Exam 2 Flashcards
1
Q
Cell-mediated immunity: entirely associated with cell surfaces, T-cell receptors, that are unable ot “see” free antigens
A
T Cells: can regulate the immune responses of other cells (CD4) or indirectly kill cells (CD8) that carry specific antigens
- lymphocytes produced in red bone marow, migrate to thymus (primary lymphoid organ) where they mature (VDJ recombination of T cell receptor) and undergo selection
- T cell receptors must recognize self MHC proteins needed for activation, but not the self antigens (self tolerance) that the MHC presents (T-cell eliminated in thymus if criteria not met)
- “naïve” T cells recirculate only between the blood and lymphoid organs, do not enter other tissues; activated in secondary lymphoid organ
(Ex. Spleen, tonsils, or lymph nodes) - T-cell receptors are transmembrane proteins with constant and variable region, like antibodies; composed of 2 chains (alpha and beta)
- T-cell receptors recognize only a processed peptide fragment that the APC’s MHC presents to the T cell receptor, unlike B-cell receptors
- other transmembrane proteins closely linked to T-cell receptors serve as coreceptors, such as CD4 and CD8
- T cell activation occurs in secondary lymphoid tissue when antigen is displayed with self MHC on mature dendritic cells (DCs)
2
Q
Cytotoxic Tcells - kill cells that are infected with viruses (or other pathogens)
A
- have CD8 coreceptor protein
- antigen-presenting cell (APC) often include dendritic cells (professional APC)
- activated by endogenous antigens bound to MHC class I proteins of dendritic cells
- activation results in the release of IL-2, TNF, and IFN-y; and they differentiate into memory cells and activated cells (clonal expansion)
- “altered-self” cells expresing the same combination of foreign peptide on MHC class I are targeted; may include tumor cells, virally infected cells, or cells with intracellular parasites
- release perforins, insert in membrane and make pores, granzymes enter infected cell and activate caspase enzymes that induce apoptosis
3
Q
Helper Tcells
A
involved in activating and directing other immune cells;
their cytokines largely determine whether an immune response is humoral or cell-mediated; no killing ability
- have CD4 coreceptor protein
- 1st signal is initiated by exogenous antigens bound to MHC class Il proteins of macrophages, dendritic cells (phagocytosis or endocytosis), and Bcells (receptor-mediated endocytosis)
- 2nd signal is a verification step, naïve TH cells express the protein CD28 that must bind to costimulatory B7 protein on professional APCs; a protective measure to ensure TH cells are responding to a foreign antigen
- when 2nd activation signal is complete the originally undetermined T-helper null cell (TH0) releases a potent T cell growth factor called interleukin 2 (IL-2), which activates the T cells proliferation pathways
- TH0 cells differentiate into TH1 or TH2 cells depending cytokine environment
-Cellular Response- IL-12 &IFN-y induces TH1 differentiation; IFN-y inhibits TH2 cells
-Humoral Response- IL-4 drives TH2 differentiation, and inhibits TH1 cell production - both T helper cell groups are able to inhibit the activation of the other group using their own cytokines
- TH1 cells communicate attack against intracellular bacteria and protozoa
- TH2 cells communicate attack against extracellular parasites including helminths
4
Q
TH1 cells mainly secrete:
A
IL-2: growth factor for Tand Bcells; natural killer cells become lymphokine- activated killer (LAK) cells
IFN-Y: inhibition of TH2 cells, strong macrophage-activating factor
TNF: major mediator of inflammation; high concentrations increase synthesis of prostaglandins, resulting in fever
GM-CSF: Granulocyte-Macrophage Colony Stimulating Factor
5
Q
TH2 cells mainly secrete:
A
IL-4: growth factor for Bcells; suppresses TH1 cell production
IL-5: stimulates Bcells for growth, differentiation, and production of antibodies; activates eosinophils
IL-10: inhibits TH1 cells, cytotoxic Tcells, NK cells, ¯ophage cytokine synthesis
6
Q
Humoral immunity: based on antibodies on cell surfaces and in body fluids (blood, lymph, etc.)
