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aware of a practice, called variolation or inoculation, and introduced it to Britain after first having her own children treated. 1798 Edward Jenner noticed immunity bestowed to milkmaids injected fluid from cowpox blister into skin of patient (orphan or prisoner) 1989- WHO announced smallpox was eradicated from the world
www.longwood.edu/staff/buckalewdw/Immlec/
Louie Louie
Louis Pasteur
1879- discovered that old bacterial cultures of Pasteurella lost virulence. Referred to injection of weakened culture a vaccine in honor of Jenner 1881- He applied the same technique vs. anthrax .and then rabies
Pasteur inoculating sheep at Msr. Rossignols farm May, 1881
www.longwood.edu/staff/buckalewdw/Immlec/
S. Kitasato
1880s- Metchnikoff discovered phagocytic cells that ingest microbes and particles cells conferred immunity
1890- von Behring and Kitasato discovered blood sera could transfer immunity liquid of blood conferred
immunity
www.longwood.edu/staff/buckalewdw/Immlec/
Elie Metchnikoff
IMMUNITY
Mechanisms used by the body as protection against agents that are foreign to the body Discrimination between self and nonself
DEFINITIONS
Antigen Any material (usually foreign) that elicits and/or is specifically bound by an antibody Pathogen Any disease causing micro-organism.
DEFINITION
Antibody A protein that interacts with a particular site (epitope) on an antigen and facilitates clearance of that antigen by various mechanisms (immunoglobulin)
DEFINITIONS
Tolerance Non-reactivity of the immune system, usually refers to "self" but may include foreign tissue in organ transplants. Autoimmunity A failure of tolerance, the immune system reacts to self.
DEFINITION
Cytokines Signaling molecules released by cells involved in innate and acquired immune response Regulate innate and acquired immune response Stimulate hematopoiesis
eg.,interferons, interleukins
TYPES OF IMMUNITY
Innate immune mechanisms Acquired immune mechanisms
INNATE IMMUNITY
Protection conferred by mechanisms that are inborn in the individual
External
Physical barriers: skin, mucus membranes Chemical barriers: pH of secretions
Internal
Phagocytes, interferon, fever
ACQUIRED IMMUNITY
Protective mechanisms that are specific against invading agents
INNATE IMMUNITY
Non-specific defense mechanisms Does not recognize every possible antigen The initial response against microbes and prevention of infection
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
INNATE IMMUNITY
Anatomical barriers
Skin
Dry, acidic T<37oC Exfoliation
Mucus membrane
Mucus secretion traps microbes Lysozymes, lactoferrin & lactoperoxidase Secretory IgA
INNATE IMMUNITY
Mechanical removal
Mucus & cilia: airways Cough & sneeze Vomiting & diarrhea Flushing by body fluids (urine, tears, saliva, perspiration)
INNATE IMMUNITY
Normal bacterial flora
Metabolic products Adhering to target host cells Depleting nutrients Clinical: opportunistic infection
INNATE IMMUNITY
Phagocytosis
Monocyte-macrophage Neutrophils Chemical mediators from basophils, mast cells, eosinophils
GRANULAR LEUKOCYTES
Eosinophil
Neutrophil Basophil
www.apsu.edu/pittsg/2020/Chapter%2017%20-%20Blood.ppt
AGRANULAR LEUKOCYTES
Lymphocyte
Monocyte
www.apsu.edu/pittsg/2020/Chapter%2017%20-%20Blood.ppt
NEUTROPHILS
Light blue granules in acid-base stain Lobed nucleus Phagocytic 54% - 62% of leukocyte Elevated in bacterial infections
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis
14-13
BASOPHILS
Deep blue granules is basic stain Release histamine Release heparin Less than 1% of leukocytes
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis
14-14
EOSINOPHILS
Deep red granules in acid stain Bilobed nucleus Moderate allergic reactions 1% - 3% of leukocytes Elevated in worm infestations and allergic reactions
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis
14-15
MONOCYTES
Largest blood cell Kidney-shaped or oval nuclei Leave bloodstream to become macrophages 3% - 9% of leukocytes Elevated in typhoid fever, malaria, tuberculosis
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis
14-16
LYMPHOCYTES
About the size of RBC Large spherical nuclei Thin rims of cytoplasm
(T cells & B cells)
Holes Human Anatomy and Physiology Tenth Edition Shier w Butler w Lewis
14-17
MAST CELLS
Found in almost all tissues and organs Derived from bone marrow cells Contain heparin, histamine & proteases Involved in allergy and anaphylactic reactions
IMMUNOBIOLOGY at http://www.ncbi.nlm.nih.gov/books/
Chemotaxis
Purposive migration towards injury in response to chemotaxins
Phagocytosis
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
Margination
Pavementing
Diapedesis
http://medweb.bham.ac.uk/http/mod/3/1/a/acute.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
INFLAMMATORY REACTION
1. Vasodilation leading to excess local blood flow 2. Increased permeability of capillary 3. Clotting of extravasated fluid in the interstitium 4. Migration of neutrophils and monocytes from blood vessels into tissue 5. Swelling
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
DEFINITION
Chemokines Soluble proteins secreted by cells that promote inflammation by enhancing leukocyte activation
i.e., margination, diapedesis & chemotaxis
INFLAMMATION
Chemical Mediators
Lysosomal compounds (proteases) Histamine Prostaglandins
Cyclo-oxygenase pathway of arachidonic acid metabolism Anti-inflammatory drugs: aspirin & COX-2 inhibitors
Leukotrienes
Lipo-oxygenase pathway
INFLAMMATION
Redness (rubor) Heat (calor) Swelling (tumor) Pain (dolor) Loss of function
INNATE IMMUNITY
Designed to recognize a few highly conserved structures present in many different microorganisms
Viruses
double-stranded RNA (dsRNA) and
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
Flare
Wheal
WBC Counts
WBCs in peripheral circulation Leukocytosis
5,000 10,000 per cubic millimeter
High WBC count acute infections, vigorous exercise, dehydration Low WBC count Typhoid fever, flu, measles, mumps, chicken pox, AIDS
Leukopenia
COMPLEMENT
A group of cytotoxic serum proteins involved in the mediation of immune responses.
