POD M&I Session 1 Immunology Big Picture PDF

Microbiology & Immunology Session 1 Course Overview Immunology Big Picture David Everly, Ph.D. [email protected] Associate Professor Microbiology and Immunology 1  Course Director Ning...

Microbiology & Immunology Session 1 Course Overview Immunology Big Picture David Everly, Ph.D. [email protected] Associate Professor Microbiology and Immunology 1  Course Director Ning Wang, PhD – Assistant Professor – [email protected] – Microbiology and Immunology – 847-578-3231 – Basic Sciences Building, 2.304 Teaches bacteriology (exam 3) and parasites (exam 5) Integrated sessions 2 Some slides used and/or modified from the RWJF with permission. 3  Overview of M&I: Immunology Exam 1 (Sessions 1-16, 15%) Exam 2 (Sessions 17-26, 15%) Innate Immune Response Adaptive Immune Response – Inflammation – Part 2 Adaptive Immune Response Abnormal Immunology – Part 1 – Hypersensitives/Autoimmunity TBL Innate Immune Response Applied Immunology – Optional (no extra credit) TBL Adaptive Immune Response – Optional (no extra credit) POPS Allergy – Optional (PLUS 0.5% EXTRA CREDIT) Overall for the course 4  Overview of M&I: Microbiology Exam 5 (Comprehensive and Exam 3 (Sessions 27-45, 20%) Sessions 59-69, 35%) Bacterial Pathogens Fungal and Parasitic Pathogens – 61 organisms – 15 fungi and 15 parasites Integrated Sessions Exam 4 (Sessions 46-58, 15%) – Skin, bone and soft tissue infections Viral Pathogens – Cardiovascular and UTI infections – 35 viruses Bioterrorism POPS Hepatitis Breakdown (approximate) – Optional (PLUS 0.5% EXTRA CREDIT) – New material 27% Overall for the course – Immunology 21% – Bacteria and Viruses 52% 5  Approach to Immunology Understand the overall process and then fill in the details (lots of details) – Overall story, characters, settings, and dialog/plot points Reaction, cells, locations, and signals/reactions High yield topics for boards Conceptually difficult and complex topics – Revisited in future courses, esp. pathology TBL (team-based learning) sessions help to put everything together 6  Approach to Microbiology Like a puzzle to solve Clinical vignette questions (exams and boards) – Recognize the disease from the clinical presentation, etc. – Know the most likely pathogen – Be prepared to answer one of the 8 pathogen questions Study the cases at the end of the lectures 7  Approach to Pathogens Each exam will have a Eight questions for each “Microbe List” microbe: – Microbes covered and – Natural reservoir responsible for on the exam. – Transmission Others may be mentioned. – Diseases Pathogens are Cumulative – Risk factors – Final exam is cumulative, many – Pathogenesis factors especially important organisms – Identification are in the integrated sessions at the end of the course – Treatment (sessions 66-68). – Prevention 8  Microbe Review Slides D2L has “Microbe Review Slides” – Grouped by type: Bacteria, Viruses, Fungi, Helminths, and Protozoa Answers 8 questions for all pathogens. All pathogens covered in the entire course – Board exam pathogens 9  Learning Objectives Explain the general purpose, components, and organization of the immune response. Distinguish the innate and adaptive immune systems. Explain the series of events that leads to innate immune responses. Describe the series of events that leads to an adaptive immune response. 10  Response to Injury Physical Chemical Immunological Other (e.g. Asbestos) By ClockFace - Own work Medical gallery of Aram Dulyan Blausen Medical 2014 Inflammatory (including immune) response to initiate repair, regeneration, induce tissue/organ repair, and remove dead and damaged cells/tissue. 11  Response to Pathogens Virus Parasite Fungus Bacteria Immune response to kill pathogens, kill infected cells, and induce tissue/organ repair. 12  Innate versus Adaptive Responses Innate Immune Response Adaptive Immune Response Immediate/initiating Delayed initial response response – Requires “learning” Crude screening methods Precise response tailored to Prevent extensive damage threat Little specialized training Components generated in required response to threat. No memory – 10th exposure is the same as Generates memory response to 1st exposure – Response to 2nd exposure is faster and more robust than response to 1st exposure 13  Pathogen or Injury Entry Recognition Alarm Innate Innate Inflammation Effector Fxn Immune Innate cell Response Recruitment 14  Barriers to Entry Our bodies have a line of defense to