1. From Blood to Host Defense Host Defense Gregory J. Bagby, Ph.D. gbagby@lsuhsc.edu Office: 310 (CSRB)

2. From Blood to Host Defense Blood –Components and function –Hemostasis and clotting The host defense system –General overview –Innate immune system pathogen recognition inflammatory response –Adaptive immune system Humoral immune system and antibodies Cell-mediated immune system

3. The Importance of the Host Defense System? Immunology is the study of the host defenses by which the body (host) protects itself from nonself or altered self. In the process, it destroys or neutralizes foreign matter, microorganisms, cells that are infected, and abnormal or altered self. Recognition, Activation and Attack Protects against: – microbial infection – viral, bacterial, yeast, fungi – non-microbial substances – “altered” self-cells The host defense system has a memory component. That is, when it sees a foreign molecule it will retain memory of the encounter so that when it sees it again it can respond more quickly and robustly.

4. Where Is the Host Defense System Located? Skin serves as a barrier Mucosal surfaces – lung, gastrointestinal track, genital track – barrier, secretions, epithelial cells, and specific cells of the immune system Liver Bone marrow and thymus gland Lymphoid tissues – spleen, lymph nodes, tonsils, lymphatic vessels A diffuse system

5. What Are the Cells of the Immune System? Blood leukocytes – granulocytes, monocytes, lymphocytes, natural killer cells. Tissue-resident cells –Macrophages & dendritic cells in lung, skin, liver, barrier tissues –Lymphocytes in mucosal tissues and lymphoid tissues –NK cells lymphoid tissues –Mast cells in almost all tissues –All these cells can be found in other tissues

6. Where Are Cells of the Immune System Produced? Cell CategoryLocation GranulocytesBone marrow MonocytesBone marrow LymphocytesBone marrow; Mature in bone marrow (B cells and NK cells) and thymus (T cells); Reside and activated in peripheral tissues and lymphoid organs Mast cellsBone marrow, then reside in most tissues

7. How Are Immune Cells Related to Each Other? General or Early NameDifferentiated Name GranulocytesNeutrophils; Basophils; Eosinophils MonocytesMacrophages, microglial cells, Kupffer cells, dendritic cells – antigen presenting cell T lymphocytesT helper; Cytotoxic; Regulatory Naïve; Memory; Effector B lymphocyteNaïve; Memory; Plasma cell; Dendritic cell NK cell (lymphocyte derived) Mast cell NK cell Mast cell

8. How Do Cells of the Immune System Communicate with Each Other and with Other Cells? Cell to cell contact via adhesion molecules, receptors and immunoglobulins. Production and secretion of signaling proteins called cytokines, chemokines and growth factors, as well as immunoglobulins. Production of lipid mediators Serve as autocrine, paracrine or hormone mediators

9. Cytokines, Chemokines and Growth Factors Regulate immune cell proliferation, differentiation and function. Names –Interleukins 1 to >30 –Interferons (α,β,γ) –Growth factors (e.g. granulocyte colony-stimulating factor) –“Functional” names like tumor necrosis factor, macrophage inhibitory peptide –CC, CXC, etc chemokines More than a 100 of these.

10. The Host Defense System Can Be Divided into Two Categories: Innate host defense system (nonspecific) –Includes barriers such as the skin, and the lining fluid and cells that line the airways and gastrointestinal track. –Many cells of the innate system have receptors that bind (recognize) limited number of foreign molecules. –Innate cells become activated and have ability to destroy foreign body. Adaptive (Acquired) host defense system (specific) –Limited number of cells recognize a large array of foreign molecules or region of molecules called an antigen. –Cells of adaptive system recognize molecular shapes that are nonself and proliferate and become activated to mount a defense leading to destruction of the antigen or a cell infected by the antigen (nonself).

11. Innate vs. Acquired Immunity Recognition (Differences btw/ Inn. Vs. acq.) Innate recognition on many cells that are capable of mounting a defense. Specific recognition by a few cells that need to expand before an effective defense can be mounted. Eradication of pathogen Innate Immunity Adaptive Immunity Fast Slow Activation Attack Innate Adaptive

12. Innate Immunity Adaptive Immunity Receptors for detection of microorganisms PRRs: Encoded in the germline TCRs / BCRs: Generated randomly by gene recombination Receptor repertoire Limited Unlimited Cells Monocytes / Macrophages Polymorphonuclear Dendritic T & B Lymphocytes Specificity Molecular Patterns shared by classes of microbes Broad Structural details (e.g., specific peptides) Narrow Reaction Immediate 3-5 days Memory No Yes

13. How Do the Innate and Adaptive Limbs of the Immune System Interact to Defend the Host from Foreign Invaders? Cells of the innate system recognize something as foreign or abnormal and initiates a host defense response –produces cytokines –kills the invader by producing toxic substances and phagocytosis –Initiates response of the adaptive system by presenting antigen In response to antigen specific cells of the adaptive system expand in number to recognize, attack and kill the foreign invader. The adaptive system calls upon cells of the innate system to help in ridding the body of the invader.

14. What Are the Cells of the Innate and Adaptive Immune Systems? CategoryCells Innate immune systemMonocytes/Macrophages Granulocytes Mast cells NK cells Dendritic cells Adaptive immune systemT lymphocytes T helper cell Cytotoxic T cell T regulatory cell B lymphocytes/Plasma cell

15. From Blood to Host Defense Blood –Components and function –Hemostasis and clotting The host defense system –General overview –Innate immune system pathogen recognition inflammatory response –Adaptive immune system Humoral immune system and antibodies Cell-mediated immune system