Neisseria meningitidis

Abdulmajid Alomari, Jamaan Al-dossary, Muhammed Aldurihim,

Majed Almutairi, Tariq Alnaam

Supervised by: Mohammed Alissa

Neisseria meningitidis (or meningococcus ) is a Gram negative, diplococcus, encapsulated, aerobic bacterium that can cause meningitis and
other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. It is part of the normal flora of nasopharynx (about
5%-10%). Based upon variation in the capsule, N. meningitidis bacteria are divided into thirteen serogroups. Serogroups A, B, C, Y, and W135
are responsible for the majority (>90%) of meningococcal meningitis and meningococcemia cases.

Virulence Factors

Type IV Fimbriae: are important for initial

adhesion to host cell surfaces and
establishment of infection.
Lipooligosaccharide (LOS): the molecule
that allow N. meningitidis to escape from
innate immune system especially dendritic
cell.
Polysaccharide capsule: allows the
bacteria to survive extracellularly, by
protecting it from complement dependent
bacteriolysis and phagocytosis.
IgA1 protease: cleaves human IgA1 witch
has an essential rule in preventing bacterial
adhesion to mucosal surfaces. Therefore,
the bacteria now have greater ability to
stay in the nasopharynx .
The ability to utilize gene switching and
express phase-varible protiens on its
surface such as ProA and ProB to response
to environmental changing and thats may
lead to creat genetic diversity.
Receptors: [e.g. : transferrin-binding
proteins (TbpA, TbpB)] able to bind to
human transferrin and lactoferrin that
provide the bacteria with iron for growth.
These receptors are
CrgA protein: has a significant rule in
regulation of gene expression during the
infectious cycle of N. meningitidis.

Immune Response
Innate Immunity:
Mechanical mechanisms: serve the
purpose of preventing infection and for
controlling nasopharyngeal colonization to
prevent possible invasion of the
intravascular space and CNS.
Physical mechanisms: for preventing
infection of the human nasopharynx ,
laryngeal disclosure, and the cough reex
which are non-specic for preventing
infection .
Production of hydrogen peroxide by
epithelial cells which act as general
bactericide
Macrophage activation Produces proinflammatory cytokines (IL-8, IL-1),
initiating influx of inflammatory cells (e.g..
Neutrophils) to the site of infection.
Neutrophils destroy N. meningitidis using
ROS, NO, etc.
Adaptive Immunity :
Antigen presentation: dendritic cells
facilitate activation of T cells.
IgA Secretion
TNF and IFN: produced by CD4 T cells
(TH1) activate macrophages to exert
bactericidal activity on organisms using
reactive oxygen species. Activated
Macrophages recruit more inflammatory
cells to the site of infection to clear N.
meningitidis by the release of cytokines.

Life Cycle
1. Transmission
From person to person
by droplets from
respiratory system

2. N. meningitidis colonizes the

Nasopharynx then invades the epithelium
tissue and
vascular system by
4 steps which are:

Host Risk Factors

(A) Initial attachment: N.

meningitidis adheres to the endothelium via
Tfp or Type IV pili.
(B) Proliferation: bacteria divide
progressively leading to the formation of
large aggregates along the vascular wall
(microcolony). Numerous proteins including
actin, ezrin and junctional proteins are
recruited to the cortical plaque that forms
under the bacterial microcolony. As a
consequence, cellular junctions are
weakened and open (junctional openings).
(C) Exit and propagation: After several
cycles of proliferation, the transcriptional
pattern of the bacteria changes.
Expression of the pptB gene is induced and
leads to a post-translational modification
on Tfp promoting the detachment of a
small number of bacteria from the
microcolonies. Detached bacteria can then
exit the vessel lumen through opened
junctions (exit) or propagate to other sites
and initiate a new cycle (propagation)
(D)Vessel occlusion: The microcolonies
eventually fill the vessel lumen as
observed post-mortem in patients.

The infection seems higher among male

until age 45 years, then it will become
higher in women.
The risk of getting infection will increase
in young children because they lack of
protective serum bactericidal.
Some defects in complement system may
also lead to rapid fatal
meningococcemia in the patient who lack
properdin in the alternative complement
pathway.
The susceptibility of getting infection
also will increase in people who have
done splenectomy surgery.

Environmental and Behavioral

Risk Factors

3. Bacterial invasion to meninges , and

cause Neisseria meningitis.

The climatic conditions play an important

role in the risk of getting infection.
Infection of the upper respiratory tract
and co-infection such as mycoplasma
pneumonia, influenza and other
respiratory viral infections will increase
the risk of getting infection by N.
meningitidis beside some invasive
diseases.
In addition, the exposure to tobacco
smoke by active and passive smoking
may increase the risk of getting
infection.
The closed population such as militia
recruits and Haj pilgrims will increase the
risk of getting infection.
Some studies suggest that students who
live in campus have an over threefold
increased risk relative to the off-campus
population. Because they live in close
population.
Some microbiologists who work with N.
meningitidis in an open laboratory bench
may get infection.

Diagnosis

Sample: Cerebrospinal Fluid

Gram stain: Gram negative intracellular
diplococcic
Culture : Chocolate Agar at 37C with
5% CO2 (large, colorless-to-grey,
opaque colonies)
Biochemical tests: Oxidase positive\
Catalase positive\ Carbohydrate
utilization test (Ferments glucose and
maltose)\ API NH
Phenotypic typing Methods:
Serogrouping: K antigen
Molecular typing Methods: PCR

Conclusion: several strategies can be used

by Neisseria meningitidis to survive
intracellulary. N. meningitidis can live inside
the neutrophils intracellularly and by this
mechanism the bacterium can circumvent the
immune system and start moving within the
body and cause infection to inflamed tissues.

References: Mucosal Immunology centers of disease control and prevention Immunity Against Mucosal Pathogens , Michael Vajdy Editor
Medical Bacteriology 2006 by Abilo Tadesse, Meseret Alem DeVoe, I. W., & Gilchrist, J. E. (1978). Piliation and colonial Morphology Among
Laboratory strains of Meningococci. Journal of Clinical Microbiology , 379-384. Singleton, T.E., Massari, P., Wetzler, L.M. (2005). Neisserial
Porin-Induced Dendritic Cell Activation Is MyD88 and TLR2 Dependent. Journal of Immunology, 174: 3545-3550. The National Center for
Biotechnology Information (Neisseria meningitidis: Biology, Microbiology, and Epidemiology).