A
B Cells: bind specific to free (soluble) antigen or particulate antigen with its membrane bound antibody (B cell receptor); also serves as APC to TH cells
- B cells produced in red bone marrow; immunoglobulin (Ig) synthesis occurs
- tested for auto-reactivity by the immune system before leaving the bone marrow
- if highly reactive to self:
Clonal deletion- removal, usually by apoptosis
Receptor editing- opportunity to rearrange their conformation via RAG (recombination activating gene)
Anergy- B cells enter a state of permanent unresponsiveness and fail to respond ot their specific antigen - Ig is encoded by different segments of DNA, a V(variable) segment, a D(diversity) segment, a J (joining) segment, and a constant region; variable regions are shuffled by RAGs
- each Ig consists of 2 identical short polypeptides called light chains and 2 identical longer polypeptides chains called heavy chains; held together by disulfide bonds to form a Y-shaped molecule
- each “arm” is called Fab (fragment antigen-binding) region and the “stem” is called Fc (fragment crystallizable) region
- the heavy chain constant region is translated from 1of 5possible DNA sequences named u (mu), o (delta), y (gamma), a (alpha), E (epsilon), which give rise to a particular class of immunoglobulin
- immunoglobulins IgM (monomeric form) and IgD are present on mature “naïve” Bcells
- Bcells recirculate only between blood and lymphoid organs, activated in secondary lymphoid organ (Ex. lymph nodes, MALT, which includes tonsils and appendix)
- Bcells recognize their cognate antigen in its native form with its B-cell receptors (antibodies) ; each Ig can bind 2 identical epitopes
- binding of antigen to Ig on surface of appropriate Bcell is usually not sufficient to
activate the B cell to multiply; so, B cell (APC) internalizes antigen-antibody complex and incorporates portions of antigen (epitope) on MHC II - specific TH2 cell recognizes antigen displayed by B cell; cytokines such as IL-4 are released from TH2 cell to activate B cell; produces memory cels and plasma cells that secrete antibodies against the identical antigen
7
Q
Complement
A
- consists of approx. 30 different proteins
- circulate freely in blood plasma, generally in inactive form (zymogen)
- complement can be activated by classical pathway (antigen-antibody complex) or alternative pathway (spontaneously) or lectin pathway (cell wall polysaccharides of certain bacteria and fungi)
- complement proteins (C3b) coat pathogen surface (opsonization), thus promoting phagocytosis and destruction by macrophages and neutrophils, which have receptors for C3b
- C5a is an important chemotatic protein, helping recruit inflammatory cells
- complement C5b initiates pathway for membrane attack complex (MAC) that forms pores in pathogens that have lipid membrane to induce lysis
8
Q
Interferons (IFN-a, IFN-b, IFN-y)
A
- a class of proteins synthesized upon parasitic infection of a cell
- act as messengers to protect normal cells in vicinity from becoming infected
- IFN-a and IFN-b induce the degradation of RNA and block protein production
- IFN-y is produced by TH cells and natural killer cells to stimulate in the cellular response
9
Q
Phylum: Platyhelminthes
A
Platyhelminthes (flatworms): phylum containing simplest bilateraly symmetrical animals
- most platyhelminthes are parasitic
- acoelomate body plan (no body cavity other than the gut); rarely has anus
- triploblastic (composed of three fundamental cell layers) Ex. mesoderm, ectoderm, and endoderm
- dorsoventrally flattened (greater surface area to respire by diffusion)
- tegument (surficial covering of a multicelular organism, an integument)
- parenchyma (loosely arranged mass of fibers and cells of several types)
10
Q
Subclass: Digenea
A
Digenetic trematodes (flukes): a subclass within the class Trematoda
- digeneans parasitize all classes of vertebrates
- develops in at least two hosts
- first host is a mollusk (most often a gastropod) or very, rarely an annelid
Domain: Eukaryota
Kingdom: Animalia
Plylum: Platyhelminthes
Class: Turbellaria
Monogenea
Cestoidea
Trematoda
Subclass: Digenea
Aspidobothrea
11
Q
Body Form
A
Most are dorsoventrally flattened and oval ni shape; others as thick as they are wide
- length ranges from 1.0 m to 6.0 cm
12
Q
different suckers
A
Oral sucker: muscular sucker that surrounds the mouth
Acetabulum: ventral sucker of a fluke
Distome: fluke with two suckers, oral and ventral
Monostome: fluke that lacks a ventral sucker
Amphistome: fluke with the ventral sucker located at the posterior end
13
Q
Tegument: surficial covering of a multicellular organism, an integument
A
- distal cytoplasm: anucleate layer of cytoplasm above a “sunken epidermis”
- cytons: cel bodies containing nuclei; lie beneath superficial muscle layer
- internuncial processes: channels that connect cytons ot distal cytoplasm
- syncytial: describes the continuous distal cytoplasm with no intervening cell membranes
- spines: consist of crystalline actin; often present in certain areas of the tegument
- spines lie above the basement membrane of distal cytoplasm
- most flukes can absorb small molecules including amino acids and hexoses
14
Q
Muscular system
A
- circular muscles lies beneath the basal membrane of tegument
- longitudinal and diagonal layers underlying the circular muscles envelop body - muscle fibers are smooth, often in syncytial clusters
- myocyton: cell body of a muscle cell where nuclei occur; connect to fiber bundles
15
Q
Nervous system: cerebral ganglia with orthogonal nervous system
A
orthogon: describes the ladderlike arrangement of nervous system in flatworms
- 3 main pairs of longitudinal trunks (dorsal, ventral, and lateral)
- cross-connected by a series of transverse commissures
- sensory endings extend from tegument; many types in cercaria and miracidium
tangoreceptors- receptors sensitive to touch
chemoreceptors- sensory receptor that responds ot chemical stimuli (some strikingly similar to olfactory receptors of vertebrate nasal epithelium)
eyespots: allows organism to distinguish light direction
16
Q
Excretion: removal of waste takes place across tegument, epithelial lining of gut,
exocytosis of vesicles, and via excretory system
A
- removal of waste products of metabolism
- removal of unnecessary or harmful substances
- regulation of internal osmotic pressure
- regulation of internal ionic composition
17
Q
Protonephridia
A
excretory system that is closed at the inner end by a flame cell and opens by a pore at the distal end
18
Q
Flame bulb: specialized hollow excretory or osmoregulatory structure
A
- one or several small cells containing a tuft of flagella
- situated at the end of a minute tubule
- connected tubules ultimately open to the outside
- rod-like extensions of the flame cel form a filtering apparatus (weir)
- ductules of flame cells join collecting ducts that eventually feed into an excretory bladder that opens outside through a single pore
19
Q
Flame cell formula: represents the number and arrangement of flame cells
A
used as a taxonomic character
20
Q
Flame cell formula Steps:
A
1 Draw a vertical line down the center from anterior to posterior end. 2[( )+( )]
2. Draw a horizontal line where the main
collecting ducts bifurcate.
