Introduction to the Immune System Adaku Ofoegbu, P3 Student Pharmacy Biomedical Preview Program adaku.ofoegbu@bison.howard.edu Overview General Introduction to Immune System Types of immunity Cells and organs Antigens Antibodies Major Histocompatibility Complex (MHC) Types of Immunity • Innate Immunity ▫ This is your body’s first line of defense against infection! ▫ This type of immunity is nonspecific • Adaptive Immunity ▫ This immunity comes into play when an antigen is introduced to the body ▫ This type of immunity is specific to the antigen and is the basis for the “memory” of your immune system Examples of components of innate immunity • ANATOMIC ▫ Skin (dermis and epidermis) and mucous membranes • PHYSIOLOGIC ▫ Temperature ▫ Sebaceous gland secretions (pH of 3 – 5) ▫ Chemicals (such as lysozyme and interferon) • PHAGOCYTIC ▫ Phagocytic white blood cells (monocytes, macrophages, etc) eat whole microorganisms! • INFLAMMATORY ▫ Inflammation leads to serum proteins with antibacterial activity going to site of tissue damage or infection Examples of adaptive immunity • Lymphocytes • Antibodies Humoral vs. Cell-Mediated Immunity Humoral Immunity Cell-mediated Immunity • This immune response is primarily seen in the blood (hence “humoral”) and involves macromolecules such as: ▫ Antibodies ▫ Complement proteins • Antibodies tag foreign bodies (also known as antigens) so that the immune cells can destroy them • Complement proteins basically poke holes into bacterial cells and cause them to lyse • This immune involves cells such as ▫ T-cells ▫ Phagocytes • In this immune response, Tcells activate other immune cells to enhance the immune response Lets talk about the cells first! Cells of the Immune System • Hematopoietic stem cells (HSC)* • Lymphoid cells ▫ Natural killer cells (NK cells) ▫ B lymphocytes ▫ T lymphocytes • Granulocytic cells ▫ basophils, neutrophils, eosinophils • Dendritic cells • Monocytes Hematopoietic Stem Cells* • These are the stem cells for ALL blood cells, including red blood cells (RBCs) and white blood cells (WBCs) • These cells are located in the bone marrow • (These are not actual immune cells but this is where they originate) Lymphoid Cells • These cells circulate in the blood and lymph to protect you from foreign pathogens in the body • They make up 20-40% of your white blood cells • The lymphoid cells include natural killer cells (NK cells), B lymphocytes, and T lymphocytes Lymphoid Cells • Natural killer cells can recognize body cells that are infected by viruses or are cancerous and kill them without using antibodies! Lymphoid Cells • T lymphocytes (aka T cells) are comprised of the helper T cells and the cytotoxic T cells ▫ Helper T cells have CD4 markers on them (hence the CD4 count used in HIV patients) ▫ Cytotoxic T cells have the CD8 markers on them • Special cells called antigen-presenting cells present antigens to the T lymphocytes, which will initiate a cascade immune response to the antigen Lymphoid Cells • B lymphocytes (aka B cells) make up the humoral immune response and make antibodies • They are are comprised of the effector cells and memory cells ▫ Effector cells directly bind to free-floating antigen in the body (T cells cannot do this) ▫ Memory cells Granulocytic Cells • The granulocytic cells are essentially white blood cells that have granules in their cytoplasm that can be seen under a microscope Granulocytic Cells • Neutrophils make up 50-70% of circulating white blood cells and are phagocytes that tend to eat bacteria • Eosinophils make up 1 – 3% of circulating white blood cells and tend to eat parasites • Basophils make up <1% of circulating white blood cells and are involved in some allergic reactions ▫ Mast cells have a similar function as basophils and are found in the tissues (as opposed to circulating in the blood) Dendritic Cells • Dendritic cells are very potent antigenpresenting cells • They are unique because they do not need to be activated before they can present antigen to the T cells Monocytes • Monocytes are a type of white blood cell that is phagocytic • They are among the largest in size of the white blood cells • They circulate in the blood, then enter the tissues and become macrophages Thymus --site of T cell growth and maturation Bone Marrow --site of B cell growth and maturation The Lymphatic System --consists of the lymph nodes, spleen Mucosal-associated lymphatic tissue (MALT) --Peyer’s patches in small intestines, What are antigens? • Antigens are substances that can be recognized by antibodies or by T-cells • Antigens can cause immunogenic and/or antigenic responses ▫ Immunogenicity – causing an immune response ▫ Antigenicity – the ability to combine with T-cell receptors or antibodies ▫ A substance can be antigenic but not immunogenic! Facts about Antibodies Antibodies are made by your B cells Antibodies are comprised of 4 peptide chains There are two heavy (H) chains and two light (L) chains IgG IgA LONGEST half life Four forms of IgG (IgG1, IgG2 , IgG3, IgG4) Activates complement (in order of best to worst (3, 1, 2 ,4) Fc region binds to phagocytes (in order, best to worst (1 and 3, 2, 4) Used for SECONDARY IMMUNE RESPONSE Participates in precipitation (form a lattice) reactions with immunogens and opsonization (complement pathways) γ2κ2 γ2λ2 IgM Found in nasal secretions Forms LINEAR polymers joined by Jchain α2κ2 α2λ2 IgE SHORTEST half life PENTAMER (five units attached when floaing in blood) Pentamer connected via J-chain BEST FOR BINDING COMPLEMENT (the C1q) NO CLASS SWITCHING **MDs don’t have class!** Monomers present on B cells (mature) NO HINGE PRIMARY IMMUNE RESPONSE Participates in agglutination and opsonization µ2κ2 µ2λ2 IgD Plays role in TYPE I allergic response Binds to mast cells and basophils helps cause degranulation when crosslinked NO HINGE Present on mature Bcells NO CLASS SWITCHING **MDs don’t have class!** Ɛ2κ2 Ɛ2λ2 δ2κ2 δ2λ2 **Antibody has four chains; two light chains – κ (60%) and λ (40%), and two dark chains (gamma, alpha, mu, epsilon, or delta) Major Histocompatibility Complex • MHC is a type of molecule that exists on the surface of your body’s cells • There are two types of MHC: ▫ MHC I – found on virtually all body cells ▫ MHC II – found on the antigen presenting cells • The CD4 on helper T cells looks at the MHC II on the antigen presenting cells • The CD8 on cytotoxic T cells looks at the MHC I on your body cells MHC I • MHC I is present on virtually all body cells and is how your immune system knows which cells belong to itself! • The cytotoxic T cells with CD8 look in the peptide binding cleft for an unusual peptide pattern (could be the result of a viral infection, for example), and if the peptide is identified as foreign, the cell is marked for destruction!