Immunity to microbes - I

Dr. Feyan M. Abdullah

Hawler Medical University
College of Medicine
Microbiology, Physiology and Genetic Dep.
Medical Microbiology Unit
LG6
Overview
 Infectious disease is the major cause of morbidity and mortality
worldwide.

 From the moment of birth, the host is constantly exposed to a wide

variety of microbes.

 In general, the host manages to either eliminate or ward off these

invading organisms, and a symbiosis is achieved between microbes
and the host.

 Different microbes require different mechanisms for elimination.

 The key events during infection include:-
o Entry of the microbe
o Invasion and colonization of host tissues
o Evasion of host immunity
o Tissue injury or functional impairment.

 Microbes enter the body through a number of natural routes

including:-
o Respiratory tract,
o Gastrointestinal tract
o Genitourinary tract
o Through broken skin and mucous membrane
 Many features of microorganisms determine their virulence, and
many diverse mechanisms contribute to the pathogenesis of
infectious diseases.
 The more virulent a pathogen is, the better able it is to resist the
immune system.
 Microbes cause diseases either by
o Killing the host cells they infect
o Releasing toxins that can cause tissue damage and functional
derangements in neighboring or distant cells and tissues that are not
infected.
o Stimulating innate and adaptive immune responses that kill the
microbes, but also may injure and impair the function of normal
tissues.

A G lov,
.
 Microbes can cause diseases of varying severity and chronicity.
mostly in helminths
 Infection my be asymptomatic and resolves without intervention.
 The immune system responds in specialized and distinct ways to
different types of microbes to combat these infectious agents most
effectively.
 A typical host immune response is rapidly triggered by the infection,
wanes as the infection is cleared, and leaves memory cells that can
provide long-term protection.
 Generally, pathogenic microorganisms are either true pathogens or
opportunistic pathogens.
 True pathogens were those capable of causing diseases in the host
irrespective of the host’s immune system.
 Thus, they cause diseases in immunocompetent and immuno-
compromised individuals and persons with slight imbalances of the
immune system.
 Opportunistic pathogens mostly included the normal flora and only
cause diseases in immunocompromised individuals as well as when
they occur in parts of the body that were not natural to them

 Examples of some opportunistic pathogens :-

• Staphylococcus aureus is an example of an extracellular bacterium

can cause staphylococcal pneumonia.

• Opportunistic invasions are a major problem in hosts immuno-

compromised condition….. Candida albicans.
 In order for a pathogen to establish an infection in a susceptible host,
it must breach physical and chemical barriers as a result more
directed innate immune responses come into play at or near the site
of infection.
example
recatfor
Tool like
Pattern recognition receptors eg. TLRs…etc Infection clearance
cells; e.g. DC, macrophage, neutrophils, NK
cells, basophils eosinophil and Tissues injuries
Inflammatory mediators ; eg. cytokines,
complement system, C-reactive "inflammatory Mediators memory cells
protien…etc.
Chronic state and recurrent
Later activation of adaptive infection.
immune responses (T and B cells).
Disability or death

 The survival and pathogenicity of microbes in a host are critically

influenced by the ability of the microbes to evade or resist
(mechanisms for surviving ) the effector mechanisms of immunity.
 In many cases, these innate responses can lead to the resolution of
infection.
o Defects in the mucociliary lining of the respiratory tract (as in cystic
fibrosis) are associated with an increased susceptibility to lung
infection.
o Influenza virus possess haemagglutinin on their surface that breach
physical barrier.
o Severe neutropenia or neutrophil dysfunction is associated with life-
threatening infections, usually caused by common organisms such as
Staphylococcus aureus, Gram-negative bacteria or fungi.
-

 Phagocytosis is promoted by serum factors termed ‘opsonins’ IgG

antibody, complement and mannan-binding lectin are the best
opsonins.
 Non-opsonized bacteria can still be recognized and bound by
phagocyte receptors pattern recognition receptors (PRRs) like TLR.
 The balance between host immune responses and microbial
strategies for resisting immunity often determines the outcome of
infections.
 Recurrent illnesses occur when the host response cannot eradicate
the microbe and may even contribute to the disease.
 Most pathogenic microorganisms have evolved methods of resisting
phagocytic cells:-
- Staphylococci produce potent extracellular toxins that kill phagocytes
and lead to the formation of pus, so characteristic of these
infections.
- Capsulated pathogens like Streptococcus pneumonia and Neisseria
meningitides prevent antibody and complement deposition on its
surface, thereby avoiding opsonization and phagocytic clearance.
- Mycobacterium tuberculosis, are effectively ingested by phagocytic
cells but can resist intracellular killing….. persistent bacterial
infections.
- Group A streptococci have cell surface structures called M proteins
that inhibit direct phagocytosis, mainly by preventing deposition of
complement on the organism.

 Several viruses, especially DNA viruses of the herpesvirus and

poxvirus families, and some intracellular bacteria are capable of
establishing latent infections.
 In latent viral infections, the viral DNA persists in the genome of
infected cells but no infectious virus is produced.

 Some latent microbes will on occasion become activated and start

replicating, especially if the immune system is weakened for any
reason.
 Those pathogenic microbes that have evolved to resist innate immunity,
and protection against such infections is critically dependent on
adaptive immune responses.

