Immune System - BIOB1220 Anatomy & Physiology PDF

Immune System BIOB1220 Anatomy & Physiology David Jahanlu, MD. PhD.  Immune System We are surrounded by pathogens Tissues Organs or Antigens...

Immune System BIOB1220 Anatomy & Physiology David Jahanlu, MD. PhD.  Immune System We are surrounded by pathogens Tissues Organs or Antigens Antigens, is any molecule that is Cells recognized by our immune system Molecules …in our respiratory tract They are all over our skin …in our alimentary tract Identify the threat Inflammation Mounting an attack … is the body's response to Eliminating a pathogen injury or harm, and initiating Removing toxins of the healing process Destroying tumor cells Remembering the offender Specific for Adaptive immunity Immune System Cells Myeloid progenitors Lymphoblasts Myeloblasts Monocytes Small lymphocytes Polymorphonuclear cells Phagocytes Adaptive immunity Granulocytes Innate immunity Immune System Cells Allergic reactions Parasitic infection Most abundant Parasitic infection Helminths First responders Autoimmunity Allergic reactions Bacterial infection Living in the tissue Fungal infection Under the skin mostly Phagocytosis Bacteria and parasites Polymorphonuclear cells Allergic response Anaphylactic shock Granulocytes  1- damage to the physical Immune System barrier let the Antigens pass The first line of defense in our immune system is physical and chemical barriers such as skin and mucosa 4- cytokines also attract Dendritic cells and neutrophils 2- tissue macrophages are the cell process the 6- Dendritic cells first that phagocyte antigens pathogen and display some of its protein fragments, or 3- if necessary, they release Cytokines, antigens, on their surface which start inflammatory process 7- Extra-cellular antigens 5- Neutrophils migrate to infection are either MHC-1 or MHC-2 sites, where they engulf and destroy pathogens; their dead remains 8- As "antigen-presenting cells" accumulate as pus, a whitish (APCs), they migrate into lymph discharge at the site of infection nodes to activate Lymphocytes for adaptive immunity This is a part of Innate immune system providing a rapid, non-specific response to pathogens through physical barriers, immune cells, and inflammatory reactions Immune System Lymphocytes Week 12 : T-cell precursors (Thymocytes) start leaving the bone marrow toward Thymus Thymus is a fatty lymphoid organ in front of chest At puberty Thymus gradually This migration continues until decreases in size and activity At this stage, no receptors have some months after birth (thymus involution) developed, so it is referred to as the Double Negative stage During development in thymus, 3 At that point they are proteins start to express on the referred as Double Positive T-cell receptor (TCR) gene surface, called CD3, CD4 and CD8 rearrangement process happens and they develop a unique receptor with alpha and beta chains that can recognize specific antigens Thymocytes that survived get matured into single-positive CD4⁺ or CD8⁺ Naive T-cells These cells are now capable of interacting with antigens presented by Major These cells exit the thymus Histocompatibility Complex (MHC) molecules as naïve T-cells, ready to respond to foreign antigens At this stage, only cells that can in lymph nodes and spleen bind with MHC molecules will survive Immune System Lymphocytes MHC-I will be presented for Naive t-cells with CD8 receptors MHC-1 presents intracellular These T-cells then differentiate into proteins form viruses or tumors cytotoxic T-cells, which can then leave the lymph node to target and destroy infected or cancerous cells MHC-1 These T-cells then differentiate into different T-helpers (TH1, TH2, TReg) with their specific role in immune functions and helping B-cells MHC-2 MHC-II will be presented for MHC-2 presents extracellular Naive t-cells with CD4 receptors proteins such as bacterial proteins Lymph node Immune System Lymphocytes B-cells are those lymphocytes that develop and differentiate in the bone marrow First they assemble a surface receptor, that has heavy and light chains, they are called Immature B-cell at this stage Antigen When they catch a matching antigen, Antigen binding site their receptor-antigen complex enters the B-cell, and after processing, present it as a MHC II protein, on the surface Immature B-cells will leave the bone marrow and enter the lymphatic system as Naive B-cells, where they can encounter a specific antigen that matches their unique binding site Naive B-cell  Then a T-helper cell with a matching Immune System Lymphocytes receptor to the MHC II complex fully activates the B-cell, allowing it to proliferate and differentiate into antibody- cell and Memory B-cell producing Plasma cells B-cells C I I MH At this stage, B-cell are partially MHC activated and functioning as an II antigen-presenting cell (APC) When they catch a matching antigen, their receptor-antigen complex enters the B-cell, and after processing, present it as a MHC class II protein, on the surface Immune System Lymphocytes Plasma cell Memory B-cell …are specialized, antibody-producing cells, produces …critical component of the immune system’s ability to thousands of antibodies per second, releasing them into the recognize and respond quickly to previously encountered bloodstream and tissues pathogens These antibodies circulate throughout the body, seeking out Unlike plasma cells, which are short-lived, memory B-cells and binding to the specific