|
|
|
|
|
|
Virology Virology - Introduction Viruses are obligate intracellular parasites Viruses are considered nonliving because they cannot reproduce on
their own Viruses contain DNA or RNA either of which is double or single
stranded Refers to range of tissue virus can infect Most viruses can only infect a specific type of
tissue within a host Host range is determined by receptors found on found
on tissue cell surfaces Viral Size Determined by electron microscopy; viruses cannot be
seen under light microscope Viruses range from 20 to 10000 nm Virology - Structure A viron is a complete fully developed
particle composed of nucleic acid and surrounded by a protein coat Nucleic acid Capsid
and Envelope Nucleic Acid Double stranded DNA Single stranded DNA Double stranded RNA Single stranded RNA Nucleic acid can be 1% to 50% of weight of virus particle Capsid
and Envelope The protein coat surrounding the nucleic acid is a capsid Capsid is composed subunits called capsomeres Capsid of some viruses is enclosed by an envelope
consisting of lipids, proteins & carbohydrates Some envelopes are covered with carbohydrate-protein
complexes called spikes Virology - Structure Virology - Phage Replication Phases Attachment Penetration Biosynthesis Maturation Release Lysogeny Virology - Phage Replication Attachment - bacteriophage attaches to cell
wall Penetration - phage makes opening in cell and injects DNA Biosynthesis - phage DNA directs synthesis of viral protein &
nucleic acid Maturation - Viral components are assembled into virions Release - Host cell lyses and virions are
released into surrounding medium Lysogeny
- Instead of biosynthesis, maturation & release, nucleic acid is
integrated into genome becoming a prophage Virology - Replication Animal
Viruses Attachment - uses receptors on cell surfaces often
using “spikes” on virus Penetration - whole virus enters cell via endocytosis; enveloped viruses can fuse with cell
membrane Uncoating - Virus capsid is removed
Biosynthesis - early & late transcription produce
virus enzymes, viral nucleic acid & capsid
proteins, respectively Maturation - virus particles are assembled Release - Virus particles are exported Virology – Replication RNA
containing viruses produce reverse transcriptase to make complimentary DNA DNA then directs synthesis of viral components Virology - Survey Human Viruses Viruses are grouped by families
(See table in Text) Similar DNA sequences & structure Virology - Cancer Cancer causing viruses first identified in chickens Cancer causing viruses use genes derived originally from host Cancer causing process is called tranformation Virology - Cancer Cancer causing viruses in humans Epstein-Barr virus (a herpes like virsus and Burkitt’s lymphoma
(a relatively rare cancer in children in Herpes virus associated with cervical cancer Human papilloma virus
causes genital warts but can also cause cervical cancer (some strains) Nature of Disease Introduction - Definitions Normal Bacteria & Host Koch’s Postulates Patterns of Disease Spread of Infection Nosocomial
Infections Disease - Introduction Pathogens - disease causing with special properties that permit host
invasion Disease - when microorganism overcomes host defenses; an abnormal
physiological state Pathology - the study of disease Etiology - the cause of disease Infection - invasion & growth of pathogen in host Pathogenesis - development of disease Disease - Normal Bacteria Animals - germ free in utero but are
colonized almost immediately after birth Different bacteria are normally associated with different parts of
body Transients - microorganisms that may occasionally be found associated
with the host Disease - Normal Bacteria Skin S. epidermidis/S. aureus Gastrointestinal Tract Gram negative bacteria (large intestine) S. mutans (mouth) Genito-Urinary
Tract Lactobacillus Antagonism - normal bacteria prevent growth of others Bacteria and host have symbiotic relationship (living together) Three types of symbiosis Commensalism (one benefits) Mutalism (both benefit) Parasitism (one benefits & other harmed) Opportunistic - do not cause disease normally Disease - Koch’s Postulates Etiology or cause established using Koch’s postulates same pathogen present in every instance of disease pathogen isolated in pure culture isolated pathogen causes disease when reintroduced
into a healthy host pathogen re-isolated from the now diseased host Disease - Patterns Predisposing factors make hosts more susceptible & include: age gender climate level of fatigue nutrition Disease - Patterns - Development Incubation period - time between infection & first signs Prodromal
period - first mild signs Illness period - period when all symptoms are present Decline period Convalescence period Disease - Spread of Infection Reservoirs of Infection a continuing source of infection Reservoirs include: Human - people who have disease or are carriers
