Introduction to Infectious diseases: Host
Pathogen Interactions pg.695-699
With the advent of antimicrobials as a defense to
infectious agents we believed that soon these
agents will be eliminated , but microbes
developed resistance to these antimicrobial
(antibiotic resistance)
Ex. Pnemococci- penicillin
Enterococci and Staph.- Vancomycin
1999 outbreak in N.Y. of encephalitis due to
West Nile virus
2003 SARS was first recognized, caused by
corona virus.
The role of infectious agents in the etiology of a
disease once believed to be non infectious
H.pylori- peptic ulcer and gastric malignancy
Papilloma- most impt. cause of invasive
cervical cancer
Herpes virus type 8- Kaposis sarcoma
EBV- Lymphoma and Hodgkins disease.
Other possible diseases of unknown cause
but may have infectious etiology
Rheumatoid arthritis
Sarcoidosis
Inflam. Bowel dse
Emergence of infectious dse due to
Increase in population
Immunocompromised host- to prevent
transplant rejection and treat ca. and
inflammatory dse.
-some
infections like HIV, Influenza and
Syphilis
AIDS has brought to prominence once-obscure
organism Pneumocyctis, C. parvum and M.
avium.
Host factors in infection
For infectious process to occur ther must be a
susceptible host and a virulent organism
There are many host factors to be
considered like
-age, immunizations, prior/coexisting
illness, nutrition, preg., emotional state,
level of host defense (immune system)
- Medical care
-1) contact with pathogen
during hospitalizations 2) breaching
of skin or mucosal surface 3) intro of
foreign bodies 4) alteration of natural
flora with the use of antibiotics and
5)treatment with immunosuppressive
drugs.
The immune response
Innate immunity
-exploit molecular patterns found
specifically in pathogenic org. (pattern
signatures) these are recognized by host
molecules that directly interfere with the
pathogen. Innate immunity serves to protect the
host without prior exposure to an agent, it also
functions as a warning system that activates
component of adaptive immunity.
Ex.
Defensins- simple peptides found on
the skin and mucosal surfaces
Macrophages- engulf and kill microbes
Complement system
Example of response
Lipopolysaccharide (LPS)- even
minute amount are detected by LPS
binding proteins, CD4 and toll-like
receptor 4, there would also be
production of cytokines by
macrophages via transcriptional
activator NFkB. This would lead to
inflammation and secretion of enzymes
that enhance clearance of microbes. It
also initiates specific or adaptive
immune response.
Adaptive immunity
Cellular immunity
T-lymphocytes, macrophages,
NKcells
- primarily recognize and combats
micro. that proliferate intracell.
Ex.-Bacteria (Mycoplasma,
Chlamydia, Listeria, Salmonella and
Mycobactria) Parasites (Trypanosoma,
Toxoplasm and Leishmania) and Fungi
(Histoplasma, Cryptococcus and
Coccidiodes)
T-lymphocytes- activated by macrophage
and B-lymphocytes, w/c serves antigen
presenting cells
-once activated it may act as
Cytotoxic t-cell directly attacking the
organism or Helper t-cell w/c stimulates
the prolif of b-cells and the procuction
of Ig.
T-cell and B-cell communicate with
each other Ex. Stimulation ofCD40-↑
B-cell response
Stimulation of B7-CD28
activation of CD4- helper T-cell
-elaborate cytokines
(interferon) tat inhibit growth of
pathogen or stimulate killing by
macrophages and cytoxic T-cells.
Cytokines also augment immunity by
stimulating inflammatory response
 (fever, acute phase reactants and prolif
of WBC) adverse effect of cytokines-
Septic and toxic shock.
Reticuloendothelial system (RES)
Comprised of monocyte derived
phagocytic cells found in:
Liver- Kupffer cells
Lungs- Alveolar macrophage
Spleen and Kidney- Mesangial
Brain- Microgial
Lymphnode
They clear organism by killing them but
they work more efficiently when
pathogen are first opsonized by
complement system such as C3b and/or
antibodies.
