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Lecture-4 Bacterial Pathogenesis

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0% found this document useful (0 votes)
84 views29 pages

Lecture-4 Bacterial Pathogenesis

Uploaded by

Mudin Haji
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Bacterial Pathogenesis

November 27, 2024 Ayelign D. BSc, MSc, MSc 1


Bacterial Pathogenesis
Date: 4/11/2024 Session No: 4 Duration: 1hr

Learning objectives
 To define/interpret term used in pathogenesis

 To explain mechanism of bacteria pathogenesis

 To understand the host-pathogen relationships

To describe defence mechanisms of the host

November 27, 2024 Ayelign D. BSc, MSc, MSc 2


Terms and definitions
1. Symbiosis: The ability to live in the tissues of the host with
mutual benefit. Neither of them are harmed.
2. Commensalism: The ability to live on the external or internal
surface of the body with out causing disease. “Eating at the same
table”
3. parasitism: one ( the host) is harmed and the other(the parasite )
is benefited .
The outcome of the host- parasite relationship depends on a
balance between
 the virulence of the parasite and
 the resistance of the host.

November 27, 2024 Ayelign D. BSc, MSc, MSc 3


1. Infection: - An invasion & multiplication of bacteria in a
host cells, leading tissue damage and disease.
2. Pathogen: - bacteria, viruses, fungi, or parasites, that can
cause disease in a host.
3. Virulence:- factors helps to boost degree of
pathogenicity, ability to cause disease & damage host
cell
4. Colonization: - growth of bacteria in a host without
necessarily causing disease.
5. Infectious Dose: - The minimum number of bacteria to
cause infection in a host.
November 27, 2024 Ayelign D. BSc, MSc, MSc 4
1. Symptom: - A manifestation of disease sign by the host, (fever,
pain, inflammation) indicate the presence of an infection.
2. Endotoxin: - A toxic component of Gram-negative bacteria
trigger immune responses when released into the host's
bloodstream.
3. Exotoxin: - Toxic proteins secreted by bacteria into their
surrounding environment, can cause damage to the host
4. Incubation Period: - Time interval between initial infection &
appearance of symptoms, can vary depending on the bacterium
and host factors.
5. Opportunistic Infection: -Infection in immune compromised
or vulnerable hosts.
November 27, 2024 Ayelign D. BSc, MSc, MSc 5
Bacterial pathogenesis
• Bacterial pathogenesis involves various mechanisms
and factors that enable bacteria to infect hosts, evade
the immune system, and cause disease.
Contributing factors includes:
• 1. Adherence Factors
• Adhesins: Surface proteins that allow bacteria to attach
to host tissues. (Fimbriae, pili)
• Biofilm Formation: Many bacteria can form biofilms,
bacterial communities encased in a protective matrix,
making more resistant to host defences and antibiotics.
November 27, 2024 Ayelign D. BSc, MSc, MSc 6
• 2. Invasion Mechanisms
• Invasive Enzymes: Enzymes (hyaluronidase coagulase,
collagenase) help bacteria penetrate host tissues by
breaking down extracellular matrix components.
• 3. Toxin Production
• Exotoxins: damage host tissues or interfere with cellular
functions. (Botulinum toxin, cholera toxin).
• Endotoxins: (LPS) induce immune responses, leads to
inflammation and septic shock.
• 4. Immune Evasion
• Capsules: some bacteria produce it to protect from
phagocytosis by host immune cells.
November 27, 2024 Ayelign D. BSc, MSc, MSc 7
• Antigen Variation: Some bacteria can change their surface
antigens, difficult to recognize and attack by immune system.
• Inhibition of Complement System: interference of
complement activation system, reducing opsonisation and lysis.
• 5. Nutrient Acquisition
• Siderophores: bacterial competition for iron (essential
nutrients) with host cells.
• 6. Environmental Adaptation
• Antimicrobial Resistance: Resistance to antibiotics &
disinfectants, allow bacteria to survive in hostile environments.
November 27, 2024 Ayelign D. BSc, MSc, MSc 8
BACTERIAL VIRULENCE FACTORS

November 27, 2024 Ayelign D. BSc, MSc, MSc 9


General Concepts

• Host Susceptibility
• Resistance to bacterial infections is enhanced by
phagocytic cells and an intact immune system.
• Initial resistance is due to nonspecific mechanisms.
Specific immunity develops over time.
• Susceptibility to some infections is higher in the very
young and the very old and in immunosuppressed
patients.
November 27, 2024 Ayelign D. BSc, MSc, MSc 10
• Bacterial Infectivity
Bacterial infectivity results from disturbance
in the balance between bacterial virulence &
host resistance.
The objective of bacteria is to multiply rather
than to cause disease;
it is in the best interest of the bacteria not to
kill the host.

