Infectious Diseases
Categories of Infectious Agents
P. B. Casuela, Jr. MD, FSP
Prions – Prions – composed only of a modified host protein that can cause transmissible spongiform encephalopathy
Inflammation – tissue reaction to injury of whatever etiology
Viruses – Viruses – obligate intracellular parasites that are dependent on host cell metabolism for their replication
Infection – tissue reaction to injury due to microbiologic agents
-
Classified by the nucleic acid content of the core (DNA or RNA) and by the shape of their protein
Importance of Infectious Diseases 1.
They are major causes of morbidity and mortality
2.
Greater transmission (vertical or horizontal) than any
coat or capsid
elements that encode bacterial virulence factors
other disease. 3. 4.
Bacteriophages, Plasmids, Transporons – Transporons – mobile genetic -
Versatile diseases evolving and adapting through
Can infect bacteria and incorporate themselves
time.
in their genome --> converting to virulent one or
Some are self-limiting and requires no specific
an antibiotic-resistant one -
treatments.
Exchange of these elements between strains & species endow survival advantage
5.
Many are preventable.
6.
Association with congenital diseases:
Varicella (German measles) -
multiple
congenital
anomalies
Bacteria – Bacteria – prokaryotes that lack nuclei and ER -
Relatively rigid cell wall, classifiable as gram (-) or Gram (+)
-
Syphilis
Bacteria synthesize their own DNA, RNA and proteins, but depend on the host for favorable
HIV 7.
conditions
Association with neoplastic conditions -
Enterobacter pylori – gastric CA
Second to viruses as most frequent & diverse class of human pathogen
Herpes (Type 2) genitalis virus and HPV – squamous cell carcinoma of the cervix
Chlamydiae, Rickettsia and Mycoplasmas – Mycoplasmas – similar to bacteria in that they divide by binary fission and are
Ebstein-Barr virus – Nasopharyngeal CA
susceptible to antibiotics but lack:
Burkitt’s lymphoma S. japonicum ,Aspergillus flavus: Hepatocellular CA
-
Cell wall – Mycoplasma
S. hematobium: urinary bladder transitional cell CA
-
ATP synthesis – Chlamydia
Clonorchis sinensis & Opistorchis felineus
cholangiocarcinoma
Transmitted by insect vectors - Rickettsia
Fungi – Fungi – possess thick, ergosterol-containing cell walls and grow as perfect, sexually producing forms in vitro and as
Epidemiology – Epidemiology – Branch of medicine dealing with the incidence
imperfect forms in vivo, which include budding yeasts and
and prevalence of diseases in large populations and with
hyphae -
detection of the source of epidemics of infectious disease.
Classified as: Dermatophytes Dermatophytes Subcutaneous
Incidence Rate – Rate – occurrence in 100,000 population per given time
Systemic Opportunistic
Protozoa – Protozoa – parasitic, single-celled organisms endowed
Prevalence – widespread; of wide extent or occurrence
with motility, pliable plasma membranes and complex
Endemic – Endemic – belonging exclusively or confined to a particular place.
cytoplasmic organelles -
Epidemic – Epidemic – affecting many persons at the same time and
Classified as: Flagellates Intestinal
spreading from person to person in a locality where the diseas
is not permanently prevalent.
Blood-borne
Helminths – Helminths – parasitic worms that are highly differentiated multicellular organisms
Pandemic – Pandemic – prevalent throughout an entire country , continent,
-
or the whole world.
