by moving across the walls of capillary vessels; they can also release cytokines in order to signal and recruit other cells to an area with pathogens Mast cells are found in mucous membranes and connective tissues; important for wound healing and defense against pathogens via the inflammatory response; when activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade (histamine, a mediator that causes blood vessels to dilate, thus increasing blood flow and cell trafficking to the area of infection) Neutrophils are phagocytic cells (fastest and most abundant) that are also classified as granulocytes because they contain granules in their cytoplasm, which are very toxic to bacteria/fungi and can cause them to stop proliferating or die on contact (bone marrow makes about 100 billion new cells per day are are therefore typically the first cells to arrive at the site of an infection) Eosinophils are granulocytes that target multicellular parasites; secrete a range of highly toxic proteins/free radicals that kills bacteria/parasites Basophils are also granulocytes that attack multicellular parasites; release histamine like mast cells; use histamine to make basophils/mast cells key players in mounting an allergic response Natural Killer (NK) cells do NOT attack pathogens directly. Instead, they destroy infected host cells in order to stop the spread of an infection. Dendritic cells are antigen-presenting phagocytic cells that are located in tissues, and can contact external environments through the skin, the inner mucosal lining of the nose, lungs, stomach, and intestines (act as a bridge for the innate and adaptive immune systems) Chemotaxis is the attraction and movement of macrophages to a chemical signal; uses cytokines/chemokines in order to attract macrophages and neutrophils to the site of the infection Agglutination uses antibodies to cluster and bind pathogens together, much like a cowboy rounds up his cattle Adaptive Immunity: Adaptive immune system uses specific antigens in order to strategically mount an immune response (much slower to - - - - 1. 2. 3. - respond to threats than the innate immune system) → relies on fewer types of cells, B and T cells Lymphocytes refers to B and T cells that are derived from specific types of stem cells B cells form and mature in the bone marrow; the naive B cells then move into the lymphatic system to circulate throughout the body; within the lymphatic system, B cells encounter an antigen, which then starts the maturation process for the B cell; when a naive B cell divides/differentiates, both plasma & memory B cells are made T cells are formed in the bone marrow and migrate to the thymus to mature/become T cells. In the Thymus, they develop T cell receptors and other receptors called CD4 and CD8 receptors (one or the other, NOT both). T cell receptors can only recognize antigens that are bound to certain receptor molecules called MHCI and MHCII, which are membrane-bound surface receptors on antigen-presenting cells like dendritic cells/macrophages. Finally, in order to ensure T cells will perform properly once they have matured and released from the thymus, they undergo two selection processes: Positive selection ensures MHC restriction by testing the ability of MHCI/II to distinguish between self/nonself proteins. In order to pass the positive selection process, cells must be capable of binding ONLY self-MHC molecules. If these cells bind nonself molecules instead of self-MHC molecules, they fail the positive selection process and are eliminated via apoptosis Negative selection tests for self tolerance, meaning that it will test binding capabilities of CD4/CD8 specifically. The ideal example of self tolerance is when a T cell will only bind to self-MHC molecules presenting a foreign antigen. If a T cell binds, via CD4/8, a self-MHC molecule that isn’t presenting an antigen, or a self-MHC molecule that presents a self antigen, will fail negative selection and be eliminated by apoptosis. After selection, we are left with three cell types: Helper T (TH) cells express CD4 and help with the activation of TC cells, B cells, and other immune cells Cytotoxic T (TC) cells express CD8 and are responsible for removing pathogens and infected host cells T regulatory cells express CD4 and another receptor, called CD25. T regulatory cells help distinguish between self/nonself molecules, thus reducing the risk of autoimmune diseases Humoral immunity is the immunity from serum antibodies produced by plasma cells. More specifically, someone who has never been exposed to a specific disease can gain humoral immunity through administration of antibodies from someone who has been exposed to and survived the same disease (refers to the bodily fluids where these free-floating serum antibodies bind to antigens and assist with elimination) Role of Phagocytes in Innate/Nonspecific Immunity: First Line: keeps out → skin, mucous membranes, stomach acids, etc. Second Line: inflammatory response (basically brings blood, fluid, cells, to the area in order to fight off the pathogen) and phagocytes Phagocytes are basically a class of cell that eats up things (typically foreign antigen) Phagosomes are basically vesicles that contain the foreign particle that you want to get rid of The phagosome will then take particles from the thing it just ate and attach it to an MHC II to present it to a T cell (therefore many phagocytes are antigen presenting