3. Starting anteriorly from the upper quadrant count the number of flame cells in a common
cluster. Add this number to other number of
flame cells in the remaining cluster. 2[ (3+3+3) +()]
4. Repeat with the lower quadrant working from anterior to posterior.
2[(3+3+3) + (3+3+3)]
21
Q
Digestion- digestion in most flukes is predominantly extracellular in the ceca
waste is expelled through
A
- excretory system or tegument
- stored in worm tightly bound to protein
- periodically regurgitated
22
Q
Cytokines
A
- cytokines are protein hormones utilized by immune cells to communicate
- can affect same cells that produce them, cells nearby, or cells distant in body
Ex. interferon, interleukin, growth factors, etc.
23
Q
Cell Signaling
A
- ligand binds to a specific cell receptor protein, initiating intracellular signal cascades
- ligands may be located on cell surface of neighboring cells, dissolved in blood (cytokines) or on the surface of or secreted by pathogens
- cascades may activate transcription factors or proteins that control gene induction, phagocytosis, apoptosis, or secretion
24
Q
Cell Signaling
Ex. JAK-STAT pathway: 3 main components include
A
- receptor
- Janus Kinase (JAK)
- Signal Transducer and Activators of Transcription (STAT)
- transmembrane receptor, activated by cytokine
- activates the JAK protein, which adds phosphate groups (P) to the receptor
-Kinases: are proteins that add phosphate groups to other proteins
-Phosphate groups: act as “on” and “of” switches on proteins - STAT is recruited and itself becomes phosphorylated, forms dimer, and moves into the cell nucleus, where it binds to DNA promoter region
25
Pattern Recognition Receptors- receptors with broad specificity that bind to molecules on the surface of pathogens; stimulated by PAMPs
- Pathogen-associated molecular patterns (PAMPs): small molecular motifs conserved within a class of pathogens
A. Scavenger receptors: bind lipoproteins and lipopolysaccharides from bacterial cells including Gram-positive bacteria (lipoteichoic acid) and Gram-negative
bacteria (lipopolysaccharide)
B. Complement receptors: integral membrane proteins that recognize fragments of complement and mediate various defense functions, including phagocytosis
C. Toll-like receptors (TLRs): single, membrane-spanning, receptors that recognize structurally conserved molecules of carbohydrates, nucleotides, and proteins derived from viruses, bacteria, protozoa, and helminthes parasites
26
Four important aspects of immune response include:
1. nonself recognition: ability to distinguish self-antigens from nonself
2. antigen-specific: recognizes and is directed against specific antigens
3. systemic response: immunity is not restricted to initial infection site
4. "memory": recognizes and mounts stronger atack on previously encountered pathogens
27
Basis of self and nonself recognition
Major histocompatibility complex (MHC): cell surface glycoproteins, highly polymorphic
A. MHC class I proteins
- presents in every nucleated cell of the body (few exceptions)
-Cytotoxic T cells (CD8) respond to endogenous antigen bound to MHC class I proteins
B. MHC class II proteins
-found only on antigen presenting cells (macrophages, B cells, and dendritic cells)
-TH cells (CD4) respond to exogenous antigen bound to MHC class II proteins
28
Different Ig
IgM: pentamer, 1st antibody secreted during primary immune response; monomer, present on surfaces of B cells
IgG; monomer, major antibody secreted during the secondary response; 75% of plasma antibodies
IgD: monomer, present only on surfaces of Bcells; serves as antigen receptor
IgA: dimer, most abundant form of antibody in body secretions; high density of IgA-secreting plasma cels in MALT
IgE: Fc binds to mast cells, basophils, etc.; often secreted in response to helminth worms; low conc. in plasma
29
Plasma B cells: are large B cells that have been exposed to antigen
- produce and secrete large amounts of antibodies
- short lived cells and undergo apoptosis when the inciting agent that induced immune response is eliminated
30
Memory B cells: specific to antigen encountered during primary immune response
- can respond quickly following a second exposure to same antigen
- long lived cells
31
Human immunodeficiency virus (HIV): a retrovirus that attacks the body's immune system; causes AIDS
A. HIV mounts direct attack on TH cells by binding to CD4 proteins on cell surface; monocytes are infected because they also express CD4
B. HIV kills TH cells, via apoptosis, faster than they can proliferate over time
C. HIV-encoded proteins also cause a decrease in the expression of MHC class I on infected cells, so these cells are less likely to be recognized and are killed by NK cells
D. when CD4+ Tcell numbers decline below a critical level of 200 cells per uL, cell-mediated immunity is lost
32
Acquisition of nutrients:
Feeding and digestion- varies with nutrient type and habitat within the host
Ex. flukes of lungs, intestine, urinary bladder, rectum, and bile ducts draw a plug of tissue into their oral sucker and use pharynx as a pump to erode tissue
Ex. flukes living in blood vessels are immersed in its semifluid blood food, so has no necessity ot breach host tissue