With complex life cycles; most alternate between sexual reproduction in definitive hosts and asexual reproduction in intermediate hosts
General Principles of Microbial Pathogenesis Pathology deals with host response to different infectious
Ectoparasites – Ectoparasites – arthropods (lice, ticks, bedbugs, fleas) that attach and live on the skin
agents, the different classes of agents, their mode of
-
transmission, how they cause disease, and possible outcome
Can be vectors for other pathogens
(biologic behavior). Transmission and Dissemination of Microbes The Triad
Patient: Patient: Age
Hosts Barriers to Infection -
secretory-excretory products
Physiology Genetics
-
Respiratory tract – tract – mucociliary blanket of upper air passages, cough reflex, alveolar macrophage
Immune state Malnutrition
st
1 – intact host skin, mucosal surfaces & their
-
GIT – GIT – acid gastric juice, viscous mucous layer covering the gut, lytic pancreatic enzymes & bile detergents, secreted IgA antibodies
Environment:
Infectious Agent:
Extraneous factors
“Koch’s Postulate”
Sanitation
Pathogenicity/Virulence
serves as a defense against invading microorganisms,
Climate and temperature
Tropism
vagina with low pH is protective
-
-
GUT – GUT – regular flushing of the urinary tract with urine
Skin – Skin – dryness and constant shedding of impermeable keratinized epithelium and competition from commensal bacteria st
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Spread and Dissemination of Microbes -
Some microorganisms proliferate locally at site of infection
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Others penetrate the epithelial barrier & spread to other sites via the lymphatics, the blood, or nerves
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Major manifestations of infectious disease may arise at sites distant from those of microbe entry
-
Placental-fetal route is an important mode of transmission
Release of Microbes from the Body -
In transmission of disease, exit of the organism in the host’s body is as important as its entry
-
Depends on the location of the infection: skin shedding, coughing, sneezing, voiding in urine/stool, through insect vectors
Mode of transmission:
Respiratory, fecal-oral, sexual routes, direct contact, through blood & blood products, through vertebrate & invertebrate vector, zoonotic transmission How microorganisms cause disease
Infectious agent can contact or enter host cells and directly cause cell death
May release toxins, enzymes
Viruses once inside the host cells can
Can induce host cellular responses (though directed
kill &/or cause tissue damage thru:
against the invader) cause additional tissue damage,
1.
Inhibit host cell DNA, RNA or protein synthesis
usually immune-mediated
2.
Viral proteins may insert into the host cell’s plasma membrane & directly damage its integrity/ promote
Mechanisms of Viral Injury
cell fusion
Viruses can directly damage host cells by entering them and
3.
May lyse host cells
replicating at the host’s expense
4.
May manipulate programmed cell death (apoptosis)
5.
Viral proteins on the surface of the host cells
Tissue tropism -
recognized by the immune system will cause
Predilection of viruses for certain cells and not others
Factors that determine tissue tropism: 1.
Host cell receptors for the virus (major)
2.
Cellular transcription factors that recognize viral enhancer & promoter sequences
3.
Anatomic barriers
4.
Local temperature, pH, host defenses
lymphocytic attack 6.
May damage cells involved in host antimicrobial defense, leading to secondary infections
7.
Viral killing of one cell type may cause the death of other cells that depend on them
8.
Some can cause proliferation & transformation transformation of cells resulting in cancer st
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Mechanisms of Bacterial Injury 1.
Bacterial Virulence – Virulence – depends on the ability of the
Spectrum of Inflammatory Responses To Infection 1.
bacteria to adhere to host cells, invade cells and
Suppurative Inflammation (Neutrophils) -
tissues, or deliver toxins o
extracellular gram positive cocci and
Pathogenic bacteria have virulence genes
gram-negative rods
that encode proteins that confer these
o
-
Secondary to/increased by vascular permeability
properties – grouped together in clusters
and leukotaxis of neutrophils attracted by
called “ pathogenicity islands” islands”
bacterial peptides, which contains N-formyl
Increase in concentration in tissues of
methionine residues
bacteria will increase virulence factors 2.
Caused by “pyogenic” bacteria, mostly
-
Follows the path of acute inflammation
Bacterial Adherence to Host Cells o
Adhesins – bacterial surface molecules that
bind o
-
Fibrillae – covering the surface of Gram(+)
Vascular events
Cellular events
Recruitment of leukocytes into the site of infection
organism, S. pyogenes composed of
lipoteichoic acids and M protein, protein F o
neutrophils towards the site of
Fimbriae or pili – – filamentous proteins on
inflammation
the surface of Gram (-) bacteria, tip determine 3.