(infected but no symptoms) Zoonoses - wild or domestic animals that transmit disease to
humans Nonliving - soil & water Disease - Spread of Infection Transmission Direct contact Fomites - inanimate objects Droplet - saliva, mucus coughing or sneezing Medium - food, water air Airborne - carried > 1 meter Arthropod - insect vectors Disease - Nosocomial
Infection Acquired during
hospitalization or a stay in other health care facilities Occurs at 5-15% Can be normal organisms
introduced into wrong part of body during invasive procedures Opportunitic
drug resistant G-, e.g. Pseudomonas Compromised host burns wounds immune suppressed (disease or drugs) Chain of Transmission Direct contact Fomites Control Aseptic techniques Proper cleaning storage Maintenance Properly trained staff Problems Multiple drug resistance Nonuse of effective cleaning agents Training of staff Mechanisms of Pathogenicity Introduction Entering the Host Penetrating Host Defenses Damaging Host Cells Pathogenicity - Introduction Pathogenicity is the ability of a pathogen to produce disease by overcoming host
defenses Virulence is the degree of pathogenicity Expressed as LD50 (lethal dose necessary to kill 50%
of the inoculated hosts) ID50 is also used (dose necessary to infect 50% of
the inoculated hosts) Pathogenicity – Entering Host Route of entry is called Portal of Entry Usual portals include mucous membranes Conjunctiva (eyes) Respiratory tract Gastrointestinal tract Genitourinary tract Respiratory most common Microorganisms are inhaled on moisture droplets or
dust particles Genitourinary through mucous membranes and direct contact Gastrointestinal through food water and contaminated fingers Pathogenicity – Entering Host Most microorganisms cannot penetrate skin but can gain access through
hair follicles and sweat ducts Can gain entry through inoculation also called parenteral insect bites injections wounds Penetrating Host Defenses Bacterial Elements that Overcome Host Defenses Capsules Cell Wall Components Enzymes Cytoskeletal Components Capsules Prevent or reduce phagocytosis Usually polysaccharide Examples Dextran
(S. mutans) Polyglutamic acid (B. anthracsis) Penetrating Host Defenses Cell Wall Components Adhesins (adhere to complementary receptors on host cells Fimbriae – interact with membrane glycoproteins
especially mannose Some microbes reproduce only in host cells Enzymes Leukocidins – destroy white blood cells Hemolysins – destroy red blood cells Kinases – digest blood clots Hyaluronidase – digests mucopolysccharides Collogenase – destroy collogen of
connective tissue Via Cell Cytoskeleton Invasins Cause actin of
microfilaments to form basket to carry bacteria into cell Found in Salmonella Damaging Host Cells Damage by metabolizing and reproducing in hosts Damage by the production of toxins Two major types of toxins Endotoxins Exotoxins Exotoxins Usually from Gram positive bacteria Usually a secreted protein product Heat Labile (60 to 80 deg C) Very toxic – low LD50 Usually specific for cell type or cell function Can be neutralized by antibodies Symptoms usually appear sooner Exotoxins
– Examples Diptheria toxin –stops protein sysnthesis;
damages heart and other organs Cholera toxin – affects intestinal cells; disrups cAMP a cell secondary
messenger Tetnus toxin – affects nerve transmission Toxic shock –affects T-cells & macrophages Listeriolysin – pore forming cytotoxin
allows cell to escape phagocytic vesicle Endotoxins Almost exclusively Gram negative Present in LPS and released with destruction of cell Heat stable – often can withstand autoclave Not easily neutralized by antibodies Produces general effects fever, aches, shock Much larger LD50 than exotoxins Endotoxins
– Examples Salmonella typhi and typhoic fever-incubation period ~ 1 week symptoms due to
LPS induced release of cytokines enter blood and multiply in spleen and liver S. enteriditis & S. typhimurium – food borne gastroenterits
– symptoms usually appear within 24 to 48 hours takes longer than with S. aureus exotoxin The Immune Response Introduction Duality of Immune System Antigens & Antibodies T-Cells & Cell Mediated Immunity Immunology - Introduction Innate resistance – genetically predetermined resistance Immunity – ability of host to counteract specific substances or
organisms Antigens - foreign substances that interact with the immune system Immunity is acquired Naturally From infection – natural active From mother to fetus – natural passive Artificially From vaccination – artificial active From immunoglobin injection – artificial
passive Vaccines made from pathogens Attenuated Inactivated Killed Serum Antiserum if contains antibodies Serum is separated into fractions – the fraction