33
Reproductive system:
- most trematodes are hermaphrodites, and some can self-fertilize
- always cross-fertilize if 2 or more digeneans are in the same host
- exception are schistosomes that are dioecious
- ectolecithal system: yolk is contributed by vitelline cells, yolk not stored in female gamete
34
Male Reproductive system:
testes: usually 2, number varies with species
- each testis has a vas efferens that ultimately connects to vas deferens
- internal seminal vesicle: located within cirrus pouch, stores sperm
cirrus: male copulatory organ; cirrus pouch encloses the cirrus
35
Digenea: Form and Function
Female Reproductive system:
ovicapt: sphincter muscle that controls the release of oocyte from the ovary
Laurer's canal: vestigial vagina
Mehlis' gland: unicellular mucous and serous glands surrounding the ootype
ootype: a slightly expanded area of the oviduct that is surrounded by Mehlis' gland
vitellaria: a group of vitelline glands that produce vitelline cells
- vitelline cells produce the bulk of the shell material and yolk of the egg
oogenotop: "egg forming apparatus"
36
Development
Polyembryony: development of a single zygote into more than one offspring
- Somatic cell: contributes to body tissue of the embryo
- Propagatory cell: stem cells
- they are germinal cells in reproducing forms
Ex. additional embryo in miracidium, sporocyst, or redia
- give rise to germ cells in sexual adults
Ex. sperm and egg
37
Pathogen: any organism or substance that produces a disease state
Pathogenicity: encompasses the total sum of consequences regarding the presence of a foreign species in the host
- a parasite is pathogenic if it causes changes in hte anatomy, physiology or behavior of the host
Virulence: deals with the consequences of the presence of the foreign species on the transmission of the hosts genes
- a parasite is virulent if it reduces host reproductive success
38
Digenean: Leucochloridium variae
- definitive hosts include warblers
- embryonated eggs are ingested by the terrestrial snail (Succinea ovalis)
- sporocyst divided into 3 parts:
1. central body in snail's hepatopancreas
2. tube connecting the central body to the broodsac
3. broodsac in the head-foot of the snail and enters its tentacles
- brightly colored broodsac pulses in enlarged snail tentacle
- tailless cercariae develop in branched sporocysts; metacercaria encyst in broodsac
39
Digenean: Alaria americana
Parasite of wolves, foxes, coyotes, and the domestic dog (humans are accidental hosts)
- miracidia hatch out of egg and penetrate snail
- sporocysts shed cercariae - cercaria penetrate tadpole
- mesocercaria develop in tadpole
(infective to next host, either paratenic or definitive host)
- water snake (paratenic host) eats infected tadpole or frog
- canid eats infected snake and mesocercariae are freed by digestion
- mesocercariae penetrate gut, move to diaphragm & then lungs (metacercaria)
- (after 5 weeks) they migrate up the trachea and then to the small intestine
40
Alaria americana Pathology:
- mature Alaria sp. very pathogenic causing severe enteritis
- often kills host in severe infections
- can be fatal in humans when accumulated in large numbers
41
Alaria americana Epidemiology:
- found in various species of Canidae in northern North America
- mesocercariae are pathogenic to human
- acquired by eating undercooked frogs' legs
- transmammary transmission of mesocercariae to offspring via milk
42
Population structure:
set of quantitative descriptors of a host population, including prevalence of infection, incidence, abundance or density, intensity, variance of a frequency distribution, and curve of best fit
43
prevalence
percentage in individuals of a single host species infected at a given time
44
incidence
the number of new infections per unit time divided by the number of uninfected hosts at the beginning of the measured time
45
Abundance or density:
average number of parasites of one species per sample of host individuais of the same species, equal the arithmetic mean
46
Intensity:
the number of parasites of one species in an infected host
47
Mean intensity:
the average number of parasites of one species per infected hosts in a sample
48
Aggregated or overdispersed:
a situation in which most of the parasites occur in a relative minority of hosts and most host individuals are either uninfected or lightly infected
49
Parasite community:
the number of different parasite species infecting a single host individual
50
Macroepidemiology:
study of the effects of large scale factors, such as climate and culture, on distribution of disease in a population
51
Microepidemiology
study of the effects of small scale factors, such as parasite strains, host genetic variation, on distribution of disease in a population
52
Landscape epidemiology
approach of epidemiology that employs all ecological aspects of a nidus
- by recognizing certain physical conditions, the epidemiologist can anticipate whether a disease can be expected to exist
53
Nidus
specific locality of a given disease; result of a unique combination of ecological factors that favors the maintenance and transmission of the disease organism
54
Digenean: Schistosoma spp.
