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Viruses
• Small amounts of genetic material
surrounded by a protein envelope

Viruses and Immunology • Pathogens of bacteria, plants, and

animals
Prepared by: Pamela M. Aducal, RPh
Examples:
COVID-19,Ebola and Human
Immunodeficiency Virus (HIV)
Rhinovirus, which causes common
colds

Architecture of a Typical Virus Particle

Basis for Differentiating Viruses
• Presence of a genome of DNA or RNA
• Presence of an envelope
• Nature of the nucleic acid
• Linear versus circular
• Small versus large
• Single-stranded versus double-stranded
• Mode of incorporation
• Nucleic acid remains separate versus nucleic acid joins with host
chromosome

Vertebrate Viruses and Diseases they cause

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Virus Life Cycle: Lytic Pathway

• Involves the virus lysing the cell it
infected
• Virus binds to the cell membrane
and releases its DNA into the cell
• DNA is:
• Replicated by host DNA polymerases
• Transcribed by host RNA polymerases
• New virions are produced and
released from the cell

Virus Life Cycle: Lysogenic Pathway

• Viral DNA incorporates into the host DNA but does not
lyse the cell
• Example - Simian virus 40 (SV40)

Simian Virus 40 Life Cycle Mechanism of Viral Infections

- SV40 is a monkey virus that was • Virus must attach to the host cell before it can penetrate
administered to human populations by • Common method of attachment involves the binding of one of the spike proteins
on the envelope of the virus to a specific receptor on the host cell
contaminated vaccines which were
produced in SV40 naturally infected • Example - HIV attachment to a helper T cell
monkey cells.

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Retroviruses Life Cycle of a Retrovirus

• Replication is backward compared to the central dogma of
molecular biology
• DNA is made from RNA
• Genome is a single-stranded RNA
• Once it infects the cell, the RNA is used as a template to make a
double-stranded DNA
• Enzyme used is a virally encoded reverse transcriptase
• DNA produced by reverse transcription must be
incorporated into the host DNA
• Facilitated by long terminal repeats (LTRs)

How Retroviruses act as a Vector in Gene Therapy

Importance of Retroviral Research
•Retroviruses have been linked to cancer
•AIDS treatment and finding a definitive cure are
among the primary goals of retroviral research
•Retroviruses can be used in gene therapy

Typical Retrovirus Genes Summary of Retroviruses

• Retroviruses have a genome based on RNA
• When they infect cells, their RNA is turned into DNA by RT
• DNA is then incorporated into the host’s DNA genome as a
part of the replication cycle for the virus
• Retroviruses all have certain genes in common
• Some retroviruses also have identifiably unique genes
• Example - Sarcoma oncogene carried by the Rous sarcoma
virus

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The Immune System Improper Functioning of the Immune System

• General term for many cellular and enzymatic processes that
allow organisms to defend themselves from bacteria, viruses, • Results in autoimmune
and parasites diseases
• Has the ability to distinguish self from nonself • Results in allergies
• Operations can be a matter of life and death
• Suppression can save lives as well as take them

Vaccine Functioning of the Immune System

• Weakened or killed form of an infectious agent that is injected into an
organism so that it will make antibodies against the true infectious agent • Important aspects to the immunity process
• Action of vaccines depends on exposure to the infectious agent in a • Those that operate on the cellular level
weakened form • Those that operate on the molecular level
• Immune system mounts an attack and retains memory of the • Essential to consider whether the immune system is
exposure acquired or whether it is always present
• In subsequent encounters, the immune system can launch a quick • Leukocytes
and effective defense

Innate Immunity Cells of the Immune System: Dendritic Cells

• Found in the skin, the mucous membrane, the lungs, and the spleen
•First line of defense in the immune system
• Use suction-cup-like receptors to grab onto invaders and then engulf
•Has several parts them via endocytosis
• Physical barriers • Travel through the lymph to the spleen, where they present the
antigens to helper T cells (TH cells)
• Cells of the immune system • Helper T cells release cytokines that stimulate killer T cells and B cells
• Dendritic cells • Members of a class of cells called antigen-presenting cells (APCs)
• Macrophages • Antigen-presenting cells: Display antigens on their surface and activate the
• Natural killer (NK) cells acquired immune system

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Dendritic Cells and the Other Cells of the Immune System Functions of Dendritic Cells

Cells of the Immune System: Natural Killer (NK) Cell Aspects of Acquired Immunity
• Member of a class of leukocytes called • Acquired immunity depends
lymphocytes on two types of lymphocytes
• Derived from a lymphoid stem cell • T cells
• Kills infected or cancerous cells • Killer T cells destroy infected
cells
• Secretes cytokines that call up other cells
• Helper T cells are involved in the
• Works with dendritic cells process of B-cell maturation
• Helps decide whether to activate the • B cells
acquired-immunity system
• Play a role in the production of
• Stimulated by interferon, which was antibodies
employed as treatment for cancer.

