MICROBIOLOGY PPT LECTURE NOTES | Karya Tulis Ilmiah

(1)

Bacterial Infection and

Immunity

(2)

Symbioses

 Commensalism: one

partner benefits and the other is neither harmed nor benefited.

 Mutualism: both

partners benefit.

 Parasitism: one partner

benefits at the expense of the other.

(3)

Role of the resident flora

• _{Members of the resident flora in the intestinal tract}

synthesize vitamin K and aid in the absorption of nutrients.

• Members of the resident flora on mucous membranes

and skin may prevent colonization by pathogens and possible disease through “bacterial interference”.

• _{The normal flora may} _antagonize_{other bacteria}

through the production of substances which inhibit or kill nonindigenous species.

• _{The normal flora stimulates the development of}_certain

tissues, i.e., the caecum and certain lymphatic tissues (Peyer's patches) in the GI tract

• _{The normal flora stimulate the production of}

(4)

 Hospital acquired infection: _{Infections acquired during hospital stays.}  _Pathgen: _{A microorganism capable of causing sisease.}

 _Nonpathogen: _{A microorganism that does not cause disease; may be part of the normal flora}.

 _{Opportunistic pathogen:} _{An agent capable of causing disease only when the host’s}

resistance is impaired (ie, when the patient is “immunocompromised”).

 _{Pathogenicity:} _{The ability of an infectious agent to cause disease}

 _Virulence: _{The quantitative ability of an agent to cause disease. Virulent agents cause disease when}

introduced into the host in small numbers. Virulence involves invasion and toxigenicity. LD 50 (age /sex /health /route of entry, etc )

 LD50: The number of pathogens required to cause lethal disease in half of the exposed hosts is called an LD50.

 ID50: _{The number of pathogens required to cause disease (or, at least, infection) in half of}

the exposed hosts is called the ID50

 Adherence_{(adhesion, attachment): the process by which bacteria stick to the surfaces of host cells.}

Once bacteria have entered the body, adherence is a major initial step in the infection process. The terms adherence, adhesion, and attachment are often used interchangeably.

 _Invasion: _{The process whereby bacteria, animal parasites, fungi, and viruses enter host cells or}

tissues and spread in the body.

 _{Toxigenicity:} _{The ability of a microorganism to produce a toxin that contributes to the development}

(5)

 Koch’s Postulates

 Molecular Koch’s

Postulates

 Molecular Guidelines for

Establishing Microbial Disease Causation

Koch's postulates

 I_Isolated _solated

– _{diseased not healthy}_{diseased not healthy}

people people  GGrowthrowth

– _{pure culture}_{pure culture}

 IInduce disease nduce disease

– _{susceptible animals}_{susceptible animals}

 RRe-isolated e-isolated

(6)

Pathogenesis



Pathogenesis is a multi-factorial

process which depends on the

immune status

of the host, the

nature of

the species or strain

(

virulence factors

) and

the

number

of organisms in the initial

exposure.

(7)

Source of

infection

_infection

 Exogenous infection : patient, carrier, diseased

animal or animal carrier.

 Endogenous condition : most are normal flora,

cause infection under abnormal condition.

• _A

_{irborne droplets}

• _F

_ood

• _W

_ater

• _S

_{exual contact}

Transmission

 Respiratory

 Gastroenteric  _{Genitourinary tract}  closely contact

 insect bitting  blood transfusion

 _{Parenteral route}  Mucous membranes

Routes of

infection

(8)

According to

infectious sites

 Local infection

 _{Generalized or systemic}

infection

1. Toxemia : is the presence of exotoxins in the blood.

2. Endotoxemia : is the presence of endotoxins in the blood.

3. Bacteremia : is an invasion of the bloodstream by bacteria. 4. Septicemia : illness that occurs

when poisonous substances (toxins) produced by certain bacteria enter the bloodstream. 5. Pyemia : is caused by pyogenic

microorganisms in the blood.

 _{Inapparent or subclinical}

infection

 Latent infection

 _{Apparent infection : cause}

apparent clinic syndrome

 Carrier state: carrier

According to

infectious state

(9)

(10)

Environmental signals often control the expression of the virulence genes. Common signals include:Temperrature/Iron availability : C diphtheriae /low ion/Osmolality /Growth phase/pH/Specific ions

BACTERIAL VIRULENCE FACTORS

(11)

1. Adherence Factors

1. Tissue tropism:

2. Species specificity:

3. Genetic specificity within a species:

 Hydrophobic interactions  Electrostatic attractions

 Atomic and molecular vibrations resulting from

fluctuating dipoles of similar frequencies

 Brownian movement

 Recruitment and trapping by biofilm polymers

(12)

(13)

(14)

Adhesion

adhesin adhesin EPITHELIUM EPITHELIUM receptor receptor BACTERIUM BACTERIUM fibronectin fibronectin lipoteichoic acid lipoteichoic acid F-protein F-protein mannose mannose Type 1 Type 1 galactose galactose

– glycolipids _glycolipids – glycoproteins _{glycoproteins}

E. coli

(15)

2. Invasion of host cells & tissues

(16)

3. Toxins



Exotoxins



Endotoxins

Exotoxins

 Produce in vitro cause food poisoning:

botulin, staphylococcal enterotoxin, etc.