Family: Schistosomatidae: have no 2nd intermediate host in their life cycles
- mature in the blood vascular system of their definitive host
- most species are dioecious
Genus: Schistosoma: refers to the "split body" of the male
considerable sexual dimorphism exists which include:
- males have tegumental tubercles
- males are shorter and stouter than females
- males have a ventral longitudinal groove (gynecophoral canal)
55
Schistosomes host specificity
Schistosoma mansoni: found in the portal veins draining the large intestine - moderate host specificity
- reservoir host include: rodents and monkeys
Schistosoma haematobium: prefers the veins of the urinary bladder
- most host specific (no known reservoir hosts)
Schistosoma japonicum: more concentrated ni the veins of the small intestine - least host specific
- reservoir hosts include: rodents, cats, dogs, pigs, cattle, horses, and deer
56
Digenean: Schistosomes
Pathology
Migratory phase: time from penetration until schistosome is reproductively mature
- often no symptoms or dermatitis reaction
Actute phase (Katayama fever): occurs when schitosomes begin producing eggs
- sufficient time and exposure has elapsed to elicit humoral response
- egg production dramaticaly increases antigen release causing:
chills, fever, fatigue, headache, malaise, muscle aches, GI discomfort etc.
Chronic phase:
S. mansoni- hepatic and pulmonary cirhosis, hepatosplenomegaly
S. haematobium- bladder wall becomes ulcerated, bloody urine (hematuria)
S. japonicum-hepatic and pulmonary cirhosis, hepatosplenomegaly; cerebral schistosomiasis
57
Digenean: Schistosomes
Epidemiology
- Human waste water containing intermediate host is #1 empidemiological factor
S. mansoni: broad distribution: Africa, Middle East, South America, and Caribbean
S. japonicum: limited ot Japan, China, Taiwan, the Philippines, and Southeast Asia
S. haematobium: limited ot Africa and adjacent regions
- schistosomes may live 20 to 30 years
- Schistosomiasis transmission has been reported from 78 countries
- More than 75.3 million people were treated for schistosomiasis in 2021
- 200,000+ deaths per year
Concomitant immunity: host is protected against new infections, but the parasite eliciting the immunity remains alive and unaffected
58
Digenean: Fasciola hepatica
Parasite of ruminants (cattle, goats, sheep, deer, etc.), and humans
- adult parasite feeds on lining of bile ducts
59
Digenean: Fasciola hepatica
Pathology
- much necrosis results from migration of flukes through liver parenchyma (2 months)
- anemia sometimes results from heavy infections
- worms in in bile ducts cause inflammation, edema, and stimulates fibrosis
- migrating juveniles cause ulcers in ectopic locations: eyes, brain, skin, &lungs
Ruminants
- enormous losses in livestock because of mortality
- reduction of milk and meat products; and especially spoiled livers
- secondary bacterial infections
- expensive anthelmintic treatment
60
Digenean: Fasciola hepatica
Epidemiology
- can live as long as 11 years
- infection begins when metacercarial cyst is ingested from water or vegetation
- human often infected by eating watercress
- sheep, cattle, goats and rabbits are most frequent reservoirs of infection in US
- few human cases in US; most common in the South and West
- human infections occur Europe, northern Africa, Cuba, South America, & other locales
- WHO estimate 2.4 million persons were infected with fascioliasis worldwide in 2018
61
Digenean: Ribeiroia ondatrae
- national attention in 2007 regarding widespread reports of deformed amphibians
- 1st intermediate host are various freshwater snails
- 2nd intermediate hosts are fish and larval amphibians (frogs and salamanders)
- large numbers of metacercariae encyst where hind limb buds form ni tadpoles
- encysted metacercariae cause deformation of hind limbs
- definitive hosts include herons, hawks, and badgers
62
Digenean: Dicrocoelium dendriticum
- common ni the bile ducts of sheep, cattle, goats, deer, and pigs
- no need for aquatic environment for any life cycle stages
63
Digenean: Dicrocoelium dendriticum
Pathology
- conditions of dicrocoeliasis is similar to fascioliasis, but less severe
- no trauma ot gut wall or liver parenchyma (no migrating juveniles)
- chronic constipation, bile duct inflammation, fibrosis, and hepatocyte degeneration
64
Digenean: Dicrocoelium dendriticum
Epidemiology
- common throughout most of Europe, Asia, Africa, North and South America
- acquired by accidental ingestion of ants on fresh herbs or vegetables
65
Digenean: Clonorchis sinensis
Pathology
- erosion of epithelium in larger bile ducts & main branches
- inflammation becomes prominent, fibrosis, necrosis and atrophy of surrounding liver tissue
- trapped eggs become surrounded by granulomas, interfering with liver function
- eggs and sometimes entire worms become nuclei of gallstones
- cancer of the bile duct si often associated with clonorchiasis
66
Digenean: Clonorchis sinensis
Epidemiology
-can live 8 years in humans
- clonorchiasis is common in countries that eat raw fish
- reservoir hosts include dogs, cats, pigs, and rats that contaminate streams
