Host Defense against Infection
a.
The microorganisms that are encountered daily in the life of a healthy
individual only occasionally cause perceptible disease.
b.
Most are detected and destroyed within hours by defense mechanisms that
are not antigen-specific and do not require a prolonged period of induction:
these are the mechanisms of innate immunity.
c.
Innate immunity consists of:
i.
epithelial barriers (mechanical, chemical and microbiological) to
infection.
ii.
activation of alternative pathway of complement.
iii.
cellular immunity provided by phagocytes.
d.
The innate immune response also produce inflammatory mediators that
recruit new phagocytic cells to local sites of infection in an early
non-adaptive host response to infection.
e.
Only if an infectious organism can breach these early lines of defense
will an adaptive immune response ensue.
f.
The adaptive immune response:
i.
generates antigen-specific effector cells that specifically target the
pathogen.
ii.
memory cells that prevent subsequent infection with the same
microorganism.
2.
Principles of Innate and Adaptive Immunity
a.
The phagocytes of the innate immune system provide a first line of
defense against many common microorganisms and are essential to the control of
common bacterial infections.
b.
However, they cannot always eliminate infectious organisms, and there are
many pathogens that they cannot recognize.
c.
The lymphocytes of the adaptive immune system have evolved to provide a
more versatile means of defense that, in addition, provides an increased level
of protection from a subsequent re-infection with the same organism.
d.
The cells of the innate immune system play a crucial part in the
initiation and subsequent direction of the adaptive immune responses.
e.
Moreover, since there is a delay of 4-7 days before the initial adaptive
immune response takes effect, the innate immune response has a critical role in
controling infections during this period.
3.
Phases of Immune response
a.
Innate Immunity (0-4 hr): epithelial barriers to infection.
b.
Early induced response (4-96 hr):
i.
do not generate lasting protective immunity.
ii.
these early phases help to keep infection under control while the
antigen-specific lymphocytes of the adaptive immune response are activated.
iii.
moreover, cytokines produced during these early phases play an important
part in shaping the subsequent development of the adaptive immune response and
can determine whether the response is predominantly T-cell mediated or humoral.
c.
Late adaptive response (> 96 hr): occurs late because rare,
antigen-specific cells must undergo clonal expansion before they can
differentiate into effector cells.
d.
Protective immunity:
i.
the response to re-infection is much more rapid.
ii.
pre-formed antibodies and effector cells act immediately on the pathogen.
iii.
immunological memory speeds a renewed adaptive response.
4.
Phases of Infections and Host responses
|
Stage
of Infection |
Protection
against Infection |
|
Adherence
to epithelium |
Normal
flora Local
chemical factors Phagocytes
(especially in lung) |
|
Local
infection, penetration of epithelium |
Wound
healing Antibacterial
proteins and peptides Phagocytes |
|
Local
infection of tissues |
Complement
(alternative pathway) Phagocytes Cytokines Natural
killer cells Activation
of macrophages |
|
Lymphatic
spread |
Phagocytes Antigen
trapping Natural
killer cells |
|
Adaptive
immunity |
Specific
antibody T-cell
dependent macrophage activation Cytotoxic
T cells |
5.
Location of Pathogens in body
a.
Pathogens can be found in various compartments in the body, where they
must be combated by different host defense mechanisms.
b.
Virtually all pathogens have an extracellular phase where they are
vulnerable to antibody-mediated effector mechanisms.
c.
However, intracellular phases are not accessible to antibody, and these
are attacked by T cells.
|
|
Intracellular |
Extracellular |
||
|
Site
of infection |
Cytoplasmic
|
Vesicular |
Interstitial
spaces, blood, lymph |
Epithelial
surfaces |
|
Organisms |
Viruses Chlamydia
spp. Listeria
monocytogenes Protozoa |
Mycobacteria
Salmonella
typhimurium Leishmania
spp. |
Viruses Bacteria Protozoa Fungi Worms |
Neisseria
gonorrhoea Worms Mycoplasma Streptococcus
pneumoniae Vibrio
cholerae |
|
Protective
Immunity |
Cytotoxic
T cells NK
cells T-cell
dependent macrophage activation |
T-cell
and NK-cell dependent macrophage activation |
Antibodies Complement Phagocytosis Neutralization |
Antibodies,
esp. IgA Inflammatory
cells |
6.
Direct mechanisms of Tissue damage by Pathogens
|
|
Direct
mechanisms of tissue damage by pathogens |
||
|
Pathogenic
mechanism |
Exotoxin
production |
Endotoxin |
Direct
cytopathic effect |
|
Infectious
agent |
Streptococcus
pyogenes Staphylococcus
aureus Corynebacterium
diphtheriae Clostridium
tetani Vibrio
cholerae |
Escherichia
coli Haemophilus
influenzae Salmonella
typhi Shigella Pseudomonas
aeruginosa Yersinia
pestis |
Variola Varicella-zoster Hepatitis
B virus Polio
virus Measles
virus Influenza
virus Herpes
simplex virus |
|
Disease |
Tonsilitis,
scarlet fever Boils,
toxic shock syndrome Food
poisoning Diphtheria Tetanus Cholera |
Gram-negative
sepsis Meningitis,
pneumonia Typhoid Bacillary
dysentery Wound
infection Plague |
Smallpox Chickenpox,
shingles Hepatitis Poliomyelitis Measles Influenza Cold
sores |
7.
Indirect mechanisms of Tissue damage by Pathogens
|
|
Direct
mechanisms of tissue damage by pathogens |
||
|
Pathogenic
mechanism |
Immune
complexes |
Anti-host
antibody |
Cell-mediated
immunity |
|
Infectious
agent |
Hepatitis
B virus Malaria Streptococcus
pyogenes Treponema
pallidum Most
acute infections |
Streptococcus
pyogenes Mycoplasma
pneumoniae |
Mycobacterium
tuberculosis Mycobacterium
leprae Lymphocytic
choriomeningitis virus HIV Schistomas
mansoni |
|
Disease |
Kidney
disease Vascular
deposits Glomerulonephritis Kidney
damage in secondary syphilis Transient
renal deposits |
Rheumatic
fever Hemolytic
anemia |
Tuberculosis Tuberculoid
leprosy Aseptic
meningitis AIDS Schistosomiasis |