 Adaptive responses are effective against even virulent microbes because

they generate large numbers of effector cells and Abs that function to
eliminate the microbes and memory cells that protect the individual
from repeated infections.
secondary infections
 It typically takes several days for adaptive immune responses to fully
develop.

 When the immune responses are unable to destroy the pathogens in

the body, so the person harbors and spread the infection in the
environment ( carriers)…. typhoid fever, tuberculosis, hepatitis B and C
carriers.
 Inherited and acquired defects in innate and adaptive immunity are
important causes of susceptibility to infections.
 For example common acquired causes of immunodeficiency include HIV
infection and therapeutic immunosuppression.
 Less common, there are a large number of inherited immunodeficiency
syndromes caused by mutations in single genes whose major clinical
consequence is increased infections.

 Individuals with Ab deficiency are prone to repeated infections with

pyogenic bacteria but Ig replacement therapy markedly reduces the
frequency of these bacterial infections.

 Patients with impaired cell-mediated immunity have difficulty in

controlling and eradicating infections with viruses such as measles, and
herpes. They also show increased susceptibility to mycobacteria,
pneumocystis…etc.
 Recurrent viral or fungal infections suggest the possibility of an
underlying T cell defect.
 Aging individuals also show increased susceptibility to infection,
presumably because of reduced adaptive immune responses.

 The growth in numbers of iatrogenically immunosuppressed patients

receiving immunosuppression who are at risk from ‘opportunistic’
infections.

 Newly emerging infections are able to spread in part because of the

absence of herd immunity, resulting in epidemics and pandemics.
 Most of these new infections are caused by viruses that develop novel
strains because of re-assortment between the genomes of existing
human strains and animal strains…eg. Influenza virus and coronavirus.
Non specific defense mechanisms
 Many treatment strategies have been failing and making it difficult in
controlling diseases.
 Successful treatment of infections including the enhancement in both
the use of antimicrobial (for bacterial infections) and the host’s immune
defenses.
 As a result of the development of drug resistant strains in many
treatment cases, the enhancement of mostly innate immune response
together with the adaptive immune response will go a long way in
treating patients without difficulty…eg. methicillin-resistant
Staphylococcus aureus (MRSA)
 While vaccines have considerable benefits over drug treatments, the
major limitation in developing novel vaccination approaches is our lack
of understanding of immunity to many emerging pathogens for example
COVID19 vaccines.
 Analysis of immune responses is a valuable clinical assay for infections.

 Measurement of serum Abs specific for particular microbes is helpful

for detecting infections in which the microbe cannot be cultured, or is
not detectable in the blood by molecular assays, or is present in tissues
that are not readily accessible.
 The presence of IgM antibodies is indicative of recent infection, whereas
the presence of only IgG suggests past infection.

 Other tests include assays for T cell responses, such as tests for skin
reactions to microbial antigens and estimation of cytokine (e.g., IFN-γ)
release after activation of peripheral blood cells with antigens, used to
detect infection with Mycobacterium tuberculosis.
Innate-adaptive and microbes interaction
 Nonspecific or natural resistance refers to barriers, secretions, and
normal flora that make up our external defenses… first line of defense.
 Phagocytes, NK cells and complement are also involved.
 Loss of a major part of the skin (secondary to burns, acids, etc.)
immediately exposes the host to marked susceptibility to infection.
 Different types of pathogens elicit the production of different classes of
chemokines that facilitate the inflammatory response,for example:-
• Acute infection by Streptococcus pneumoniae results in the production
of chemokines, particularly IL-8, that call for the neutrophils required to
eliminate the bacteria.
• Infection with Borrelia burgdorferi leads to a more chronic condition
eventually requiring action by macrophages and lymphocytes and
provokes the secretion by activated macrophages of chemokines that
attract the required cells.
 In general, however, it is the mobilization of the phagocytic cells such
as monocytes /macrophages and polymorphonuclear leukocytes that
ingest invading microorganisms and kill them.
 TLRs are also playing a role in adaptive immunity, and the DC
appears to be playing a key role in linking the innate and adaptive
immune responses.
 After activation of the TLRs, the DCs are transformed into more
mature cells with a high expression of MHC and the co-stimulatory
molecules CD80 and CD86.
 The DCs then migrate to the lymph nodes to activate antigen-specific
naïve T cells.
 The production of IL-12 drives these cells to Th1 cells which produce
interferon-δ, whereas IL-4 drives them toward Th2 cells producing IL-
4, IL-5, Il-10, and IL-13.
 Immunity mostly categorized to five categories of pathogenic
microorganisms:
1. extracellular bacteria
2. intracellular bacteria
3. fungi
4. viruses
5. protozoan and multicellular parasites (helminthes).

 This separation provides a useful context for discussing immunity

because the dominant immune responses to these types of infections
are different.
REFERENCES
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• Cellular and Molecular Immunology.10th ed. Abul K. Abbas et al.
2022.
• Kuby IMMUNOLOGY. Jenni Punt et al. 8th ed.
• Jawetz, Melnick, & Adelberg’s; Medical Microbiology.27th ed. 2016.
• Review of Medical Microbiology & Immunology. Warren Levinson et
al. 15th. ed.2018.
• OTHER SOURCES…..