containing antibodies is the gamma fraction – gamma globulin Immunology – Lymph System Bone morrow Thymus gland Spleen Lymph nodes Immunology – Duality Two parts to immune response Humoral Cell Mediated Usually accomplished by white blood cells derived from hemopoetic stem cells Humoral Mediated by B-cells (bursa) derived from stem cells found in bone
marrow Produce circulating antibodies found in the gamma
globulin fraction of blood serum Defend against bacteria, viruses and toxins in blood
and lymph Cell-Mediated Mediated by T-cells (Thymus derived, i.e. white
blood cells that mature in the thymus gland Defend against intracellular viruses, multi-cellular
parasites, transplanted tissue and cancer cells Immunology – Antibodies Immune response characterized by interaction between antigens and
antibodies Antigens Foreign substances Molecular weight > 10,000 daltons Proteins, lipoproteins, glycoproteins Antigenic determinants are that portion of antigen
which reacts with a specific antibody Antigens have many determinants Hapten – a low molecular weight substance combined with a
carrier molecule Antibodies are proteins produced by B-cells in response to an antigen Antibodies have two binding sites per molecule Immunology – Antibodies Antibody molecule is a dimer Connected by –S-S- bonds Variable and constant region Fab and
Fc Immunology – Antibodies Antibody classes –circulating antibodies consist of five classes IgG - most prevalent IgM – 5 monomers involved in complement fixation &
agglutination IgA – secreted protects mucosa IgD – antigen receptors on B-cells IgE – bind to mast cells & basophils;
involved in allergic reaction Antibody Production Mature B-cells circulate in blood; each producing a
slightly different antigen receptor B-cells not needed undergo cell death B-cells becomes activated when antigen reacts
antigen receptors on cell surface Activated B-cells produce a clone of plasma cells
and memory cells Antigen ingested by antigen presenting cell (apc) Antigen broken down into smaller pieces for presentation Immunology – Antibodies Immunology – Antibodies Antigen presenting cell presents antigen and self antigen to helper
T-cell Self antigen keeps immune system from forming antibodies against
itself, i.e. immune system will not form antibodies against a self-self
combination Immunology – Antibodies Helper T-cell interacts between antigen presenting cell and B-Cell to
activate B-cell to produce plasma cells Plasma cells secrete antibody Immunology – Antibodies Antibody Production (continued) Plasma cells secrete antibody (IgG)
Memory cells recognize antigen from previous
encounters; produce plasma cells faster T-cells and B-cells that react with self are
destroyed during fetal development Immunology – Antibodies Antigen-Antibody Binding Antigen binds to variable region forming
antigen-antibody complex IgG binding inactivates viruses and toxins Agglutination reduces number of active particles and
enhances phagocytosis Activates the complement cascade Opsonization enhances phagocytosis Immunological Memory Circulating antibody is called titer First antigen contact is primary response; second is secondary Secondary response is usually faster with a significantly greater
antibody titer Cell Mediated Immunity Introduction Cytokines Components of Cell Mediated Immunity Cell Mediated Immunity Introduction Involves specialized lymphocytes call T-cells T-cells mature in thymus Response to intracellular viruses, multicellular parasites, transplanted tissues and cancer Cytokines are chemical messengers Interleukins are cytokines that allow leukocytes to communicate Interferons are cytokines that protect against viruses Chemokines
cause leukocytes to move to site of infection Components Helper T Cells (TH ) Cytotoxic T Cells (TC ) Delayed Hypersensitivity T Cells (TD) Suppressor T Cells (TS) Activated Macrophages Natural Killer Cells Helper T Cells Activate B-cells Activate cytotoxic T cells Activate other helper T cells Cytotoxic
T Cells Used to attack intracellular pathogens such as viruses, some bacteria, multicellular parasites Attaches to target
cell Releases protein perforin
which pokes holes in target cell inducing lysis T cells continue as long as antigen is present Delayed Hypersensitivity T Cells Involved in allergic reactions like response to
poison ivy and transplanted tissue rejection Originally named because transfer of cell
transferred immunity to TB Probably a subpopulation TH cells and TC
cells Suppressor T Cells Appears to regulate immune response Probably a subpopulation of helper cells Activated Macrophages Stimulated by ingestion antigens and cytokines from
helper T cells Acquire enhanced ability to digest via phagocytosis virus infected cells and intracellular
bacteria infected cells Can be antigen presenting cells Nautral
Killer Cells Kill virus infected cells, tumor cells and large
parasites Not immunologically
specific like cytotoxic T cells |
|
|
|
|
|