COMPLEMENT
Activated by Antigen-antibody complexes
classical pathway
COMPLEMENT
Actions
Lysis of microorganisms or infected cells Opsonization
Enhance phagocytosis by attaching to antigen
Chemotaxis
Attract phagocytes to infection
COMPLEMENT ACTIVATION
www.utmem.edu/obgyn/res_pres/ faculty_pres/ImmunologyMicrobiology_Thorpe.pdf -
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
COMPLEMENT ACTIVATION
C3a C5a
Vascular Stimulate permeability release histamine Activation of cells from mast phagocytes (inflammation &
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
FEVER
Tissue Necrosis Factor-alpha, TNF- & Interleukin-1, IL-1
Produced by activated macrophage & leukocytes Act on anterior hypothalamus
FEVER
FUNCTIONS
Alters temperature vs. microbial growth Enhance secretion of inflammatory proteins in immune cells
Heat shock proteins, hsp
INTERFERON
Source: http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/if.html
ACQUIRED IMMUNITY
2 TYPES Cellular Immunity Humoral Immunity
ACQUIRED IMMUNITY
Cellular immunity
Cell-mediated immunity Immune response mediated T lymphocytes, including macrophages
Humoral Immunity
Antibody-mediated immunity Immune response mediated by Blymphocytes & plasma cells
ACQUIRED IMMUNITY
PLASMA CELLS
DIFFERENTIATE FROM B LYMPHOCYTES DURING IMMUNE RESPONSES SECRETE ANTIBODIES
Antigenbinding site
V
Disulfide bridge
Light chain
C
C C
V V C C
Plasma chain Heavy chains membrane chain Disulfide bridge T cell B cell Cytoplasm of B cell Cytoplasm of T cell (a) A B cell receptor consists of two identical heavy (b) A T cell receptor consists of one chains and two identical light chains linked by chain and one chain linked by several disulfide bridges. a disulfide bridge.
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
TYPES OF IMMUNITY
Natural active immunity
Immunization is a natural outcome of infection
TYPES OF IMMUNITY
Artificial passive immunity
Individuals receive antibodies that play no role in the antibody production process used to cure a person suffering from a disease
CHEMICAL COMPLEXITY
A CERTAIN DEGREE OF PHYSICOCHEMICAL COMPLEXITY
ANTIGENICITY
ANTIGENIC DETERMINANT or EPITOPE
PORTION OF AN ANTIGEN THAT BINDS SPECIFICALLY WITH THE BINDING SITE OF AN ANTIBODY OR A RECEPTOR ON A LYMPHOCYTE
http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/innate/epsig.html
HUMORAL IMMUNITY
MEDIATED BY SERUM ANTIBODIES SECRETED BY B CELLS
ACTIVATION OF B CELLS
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
HUMORAL IMMUNITY
Antigen presenting cells contacts and activates helper T cells Cytokines (protein signals) released B and T cells activated
B cell
2
TCR
CD4 Cytokines
Helper T cell
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
HUMORAL IMMUNITY
B cells divide (clones)
B-cells release antibody (Plasma cells) Memory cells formed
ANTIBODY STRUCTURE
4 CHAINS
2H, 2L CHAINS
REGIONS
VARIABLE & CONSTANT
FRAGMENTS
Fab
ANTIGEN BINDING
Fc
BIOLOGICAL FUNCTIONS
http://www.biology.eku.edu/RITCHISO/301notes4.htm
ANTIBODY STRUCTURE
HEAVY CHAINS, H CHAINS
2 H CHAINS 5 ISOTYPES
IgM IgG IgA IgD IgE
HEAVY CHAIN
ANTIBODY STRUCTURE
LIGHT CHAINS, L CHAINS
2 L CHAINS 2 MAJOR CLASSES
KAPPA, LAMBDA,
IMMUNOGLOBULINS
IgG
PREDOMINANT IMMUNOGLOBULIN STRUCTURE
2 H CHAINS 2 L CHAINS (EITHER OR )
IMMUNOGLOBULINS
IgG
REPRESENT 15% OF TOTAL PROTEIN HALF-LIFE: 23 DAYS (LONGEST OF Igs) ONLY SUBCLASS THAT CAN PASS THROUGH PLACENTA OPSONIN