- widely distributed in Japan, Korea, China, Taiwan, and Vietnam
- eating frozen, dried, or pickled fish imported from endemic areas has caused infection
- metacercariae wil withstand freezing, drying, pickling, salting, and smoking fish
- may be futile to get milions of people to break century old habit
- educating people to cook fish not option for many because fuel is luxury
- fish farms contaminated with human feces ("night soil") used as fertilizer throughout much of Asia
67
Digenean: Paragonimus westermani
Pathology
- once in lung or ectopic site, worm stimulates an inflammatory response
- parasite becomes enshrouded in a granuloma
- eggs in surrounding tissues result in pseudotubercles
- worms in spinal cord can cause paralysis
- fatal cases are seen when Paragonimus spp. locate ni heart or brain
- pulmonary cases are rarely fatal; chronic cough, breathing dificulty, sputum containing blood
68
Digenean: Paragonimus westermani
Epidemiology
- reservoir hosts often include felids, canids, rodents and pigs
- worms can live 10 to 20 years
- human become infected by eating raw or insuficiently cooked crustaceans - marination in brine, vinegar, or wine have no affect on metacercariae
- exposure can also come from contaminated fingers and cooking utensils
- some ethnic groups use of juices strained from crushed crab or crayfish for
medicinal purposes (poultice)
- variety of mammals and some birds can serve as paratenic hosts
Ex. Guinea pigs: considered a delicacy in Ecuador and Peru
69
Praziquantel (Biltricide)
- developed by Bayer and Merck in the mid 1970s
- on the World Health Organization's List of Essential Medicines
-drug of choice by CDC efective against: Alariasis, Clonorchiasis, Paragonimiasis, Dicrocoeliasis, Schistosomiasis, Dipylidiasis, Hymenolepiasis, Taeniasis
- increases calcium ion permeability of membranes; induces contraction ¶lysis
- available in the United States as Biltricide by Bayer 1( dose pack - 6 tablets - $105.00)
70
Albendazole (Albenza)
- developed by SmithKline in 1972
- broad-spectrum anhelmintic
- on the World Health Organization's List of Essential Medicines
- alternative drug of choice by CDC efective against: Clonorchiasis
- binds to colchicine-sensitive site of tubulin eliminating its polymerization into microtubules leading to impaired uptake of glucose
- available in the United States as Albenza by GlaxoSmithKline 1( dose pack - 2tablets - $215.00)
71
Triclabendazole (Egaten)
- on the World Health Organization's List of Essential Medicines
- drug of choice by CDC efective against: Fascioliasis
- binds ot beta-tubulin preventing the poymerization of microtubules leading to impaired uptake of glucose and depletion of glycogen
- not available ni the United States, but is available through CDC
72
Cestoidea
Cestoidea: a class within the phylum Platyhelminthes
- monoecious parasites, hermaphrodites
- acoelomate; no digestive system
- adults live in the digestive tract of vertebrates
73
Cestoidea anatomy
Scolex: "head" or holdfast organ of a tapeworm
- may have suckers, grooves, hooks, spines, glands, or tenatacles
- contains the neural ganglia of the worm
Neck: an undifferentiated zone located between the scolex and the strobila
- contains stem cells responsible for giving rise to new proglottid
Strobila: region of tapeworm behind the scolex &neck; chain of proglottids
Proglottid: a segment in a strobila that includes male &female reproductive organs
-proglottid can copulate with itself, with others in its strobila; or with those in other worms, depending on the species
74
proglottid type
Polyzoic: a strobila consisting of more than one proglottid
Monozoic: tapeworm whose "strobila" consists of a single proglottid
75
detaching proglottids
Strobilation: formation of a chain of proglottids by budding
Gravid: a proglottid containing fuly developed eggs or shelled embryos
Apolysis: disintegration or detachment of a gravid tapeworm segment
Anapolysis (pseudoapolysis): detachment of senile proglottid after ti has shed its eggs
Hyperapolysis: detachment of a proglottid while still immature, before eggs are formed
- may lead an independent existence in the gut while maturing
76
overlapping proglottids
Craspedote: posterior edge of each segment overlaps the anterior edge of next segment Acraspedote: posterior edge of proglottid does not overlap the anterior edge if the next
77
scolex specifics
Acetabula: a sucker on the scolex of a tapeworm; normally 4 acetabula on a scolex
Bothridia: usually in groups of 4;can have highly mobile, leaflike margins with adaptations for adhesion
Rostellum: dome-shaped area on the apex of the scolex, often with hooks
Bothria: usually 2 in number (dorsal and ventral), and take the form of shallow pits
78
Microtriches: are numerous minute finger-shaped tubes that extend out of tegument
- increases the absorptive area of the tegument
- completely cover the worm's surface
- glycocalyx is found on the surface membrane of microtriches
- below microtriches is a layer of distal cytoplasm
79
Cestoidea: Form and Function
Muscular system
- muscle cells consist of 2 portions: contractile myofibril and noncontractile myocyton
