Infectious diseases related to pathology

1. INFECTIOUS DISEASES

2. Infectious Diseases
 An infectious disease is a disease resulting
from the presence of pathogenic microbial
agents, including viruses, bacteria, fungi,
protozoa, multicellular parasites and aberrant
proteins known as prions. These pathogens
are able to cause disease in animals and
plants.

3. Mechanisms of Viral Injury
 Once viruses are inside host cells, they can
damage or kill the cells by a number of
mechanisms:
 1. Direct cytopathic effects: Some viruses kill
cells by-
 preventing synthesis of host macromolecules (e.g.,
host cell DNA, RNA, or proteins),
 by producing degradative enzymes and toxic proteins,
or

4.  For example, poliovirus inactivates cap-binding
protein, which is essential for translation of
host cell mRNAs but leaves translation of
poliovirus mRNAs unaffected.
 Some viruses can stimulate apoptosis by
production of proteins that are pro-apoptotic.
Viral replication also can trigger apoptosis of
host cells by cell-intrinsic mechanisms, such as
perturbations of the endoplasmic reticulum
during virus assembly, which can activate
proteases that mediate apoptosis (caspases).
Mechanisms of Viral Injury
(contd.)

5.  2. Antiviral immune responses: Viral proteins
on the surface of the host cells may be
recognized by the immune system, and the
host lymphocytes may attack virus-infected
cells. Cytotoxic T lymphocytes (CTLs) are
important for defense against viral infections,
but CTLs also can be responsible for tissue
injury. Acute liver failure during hepatitis B
infection may be accelerated by CTL-mediated
destruction of infected hepatocytes (a normal
response to clear the infection).
Mechanisms of Viral Injury
(contd.)

6.  3. Transformation of infected cells into benign
or malignant tumor cells: Different oncogenic
viruses can stimulate cell growth and survival
by a variety of mechanisms, including-
 expression of virus-encoded oncogenes,
 anti-apoptotic strategies, or
 insertional mutagenesis (in which the function of
host genes is altered by viral genes inserted into
the host genome)
Mechanisms of Viral Injury
(contd.)

7. Mechanisms of Bacterial Injury
Bacterial damage to host tissues depends on
the ability of the bacteria to adhere to host
cells, invade cells and tissues, or deliver
toxins. Pathogenic bacteria have virulence
genes that encode proteins that confer these
properties.

8. 1. Virulence of Intracellular
Bacteria
 Facultative intracellular bacteria infect either
epithelial cells, macrophages or both. The
growth of bacteria in cells may allow the
bacteria to escape from certain effector
mechanisms of the immune response (e.g.,
antibodies), or it may facilitate spread of the
bacteria.
Mechanisms of Bacterial Injury
(contd.)

9.  Bacteria have a number of mechanisms for
entering host cells. Some bacteria use the host
immune response to gain entry into
macrophages.
 Coating of bacteria with antibodies or the
complement protein C3b (opsonization)
normally results in phagocytosis of bacteria by
macrophages.
 Like many bacteria, M. tube rculo sis activates
the alternative complement pathway, resulting
in opsonization with C3b. Once coated with
Mechanisms of Bacterial Injury
(contd.)

10.  Within macrophages, most bacteria are killed
when the phagosome fuses with an acidic
lysosome to form a phagolysosome, but
certain bacteria elude this host defense. For
example, M. tube rculo sis blocks fusion of the
lysosome with the phagosome, allowing it to
proliferate unchecked within the macrophage.
Mechanisms of Bacterial Injury
(contd.)

11.  Gram-negative bacteria use a complex
secretion system to enter epithelial cells. This
system consists of needle-like structures
projecting from the bacterial surface that bind
to host cells, form pores in the host cell
membrane, and then inject proteins that
mediate rearrangement of the cell
cytoskeleton, facilitating bacterial entry.
Mechanisms of Bacterial Injury
(contd.)

12.  Figure: Molecules on the surface of gram-
negative and gram-positive bacteria involved in
pathogenesis.
Mechanisms of Bacterial Injury
(contd.)

13.  Once in the cytoplasm, bacteria have different
strategies for interacting with the host cell.
Shig e lla and E. co li inhibit host protein
synthesis, replicate rapidly, and lyse the host
cell within 6 hours.
Mechanisms of Bacterial Injury
(contd.)

14. 2. Bacterial
Toxins
 Any bacterial substance that contributes to
illness can be considered a toxin. Toxins are
classified as
 Endotoxins, which are components of the
bacterial cell, and
 Exotoxins, which are proteins that are secreted by
the bacterium
Mechanisms of Bacterial Injury
(contd.)

15. 2.1 Bacterial endotoxin:
 Bacterial endotoxin is a lipopolysaccharide (LPS) that is
a large component of the outer membrane of gram-
negative bacteria. LPS is composed of a long-chain fatty
acid anchor connected to a core sugar chain, both of
which are very similar in all gram-negative bacteria.
 The response to bacterial LPS can be both beneficial
and harmful to the host. The response is beneficial in
that LPS activates protective immunity in several ways,
including induction of important cytokines and
chemoattractants (chemokines) of the immune system
as well as increased expression of co-stimulatory
molecules, which enhance T-lymphocyte activation.
Mechanisms of Bacterial Injury
(contd.)

16.  However, high levels of LPS are thought to
play an important role in septic shock,
disseminated intravascular coagulation (DIC),
and adult respiratory distress syndrome,
mainly through induction of excessive levels of
cytokines such as TNF, IL-1, and IL-12.
Mechanisms of Bacterial Injury
(contd.)

17. 2.2 Bacterial exotoxins
Exotoxins are secreted proteins that cause cellular injury and
disease. They can be classified into broad categories by their
site and mechanism of action. These are briefly described
below:
 A)Enzymes: proteases produced by S. aure us
 B)Toxins: altering intracellular signaling or regulatory
pathways: ex. A-B toxins by V. cho le rae
 C) Neurotoxins: Neurotoxins produced by Clo stridium te tani
 D) Superantigens: Superantigens are bacterial toxins that stimulate
very large number of T lymphocytes. Ex. Superantigen produced by
Streptococcus pyogenes
Mechanisms of Bacterial Injury
(contd.)