November 27, 2024 Ayelign D. BSc, MSc, MSc 11


• Host Resistance

• Numerous physical and chemical attributes of the host protect


against bacterial infection.
• These defences include the antibacterial factors in secretions
covering mucosal surfaces and rapid rate of replacement of
skin and mucosal epithelial cells.

• Once the surface of the body is penetrated, bacteria encounter


an environment virtually devoid of free iron needed for
growth, which requires many of them to scavenge for this
essential element.
November 27, 2024 Ayelign D. BSc, MSc, MSc 12
Defence mechanisms of the host
• There are two defence mechanism of our body
• Non-specific/ innate/ defence mechanisms
• Specific / adaptive/ acquired/

1. Non-specific defence mechanisms


• provides the first line protection against pathogenic
microorganisms and are not specific to pathogens.

• Most non-specific defences are natural and offer protection


from the moment of birth.
• The non-specific defences include:
• Physical barrier - Inflammatory response
• Chemical barrier - Phagocytosis
• Normal microflora
November 27, 2024 Ayelign D. BSc, MSc, MSc 13
I. Physical barrier
a. Skin:- The outer surface of the skin layer is composed of keratin
which is not readily degraded by most microorganisms
 Also - prevents attachment.
 Impermeable to most pathogens.
b. Mucous Membranes
c. The whirling of system of bones
 Projected to nasal cavities
 Essential for trapping of entering microbes
d. Fluid flow
• Movement of fluids across the surface of body tissues protects
the body from accumulation of microorganisms. Example, saliva
washes microorganisms in the oral cavity to the stomach. Tears
continuously remove microorganisms from the eye.
November 27, 2024 Ayelign D. BSc, MSc, MSc 14
2. Chemical Barriers
• These are secretions of body which have an
antimicrobial activity. These include:
– Lysozyme
– Acidity
3. Phagocytosis
• Phagocytosis is a process of engulfing & destroying
an organism or other foreign body and digest with
enzyme contained in cytoplasmic (lysosomes)
granules of phagocytic cells.
• During Phagocytosis, the m/o is engulfed by
pseudopodia of phagocytic cell
November 27, 2024 Ayelign D. BSc, MSc, MSc 15
4. Normal Microbial flora
• Normal microbial flora is microbial population
frequently found in association with particular
tissue that typically does not cause disease.
5. Compliments
• are plasma proteins found in inactive form
and activated cascade reaction.
• They are named from C1-C9

November 27, 2024 Ayelign D. BSc, MSc, MSc 16


Role of complements
Opsonisation: coating of pathogens and facilitates for
• Phagocytosis e.g., C3a
• Chemo attractants e.g., C5a
• -Bacterial lysis (C8C9)

6. Inflammatory response
• Inflammatory response is a non specific immune response to
infection or injury and designed to remove cellular debris,
localizing invading microorganism and arrest the spread of
infection.

Role of inflammation
 delivers additional cells of effector molecules to the site of
infection
 prevent the spread of infection
 promote the repair of injured tissue
November 27, 2024 Ayelign D. BSc, MSc, MSc 17
7. NK cells / natural killers/
are lymphocytic in origin which kill virus infected
cells with antigenic stimulation
8. Adaptive immunity
• Occurred if the host couldn’t overcome the disease by
the innate immune defense mechanism.
– Occurred due to or following exposure to antigen
– Is specific (response to particular pathogen)
– It is mediated by lymphocytes (T- and B-cells)

November 27, 2024 Ayelign D. BSc, MSc, MSc 18


Humeral & Cell mediated immune response
1. Humoral immune response
– Is mediated by antibody which are produce b-cells
(antigen stimulated cells i.e. plasma cells)
– involves 5 classes of immunoglobins IgA, IgD, IgE, IgG,
IgM
Role of antibody
– Neutralization
– Oppsonization
– Complement activation
November 27, 2024 Ayelign D. BSc, MSc, MSc 19
Cell mediated immunity:
• is immunity mediated by sensitized (exposed to antigen)
cells called T-lymphocyte and their cytokines.