- contractile portion contains actin and myosin fibrils, and it is nonstriated
- myocytons comprise most of the cestodes parenchyma
- bundles of longitudinal and circular muscle fibers lie below the distal cytoplasm
- more powerful musculature lies below the superficial muscles
80
Cestoidea
Nervous system
-nervous system of cestoidea displays the orthogon plan typical of Plathyhelminthes
-main nerve center is located in the scolex
-innervation of ganglia, commissures, and motor and sensory neurons occur at the main nerve center, complexity often depends on complexity of scolex
-sensory function most likely includes tactoreception and chemoreception
81
Cestoidea: Form and Function
Excretion and Osmoregulation
- main excretory canals run from the scolex to the posterior end of strobila
- canals empty at the end of the strobila when terminal proglottids detach
- excretory ducts are lined with microvilli
- flame cell protonephridia provide motive force to the fluid in the system
- end products of cestode energy metabolism are excreted through the tegument
- osmoregulation is also function of tegument
82
Cestoidea: Form and Function
Reproductive system
- monoecious; few exceptions
- in mature proglottid, sperm is transferred and oocytes are fertilized
- usually male organs mature first, sperm is stored until maturation of the ovary
Protandry (androgyny): maturation first of male gonads and then of females
- in a few species the ovary matures first, known as protogyny
- may be an adaptation that prevents self fertilization of the same proglottid
- usually reproductive pores of both sexes open into a genital atrium
83
Cestoidea: Form and Function
Male
- one to many testes, each has vas efferens, unites into common vas deferens
- sperm channeled toward the vaginal opening
-cirrus pouch: amuscular sheath containing cirrus
- the male copulatory organ is the muscular cirrus, which may have spines
84
Cestoidea: Form and Function
Female
- ovary and associated structures
- the entire complex is known as the oogenotop
- vitelline cells contribute yolk and shell material ot the embryo
- oocytes leave ovary through the oviduct, which has a sphincter, or oocapt
85
Cestoidea: Form and Function
Development
(1) embryogenesis within the egg gives rise to larva (oncosphere - a six hooked larva hatched from an egg of a eucestode; also known as hexacanth)
(2) oncosphere hatches and penetrates extraintestinal site
(3) metamorphosis of the larva into a juvenile (metacestode) in extraintestinal site
(4) metacestode develops into adult in the intestine
86
Diphyllobothrium latum
- broad fish tapeworm
- occurs ni humans, bears, cats, dogs, and other fish-eating carnivores - adults live in small intestine
- 10 meters length; >4,000 proglottids; sheds 1million eggs per day
- eggs released through uterine pore
87
Diphyllobothrium latum
pathology
- pernicious anemia; large amount of B12 absorbed by tapeworm
- Sparganosis: infectious disease caused by migrating plerocercoids in host tissues
- can reach 35cm in length; can live for at least 30 years
(1) swallowing procercoid-infected copepods in drinking water
(2) eating amphibians, reptiles, and mammals containing plerocercoids
(3) applying plerocercoid-infected flesh to wounds as a poultice
88
Pseudophyllidea: Diphyllobothrium latum
Epidemiology
-eating undercooked freshwater fish
- accidental ingestion of copepod from unfiltered water
- insufficiently cooked frog, snake, or pig
- poulticing inflamed area or wound with split frog
89
Cyclophyllidea: Taenia saginata
- beef tapeworm
- occurs in humans in countries where beef is eaten
- 3to 5meters length; >2,000 proglottids
- adult beef tapeworm lives in small intestine
- gravid segments detach and pass out with feces or migrate out of anus
- proglottid begins to dry and ruptures, thus releasing eggs
- larvae (hexacanth) remain viable for weeks
90
Cyclophyllidea: Taenia saginata
Pathology
- may be asymptomatic
- symptoms of dizziness, headache, abdominal pain, diarrhea, and nausea
- intestinal obstruction with need for surgical intervention sometimes occurs
- loss of appetite is not frequent -
- delirium is rare
91
Cyclophyllidea: Taenia saginata
Epidemiology
- infection is highest where beef is a major food and sanitation is deficient
- one person who defecates in pasture can infect entire herd
- use of human feces as fertilizer (night soil)
- cattle are coprophagous
92
Cyclophyllidea: Taenia solium
-pork tapeworm
- most dangerous adult tapeworm to humans
- humans can serve as definitive and intermediate host
- life cycle same as beef tapeworm except the normal intermediate host is pig
- humans become an intermediate host when the eggs are accidentally ingested or agravid proglotid ruptures releasing eggs before it leaves the body
- humans become a definitive host when ingesting cysticerci in undercooked pork
93
Cyclophyllidea: Taenia solium
Pathology
- cysticerci can be found in any organ and tissue including:
(1) subcutaneous connective tissues
(2) eye
(3) brain (epilepsy, blindness, paralysis, disequilibrium, disorientation, etc.)