cells) Types of Immune Responses: Innate & Adaptive, Humoral vs. Cell-Mediated: B lymphocytes participate in the humoral response (relating to antibodies and the pathogen just floating around, not really infected cells yet) T lymphocytes participate in the cell mediated response (relating to the actual infection of the cell) B Lymphocytes (B Cells): B cells have membrane bound antibodies (Immunoglobulins) on their surface → Each B cell has its own antibody (differing - variable portions of the antibody) Self responding combinations of these B cells with the antibodies are weeded out, when a B cell finds an antigen it binds to, it is then activated (starts cloning himself) Some go on to become memory cells that stick around for a long time - Effector cells are cells that turn into plasma cells that are basically antibody factories producing a shit ton of the antibodies for that particular antigen Epitope is the part of the antigen that is recognized by the immune system Opsonization is when you attach antibodies to antigens, marking them for destruction by the immune system We still haven’t discussed what occurs when pathogens actually infiltrate cells within the body Professional Antigen Presenting Cells (APC) & MHC II Complexes: First, a phagocytotic engulfs a pathogen, nothing specific about this process, but then it degrades it and ends up using the foreign invader’s pieces to present it via MHC II to Helper T Cells A B cell will also engulf a pathogen and degrade it. It will then also end up proliferating and making a shit ton of antibodies but it will ALSO end up taking pieces of the invader and present the antigens via MHC II (VERY SPECIFIC) to Helper T Cells - Helper T Cells: Cytotoxic T Cells attack cells that have already been infected or are abnormal in some way (cancer cells) Helper T Cells are basically the alarm of the immune system by (dendritic cells are the best at activating helper T cells) Like the B cells, helper T cells are all unique from one another and will only bind to their specific antigen on an MHC II When activated, they also become effector (raises the alarm by releasing cytokines to warn surrounding cells) and memory Th cells B cells become activated when an active TH cell activates it by binding to its MHC II Cytotoxic T Cells: B cells and dendritic cells will take in pathogens and present them via MHC II Also, all nucleated cells will present (included B and dendritic cells) will present self components MHC I (to prove that it is healthy) The difference is Helper T cells bind to MHC II while cytotoxic T cells will bind to MHC I Cytotoxic T cells that go on to become effectors go on to kill the infected cells (tells it to kill itself via perforins which make holes in the cell or granzymes that make the cell kill itself) BASICALLY B cells target shit that’s just floating around while T cells target actual cells (whether it be B/dendritic cells presenting information or every type of cell presenting information) Review of B cells, CD4+ T Cells, & CD8+ T Cells: Effector B cells which are the antibody factories are commonly referred to as plasma cells CD4+ T cells are the Helper T Cells (most) CD8+ T cells are the Cytotoxic T Cells (most) When TH cells (alarm) become active, their effectors go and activate B cells while the memory ones make more of itself in order to stick around in case of future infection When TC cells (killers) become active, their effectors go and actually kill off the infected cells while the memory ones make more of itself in order to stick around in case of future infection Clonal Selection: Each daughter cell of a B cell will have a different variable region on their surface antibodies (very specific but very powerful if it finds the correct antigen) T cells mature in the thymus. When these T cells divide, each daughter cell has different receptors as well that bind to MHC proteins (I and II depending on what kind of T cell it is) T and B cells will migrate to the lymph nodes and wait to find their particular “criminals” to bind to When activated, the daughter cells will have the same receptors (more effector cells are made than memory cells) Self vs. Non-Self Immunity: Since B cells are created at random, it could technically form B cells that bind to yourself (i.e. your own insulin) → a way to keep your body from killing yourself, you end up destroying any B cells that react to self things (you only want B cell to - 1. 2. attack foreign things) This differentiation of self vs. non-self in the bone marrow (B cell “vetting”) If the B cell recognizes self in the bone marrow, it will be killed In the lymph node, the B cell will be killed if it does not recognize foreign particles If the T cell reacts to self in the Thymus, it will be killed In the lymph node, the T cell will be killed if it does not recognize foreign particles B cells don’t really need to get into circulation from the lymph node, they just release antibodies into circulation basically Blood Cell Lineages: Multipotent, hematopoietic, stem cells gives rise to two main lineages (10 total cells): Myeloid: RBC, megakaryocyte (makes platelets), neutrophil, basophil, eosinophil, monocyte (goes on to form macrophages), and mast cells Lymphoid: goes on to make NK, B, and T cells Dendritic cells come from both lineages (if it comes from myeloid, it is differentiated from the monocyte but if it comes from the lymphoid lineage it comes straight from the lymphoid)