ZOO 4232 Human Parasitology Lecture Schedule

Fall Semester, 2023

Date Topic Instructor

August 23 (Wed) Introduction to Course P. Kima

25 (Fri) Primer/Review-The Eukaryotic Cell P. Kima

28 (Mon) Primer/Review- The Host Immune Response P. Kima

30 (Wed) Primer P. Kima

September 1 (Fri) Primer P. Kima

4 (Mon) No Class - Labor day

6 (Wed) Protozoa: General Features/Visceral Protozoa P. Kima

8 (Fri) Visceral Protozoa (Amoeba and Ciliates) P. Kima

11 (Mon) Visceral Protozoa (Amoeba and Ciliates) P. Kima

13 (Wed) Visceral Protozoa (Flagellates) P. Kima

15 (Fri) Visceral Protozoa (Flagellates) P. Kima

18 (Mon) Visceral Protozoa (Flagellates) P. Kima

20 (Wed) Visceral Protozoa (Flagellates) P. Kima

21-22 (Thu/Fri) Exam 1 (Eukaryotic cell/Immune Response/Visceral Protozoa)

Eukaryotic Cells
 The Eukaryotic Cell
• Membrane enclosed compartments
- Compartmentalized Functions
• The Plasma Membrane
• The cell cytoskeleton/motility
• Other cell organelles – Golgi, Mitochondria,
Endoplasmic reticulum
• Signal Transduction and Cell activation
– Endocytosis and phagocytosis
– Release of cytokines
• Nucleus
 Membranes – composition and function
• Membranes are composed of a lipid bilayer
(phospholipids, cholesterol, sphingolipids) and
proteins. Also, carbohydrates linked to both
proteins and lipids
• Plasma membrane: -
– Provides a selective permeable barrier
– Transports solutes,
– Responds to external signals,
• Other membranes in cell
– ensure compartmentalization
– are the locus of biochemical activities
– also in energy transduction
 Membranes – cont’d
• Membrane proteins can be
grouped in three distinct classes:
– Integral proteins span the membrane
(transmembrane proteins). Includes
receptors, integrins, transporters and ion
channels
– Peripheral proteins are associated by
non covalent bonds to membrane but
located entirely outside of lipid bilayer.
Includes cytoskeletal proteins, signal
transducing molecules etc.
– Lipid anchored proteins are covalently
linked to membrane via a lipid molecule,
on either the cytoplasmic or extracellular
surface. Example:
glycophospatidylinositol (GPI) linkage.
Includes receptors, enzymes, signal
transducing proteins.
 Cell Membranes
Fluid-mosaic model
Davison-Danielli model
(Singer and Nicolson)
 GPI anchored molecules on the
surface of trypanosomatides

Figure 1. Schematic structure of trypanosomatid-derived GPI-anchor and related

structures: (a) GIPL, (b) GPI-anchored glycoprotein, and (c) LPG. Etn, ethanolamine;
Man, mannose; Gal, galactose; GlcN, unacetylated glucosamine; Ins, inositol and P,
phosphate
 Proteolytic molecules associated
with surface of parasites

Extracellular parasite proteases. CPs: cysteine proteases, pink scissors; SPs: serine
proteases, green scissors; MMPs: matrix metalloproteases, blue scissors; ECM
extracellular matrix; EDG: electron-dense granules; POP: prolyl oligopeptidase;
PAA: plasminogen activator activity; CatB: cathepsin B
 Outer membrane of worms: Tegument of Schistosome

Multilaminate
membrane

G.N. Gobert et al. / International Journal for Parasitology 33 (2003) 1561–1575

 The Eukaryotic Cell
• Membrane enclosed compartments
- Compartmentalized Functions
• The Plasma Membrane
• The cell cytoskeleton/motility
• Other cell organelles – Golgi,
Mitochondria, Endoplasmic reticulum
• Signal Transduction and Cell activation
– Endocytosis and phagocytosis
– Release of cytokines
• Nucleus
 The cytoskeleton