 Produce in vivo:

Systematic toxic effects : e.g. diphtheria, tetanus, and streptococcal erythrogenic toxins.

Local toxic effects : e.g. cholera, and toxigenic E. coli enterotoxins. ActiveActive BindingBinding

A A Cell surface Cell surface B B

 Antibodies (anti-toxins) _{Antibodies (anti-toxins)}

neutralize

(17)

(18)

(19)

E

ndotoxins

 _{LPS Lipopolysaccharide:}

core or backbone of CHO

side chains of CHO: "O" antigen Lipid A

 _{Cell wall lysis required}

 formaldehyde and heat resistant  _{poor antigen as free molecule}  Endotoxin effects

 Fever-_{pyrogen 1 microgram/ kg}

 Leukopenia and leukocytosis necrosis  Shwartzman phenomenon and

disseminated intravascular coagulation (DIC).

 Endotoxemia and shock

 _{Lethal 1 milligram/ kg Identification:}

Limulcyte assay

 N_Non-specific inflammation. _{on-specific inflammation}  C_Cytokine release_{ytokine release}

 C_Complement activation_{omplement activation}  B cell mitogens_{B cell mitogens}

 P_Polyclonal B cell activators _{olyclonal B cell activators}  A_Adjuvants_djuvants

(20)

(21)

Peptidoglycan of Gram-

_{Peptidoglycan of}

Gram-positive bacteria

positive bacteria



May yield many of the same biologic

(22)

4. _4.

Enzymes

_Enzymes

 Tissue-degrading

enzymes

 IgA1 proteases:

split IgA1, an

important secretory antibody on

mucosal surfaces, and inactivate its antibody activity.

1. H. influenzaeH. influenzae

2. S. pneumoniaeS. pneumoniae

3. N. gonorrhoeaeN. gonorrhoeae

4. N. meningitidisN. meningitidis

 Some pathogens evade

phagocytosis or leukocyte microbicidal mechanisms by adsorbing normal host

components to their surfaces. A few bacteria produce

soluble factors or toxins that inhibit chemotaxis by

leukocytes and thus evade phagocytosis.

5. Antiphagocytic

factors

(23)

A

ntiphagocytic

_{ntiphagocytic}

S

_S

ubstances

_ubstances



1. Polysaccharide capsules

_of_{S. pneumoniae}_,_{Haemophilus influenzae}_,

Treponema pallidum ; B. anthracis and Klebsiella pneumoniae.



2. M protein

and

fimbriae

_{of Group A streptococci}



3. Surface slime

(

_{polysaccharide) produced as a biofilm by Pseudomonas}

aeruginosa



4. O polysaccharide

_{associated with LPS of E. coli}



5. K antigen

_{(acidic polysaccharides) of E. coli or the analogous}

Vi

antigen

of Salmonella typhi



6.

_{Cell-bound or soluble}

Protein A

_{produced by Staphylococcus aureus. Protein A}

attaches to the Fc region of IgG and blocks the cytophilic (cell-binding) domain of the Ab. Thus, the ability of IgG to act as an opsonic factor is inhibited, and opsonin-mediated ingestion of the bacteria is blocked.

(24)

Protein A inhibits phagocytosis

immunoglobulin

immunoglobulin _{Protein A}_{Protein A}

Fc receptor Fc receptor BACTERIUM BACTERIUM PHAGOCYTE PHAGOCYTE r r r peptidoglycan peptidoglycan Complement

Complement _fibrinogen_fibrinogen

M protein M protein

M protein inhibits phagocytosis

(25)

6. Intracellular

pathogenicity

Some bacteria live and grow within

polymorphonuclear cells, macrophages, or

monocytes by avoiding

entry into phagolysosomes and living within the

cytosol of the phagocyte, preventing

phagosome-lysosome fusion and living within the phagosome, or being resistant to lysosomal enzymes and surviving

(26)

7. Antigenic heterogeneity

 Antigenic type of bacteria may be a marker for

virulence, related to the clonal nature of pathogens, though it may not actually be the virulence factor.

 Some bacteria may make frequent shifts in the

antigenic form of their surface structures in vitro and presumably in vivo, allowing the bacteria to evade the host’s immune system.

