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Immunity To Extracellular Bacteria

Immunity to extracellular bacteria involves both innate and adaptive immune responses. Innate responses include complement activation which enhances phagocytosis and recruits leukocytes. Phagocytes express receptors that promote bacterial uptake and killing. Toll-like receptors activate phagocytes and induce cytokine production. Adaptive responses generate antibodies and T cells against bacterial antigens. However, immune responses can also cause immunopathology through cytokine storms, autoimmune reactions, and superantigen activation of T cells. Bacteria employ strategies like capsules, toxins and antigenic variation to evade these immune defenses.

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Noor Nawawra
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59 views23 pages

Immunity To Extracellular Bacteria

Immunity to extracellular bacteria involves both innate and adaptive immune responses. Innate responses include complement activation which enhances phagocytosis and recruits leukocytes. Phagocytes express receptors that promote bacterial uptake and killing. Toll-like receptors activate phagocytes and induce cytokine production. Adaptive responses generate antibodies and T cells against bacterial antigens. However, immune responses can also cause immunopathology through cytokine storms, autoimmune reactions, and superantigen activation of T cells. Bacteria employ strategies like capsules, toxins and antigenic variation to evade these immune defenses.

Uploaded by

Noor Nawawra
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© © All Rights Reserved
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Immunity to Microbes

Part 2

Immunity to Extracellualr
Bacteria
Studying for the course
Pathogenicity of Extracellular Bacteria

l Capable of replicating outside host cells

l Two principal mechanisms of disease:


1– induce inflammation: tissue destruction
at the site of infection
2- release toxins: diverse pathologic effects
Endotoxins vs Exotoxins

l Endotoxins:
– components of bacterial cell walls
– strong inducers of inflammation
l Exotoxins:
– actively secreted by the bacteria
– cytoxic
– interfere with normal cellular functions
without killing cells
– production of cytokines that cause disease
Numbers of Invading Microbes
l ID50: =Median Infectious Dose= dose required to
infect 50% of the test population.
– If I have 100 rabbits, ID50 would be quantity that would
infect 50 rabbits

l LD50: dose required to kill 50% of the test


population.
– If I have 100 rabbits, LD50 would be quantity that would
kill 50 rabbits
Mechanisms of
Adhesion
l Molecules on the
surface of the
pathogen are known
as adhesins (ligands)
and bind to receptors
on the cells of the
host
– Glycocalyx
– Fimbriae
– M protein
– Opa protein
Surviving Host Defenses
Antiphagocytic factors:
fight primary host
defense:
l Leukocidins – toxic to
white blood cells
l Capsule
l Survival inside
phagocytes
Virulence factors: Host Tissue
Damage
Direct Damage:
l Exoenzymes
(mucinases,
keratinases,
collagenases,
hyaluronidases,
coagulases,
bacterial kinases)
l Toxins
Indirect damage:
l Damaging
immune reaction
Endotoxins—Part of the outer portion of
the cell wall (Lipid A) of G(-) bacteria

Source: Gram –

Relation to microbe: Present in LPS of outer membrane

Chemistry: Lipid

Fever? Yes

Neutralized by antitoxin? No

LD50: Relatively large


The Fever Caused by An Endotoxin
Exotoxin—toxin released from mostly
G(+) cells

Source: Mostly Gram +

Relation to microbe: By-products of growing cell

Chemistry: Protein

Fever? No

Neutralized by antitoxin? Yes

LD50: Small

Many exotoxins are result of a lysogenic conversion


Bacillus cereus, Bacillus
Salmonella typhi, E.coli, Vibrio cholera,
anthrcis,Staphylococcus aureus,
Shigella
Streptococcus pyogenes
CHARACTERISTIC G-POSITIVE BACTERIA G-NEGATIVE BACTERIA

Structural
Outer membrane
Absent Present
Peptidoglycan layer
Thick Thin
Lipopolysaccharide
Absent Present
Teichoic acids Present in many species
Absent
Capsule, pili, flagella Present in some species Present in some species

Fubc4onal
Lysozyme sensitivity
Very sensi4ve Largely resistant
Antibiotic permeability Very permeable to most Impermeable to many