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/nk/nknomhc.html
IMMUNOGLOBULINS
IgG
ROLE IN ANTIBODY-DEPENDENT, CELLMEDIATED CYTOTOXICITY, ADCC ACTIVATION OF COMPLEMENT SYSTEM NEUTRALIZATION OF TOXIN IMMOBILIZATION OF BACTERIA NEUTRALIZATION OF VIRUSES
IMMUNOGLOBULINS
IgM
CONSIST OF 5 Ig UNITS, PENTAMERIC DOES NOT CROSS THE PLACENTA
SYNTHESIZED BY THE FETUS
ELEVATION INDICATES INFECTION ANTIBODIES FOR RBC ANTIGENS ACTIVATES COMPLEMENT SYSTEM
IMMUNOGLOBULINS
IgA
FOUND IN SECRETIONS, eg., SALIVA, TEARS, SWEAT, MUCUS COLOSTRUM, INITIAL MILK IN MATERNAL LACTATION DIMERIC FORM IN BODY SECRETIONS ROLE IN MUCOSAL INFECTIONS DOES NOT ACTIVATE COMPLEMENT BACTERICIDAL vs. GRAM NEGATIVE BACTERIA
IMMUNOGLOBULINS
IgE
HAS SHORTEST HALF-LIFE, 2 DAYS LOWEST SERUM LEVELS Fc PORTION BINDS TO MAST CELLS AND BASOPHILS DOES NOT ACTIVATE COMPLEMENT ELEVATED IN PARASITIC INFECTIONS MEDIATES HYPERSENSITIVITY RXNS
IMMUNOGLOBULINS
IgD
PRESENT ON SURFACE OF B LYMPHOCYTES
ROLE IN B CELL MATURATION ANTIGEN RECOGNITION BY B CELLS
DEFINITION
Class switching
Process by which a B lymphocyte producing IgM and IgD switches to production of secondary immunoglobulin class (IgE, IgA or IgG), with the same antigen binding specificity
CELLULAR IMMUNITY
ANTIGEN-SPECIFIC ARM OF CELLMEDIATED IMMUNITY CONSISTS OF THE T LYMPHOCYTES
CELLULAR IMMUNITY
T CELLS- CELL MEDIATED IMMUNITY
CYTOTOXIC T CELLS, CTL CELLS OR CD8 CELLS HELPER T CELLS, TH CELLS OR CD4 CELLS SUPPRESSOR T CELLS MEMORY T CELLS
www.utmem.edu/obgyn/res_pres/ faculty_pres/ImmunologyMicrobiology_Thorpe.pdf -
CD8 molecule
http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/innate/mhc1t8.html
ACTIVATION OF CTL-CELL
1 A specific cytotoxic T cell binds to a 2 class I MHCantigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. Cytotoxic T cell Perforin The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. 3 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.
Target cell
Peptide antigen
Cytotoxic T cell
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
CELLULAR IMMUNITY
Cytotoxic T cells recognize infected self cells Bind to cell and initiate apoptosis (process of cell self-destruction)
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/intro/bcell/bcellt4.html
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
biology.umt.edu/biol103/lecturenotes/ Driver/Driver%20spring%2005/Biol%20103%20Chap%
T CELLS
vs. VIRAL INFECTIONS DEFICIENCY:
DIGEORGES SYNDROME
Autoimmune Disease
Loss of tolerance to self-antigens Mechanisms
Destruction of cell or tissue barriers
eg. sympathetic opthalmia
Molecular mimicry
eg. rheumatic fever, diabetes, ms
IL1
TCR HELPER T CELL CD4 ACTIVATE B-CELLS Igs
IMMUNOBIOLOGY at http://www.ncbi.nlm.nih.gov/books/
The nude mouse has a defect in its immune system, and can only live if protected from pathogens. The mouse has a transplant of rabbit skin, and can't reject the foreign tissue. Mice with immune deficiencies are very useful in cancer research because human cancer cells can grow into tumors allowing new ways to test cancer therapy.
http://www.biology.arizona.edu/immunology/tutorials/immunology/intro.html
References
GANONG, W: REV of MEDICAL PHYSIOLOGY, 22nd ed, Chapter 27 GUYTON & HALL. MEDICAL PHYSIOLOGY, 10th ed, Chapters 33 & 34 LODISH etal: MOLECULAR CELL BIOLOGY, 3rd ed, Chapter 27 VANDER, SHERMAN & LUCIANO. HUMAN PHYSIOLOGY, 6th ed, Chapter 20