Humoral immunity
Composed of Antibodies, Complement
cascades and phagocytic cells- targets
extracellular pathogens including most
of the encapsulated organism(complex
polysaccharide coat)
Antibodies- Ig- are complex
glycoproteins that are produced by
mature B-cells that circulate in body
fluids, and are secreted on mucosal
sufaces.
- they specifically recognize
and bind to foreign antigens and not
reacting with self.
Classes of Ig
Ig G- predominates and persist
Ig M- earliest
Ig A Secretory- found mucosal surfaces
Ig A Monomeric- found in serum
Ig E- allergy and parasitic
Function
Directly impede pathogen
Neutralize secreted toxin and enzymes
Facilitate removal of antigen
Participate in cell mediated immunity
by promoting antibody
dependent cell cytotoxicity
Promote deposition of complement
components on the surface of org.
Complement system- consist of
group of serum proteins that function
cooperatively, self regulating enzymes
that adhere to-, disrupt- surface of
pathogen. Adherent protein like C3b
can act as opsonin. The terminal
components C78&9 can directly kill
pathogen (esp. Neisseria) by forming
the Membrane Attack Complex (MAC)
and disrupting the integrity of
pathogens membrane. Another
component the C5a- act as a
chemoattractant for PMN.
Complement activation
Classical- activated primarily by
immune complexes (antibody bound
to antigen)
Alternative- activated by microbial
component, frequently in the absence
of antibody.
PMN’s- short lived WBC that engulf
and kill invading microbes, are first
attracted to inflammatory sites by C5a.
they localize to the site by adhering to
cellular adhesion molecules expressed
in the endothelial cells (selectins-
CD62, ELAM-1)in response to
inflamm. Cytokines like TNFα and
interleukin-1.Cytokine mediated
upregulation and expression of ICAM-1
on endothelial cell then later this
receptor binds to β2 integrins on PMN
thereby facilitating diapedesis
Laboratory investigation
Should be directed at est. an etiologic
dx. In the shortest possible time, lowest cost and
least discomfort to the patient. Cultures must be
performed in manner that minimizes
contamination to maximize the yield. Gram
staining should be interpreted carefully and
should correspond to the culture result. In case
where a diagnosis appears difficult, serum should
be stored during the acute phase of the illness for
detection of antibody titer. Bacterial and fungal
antigens can sometimes be detected in body
fluids. PCR for amplification of minute amounts
of forign nucleic acids.
Treatments
Life threatening conditions –such as
Bacterial meningitis or sepsis, Viral encephalitis,
or malaria(falciparum ) must be treated
immediately, often before a specific causative
agent is identified.
Antimicrobials must be chosen
empirically and must be active against the range
of potential agent.
Direct toxicity of animicrobials
Ex.
Ototoxicity- aminoglycosides
Lipodystrophy-anti-retroviral
Hepatotoxicity- Isoniazid and
Rifampicin
Allergic reaction are common
and can be serious
Tharapy should be directed toward as
narrow a spectrum of infectious agents
 as possible to prevent superinfection
and eradication of normal flora.
In case of abscess it requires surgical
or percutaneous drainage for treatment
Surgical removal in cases of foreign
body, necrotizing fasciitis peritonitis
due to perforated organ, gas gangrene
and chronic osteomyelitis.
Glucocorticoids- H.influenza
meningitisin children and Pneumocystis
pneumonia in patients with AIDS
Activated C proteins- is the first
immunomodulatory agent for treatment
of sepsis. Other agents are
Prostaglandin inhibitors, lymphokines,
and TNF inhibitors.
Specific antibody- Rabies and
Tetanus. Also CMV
Perspective
The genetic simplicity of many infectious agents
allows them to undergo rapid evolution. Plus the
changes in the environment and host can
predispose to a particular infection.
Environmental changes, rapid global travel,
population movements and medications all
increases the impact of infectious dse.
Development of new vaccine, antibiotics and
modalities of treatment and prevention, however
pathogenic microbes will also continue to
develop new strategies of their own presenting
us with UNENDING and DYNAMIC
CHALLENGE!!!!!!!!!!!!!!!!!!!!!!

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