keep pathogens out. Specific mechanisms include: Physical – skin, cilia, tears, mucous Chemical – acid, enzymes (pepsin, lysozyme) Biological – normal flora 15  Recognition by Cells Barriers to Entry – Provide Protection Recognition Structural/Support Cells How does the body – Epithelial cells, endothelial cells, and fibroblasts recognize that there’s a problem? Resident Immune Cells – Mast cells, dendritic cells, Cells resident macrophages, – Innate immune receptors innate lymphocytes DAMPs and PAMPs (next slide) Circulating Factors Factors – Complement, etc. 16  Recognition by DAMP/PAMPs Barriers to Entry – Provide Protection Recognition How does the body recognize DAMPs that there’s a problem? – Extracellular matrix – Innate immune receptors – Intracellular components Proteins, DNA/RNA, ATP Damage/Danger-Associated Molecular Patterns (DAMPs) PAMPs Pathogen-Associated – Microbial structures Molecular Patterns (PAMPs) – DNA/RNA 17  Recognition – Alarm Recognition Alarm Recognition leads to sounding the alarm. Cells become activated and secrete factors: – Cytokines: control immune cell activation – Chemokines: control immune cell localization – Vasoactive and inflammatory agents 18  Local Inflammation Recognition Local Alarm Calor, Dolor, Rubor, Tumor – Heat, pain, redness, swelling Inflammation Alarm leads to inflammation. Vasodilation Inflammation Increased permeability – Required for tissue repair and Extravasation of white regeneration. blood cells (WBC) – Recruits cells and factors to fight Stimulation of pain infection. receptors 19  Systemic Inflammation Recognition Systemic Alarm Fever Inflammation Acute-phase response Alarm leads to inflammation. Metabolic shift Inflammation Lymphocyte activation – Required for tissue repair and Neutrophil production regeneration. – Recruits more cells and factors to fight infection. 20  Innate Cell Recruitment Recognition Mostly Phagocytes Alarm (“eaters”) Inflammation – Neutrophils – Monocytes-macrophage Innate cell – Engulf pathogens, cells, and Recruitment debris Alarm and inflammation lead Other recruited cells to innate cell recruitment. – Natural killer (NK), – From circulation, into tissue Eosinophils, Basophils – Large number of cells – Specialized functions 21  Innate Cell Function Phagocytosis (“eating”) Recognition – Destruction of pathogens Alarm Innate Reactive oxygen species, destructive enzymes, Inflammation Effector Fxn antimicrobial peptides Innate cell – Killing infected cells Recruitment – Removal of dead/dying cells and debris Innate cells perform innate effector functions. More inflammation – Cytokines, chemokines, etc. – Potentiate the inflammatory 22 response.  Other Innate Functions Recognition Alarm Innate Inflammation Effector Fxn Innate cell Recruitment Soluble factors can exert effects on innate cells and pathogens. 23  Resolution/Damage Following inflammation Recognition Alarm the process moves Innate towards resolution and Inflammation Effector Fxn restoration of normal Innate cell function. Recruitment Extensive damage or Inflammatory cycle will ongoing (chronic) continue until PAMPs and inflammation may lead to DAMPs are removed. loss of function. 24 (Also influenced by the adaptive response, next)  Pathogen or Injury Recognition Alarm Innate Innate Inflammation Effector Fxn Immune Innate cell Response Recruitment 25  Recognition Alarm Innate Innate Inflammation Effector Fxn Immune Innate cell Response Recruitment Adaptive Immune Response Builds off Innate Response 26  Adaptive Immune Response APC Immune Recognition Pathology Alarm Innate T cell Ab Effector Inflammation Effector Fxn Cytotoxicity Fxns Secondary Innate cell Lymphoid Recruitment Antibodies Organs Primary Naïve Effector CD4 Effector CD8 Effector B Immune Lymphocytes T cells T cells cells Response Lymphocyte Memory T and Development B cells 27  Lymphocyte Development Lymphocytes are B or T cells Recognition Each lymphocyte expresses a Alarm receptor with specificity for one Innate antigen. Inflammation Effector Fxn – Antigen: simplest molecular unit that an immune cell recognizes. Innate cell – Immune receptors: Recruitment B cell receptor (BCR) T cell receptor (TCR) Lymphocytes develop in Lymphocytes have 107-109 primary lymphoid organs. different specificities. Each lymphocyte has a – Each cell has a unique specificity. Lymphocyte unique specificity. 