Immune System Part 2 2024 PDF

DEFENSIVE STRATEGIES -2 Part 2: THE ADAPTIVE IMMUNE RESPONSE (Dr Tom Kelly) Dr Neil Coughlan ADAPTIVE IMMUNE RESPONSE ◼ VERY SPECIFIC RESPONSE WITH MEMORY ◼ Triggered into action by antigen presentation ◼ Antigen Presenting Cells (APC) ◼ Antigen + epitope i.e. ‘active par...

DEFENSIVE STRATEGIES -2 Part 2: THE ADAPTIVE IMMUNE RESPONSE (Dr Tom Kelly) Dr Neil Coughlan ADAPTIVE IMMUNE RESPONSE ◼ VERY SPECIFIC RESPONSE WITH MEMORY ◼ Triggered into action by antigen presentation ◼ Antigen Presenting Cells (APC) ◼ Antigen + epitope i.e. ‘active part’ ◼ Antibody ◼ MHC 1 and MHC 2 ◼ Vaccine ◼ Herd immunity ◼ Novel (emerging) pathogen + zoonosis Innate vs Adaptive Immunity https://www.youtube.com/watch?v=Dezs7HX6VPE&ab _channel=TangerineEducation Immune System: Innate and Adaptive Immunity Explained https://www.youtube.com/watch?v=PzunOgYHeyg&ab_ channel=ScienceABC Immune System, Part 1: Crash Course Anatomy & Physiology #45: https://www.youtube.com/watch?v=GIJK3dwCWCw&ab_ channel=CrashCourse Immune System, Part 2: Crash Course Anatomy & Physiology #46: https://www.youtube.com/watch?v=2DFN4IBZ3r I&ab_channel=CrashCourse Immune System, Part 3: Crash Course Anatomy & Physiology #47 https://www.youtube.com/watch?v=rd2cf5hVal M&ab_channel=CrashCourse  ADAPTIVE IMMUNE RESPONSE Myeloid cells give rise to red blood PLURIPOTENT STEM CELL IN cells, granulocytes, BONE MARROW- ‘LYMPHOID LINE’ monocytes, and platelets whereas HR = An lymphoid cells give antibody-mediated rise to lymphocytes response that and natural killer occurs when T CELL B CELL cells foreign material - antigens - are detected in the body. MATURES IN MATURES IN THYMUS GLAND BONE MARROW ORGANISES ADAPTIVE RESPONSE + CELLULAR HUMORAL RESPONSE RESPONSE  DEFINITIONS 1 ◼ ANTIGEN: A MOLECULE THAT REACTS WITH PREFORMED ANTIBODY AT THE SPECIFIC RECEPTORS ON T AND B CELLS. MOST ARE PROTEINS. INTRINSIC AND EXTRINSIC ◼ EPITOPE: THAT PORTION OF THE ANTIGEN WHICH COMBINES WITH THE ANTIBODY ◼ https://ib.bioninja.com.au/higher-level/topic-11-animal- physiology/111-antibody-production-and/immune-pathways.html More potent/powerful with repeated exposure  DEFINITIONS 2 ◼ ANTIBODY : A (soluble) MOLECULE PRODUCED BY ANIMALS IN RESPONSE TO ANTIGEN. ◼ It has the particular property of combining specifically with the antigen that induced its FORMATION (Roitt et al.). - Antibody-antigen complex ◼ HUMORAL RESPONSE ◼ PROTEINS ◼ IMMUNOGAMMAGLOBULINS Ig ◼ THERE ARE 5 CLASSES OF ANTIBODIES  DEFINITIONS 3 ◼ MHC = MAJOR HISTOCOMPATIBILITY COMPLEX ◼ TERM AROSE IN RELATION TO THE ABILITY TO ACCEPT TISSUE GRAFTS FROM AN UNRELATED DONOR AKA “TISSUE TYPING” ◼ SAME HAPLOTYPE (AT LEAST 100 GENES INVOLVVED) IF TISSUE TO BE ACCEPTED ◼ MHC 1 EXPRESSED WITH INTRINSIC ANTIGENS WHEREAS MHC 2 IS EXPRESSED WITH EXTRINSIC ANTIGEN ◼ MHC-1 associated with the CELLULAR RESPONSE ◼ MHC 2 associated with HUMORAL (soluble factor) RESPONSE ◼ ANTIGENS PRESENTED WITH MHC 1 OR 2 Figure 1-27 RESPONSE TO Intrinsic or Intra-cellular pathogens