Immunology 334Y Immunity to Bacterial Infection

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Immunology 334YImmunity to Bacterial Infection

• G A Levy
• glfgl2_at_attglobal.net
• March 26 2009

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Section I Defining the Immune System

• The function of the immune system is to protect
  us from invasion of foreign organisms such as
  bacteria and viruses.

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Figure 2-3
Fig 2.6
Fig 2.7
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• Immune system components

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Pattern Associated Molecular Patterns (PAMPS)
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Receptors with specificity for pathogen surfaces
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Toll Receptors

• Family of transmembrane proteins
• Nine genes encoding Toll proteins in Drosophila,
  ten in human
• In Drosophila, Toll-1 involved in dorsoventral
  patterning in fly embryos and anti fungal
  activity in adults
• In humans, main funcgtion is control of
  inflammatory and immune responses
• TLR2 responsible for responses to bacterial
  lipoproteins and peptiglycan
• TLR4 essential for reposnes to LPS
• TLR5 essential for responses to bacterial
  flagellin
• TLR9 responsible for recognition of of
  unmethylated CpG DNA motifs

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• Natural killer cells
• 10 of lymphoid cells
• fig 2.3 green
• - activated by - LPS
• - cytokines IL-2
• IFN-?
• IFN-?
• destroy - virus infected cells
• - tumors
• Mechanism
• - perform dependent
• - Fas/FasL dependent mechanism
• Apoptosis

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• B-1 cells
• - subpopulation of B cells
• - surface protein CD5
• - analogous to ? ? T cells
• - arise early in ontogeny
• - T cell independent (TI-2)
• - make antibody to polysaccharide antigens of
  the
• TI-2 type
• - little or no class switching
• - mainly IgM
• - appear within 48 hours
• - no memory

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Figure 2-53
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• Complement system
• - bridge between innate immunity and acquired
  immunity
• - 20 glycoproteins produced by the liver
• - inactive zymogens
• - inhibitory proteins in humans e.g. DAF

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• Early Induced Innate Response

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• Cytokines

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Cytokines
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Figure 2-41
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Figure 2-44
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Figure 10-11 part 1 of 3
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Figure 10-30
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Figure 10-31
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Figure 10-32
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Figure 10-33
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Figure 10-36
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Figure 10-35
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Figure 10-3 part 2 of 3
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Figure 10-2
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Figure 10-4
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Figure 10-5
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Figure 2-1
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Figure 10-1
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Figure 10-17
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Figure 10-31
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• Streptococcus Pyogenes Infection
• Common skin pathogen
• Pathogenic when loss of skin integrity
• Disease is immunologically mediated

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Characteristics of isolates from patients with
tissue infection due to group A streptococci
serotype and superantigen genotype
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Bacterial load and in vivo expression of
superantigens at the site of infection. Tissue
biopsy samples obtained from patients with tissue
infections caused by group A streptococci (GAS)
were classified according to clinical grade,
defined as grade 1 (no evidence of inflammation
n 7) or grade 2 (inflamed tissue erythema and
edema including cellulitis, fasciitis, and
necrotizing fasciitis n 24). Biopsy samples
were immunostained for GAS and streptococcal
pyrogenic exotoxin F (SpeF), and stainings were
evaluated by acquired computerized image analysis
(ACIA). Results are presented as ACIA values
area and intensity of positive stain (brown) in
relationship to total cell area (blue). ACIA
values 5 were used as cutoff to separate low or
high bacterial load or SpeF expression. A, Tissue
sections with high and low GAS and SpeF
expression. B, Percentages of biopsy samples with
high or low bacterial load. Statistical
difference between biopsy samples of clinical
grade 1 and grade 2 was analyzed by
Yates's-corrected 2.
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Characterization of cell infiltrates at the site
of infection. Tissue biopsy samples of clinical
grade 1 (no evidence of inflammation n 7) or
grade 2 (inflamed tissue erythema and edema
including cellulitis, fasciitis, and necrotizing
fasciitis n 24) obtained from patients with
tissue infections caused by group A streptococci
were immunostained for various cell markers, as
indicated in panels A E. F, Double staining for
CD3 (red) and CD4 (brown) cells double- and
single-positive cells are indicated by arrows. G,
Acquired computerized image analysis (ACIA) of
CD4 and CD8 (see legend to figure 1 for details).
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Expression of interleukin (IL) 1 cytokines at the
site of infection. Tissue biopsy samples of
clinical grade 1 (no evidence of inflammation n
7) or grade 2 (inflamed tissue n 24)
obtained from patients with tissue infections
caused by group A streptococci were immunostained
for IL-1 , IL-1 , and IL-1 receptor agonist
(IL-1ra), and stainings were evaluated by
acquired computerized image analysis (ACIA see
legend to figure 1 for details). Horizontal bars
indicate mean values.
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Correlation between severity of tissue infection
and Th1 cytokine levels. Biopsy samples obtained
from patients with tissue infections caused by
group A streptococci were classified according to
clinical grade, defined as grade 1 (no evidence
of inflammation n 7) or grade 2 (inflamed
tissue n 24), including 2a (cellulitis n
18), 2b (fasciitis n 4), and 2c (necrotizing
fasciitis n 2). Biopsy samples were
immunostained for tumor necrosis factor (TNF)
and interferon (IFN) , and stainings were
evaluated by acquired computerized image analysis
(ACIA see legend to figure 1 for details).
Horizontal bars indicate mean values. Expression
of TNF- and IFN- in biopsy samples of clinical
grade 1 or grades 2a 2c (A) and expression of
TNF- (B) and IFN- (C) in biopsy samples of
varying clinical grade obtained from patient
5611. Statistical differences between biopsy
samples of clinical grade 1 and grade 2 were
analyzed by Mann-Whitney U test. Significant
correlation between Th1 cytokine levels and
clinical grade of biopsy samples from 1 patient
was determined by Spearman's correlation test.
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Differential expression of specific homing
receptors in biopsy samples of varying clinical
grade. Biopsy samples obtained from patients with
tissue infections caused by group A streptococci
were immunostained for CXC chemokine receptor 4
(CXCR4), CC chemokine receptor 5 (CCR5), CD44,
and cutaneous lymphocyte antigen (CLA), and
stainings were evaluated by acquired computerized
image analysis (ACIA see legend to figure 1 for
details). Biopsy samples of clinical grade 1
(normal tissue with no signs of inflammation n
5), were compared with samples of clinical grade
2a (cellulitis) and grade 2b (fasciitis n 5).
Horizontal bars indicate mean values. Statistical
differences between biopsy samples of clinical
grade 1 and clinical grades 2a 2b were analyzed
by Mann-Whitney U test.
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