28 Development  Naïve Lymphocytes Before lymphocytes Recognition Alarm encounter their specific Innate antigen they are called Inflammation Effector Fxn naïve lymphocytes. Secondary Innate cell Naïve lymphocytes transit between the circulatory Blood Lymphoid Recruitment Organs and lymphatic systems Naïve “looking” for their specific Lymphocytes antigen. Lymphocyte – Secondary lymphoid organs 29 Development  Lymph Recirculation Lymph Fluid (lymph) from the Recognition inflamed tissue is drained Lymphatics Alarm Innate via lymphatic vessels to Inflammation Effector Fxn secondary lymphoid organs. Secondary Innate cell Recruitment – Often lymph nodes Lymphoid Organs Lymph contains inflammatory signals, antigens, and migrating immune cells. – APC, see next slide 30  Antigen Presentation by APC APC Recognition Some APC pick up antigens in the tissue, migrate to Lymphatics Alarm Innate secondary lymphoid Inflammation Effector Fxn organs, and present them Secondary Innate cell to lymphocytes. Lymphoid Recruitment – Lymph nodes normally Organs Soluble antigens in the Lymphocytes “see” their antigen lymph can also be when it is presented to them by captured and presented. antigen presenting cells (APC). 31  Primary Immune Response APC APC + antigen – specific Recognition naïve lymphocyte: Alarm Innate Initiates the primary Inflammation Effector Fxn immune response Innate cell – Priming Secondary Lymphoid Recruitment Lymphocytes are activated, Organs proliferate, and are Primary Naïve programmed. Immune Effector Lymphocytes Response Differentiate into effector Memory or memory cells 32  Adaptive Effector Cells APC Effector cells include: Recognition CD4 T cells, “Helper” Alarm – Stimulate and tailor responses in Innate other cell types. Inflammation Effector Fxn CD8 T cells, “Cytotoxic” Innate cell – Kill infected or abnormal cells Secondary Recruitment – Think hand-to-hand combat Lymphoid Organs B cells, “Antibody” Primary – Antibodies have many functions Naïve Immune – Think projectile weapons Lymphocytes Response Effector CD4 Effector CD8 Effector B T cells T cells cells 33  Effector cells migrate into the tissues and perform APC immune functions. Recognition Alarm Innate T cell Ab Effector Inflammation Effector Fxn Cytotoxicity Fxns Secondary Innate cell Lymphoid Recruitment Antibodies Organs Effector CD8 Primary Naïve Effector CD4 T cells Effector B Immune Lymphocytes T cells cells Response 34  Adaptive Memory Cells DCs Recognition Memory cells enable Alarm rapid response following Innate re-exposure. Inflammation Effector Fxn Increased cell numbers Secondary Innate cell Recruitment Increased sensitivity Lymphoid Organs Does not require priming Primary Naïve Effector CD4 Effector CD8 Effector B Immune Lymphocytes T cells T cells cells Response Memory Memory T cells B cells 35  Secondary Immune Response APC Recognition Alarm Innate T cell Ab Effector Inflammation Effector Fxn Cytotoxicity Fxns Secondary Innate cell Lymphoid Recruitment Antibodies Organs Primary Naïve Effector CD4 Effector CD8 Effector B Immune Lymphocytes T cells T cells cells Response Memory Memory Memory 36 CD4 T cells CD8 T cells B cells  Immune-Induced Pathology APC Immune Recognition Pathology Alarm Innate T cell Ab Effector Inflammation Effector Fxn Cytotoxicity Fxns Secondary Innate cell Lymphoid Recruitment Antibodies Organs Primary Naïve Effector CD4 Effector CD8 Effector B Immune Lymphocytes T cells T cells cells Response Memory T and B cells 37  Immune Pathology Hypersensitivity Autoimmunity Reaction/overreaction to Reaction to self-antigens. innocuous stimuli. Breaking tolerance to self Sensitization followed by Sensitization followed by pathological pathological CD4/CD8 T cells & antibodies CD4/CD8 T cells & antibodies Allergy, asthma, poison ivy, etc. Lupus, type 1 diabetes, rheumatoid arthritis, etc. 38  Other Considerations Much of immune function relies on getting the right cells to the right place at the right time. This is orchestrated by various chemotactic signals and adhesion molecules. The presence or absence of specific immune cell types in tissues is diagnostic of specific diseases. Immune cell accumulation is an indicator of immune system activity. 39  Immune Response APC Immune Recognition Pathology Alarm Innate T cell Ab Effector Inflammation Effector Fxn Cytotoxicity Fxns Secondary Innate cell Lymphoid Recruitment Antibodies Organs Primary Naïve Effector CD4 Effector CD8 Effector B Immune Lymphocytes T cells T cells cells Response Lymphocyte Memory T and Development B cells 40 Future Immunology Lectures