Tc=Cytotoxic T Cell has CD8+ marker RESPONSE to EXTRINSIC Or EXTRACELLULAR PATHOGEN Th Cell = Helper T Cell has CD4+ marker  ADAPTIVE RESPONSE -CELLS ◼ LYMPHOCYTES-DERIVED FROM LYMPHOID LINE (myeloid line innate immune) ◼ T AND B CELLS ◼ T RECEIVES ‘IDENTIY’ IN THYMUS ◼ B RECEIVES ‘IDENTIY’ IN BONE MARROW ◼ T HELPER CELL ORGANISES BOTH CELLULAR (CYTOTOXIC T LYMPHOCYTES) AND HUMORAL RESPONSE – THE LATTER VIA B CELLS  T CELLS ◼ THYMUS DERIVED ◼ TWO BASIC TYPES ◼ T HELPER CELLS Th CELLS CD4+ MARKER ◼ T CYTOLYTIC OR T CYTOTOXIC CELLS (Tc) CTL’S CD8+ MARKER ◼ T HELPER CELL MASTER OF ADAPTIVE RESPONSE (but attacked by Human Immunodeficiency Virus: HIV)  B CELLS ◼ PRODUCED IN BONE MARROW ◼ MATURE IN BONE MARROW ◼ B CELLS PRODUCE HUMORAL RESPONSE ◼ PLASMA CELLS (EFFECTOR CELLS) AND MEMORY CELLS ◼ PLASMA CELLS PRODUCE ANTIBODIES ◼ SHORT LIFE SPAN APOPTOSIS (programmed cell death) ◼ MEMORY CELLS SURVIVE FOR A LONG TIME AS PART OF CLONE Disulfide bonds  ADAPTIVE RESPONSE: SOLUBLE FACTORS- ANTIBODY ◼ FLEXIBLE ADAPTOR ◼ Y SHAPED ◼ TWO INNER HEAVY CHAINS ◼ TWO OUTER LIGHT CHAINS ◼ HYPERVARIABLE “HOT SPOTS” VH AND VL ◼ FAB RECEPTOR BINDS TO ANTIGEN ◼ CONSTANT REGIONS ◼ FC RECEPTOR RECOGNIZED BY AND PHAGOCYTOSED NEUTROPHILS AND MACROPHAGES  ANTIBODY TYPES ◼ IgG monomer (1) classical Y shape; main antibody in secondary immune response ◼ IgM pentamer (5); primary immune response against blood inhabiting extrinsic microbes ◼ IgA dimer (2); secondary immune response Opsoniser ◼ IgD monomer (1); function poorly understood ◼ IgE monomer (1); associated with the allergic response Figure 1-20  Figure 1-3 Active and passive immunity. Active immunity is conferred by a host response to a microbe or microbial antigen, whereas passive immunity is conferred by adoptive transfer of antibodies or T lymphocytes specific for the microbe. Both forms of immunity provide resistance to infection (immunity) and are specific for microbial antigens, but only active immune responses generate immunologic memory. Add or remove the image from My Slides  SNAKE ANTI-VENOMS ◼ Snake venom 95% Protein – polypeptide ◼ Anti-venom is antibodies -immunoglobulins ‘raised’ in horses against the antigenic venom ◼ Passive immunity – serum containing the raised antibodies inoculated into snake bite victim ◼ Some anti-venoms are POLYVALENT and will neutralize toxic venoms of several species ◼ Others are MONOVALENT and only neutralize venom of one species ◼ But NO MEMORY following recovery  OTHER ASPECTS OF IMMUNITY ◼ Vaccine ◼ Herd Immunity ◼ Epidemiology ◼ SIR models ◼ “Chain reaction-type transmission” ◼ Novel pathogen ◼ R zero ◼ Allergy  VACCINE 1 ◼ FIRST DEVELOPED BY EDWARD JENNER –PUBLISHED 1798 ◼ COWPOX RECOVERY PROTECTED AGAINST SMALL POX ◼ GAVE COWPOX AND SHOWED PROTECTED AGAINST SMALL POX ◼ LATIN VACCINUS = “OF OR FROM COWS” JENNER  VACCINE 2 ◼ VACCINE IS A PREPARATION OF MICROBIAL ANTIGEN (DEAD OR ALIVE OR AVIRULENT) ◼ ADMINISTERED TO PATIENT TO GIVE PROTECTION AGAINST THAT MICROBE ◼ PASTUER – rabies, cholera ◼ SALK - 1950/60s Polio  EPIDEMICS-1 ◼ PREVALENCE ◼ BURDEN –INTENSITY ◼ EPIDEMIC ◼ PANDEMIC ◼ ENDEMIC ◼ HYPERENDEMIC ◼ SUSCEPTIBLE HOST  EPIDEMICS-2 ◼ EPIDEMIC = SUDDEN INCREASE IN PREVALENCE ◼ PREVALENCE = % OF POPULATION INFECTED ◼ SEVERITY OF EPIDEMIC RELATED TO: R0 ; LETHALITY (AGE RELATED?); HERD IMMUNITY; NUMBER AND DENSITY OF SUSCEPTIBLE HOSTS  EPIDEMICS -3 ◼ PANDEMIC= EPIDEMIC OCCURRING OVER A VERY WIDE AREA, CROSSING INTERNATIONAL BOUNDARIES I.E. ON A CONTINENTAL, HEMISPHERIC OR GLOBAL SCALE ◼ ENDEMIC=THE CONSTANT PRESENCE OF A DISEASE WITHIN A SPECIFIED GEOGRAPHICAL AREA (LOW PREVALENCE) ◼ HYPERENDEMIC = CONSTANT DISEASE PRESENCE BUT AT VERY HIGH PREVALENCE AND IN ALL AGE GROUPS  TRANSMISSION ◼ R ZERO (R0) ◼ HERD IMMUNITY ◼ LETHALITY ◼ BIO-WARFARE ◼ VECTOR BORNE – VERY HIGH R0 ◼ SYLVATIC CYCLES ◼ RURAL, DOMESTIC AND URBAN CYCLES  NOVEL PATHOGEN ◼ Pathogen entering population-community which has no herd immunity i.e. adaptive immunity to that specific pathogen. HUGE CONCERN ◼ May arise through accidental importation ◼ Mutation producing a new ‘strain’ e.g. Influenza ◼ ‘Spanish flu’ 1918 ◼ Wuhan Covid-19? ◼ West Nile Fever virus USA 1999  HERD IMMUNITY-1 INFECTIOUS HOST IMMUNE HOST SUSCEPTIBLE HOST HERD IMMUNITY AND R0 R0= THE REPRODUCTIVE RATE OF THE PATHOGEN=NUMBER OF NEW HOSTS INFECTED BY AN INFECTIOUS HOST IN A POPULATION THAT IS 100% SUSCEPTIBLE  R0 of well known Pathogens Modified from Anderson and May (1992) INFECTIOUS Diseases of Humans OUP ◼ Measles =5 to 18 ◼ Influenza =2 to 4 ◼ Covid – 19 =4 to 8? ◼ Chicken Pox = 7 to 11 ◼ Mumps = 11to 14 ◼ Polio = 5 to 7 ◼ HIV =2 to 5 Homosexual ◼ HIV = 10 to 11 Heterosexual From Ferguson et al. 2003 Planning for smallpox outbreaks Nature 425: 681- 685 Source = Ferguson et al. 2003  LETHALITY ◼ REFERS TO MORTALITY RATHER THAN MORBIDITY - Infection Fatality Rate: ◼ PER CENT OF INFECTED CASES THAT DIE ◼ SARS-1 = 10% ◼ SARS-CoV-2 (Covid -19) = 1.4% ◼ RABIES = 100% UNLESS VACCINATED IN TIME ◼ H5N1 ? H1N1 ?  ZOONOSES ◼ VERY IMPORTANT CATEGORY OF DISEASES ◼ MAJOR FOCUS NOW IN VIEW OF SO CALLED EMERGING INFECTIOUS DISEASES EIDs e.g. COVID-19 ◼ MANY OF THESE ARE ZOONOSES ◼ MANY RESIDE IN WHAT ARE TERMED SYLVATIC OR ‘SILENT FOCI’  ZOONOSIS-1 Micro- or macro-parasite transmissible between a vertebrate animal to man So, any pathogen transmitted from fish, amphibian, reptile, bird or mammal to man is a zoonosis (plural = zoonoses) Mosquito transmitted pathogens may or may not be a zoonosis e.g. ‘human’ malaria is ‘not’, but yellow fever is.  ZOONOSIS-2 FOOT AND MOUTH VIRUS (FMD) – ‘mostly’ - MYXOMATOSIS, BLUE TONGUE VIRUS AND SMALLPOX VIRUS – NOT ZOONOSES INFLUENZA-A, RABIES, HIV, BUBONIC PLAGUE, SARS 1 , SARS 2 = Covid-19, LYME DISEASE AND BOVINE TB ARE ALL (MICROPATHOGEN) ZOONOSES MACROPARASITE ZOONOSES INCLUDE LIVER FLUKE, TRICHINOSIS, ANISAKIASIS, BEEF TAPEWORM ETC. ALL ARE REFERRED TO AS ZOONOTIC DISEASES  ZOONOSES RABIES VIRUS TICKS Lyme Disease VECTORS WHITE TAILED DEER HOST OF TICKS AND LYME DISEASE in THE USA