(27)

Bacterial siderophores compete effectively for Fe3+_{bound to lactoferrin and transferrin.}

8. The requirement for iron

 For the host, the iron

metabolism denies

pathogenic bacteria an

adequate source of iron for growth.

 For the bacteria, they have

developed several methods to obtain sufficient iron for essential metabolism, e.g., the low-affinity iron

assimilation system or the high-affinity iron

(28)

Development of the Immune

System

Development of the Immune

System

ery pl mye neu mφ lym nk thy CD8+ CD4+ CTL TH2 TH1

(29)

Components of the Immune

System

Components of the Immune

System

Humoral

Cellular

Humoral

Cellular

Specific

Nonspecific

complement, interferon,

TNF etc.

macrophages, neutrophils

T cells; other effectors cells antibodies

(30)

Balance between Infection and

Immunity

Balance between Infection and

Immunity

infection _immunity

Bolus of infection x virulence immunity

(31)

Response to Infection

infection

x

disease

Innate

immunity no disease

recov ery

adaptive immunity

re-inf ectio

n no

disease

(32)

 Beneficial:

 Protection from Invaders  Elimination of Altered Self

 Detrimental:

 Discomfort (inflammation)

 Damage to self (autoimmunity)

 Beneficial:

 Protection from Invaders

 Elimination of Altered Self

 Detrimental:

 Discomfort (inflammation)

 Damage to self (autoimmunity)

Significance of the Immune System

(33)

Innate Immunity _{Adaptive Immunity}

Components

of Innate and Adaptive

_{of Innate and Adaptive}

Immunity

Components

of Innate and Adaptive

_{of Innate and Adaptive}

Immunity

skin, gut Villi, lung cilia,etc

many protein and

non-protein secretions

phagocytes, NK cell eosinophils, K cells

physical barriers soluble factors cells none Immunoglobulins (antibody)

(34)

(35)

Chemotactic response to inflammatory stimulus Macrophage Attacking E.coli

(36)

Adaptive Immunity

(37)

Innate Immunity _{Adaptive Immunity}

Characteristics

of Innate and

_{of Innate and}

Adaptive Immunity

Characteristics

of Innate and

_{of Innate and}

Adaptive Immunity

No Immunologic memory

Antigen independent No time lag

Not antigen specific

Antigen dependent A lag period

Antigen specific Development

(38)

 Immunity of extracellular bacterial infection: antibodies (IgG, IgM, SIgA); phagocytes (neutrophils); complement; humoral immunity mainly.

 Immunity of intracellular bacterial infection:

cell-mediated immunity (delayed-type hypersensitivity, DTH response (DTH) involving TH1and macrophages) mainly.

(39)

INADEQUATE IMMUNE RESPONSES

TO INFECTIOUS AGENTS

 Causes immune suppression—an example is infection with

HIV, which alters T cell immunity and allows further infection with opportunistic pathogens.

 Release toxins that function as superantigens, initially

stimulating large numbers of T cells to proliferate but, because of the release of cytokines from T cells, ultimately suppressing the immune response and allowing the pathogen to multilply.

 Evade the immune defenses by altering their antigenic

structure—an example is that influenza virus undergoes antigenic variation by two mutational mechanisms called

antigenic shift and antigenic drift that creat new antigenic phenotypes which evade the host’s current immunity and allow reinfection with the virus.

(1)

(2)

Chemotactic response to inflammatory stimulus Macrophage Attacking E.coli

(3)

Adaptive Immunity

(4)

Innate Immunity

_{Adaptive Immunity}

Characteristics

of Innate and

_{of Innate and}

Adaptive Immunity

Characteristics

of Innate and

_{of Innate and}

Adaptive Immunity

No Immunologic

memory

Antigen independent

No time lag

Not antigen specific

Antigen dependent

A lag period

Antigen specific

Development

(5)



Immunity of

extracellular bacterial infection

:

antibodies

(IgG,

IgM,

SIgA);

phagocytes

(neutrophils); complement; humoral immunity

mainly.



Immunity of

intracellular bacterial infection

:

cell-mediated immunity (delayed-type hypersensitivity,

DTH

response

(DTH)

involving

TH1and

macrophages) mainly.

(6)

INADEQUATE IMMUNE RESPONSES

TO INFECTIOUS AGENTS

 Causes immune suppression—an example is infection with

HIV, which alters T cell immunity and allows further infection with opportunistic pathogens.

 Release toxins that function as superantigens, initially

stimulating large numbers of T cells to proliferate but, because of the release of cytokines from T cells, ultimately suppressing the immune response and allowing the pathogen to multilply.

 Evade the immune defenses by altering their antigenic

structure—an example is that influenza virus undergoes antigenic variation by two mutational mechanisms called antigenic shift and antigenic drift that creat new antigenic phenotypes which evade the host’s current immunity and allow reinfection with the virus.