BI105 Fall 2024 Pathogens and Immunity PDF

SCHEDULE Note that this is now a case study (it’ll be part lecture, part case study) PATHOGENS AND DISEASE DISEASE-C AUSING BIOLOGIC AL AGENTS ARE C ALLED PATHOGENS Can include: Viruses Bacteria Eukaryotic pathogens such as fungi or an...

SCHEDULE Note that this is now a case study (it’ll be part lecture, part case study) PATHOGENS AND DISEASE DISEASE-C AUSING BIOLOGIC AL AGENTS ARE C ALLED PATHOGENS Can include: Viruses Bacteria Eukaryotic pathogens such as fungi or animals (uni- or multicellular) – these are often referred to as parasites. Some pathogens always cause disease, while others may do so only at certain times or under certain conditions.  DISEASE SYMPTOMS ARE C AUSED BY EITHER: Cell death and tissue damage caused by pathogens directly; Toxins that pathogens secrete into the host; or The action of the host’s own immune system (e.g. fever). Some of these symptoms, while unpleasant or even dangerous, are likely to be adaptive responses to clearing the pathogen from the body.  EXAMPLE: THE DISEASE CHOLERA IS C AUSED BY THE ACTION OF CHOLERA TOXIN ON YOUR GUT CELLS VIRUSES  VIRUSES ARE NONLIVING PARTICLES WITH NUCLEIC ACID GENOMES THAT MUST HIJACK LIVING CELLS TO REPLIC ATE Defining feature – viruses do not contain the machinery needed to grow/reproduce on their own. Consist of nucleic acid genomes (either RNA or DNA) enclosed in a protein coat called a capsid. Vary greatly in their characteristics, including their host range, structure, and genome composition.  STEPS OF VIRAL REPRODUCTION 1. Attachment 2. Entry 3. Integration 4. Synthesis of viral components 5. Viral assembly 6. Release  VIRAL LIFE CYCLES - HIV Attachment & entry: Proteins on the exterior of the Integration: Most viruses incorporate their genomes into viral capsid/envelope bind to molecules on the host the genome of the host cell at least temporarily. In cell membrane, trigger reactions that internalize the retroviruses the viral genome is RNA it must first be whole virus or its genome into the host cell. reverse-transcribed into DNA  VIRAL LIFE CYCLES - HIV Synthesis and assembly: Viral genes are Release: mature viruses leave the cell, may take a expressed by the cell, viral genome is replicated, piece of the cell membrane with them as the viral and new viruses are assembled inside the cell envelope or may simply burst (lyse) the cell open TOPHAT QUESTION IMMUNE SYSTEM  IM M U N IT Y I S T H E A BI LI T Y O F A N O R GA NISM TO WA R D O FF IN T ER N A L T H R EAT S SUCH A S M ICRO BES, M I CRO BI A L TOXI N S, O R C A N CE RO US CE LLS Immune system – cells and organs in an animal’s body that contribute to these defenses. The core principle of immune function is self vs. non-self: immune cells can recognize foreign cells/molecules and treat them differently than cells belonging to the organism.  T WO T Y P E S O F I M M UN E R E SP O N SE S: IN N AT E A ND ACQ U IRE D Some immune cells just respond to conserved features found on most pathogen cells. Innate (aka nonspecific) immunity –present at birth and functions the same way regardless of pathogen. Some immune cells ”learn” the characteristics of a specific pathogen they are exposed to. Acquired (aka specific) immunity – develops after exposure to a specific pathogen and targets it specifically. INFLAMMATION IS A MAJOR COMPONENT OF HUMAN INNATE IMMUNITY In response to injury and/or pathogens, innate immune cells release paracrine signaling molecules such as cytokines and histamine that trigger inflammation INFLAMMATION IS A MAJOR COMPONENT OF HUMAN INNATE IMMUNITY Inflammation allows more phagocytes to access the damaged tissue along with other immune molecules like antibodies ACQUIRED IMMUNITY  ACQUIRED IMMUNITY REQUIRES EXPOSURE TO FOREIGN SUBSTANCES AND MUST DEVELOP IN AN ORGANISM Acquired immune responses are always induced by specific foreign molecules (antigens) that the organism has encountered during its life. It is mostly mediated by a specific class of leukocytes (white blood cells) called lymphocytes. Most important are B cells and T cells. ACQ UIR ED IM M UN IT Y IN VO LV ES SECR ET IO N O F IM M UN E CH E M I C A LS BY LY M P H O CY T E S ( HU M O RA L IM M U N IT Y) A ND DIR ECT ACT IO N O F LY M P H O CY T ES CELLS ( CE LL- M E DIATE D IM M U NITY) In humoral immunity, B cells recognize a specific antigen, differentiate, and secrete specialized proteins that target that antigen (antibodies) Antibodies then circulate through the blood and inactivate pathogens/toxins and/or mark them for destruction by other cells Helper T cells are involved in activating the B cell response  ACQ UIR ED IM M UN IT Y IN VO LV ES SECR ET IO N O F IM M UN E CH E M I C A LS BY LY M P H O CY T E S ( HU M O RA L IM M U N IT Y) A ND DIR ECT ACT IO N O F LY M P H O CY T ES CELLS ( CE LL- M E DIATE D IM M U NITY) In cell-mediated immunity, cytotoxic T cells that recognize specific antigens are activated and then attack antigen-bearing cells directly Helper T cells are also involved in activating the T cell response AC Q U I R E D I M M U N I T Y I N VO LV E S S E C R E T I O N O F I M M U N E C H E M I C A L S B Y LY M P H O C Y T E S ( H U M O R A L I M M U N I T Y ) A N D D I R E C T AC T I O N O F LY M P H O C Y T E S C E L L S ( C E L L - M E D I AT E D I M M U N I T Y ) In both types of acquired immunity, memory cells retain information that can be used to more quickly attack this particular antigen in the future THE ANTIBODIES PRODUCED BY DIFFERENT B CELL LINEAGES ARE DIFFERENT PROTEINS DUE TO DIFFERENCES IN THEIR VARIABLE REGIONS Each B cell can express one of several hundred antibody genes The DNA sequences of those genes are also altered Diversity of T cell receptors is during development of each B cell (analogous to generated in a similar way somatic mutations) to increase diversity even further – millions of possible antibody structures  M E M O RY CE LLS E N A BLE ST RO N G, R A P I D S E CO NDA RY IM M U N E RE S P O N S E S TO PAT H O GE N S T H AT H AV E BE E N E N CO UN T E R E D BE FO R E antibody in blood (arbitrary units) 10,000 Secondary A immune Relative amount of specific response 1,000 Primary immune 100 response A B 10 1 0 1 2 3 4 5 0 1 2 3 4 5 Acquired immunity Weeks after first Interval Weeks after second takes days to develop exposure to antigen A (weeks, exposure to antigen initially – innate immunity highly months, A or first exposure important at this stage even to antigen B years)  M E M O RY CE LLS E N A BLE ST RO N G, R A P I D S E CO NDA RY IM M U N E RE S P O N S E S TO PAT H O GE N S T H AT H AV E BE E N E N CO UN T E R E D BE FO R E antibody in blood (arbitrary units) 10,000 Secondary A immune Relative amount of specific response 1,000 Primary immune 100 response A B 10 1 0 1 2 3 4 5 0 1 2 3 4 5 Acquired immunity Weeks after first Interval Weeks after second takes days to develop exposure to antigen A (weeks, exposure to antigen initially – innate immunity highly months, A or first exposure important at this stage even to antigen B years) QUESTIONS?