• Cytokines are small soluble proteins secreted by cells


that can alter the behaviour of the cell itself or another.
T-cells includes
cytotoxic T-cells (destroys infected cells)
T-helper cells (CD4 cells)
Th1- secret cytokines which activate macrophages for
intracellular killing
Th2- activates B-cells for extracellular killing
Suppressor T- cells (regulate function of above T-cells
November 27, 2024 Ayelign D. BSc, MSc, MSc 20
• Adaptive immunity can be :
» Passive immunity
» Active immunity
Passive immunity
A. passive natural- occurred due to natural transferred
immunoglobulin (IgG)

B. passive artificial - occurred when Ab and lymphocytes are


given to individual which is deficient of them. (i.e., Ab and
lymphocytes of another person)
Eg. Immunoglobulin Therapy, antitoxin for diphtheria.

2. Active immunity
A. Active natural (contact with infection)
B. active artificial (immunization)
November 27, 2024 Ayelign D. BSc, MSc, MSc 21
Factors affecting host defence mechanism
1. Nutrition: Malnutrition predisposes to infection.
2. Age: The very old and the very young are particularly liable to
infection.
3. Sex: May be attributes to hormonal influence.
4. Impairment of the host immune response due to:-
• radiotherapy
• Immunosuppressive drugs including steroids
• Malignancy & HIV
• 5. Race
• 6. Climate
• 7. Occupation
• 8. Drugs
• 9. Pregnancy
November 27, 2024 Ayelign D. BSc, MSc, MSc 22
Mechanisms Of Bacterial Pathogenesis

1. Entry in to the host

2. Adherence to mucus membranes

3. Colonization by growth at the site of


adherence

4. Disease symptoms caused by:


 Invasion accompanied by inflammation
 Toxin production
November 27, 2024 Ayelign D. BSc, MSc, MSc 23
for step 1 the pathogen should evade
primary host defenses

for steps 2,3, and 4 the pathogen should


evade both specific and non specific
immunity

5. Progression or resolution of the disease

November 27, 2024 Ayelign D. BSc, MSc, MSc 24


1. ENTRY IN TO THE HOST

Portal of entry

Respiratory tract
 Gastrointestinal tract
 Genitourinary tract
 Skin (punctured, cut, burned)
 Rarely through other mucus membrane

November 27, 2024 Ayelign D. BSc, MSc, MSc 25


Table-1: Portal of entry of some pathogens
PORTAL OF ENTRY Example (PATHOGEN)
Respiratory tract Streptococcus pneumoniae
Neisseria meningidides
Haemophilus influenzae
Mycobacterium tuberculosis
GI tract Shigella dysenteriae
Salmonella thyphi
Vibrio cholerae
Skin Clostridium tetani
Rikettsiae rickettsii
Genital tract N. gonorrhoeae
Treponema pallidum
Chlamydia trachomatis

November 27, 2024 Ayelign D. BSc, MSc, MSc 26


Mode of ENTRY IN TO THE HOST…/transmission

 Ingestion
 Inhalation
 Trauma/surgical procedure
 Needle stick
 Arthropod bite
 Sexual transmission
 Vertical transmission

November 27, 2024 Ayelign D. BSc, MSc, MSc 27


Mode of entry/transmission Example (infectious agent)
Ingestion Salmonella spp, Shigella spp, Yersina spp,

Eschericia spp, Vibro spp, Clostridium botu


Bacillus cereus, Brucella spp, Listeria spp,
Campylobacter spp, etc.

Inhalation Mycobacterium spp, Mycoplasma pneumonia,


Legionella spp, Bordetella spp
Streptococcus spp, etc.
Trauma/surgical procedure Clostridium tetani etc.

Needle stick S.aureus, Pseudomonas spp etc.

Arthropod bite Ricketsia spp, Coxiella spp, Borrelia spp, Yersina


spp, francisella spp, etc.

Sexual transmission N.gonorrhoae, C.trachomatis, T.pallidum etc.

Vertical transmission S.aureus, S.agalactiae, T.palidum,

Listeria monocytogenes etc.


November 27, 2024 Ayelign D. BSc, MSc, MSc 28
November 27, 2024 Ayelign D. BSc, MSc, MSc 29

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