Two-Stage Process Leads to the Growth and Differentiation of T Cells

T-Cell Function
• As T cells differentiate, each becomes specialized for one of
several possible functions
• Killer T cells have T-cell receptors (TCRs) on their surfaces that
recognize and bind to antigens
• Proliferation of killer T cells is triggered when macrophages
bound to T cells produce small proteins called interleukins
• Killer T cells contain CD8, which helps them dock to the major
histocompatibility complex (MHC) of the antigen-presenting
cell

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Interaction between Killer T Cells and Antigen-Presenting Cells Clonal Selection

• Process by which only the cells that respond to a given antigen grow
in preference to other T cells

How Killer T-Cells work:

Killer T Cells
• Destroy antigen-infected cells by:
• Binding to them
• Releasing a protein that perforates the plasma membranes of infected cells
• Prevent the spread of viral infections by killing virus-infected host
cells
• Some memory cells remain when infection subsides and provide immunity
against later attacks from the same virus

Helper T Cells How Helper T Cells work

• Referred to as CD4 cells
• Help the cell dock to the MHC of the antigen-presenting cell

• Help stimulate killer T cells and antigen-presenting cells via

release of interleukins

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T-Cell Memory Antibodies

• Generation involves the death of most of the T cells that • Y-shaped glycoproteins
were generated by the first infection with a particular
antigen • Consist of two identical
heavy chains and two
• Small percentage of original cells that survive as memory cells
have a higher reproductive rate even in the absence of identical light chains held
antigen than does a naïve T cell together by disulfide bonds
• Each heavy chain and light
• Affected by various interleukins chain has a constant (C
• Interleukin 7 is involved in maintaining naïve killer T cells at domain) and a variable
low levels region (V domain)
• Interleukin 2 stimulates the proliferation of TC cells
• Interleukin 15 maintains memory TC cells

Antibodies (continued 1)
• V domain binds to the antigen
• Epitopes: Binding sites for antibodies on an antigen
• Each antibody can bind to two antigens
• Each antigen has multiple binding sites for antibodies

Antibodies (continued 2) Monoclonal Antibodies

• Antibody genes are inherited as small fragments that join to form a • Produced from the progeny of a single cell and are specific for
complete gene in individual B cells as they develop
a single antigen
• Enable the production of antibodies to almost any antigen in
quantity
• Used to assay for biological substances that can act as
antigens
• Two in one antibodies
• Useful tools against diseases that do not respond well to single
treatments

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Procedure for Producing Monoclonal Antibodies against a Protein Antigen X

Distinguishing Self from Nonself Distinguishing Self from Nonself (continued)

• If a cell’s receptors recognize self-antigens or MHC but with low
affinity, then the cell: • Some individual cells will still have a receptor with very low
• Undergoes positive selection affinity for a self-antigen
• Differentiates into a killer T cell or a helper T cell • Raise a requirement for a secondary signal
• If a cell’s receptors encounter self-antigens that are recognized • Several safeguards lead to the delicate balance that must
with high affinity, it undergoes a process called negative be maintained by the immune system
selection
• Negative selection (of DP cells): Process where a DP cell reacts to its
own antigens and is programmed for apoptosis, or cell death

Immune System: Summary Immune System: Summary (continued)

• Vertebrates have an immune system • Acquired immune cells also leave behind memory cells so
• Innate immunity consists of physical barriers and cellular that if the same pathogen is seen again, the body is faster to
warriors eliminate it
• Acquired immunity is based on T cells and B cells • Immune cells must be able to recognize self from nonself
• T cells and B cells are conditioned not to recognize proteins from
• Cells are generated randomly with receptors that can be
that individual
specific for an unimaginable number of antigens
• When cells encounter their specific antigens, they are • In some cases, the immune system breaks down, and a
stimulated to multiply person may be attacked by his or her own immune system
leading to an autoimmune disease