Chemotaxis – emigration of
Chemoattractant - most common exogenous agent are bacterial
Virulence of Intracellular Bacteria
products
Facultative intracellular bacteria infect either
•
epithelial cells, macrophages or both 4.
5.
Peptides that contains N-formylmethionine terminal
Bacteria may reproduce within the
amino acid and some
phagolysomes or cytosol
chemoattractant.
Bacterial endotoxin is a lipopolysaccharide that
•
Binds to specific
induces fever via host lymphokines, including tumor
transmembrane G
necrosis factor and interleukin-1.
protein-coupled receptor on
Bacterial exotoxins are composed of a binding part
the surface of leukocytes.
and a catalytic part, which ADP-ribosylates and
o
inactivates host proteins or degrades host proteins
Initiates reaction within leukocytes with the end result
Immune Evasion by Microbes
of the leukocytes migrating towards
Microbes avoid the host immune response by:
the stimulus
Remaining inaccessible within the lumen of th e small
-
intestine or rapidly entering host cells
Leukocytes infiltration varies with the age of inflammatory response and the type of stimulus.
Producing a capsule that covers antigens and
prevents phagocytosis
Changing their surface antigens
Infecting lymphocytes and damaging the host
and disappear after 24 to 48 hours
Respond more rapidly to chemokines
Attached more firmly to the adhesion
Special Techniques for Diagnosing Infectious Agents
Neutrophils first appear because they are numerous in the circulation
immune system
Leukocytes 6 – 24 hours. Apoptosis
molecule
Some can be directly observed in hematoxylin and
-
Disappear after 48 hours
eosin-stained sections
-
Exceptions – like pseudomonas – continuous
Best visualized after special stains that identify
recruitment of neutrophils for several days
organisms based upon particular characteristics of
their cell walls or coat.
Recognition of microbes
Cultures of lesional tissues are performed to separate
organisms and determine drug sensitivity
Activation of leukocytes at the site of inflammation by: o
Recognition of the offending agents, which delivers the signal
Gram stain
Most bacteria (Gram (-); (+)
Acid fast stain
Mycobacteria, Nocardia
o
Activate the leukocytes to ingest and destroys the offending agents
(modified)
o
Amplify the inflammatory reaction
Receptors for microbial products –
Silver stains
Fungi, Legionella, Pneumocystis
Periodic acid-Schiff
Fungi, amoebae
Mucicarmine/india ink
Cryptococci
Giemsa
Campylobacteria, Leishmania,
o
Bacterial lipopolysaccharide
malaria, Herpes
o
Bacterial proteoglycans and lipids
Antibody probes
Viruses, ricketssiae
o
Unmethylated CpG nucleotide
Culture
All classes
DNA probes
Viruses, bacteria, protozoa
(TLRs) Toll-like receptors
Response to:
G protein-coupled receptors o
Found in neutrophils, macrophages and other leukocytes
o
Attracted by N-formylmethionyl st
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Characteristic nuclear changes
o
Also recognizes chemokines, C5a
o
Bindings of these ligands to G protein
-
Multinucleation
couple receptor induces migration of
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Molding of nuclei
leukocytes from blood also activation of
-
Margination of chromatin
respiratory burst
Receptors for opsonins- coating of microbes to target
Formation of Inclusion Bodies
it for phagocytosis
o
o
o
Alteration of cytoskeleton organization by virus infection
C3 – also potent opsonin
Binds to microbes and phagocytes
Expresses a receptor called Type 1
microtubules, and intermediate filaments
complement receptor (CR1)
throughout the cytoplasm. Infection with
o
Normal cells have networks of
Receptors for cytokines – leukocytes
reovirus causes a perinuclear aggregation of
expresses receptors for cytokines that are
microtubules, and infection with
produced in response to microbes.
cytomegalovirus causes a modification of
Interferon-γ – secreted by natural killer cells
intermediate filaments proteins, including
reacting to microbes and by antigen
their relocation into the nuclear and
activated T-lymphocytes during adaptive
cytoplasmic inclusion bodies.
immune response
Major macrophage-activating cytokines.
