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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)


About assignments
• All assignments for the 2023 class will be
announced.
• Beware of assignments from previous years
that are accessible on the web.
• If the assignment is not announced on the
course website, it is not valid.
Neglected tropical
diseases
• Neglected tropical diseases (NTDs) are a
diverse group of 20 conditions that are mainly
prevalent in tropical areas, where they mostly
affect more than 1 billion people who live
mostly impoverished communities. They are
caused by a variety of pathogens including
viruses, bacteria, parasites, fungi and toxins.
These diseases cause devastating health,
social and economic consequences to more
than one billion people.

• They are ‘neglected’ because they are almost


absent from the global health agenda. Even
today, when the focus is on Universal Health
Coverage, NTDs have very limited resources
and are almost ignored by global funding
agencies. NTDs are diseases of neglected
populations that perpetuate a cycle of poor
educational outcomes and limited
professional opportunities and are associated
with stigma and social exclusion.
Neglected Tropical Diseases Worldwide Burden
Global Prevalence Population at Risk
Disease DALYs (million) Deaths/Yr
(million) (million)

Schistosomiasis 4.5 280,000 207 780

Hookworm 22.1 65,000 576 3200

Ascariasis 10.5 60,000 807 4200

Leishmaniasis 2.1 51,000 12 350

Trypanosomiasis 1.5 48,000 0.3 60

Chagas disease 0.7 14,000 8 25

Trichuriasis 6.4 10,000 604 3200

Leprosy 0.2 6,000 0.4 ND

Lymphatic filariasis 5.8 0 120 1300

Trachoma 2.3 0 84 590

Onchocerciasis 0.5 0 37 90

Cryptococcosis 12 400,000 1 8

(Disability-adjusted life years Wikipedia


(DALYs))
What you should know
• Difference between the innate and adaptive immune
systems (components of each system)
• The effectors of the innate immune system

• Basic structure of antibodies and functions of subtypes


• Development and tracking of the immune response
• What do antibodies see?
• What do T cells see?
• Histocompatibility and antigen presentation
• Effectors of adaptive immune system.
Classification of defense
mechanisms
Overview of the host’s response to
infection
The Immune Response:
I. Innate immunity
The Innate Immune response is defined as that
which the body mounts deploys without previous
contact with a microbe. It is not specific to a
microbe.
• Components of innate immunity:
– outer surface of body (skin)
– Linings of internal tracts
– secretions
– Phagocytic cells (macrophages, neutrophils), natural
killer cells and other bone marrow-derived cells.
– Soluble blood proteins: Complement
Effectors of innate immunity

• Induction of inflammation at site of infection; release


of chemical mediators – Interferons; complement
components …
• Phagocytosis
• Complement-mediated lysis

• Vertebrates and non-vertebrates may utilize similar


processes or mechanisms to resist infection.
Overview of the host’s response to
infection
Cells of the Immune System
(participate in inflammation)
Definitions
• Antigen - molecules that react with antibodies or T cells
– Antibody: plasma proteins produced by B cells that bind
specifically to antigens
– Immunogen: those antigens that can induce specific
immune response such as antibody production.
– Antigenic determinant (epitope): portion of antigen that is
bound by a given antibody or recognized by T cell
– Immunization: deliberate induction of an immune
response.
– Antiserum: fluid component of clotted blood that contains
antibodies. These antibodies are reactive to molecules
used for immunization or to pathogen molecules during an
infection.
II. Adaptive Immune Response

• Characteristics:- Is highly specific to infectious agent.


– Requires a lag period. Lag period shortens with each
encounter
– The magnitude of the response increases with each
encounter.
– Affinity to agent increases with exposure.
• Two categories of adaptive immunity:
– Humoral Immunity - responses attributed to
molecules in plasma, primarily antibodies (products of B
cells).
– Cellular Immunity - responses carried out by cells,
primarily T cells.
Antibody structure and function
• Are globular proteins produced
by B cells
• Are built of two types of
polypeptide chains: 2 heavy
chains and 2 light chains.
• Both chains are linked by
disulphide bonds.
• Each chain has a variable region
and a constant region.
• The variable regions of each
heavy and light chain form an
antigen binding site.
• Each antibody has two
equivalent antigen binding sites
Antibody structure and function cont’d

• Five different classes of antibodies distinguished by


heavy chains called Isotypes
– Immunoglobulin A (IgA) (Can form dimers)
– IgD found primarily on B cell surface
– IgG has 4 subclasses IgG1, IgG2, IgG3, IgG4
– IgM (can form pentamer)
– IgE (associated with hypersensitivity responses)
• Each isotypes is found in varying amounts at distinct
sites where they carryout their functions.
Antibody isotypes and their functions?
Each one is labeled by a letter, which is attached to an abbreviation of the term
“immunoglobulin” (Ig):
Antibody Type Function