Some species
Sporula4on None
Exotoxin production Some species Some species
Immunity to Extracellular Bacteria
Microbe Example of Human disease Mechanisms of Pathogenicity
Staphylococcus aureus Skin and soft tissue infections, Skin infections: acute inflammation induced by
lung abscess toxins; cell death caused by pore-forming toxins
Systemic: toxic shock syndrome, Systemic: enterotoxin ("superantigen")-induced
food poisoning cytokine production by T cells causing skin necrosis,
shock, diarrhea

Streptococcus Pharyngitis Acute inflammation induced by various toxins, e.g.,


pyogenes (group A) Skin infections: impetigo, streptolysin O damages cell membranes
erysipelas; cellulitis
Systemic: scarlet fever
Streptococcus Pneumonia, meningitis Acute inflammation induced by cell wall constituents;
pyogenes pneumolysin is similar to streptolysin O
(pneumococcus)
Escherichia coli Urinary tract infections, Toxins act on intestinal epithelium chloride and water
gastroenteritis, septic shock secretion; endotoxin (LPS) stimulates cytokine
secretion by macrophages

Vibrio cholerae Diarrhea (cholera) Cholera toxin ADP ribosylates G protein subunit,
which leads to increased cyclic AMP in intestinal
epithelial cells and results in chloride secretion and
water loss

Clostridium tetani Tetanus Tetanus toxin binds to the motor end plate at
neuromuscular junctions and causes irreversible
muscle contraction
Neisseria meningitidis Meningi4s Acute inflammation and systemic disease caused by
(meningococcus) potent endotoxin Meningitis
Corynebacterium Diphtheria Diphtheria toxin ADP ribosylates elongation factor 2
diphtheriae and inhibits protein synthesis
Innate Immunity to extracellular bacteria
(I) Complement activation
– Alternative pathway: direct binding of C3(Gram+
peptidoglycan, Gram- LPS)
– Lectin pathway: Bacteria that express mannose
– Enhanced phagocytosis of the bacteria
– Membrane attack complex (Neisseria species)
– Complement byproducts stimulate inflammatory
responses by recruiting and activating leukocytes
Innate Immunity to extracellular bacteria…/Cont.

(II) Phagocyte receptors


– Promote phagocytosis
• Mannose receptors and scavenger receptors
• Fc receptors and complement receptors

– Activation and stimulate microbicidal activities


• Toll-like receptors (TLRs)
• Fc and complement receptors
• Secretion of cytokines and chemokines ->
recruitment of leukocytes
Antibody Responses to Extracellular Microbes
T Cell Responses to Extracellular Microbes
Immune response to infection with extracellular bacteria
Injurious Effects of Immune Responses
to Extracellular Bacteria
l Neutrophils and macrophages: local production of reactive oxygen
species and release of lysosomal (granule) enzymes
l Cytokines -> acute-phase proteins -> systemic manifestations of the infection
l Septic shock: disseminated infection with circulatory collapse and
disseminated intravascular coagulation.
– Cytokine storm: TNF, IL-6, and IL-1 (also IFN- , IL-12)
– associated with defective immune responses, perhaps related to depletion or
suppression of T cells, resulting in unchecked microbial spread.
l Disease producing antibodies
– sequelae of streptococcal infections of the throat or skin (weeks or even months
after the infections are controlled)
– Rheumatic fever: cross-reactive anti-M protein antibodies-> cardiac inflammation
– Poststreptococcal glomerulonephritis: immune-complexes with bacterial antigen
l Activation of T cells by superantigen
– Staphylococcal enterotoxin B (SEB)
Activation of T cells by Bacterial
Superantigen
Immune Evasion by Extracellular Bacteria

l Resistance to innate immunity


1 – blockade of phagocytosis (polysaccharide rich capsules)
(Pneumococcus)
2 – inhibition of complement or inactivation of complement products
(capsule sialic acid inhibits alternative pathway)
3 – scavenging reactive oxygen species(Catalase+ Staphylococci)

l Resistance to adaptive immunity


1 – genetic variation of surface antigens (pilin) (Neisseria gonorrhoeae,
Escherichia coli, Salmonella typhimurium)
2 – variation in glycosidases -> alterations in surface LPS
(Haemophilus influenzae)
Thanks

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