(4) muscles
(5) heart
(6) liver
(7) lungs
(8) coelom
94
Cyclophyllidea: Taenia solium Epidemiology
- infection is highest where pork is a major food and sanitation is deficient
- eggs can be transmitted by Blowflies
- infected (domestic help) person can contaminate households or food
Ex. 1.3% Orthodox Jewish community ni New York infected by T. solium
N Engl J Med. 1992 Sep 3;327(10):692-5.
- cysticercosis is highly endemic in Mexico, Central and much of South America, sub-Saharn Africa, India, China, and other parts of eastern Asia
95
Cyclophyllidea: Echinococcus granulosus
- adults are in small intestine of carnivores, particularly dogs and other canines
- herbivores (intermediate host) are infected by eating eggs on contaminated herbage
- within liver or lungs oncosphere metamorphoses into unilocular hydatid
slyvatic cycle: life cycles that involve wild animals
Ex. (wolf-moose, lion-warthog, etc.)
urban or domestic cycle: life cycles that involve rats and domesticated animals
Ex. (dog-sheep, dog-goat, dog-pig, etc.
96
Cyclophyllidea: Echinococcus granulosus
Pathology
- hydatid cyst can occur ni any organ: liver, lungs, brain, etc.
- type and extent of pathology depends on cyst size and location
- as cyst size increases it crowds adjacent tissues and organs interfering with function
- cyst can become enormous: > 3 gallons of fluid, millions of protoscolices
- release of hydatid fluid may cause anaphylactic shock
97
hydatid cyst
- hydatid has thick outer noncellular layer and thin inner nucleated germinal layer
- brood capsules on inner layer of hydatid, each capsule has 10-30 protoscolices
- brood capsules within hydatid break down and release "hydatid sand"
98
Cyclophyllidea: Echinococcus granulosus
Epidemiology
- human becomes infected when they accidentally ingest egg when playing with dog
- some tribes in Kenya relish dog intestine roasted on a stick
- some tanners in Lebanon use dog scats as ingredient of a solution for tanning leather
- echinococcosis disease can be eliminated in infected areas by the following:
(1) general educational program
(2) denying access of dogs to offal (3) destroying stray dogs
99
Cyclophyllidea: Echinococcus multilocularis
- adult E. multilocularis mainly found in foxes
- dogs, cats, and coyotes can also serve as definitive hosts
- several species of rodent serve as intermediate host: mice, rats, voles, lemmings
- E. multilocularis metacestode is alveolar or multilocular hydatid
100
alveolar cyst
-has thin wall and germinal epithelium
- may bud externally and spread in any direction or even metastasize
101
Cyclophyllidea: Hymenolepis nana
- dwarf tapeworm (4 cm)
- one of the most common cestodes of humans
- intermediate host is optional (can develop normally in larval and adult beetles)
- human or rodent ingests egg, oncoshpere hatches out of egg in duodenum
- oncosphere penetrates mucosa and develops into cysticercoid (metacestode)
- within 6 days cysticercoid return to lumen of small intestine to attach and mature
102
Cyclophyllidea: Hymenolepis nana
Pathology
- light infections are asymptomatic
- heavy infections can occur because of autoinfection
- symptoms are similar to those previously mentioned for Taenia saginata
103
Cyclophyllidea: Hymenolepis nana
Epidemiology
- more than 20 million people infected worldwide
- prevalence of infection is highest for small children; ingestion of eggs
- ingestion of grain products contaminated with infected insects (flour beetles)
- rodent control measures and protection from their droppings
104
Cyclophyllidea: Hymenolepis diminuta
- much larger than H. nana (90 cm)
- common in rats; human infections not common
- completion of lifecycle requires an arthropod intermediate host ( > 90 insect species)
- other life cycle characteristics similar to H. nana
105
Cyclophyllidea: Hymenolepis diminuta
Pathology
- most infections are asymptomatic
- some symptoms may include nausea, abdominal pains, diarrhea, and anorexia
106
Cyclophyllidea: Hymenolepis diminuta Epidemiology
- primarily a zoonosis: a disease of animals transferable to humans
- rodent control measures to prevent insect consumption of their droppings
- protection from insects of cereals, grains or other non-cooked foods
107
Cyclophyllidea: Dipylidium caninum
- common parasite of dogs and cats all over the world; often occurs in children
- adult worms found in the small intestine
- gravid proglottids detach and either wander out of anus or is passed with feces
- when detached segment desiccates, egg capsules are released
108
Cyclophyllidea: Dipylidium caninum
Pathology
- light infections are often asymptomatic
- some individuals experience abdominal pain, diarrhea, and anal itching
109
Cyclophyllidea: Dipylidium caninum
Epidemiology
- most likely to occur in small children who kiss or are licked by infected pet
- periodic deworming of infected dogs and cats and control of fleas is essential
110
Niclosamide
- on the World Health Organization’s List of Essential Medicines
- used specifically to treat cestode infections
- alternative drug of choice by CDC effective against: Dipylidiasis, and Taeniasis
- uncouples oxidative phosphorylation severely limiting ATP production
- not available in the United States