Found in saliva, tears, mucus, breast


IgA milk and intestinal fluid, IgA protects
against ingested and inhaled pathogens.
This antibody is found on the surface of
your B cells. Though its exact function is
IgD
unclear, experts think that IgD supports
B cell maturation and activation.
Found mainly in the skin, lungs and
mucus membranes, IgE antibodies cause
your mast cells (a type of white blood
IgE cell) to release histamine and other
chemicals into your bloodstream. IgE
antibodies are helpful for fighting off
allergic reactions.
This is the most common antibody,
making up approximately 70% to 75% of
all immunoglobulins in your body. It’s
IgG
found mainly in blood and tissue fluids.
IgG antibodies help protect your body
from viral and bacterial infections.
Found in your blood and lymph system,
IgM antibodies act as the first line of
IgM
defense against infections. They also
play a large role in immune regulation.
Copied from a Cleveland Clinic publication on antibodies
Illustration of select antibody
functions
Functions of antibodies by isotype
Antibody functions
Recombination of germline gene segments in B cells and T cells to
produce antigen receptor

RNA BIOLOGY
2017, VOL. 0, NO. 0, 1–10
Analysis of the immune response in serum
Clonal selection theory
• Each B cell (and T cells)
becomes committed to produce
one species of antibody
(antigen receptor for T cells).
• B cells become committed to
antibody formation in the
absence of antigen.
• Antibody production follows
selection of B cells by antigen.
• There is affinity maturation
• Immunological memory
provides long-term immunity.
What do antibodies see?
- The region of an antigen to which
an antibody binds (called the
epitope) is determined by the
configuration of the antigen.

- An antigen can have more than 1


epitope.

- Antibody recognizes antigen in


its natural conformation
(configuration)
Antibody function cont’d
What do antibodies see?
T cells

• Develop in the thymus.


• Have an antigen receptor with similar characteristics as antibodies,
but they are not shed.
• Activated by clonal selection.
• Do not bind to antigens in their native conformation.
• Bind to antigen fragments displayed on the surface of another cell.
What do T cells see?
• The process by which antigens are
acquired, degraded and displayed
on the cell’s surface is called
antigen processing and
presentation.
• The molecule on which the
antigenic fragment is displayed is
called a Major Histocompatibility
Complex molecule (MHC) or Human
Leukocyte Antigen (HLA).
• There are two class of MHC
molecules: MHC Class I and MHC
class II.
• MHC class I binds to peptides from
molecules that are synthesized by
the cell or found in the cell
cytoplasm (Endogenous antigen).
• MHC class II binds peptides from
molecules that are internalized by
cell (Exogenous antigen).
Antigens from distinct sources are processed
through the endogenous or exogenous pathways
Distribution of MHC class I and Class II molecules
on all types of cells
Antigens from distinct sources are processed
through the endogenous or exogenous pathways
T cell Subsets and function CD8 CD4
Two types of T cells are distinguished by
their interaction with MHC molecules
and by molecules on their surface
CD8+ T cells (cytotoxic cells) interact with
MHC class I.
CD4+ T cells (helper cells) interact with
MHC class II.
Further division of CD4+ T cell on the
basis of the cytokines they produce and
their function:
TH1 secrete IL2 and Interferon
gamma;
TH2 cells secrete IL4, IL5 and IL10
CD4+ T cells and CD8+ T cells respond
to antigens from different sources
Cytokines
Classification of pathogens by the
immune response
T helper 2 response - Common
Features
• CD4+ T cells
– Elaboration of cytokines: Interleukin 4 (IL-4), IL-
5, IL-9, IL-13, IL-21 [IL-17(E) –role in worm
expulsion?)
– IL-10 (a wildcard) can be produced by Th1 and
Th2 cells. Regulates both of these responses
• Alternatively activated macrophages,
neutrophils
• Other cell types: Plasma cells secreting IgE;
basophils, mast cells
What do T cells see?
• The process by which antigens are
acquired, degraded and displayed
on the cell’s surface is called
antigen processing and
presentation.
• The molecule on which the
antigenic fragment is displayed is
called a Major Histocompatibility
Complex molecule (MHC) of Human
Leukocyte Antigen (HLA).
• There are two class of MHC
molecules: MHC Class I and MHC
class II.
• MHC class I binds to peptides from
molecules that are synthesized by
the cell or found in the cell
cytoplasm.
• MHC class II binds peptides from
molecules that are internalized by
cell.
Overview
Recombination of gene segments in B cells and T cells to produce
antigen receptor

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