antigen associated with the persist for months to years in the bone marrow, spleen, or original infection lymph nodes Most plasma cells are short-lived, typically surviving for just When the body encounters the same pathogen again (a a few days to weeks secondary infection), memory B-cells recognize the antigen much more quickly than naïve B-cells, which leads to a faster and stronger immune response Immune System Immunoglobulin (Ig) Immunoglobulin (Ig) is the structural term for antibodies, and it has five types classified based on the heavy chains they contain IgM is the largest immunoglobulin and the first antibody produced during an infection. IgM antibodies typically exist as a pentamer, The complement system is a group consisting of five antibody units joined of proteins made in liver, that It is the only antibody that does not require together by a J (joining) chain protein, which promoting pathogen destruction, T-helper cells for activation and is highly enhances their ability to bind antigens and effective in activating the complement system inflammation, and the recruitment activate the complement system of immune cells to sites of infection Immune System Immunoglobulin (Ig) Has 4 subclasses: IgG 1, most abundant subclass in the blood and plays a major role in defense against bacteria and viruses IgG 2, primarily involved in immune responses to carbohydrate antigens, such as bacterial polysaccharides Most abundant Ig in blood and extra cellular IgG3, highly effective in activating the complement system, fluids, and its major role is working as Opsonin, plays a role in fighting infections which helps a phagocyte to get a grip on bacteria IgG4, often associated with immune tolerance and is important in allergic responses Opsonization Primary antibody produced during the secondary immune response The only immunoglobulin that can pass placenta, and by this, the mother gives immunity to the newborn up to 6 months after delivery Immune System Immunoglobulin (Ig) A virally infected IgG binds to infected or cell, expresses MHC I abnormal cells and triggers on its surface natural killer (NK) cells Virus C I M H …NK-cell performs Antibody Dependent Cell mediated Cytotoxicity (ADCC), and kill the infected cell Immune System Immunoglobulin (Ig) The main antibody found in mucosa (saliva, tears, breast milk, semen …) 20% of serum immunoglobulin, with two types IgA1 and IgA2 Serves as opsonin, with receptor Plasma cells, in basement membrane of mucosal for eosinophils, neutrophils and cells, release the IgA and make a dimer, bound some macrophages together by J chain Breast milk’s IgA is an important given immunity into the GI system of newborn Immune System Immunoglobulin (Ig) only about 0.004% of serum immunoglobulins only less than 1% of serum immunoglobulins peanuts or pollens, atopic dermatitis, seasonal Main role as a signal to B-lymphocytes that allergies and asthma they are ready to leave bone marrow mostly associated with allergic and anti- parasitic responses Eosinophils, basophils and mast cells have receptors for IgE Immune System Parasitic infection : helminthic (worm) infections (e.g., schistosomiasis, hookworm) … they activate the Macrophages recognize immune system by the pathogen, but this is releasing cytokines T-helper 2 help activate too big to phagocyte eosinophils and promote the production of IgE by B-cells Eosinophils have a major role in response What happens to the IgE binds to mast cells to helminthic infections B-cell here is called and basophils and Class-switching boost their activities Eosinophils release toxic proteins that directly Mast cells are joining and Basophils release damage parasites help to activate more Interleukins, which attract more eosinophils Together, these actions break eosinophils and Th2 cells down the parasite, making it ready for phagocytosis. Immune System Class-switching or class switch recombination (CSR), is a biological mechanism that a B-cell change its Ig from one type to another Gene that express IgM heavy chain in a B-cell B-cell During helminthic infection we need IgE rather than IgG During a helminthic infection, levels of IL-4, IL-5, IL-10, and IL-13 increase This unique combination Activates an enzyme in the B-cell, called AID removes a part of DNA Activation Induced cytidine Deaminase or AID Gene that express IgE heavy chain in a B-cell Immune System An example 4 MHC-1 makes it easier for 2 cytotoxic T-cells and NK- 3 cells to do surveillance 1 Interferons affect the infected Interferons also affect the and kill infected cells The infected cell releases cell (autocrine) to interfere neighbor cells (paracrine) interferons ⍺ and β with virus replication and they present MHC-1 on their surface MHC I C I Virus INFβ M H INF⍺ MH CI Immune System An example NKs also produce interferon ɣ (INF ɣ ) INFɣ 2 I Virus INFβ 1 HC M If there’s an infected cell that doesn’t Each cytotoxic T-cell has a receptor INF⍺ have recognizable MHC-I by Cytotoxic (TCR) that can specifically recognize T-cell, then a NK-cell will kill it a particular antigenic peptide bound to an MHC molecule, this is the one they’ve got from dendritic cells the combination of Interferons (⍺, β, ɣ) with IL-12, produced by dendritic cells, is a recipe for transformation of Activated T-helpers to T-helper 1 T-helper 1 can make more INFɣ to reinforce the process, and produce IL-12 which makes natural killer cells more effective Thank you :) David Jahanlu, MD. PhD.