Furuncle or boils – recurrent, most frequent in moist hairy areas
2.
Mononuclear and granulomatous Inflammation -
Induced by viruses, intracellular bacteria, spirochetes, intracellular parasites, or helminths
-
Includes mostly lymphocytes or macrophages, depending upon the characteristics of the organism and the host plasma cells – syphilis
least two processes: first, the cell gains the capacity
Syphillis with plasma cell infiltrates 3.
for unlimited cell division (immortalization), and second, the immortalized cells acquire additional
Cytopathic-Cytoproliferative Inflammation -
heritable genetic changes by which the cell is able to
characterized by virus-mediated damage to
produce a tumor in an appropriate host.
individual host cells in the absence of host inflammatory response -
may show inclusion bodies (CMV), polykaryons, blisters and warty changes
-
Polykaryon – cell to cell fusion. Mechanism is poorly understood
Stages of Transformation: Transformation : Transformation involves at
Mechanisms of Oncogenic Transformation : There are two general patterns by which cell transformation may be accomplished: 1) the tumor virus may introduce and express a so-called transforming gene in the cells or 2) the tumor virus may alter the expression and (or) coding capacity of preexisting cellular genes. After development of a malignant phenotype the relevant segment(s) of the viral genome may or may not be retained in the transformed cells, depending on the mechanism of transformation. These mechanisms are not mutually exclusive, and both may occur in the same cell.
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Common Infectious Diseases Involving Different Organs Skin:
Development and progression of viral cytopathology Human embryo skin muscle cells were infected with human cytomegalovirus and stained at selected times to demonstrate (A) uninfected cells, (B) late virus cytopathic effects (nuclear
Furuncle
Carbuncle
Exanthematous diseases
Herpes
Tinea
Leprosy (Hansen’s disease)
Viral and bacterial meningitis/encephalitis/
NS:
inclusions, cell enlargement), (C) cell degeneration, and (D) a
meningoencephalitis
focus of infected cells in a cell monolayer (i.e., a plaque),
Rabies
Tetanus
Necrotizing Inflammation
Abcess
-
Poliomyelitis
hematoxylin and eosin stain. 4.
Caused by uncontrolled viral infection (eg fulminant hepatitis B infection), secreted bacterial toxins (Clostridium perfringes), or
-
Head & Neck:
contact- mediated cytolosis of host cells by
Conjunctivitis
protozoa (E. histolytica)
Mumps
Results in severe tissue necrosis in the absence of inflammatory infiltrates
Respiratory:
Pneumonia
Tuberculosis
URTI
Diphtheria
Bronchitis
Viral myocarditis
Acute gastro-enteritis
Diarrheal diseases
CVS:
GIT:
Caused by toxins:
E.g , α-toxin of C. Perfringens – o
Has phospholipase C that degrades lecithin
Viral
o
E. coli
o
Bacillary dysentery
o
Typhoid fever
o
TB enteritis
o
Amebiasis
Hepato-Biliary: Hepatitis
Has spingomyelinase – nerve sheath
Abscess
damage
Schistosomiasis
Cause myonecrosis
HBV – massive apoptosis o
o
o
Cholera
Infectious ulcerative diseases
Tissue necrosis
o
Cause fulminant hepatitis
GUT:
E. Histolytica – cytotoxic to epithelial cells,
UTI,
neutrophils and macrophages
STD (Gonorrhea, Chlamydia, Trichomosiasis, Syphilis,
o
Adherence to target cells
o
Complement mediated
Tuberculosis, HIV, HPV) Hematopoietic:
5.
Chronic Inflammation and Scarring
Dengue H. fever
-
Malaria
Caused by certain acute infections (Gonococcal salpingitis) or chronic infections (Schistosomiasis)
-
May be severe despite a paucity or organisms present (M. tuberculosis)
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