Gliding motility of apicomplexans; beating of flagellar and cilia

 Cell cytoskeleton and locomotion
• Functions of cell cytoskeleton: -provides
structural support to maintain cell shape -
microtubules (composed of tubulin) play
major role here, also intermediate filaments
(keratins)
• force-generating apparatus that enables cell
contractility and motility, microfilaments
(composed of actin) and microtubules
• internal framework for positioning organelles
within the interior of the cell, intermediate
filaments and microtubules;
• machinery that moves materials and
organelles within the cell, motor proteins
(kinesins and dyneins) interacting with
microtubules and microfilaments. Note -
chemical energy stored in ATP is converted
to mechanical energy that is used to move
cellular cargo.
The Cell Cytoskeleton
Giardia cytoskeleton
The complex microtubule cytoskeleton of Giardia
reconstructed by 3View® and plastic-section
tomography.A) Selected SEM slice (back-scattered electron
signal) showing eight flagella [anterior flagella (AFL); caudal
flagella (CFL); posterior-lateral flagella (PFL); and ventral
flagella (VFL)], part of the ventral disc (VD: green outline),
the bare area (BA), the lateral shield (LS), and lateral crest
(LC). B) 3-D model of a whole-cell reconstruction: ventral
disc, nucleus (N), median body (MB), and the four pairs of
flagella. C) The side-view of the model shows that the entire
microtubule cytoskeleton is located in the ventral part of the
cell. D) 5 nm tomographic slice from a montaged, plastic
serial section tomogram of a portion of the ventral disc. At the
most ventral part of the disc, there are parallel microtubules
and microribbons. The relationship of the disc to the helical
axis is as indicated: margin-facing (M) or axis-facing (A). The
bare area (BA) is also indicated. E) 5 nm tomographic slice
showing the arrangement of four basal bodies and how the
microtubules (MT) of the ventral disc originate from dense
bands (arrows). F) Model from the tomographic reconstruction
showing the supernumerary microtubules (yellow) are ventral
to the ventral disc microtubules (white). Microtubule ends are
classified as either capped (red dots, arrows) or open (green
dots). Microribbons are shown in green. One of the anterior
flagella (purple) penetrates the overlap zone. Scale bars in A–
C = 2 µm, D–F = 200 nm.
 Other cell organelles
• Endoplasmic reticulum: site of
protein and some lipids synthesis
• Golgi: (Trans-golgi-network) site
where synthesized proteins and other
materials are sorted, modified and
from where they are transported to
specific cellular destinations.
• Mitochondria: site of energy
metabolism in aerobic organisms
where oxygen is the molecular
acceptor of electrons. (Can be Site of RNA
editing, discuss Hydrogenosome)

• Cellular vesicles that are membrane

enclosed compartments involved in
molecule secretion as well as soluble
molecule and particulate entry into
the cell (endocytosis and
phagocytosis).
 The Eukaryotic Cell
• Membrane enclosed compartments
- Compartmentalized Functions
• The Plasma Membrane
• The cell cytoskeleton/motility
• Other cell organelles – Golgi, Mitochondria,
Endoplasmic reticulum
• Signal Transduction and Cell activation
– Endocytosis and phagocytosis
– Release of cytokines
• Nucleus
Signal Transduction
 Examples of signal transduction schemes
initiated at the plasma membrane
G protein coupled receptors (GPCR).
Lipid mediated signaling – PI3K signaling
It is initiated by several receptors
including phagocytic receptors and insulin
receptor
 Signal Transduction/cell activation

- Activation of enzyme activity

- Change in cytoskeletal permeability
- Activation of DNA synthesis
- Activation of RNA synthesis

- Secretion of proteins: toxins, proteases, cytokines etc

Schematic representation of the endocytic
pathway of mammal cells.
The several modes of pinocytosis are
represented at left: clathrin-dependent,
caveolin-dependent and one type of
clathrin- and caveolin-independent
endocytosis use dynamin to promote
vesicle budding; fluid-phase
pinocytosis, especially from GPI-
anchored protein-rich domains does not
use dynamin for budding. The resulting
vesicles fuse with the sorting
endosomes that deliver molecules to an
acidic environment that allows
recycling of some molecules to the
plasma membrane. The right side of the
scheme depicts internalization of big
particles by phagocytosis or big fluid
volumes by macropinocytosis, both by
emission of membrane projections
sustained by actin filaments. The
vacuoles thus formed join endocytic
pathway by successive fusion with
endosomes and lysosome.
 Endocytosis
• The uptake of particles
• Soluble molecules and small particulate
molecules are internalized by endocytosis
(bulk-phase endocytosis or receptor mediated
endocytosis)
• Internalized material is trafficked through
vesicles interconnected by tubules and are
collectively called endosomes.
• Endosomes are divided into two distinct
classes: early endosomes and late endosomes
are distinguished on the basis of buoyant
density, pH and protein composition.
• Internalized particles are moved from
endosomes into the Lysosome, the terminal
compartment in the endocytic pathway.
Lysosomes are hydrolytic organelles that
contain numerous degradative enzymes.
Endocytosis in Trichomonads
 Phagocytosis
• Phagocytosis is the process by
which specialized cells
(macrophages, neutrophils, dendritic
cells) internalize particulate material
greater than 0.5um in diameter.
• It is a receptor mediated process.
Phagocytic receptors fall in two
classes: opsonin-dependent
(opsonins are blood-borne factors
that can coat particles to be
ingested); and non-opsonin
dependent (pattern recogniton
receptors).
• Phagocytosis is actin dependent.
• Phagocytosed particles are enclosed
in phagosomes. Phagosomes may
eventually fuse with lysosomes.
 The Eukaryotic Cell
• Membrane enclosed compartments
- Compartmentalized Functions
• The Plasma Membrane
• The cell cytoskeleton/motility
• Other cell organelles – Golgi, Mitochondria,
Endoplasmic reticulum
• Signal Transduction and Cell activation
– Endocytosis and phagocytosis
– Release of cytokines
• Nucleus
 Nucleus
• DNA is packed into
chromosomes
• Most eukaryotic cells are
diploid.
• Some protozoa are haploid
at certain points in their life
cycle.
• During pairing of
homologous chromosomes,
cross over of chromosomes
may result in the formation
of recombinant
chromosomes.
• Asexual vs sexual
reproduction