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School Sores
Case 1: Week 1
Julia Shun Wei Yang Student G
PATH 417A The Immune Response
Case 1
6-year-old Stephanie O. has developed red sores around her mouth and nose.
At the start of class her teacher noticed the rash and called her parents to take
her home. Her parents take her to the family doctor who examines Steph. She
is afebrile and does not have any swollen lymph nodes. There is no rash on
her hands or feet or inside her mouth. He prescribes an antibiotic and tells
her parents that she needs to stay at home for a couple of days. He swabs the
rash and sends the swab to the Microbiology Laboratory.
What elements of the innate and adaptive
(humoral and cellular) immune response are
involved in this infection?
The Immune Response: Host Response
Innate Immune Response
Physical Barrier
●
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Normal, intact skin prevents entry of pathogens into body1
High turnover of epithelium (skin shedding) removes pathogens attached
to epithelial surface1
Chemical Barriers
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Perspiration contains lysozymes (breaks down bacterial cell wall) 2 and
lactic acid (decreases pH of skin to inhibit bacterial growth) 4
Antimicrobial peptides (AMPs) kill bacteria3
○
Defensins, histatins and cathelicidins
Innate Immune Response
Normal Skin Flora
●
Metabolize skin secretions into substances (eg. fatty acids) that hinder
pathogenic bacterial colonization2
Complement Activation (through alternate pathway, antibody-independent)
●
Complement cascade leads to recruitment of phagocytes to site of
infection (activation of mast cells leads to cytokine production4),
inflammation, phagocytosis and lysis of bacteria2
Innate Immune Response
Phagocytic Leukocytes: engulf and kill pathogenic bacteria
●
Neutrophils
○
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Formation of phagosome leads to secretion of reactive oxygen species and hydrolytic
enzymes (respiratory burst)4
Macrophages
○
Pathogen-associated molecular patterns (PAMPs) on pathogenic bacteria are recognized
by pattern recognition receptors (PRRs) on macrophages4
Natural Killer Cells
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Cytotoxic lymphocytes that induce apoptosis of infected cells7
Adaptive Immune Response
Antigen Presenting Cells (APCs): capture, process and present microbial
antigens to lymphocytes (B cells and T cells) to induce activation 7
●
Dendritic cells, macrophages and B cells
Humoral Response
●
APCs activate naive B cells, leading to clonal expansion and
differentiation into11:
○
○
Antibody-secreting plasma cells and memory B cells
Antibodies facilitate opsonization and lead to phagocytosis of bacteria
Adaptive Immune Response
Cell-Mediated Immunity
●
●
Only antigens presented by major histocompatibility complex (MHC) will
activate T cells
MHC divided into MHC I and MHC II7
○
○
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MHC I found on all nucleated cells and presents antigens found in cytosol
■ Recognized by cytotoxic CD8+ T cells (macrophage and B cell stimulation)
MHC II found only on APCs and presents antigens found in vesicles
■ Recognized by cytotoxic CD4+ T cells (kills infected cells)
After antigen eliminated, memory CD4+ and CD8+ T cells remain7
What damage ensues to the host from the
immune response?
The Immune Response: Host Damage
Host Damage
●
Cytotoxic cytokines secreted by CD8+ T cells may induce lysis of nearby
host cells13
●
In phagocytosis, neutrophils release free oxygen radicals (respiratory
burst) to kill bacteria that could damage neighbouring host cells 13
●
During inflammation histamine is released which increases blood flow to
the site of infection and leads to local swelling, redness and pain 14
●
Cell-mediated immunity against infected cells can produce red rashes 13
How do the bacteria attempt to evade these host
response elements?
The Immune Response: Bacterial Evasion
Bacterial Evasion
Inhibition of Phagocytosis
S. pyogenes contains antiphagocytic M protein and fimbriae15
●
Fimbriae encloses cell wall and helps resist phagocytosis
S. aureus produces cell-bound or soluble Protein A15
●
Protein A is capable of binding immunoglobulins, prevents opsonization 12
Bacterial Evasion
Bacterial Products that Kill or Damage Phagocytes
S. pyogenes produce streptolysin15
●
Streptolysin causes explosion of lysosomal granules in neutrophils and
subsequent death by binding to cholesterol in membranes
S. aureus produce leukocidin15
●
Leukocidin also causes lysosomal granule explosion in neutrophils by
acting on the cell membrane
Is the bacteria completely removed, does the patient
recover fully and is there immunity to future
infections with these candidate infectious agents?
The Immune Response: Outcome
Bacterial Removal
In this case Stephanie’s diagnosis is most likely Impetigo which can be caused
by Staphylococcus aureus and Streptococcus pyogenes5
●
Antibiotic treatment can clear the bacterial pathogen completely6
○
●
Patient must go through full course of treatment
Topical antibacterial creams are typically used, while oral antibiotics may
be given if the infection is severe6
Patient Recovery
●
Patient prognosis is positive (very high cure rate)8
○
○
Even without treatment rash typically clears up within two to three weeks
Scars are rare
In rare cases, impetigo may lead to9:
●
●
●
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Post-streptococcal glomerulonephritis
Toxic shock syndrome
Staphylococcal scalded skin syndrome
Soft tissue infection
Sepsis5
Future Immunity
If adaptive immune response was activated10:
●
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Patient will develop immunity to future infections by same bacteria
Some activated B cells become memory B cells
●
Re-infection leads to faster and more effective immune response due to
existence of memory B cells
Memory B cells may survive for years following initial infection
●
THE END
References
[1] Austin Community College. Immune System. Retrieved from http://www.austincc.
edu/apreview/EmphasisItems/Inflammatoryresponse.html
[2] Todar, K. (2012). Immune Defenses against Bacterial Pathogens: Innate Immunity. Retrieved from http:
//textbookofbacteriology.net/innate_3.html
[3] Brazil, M. (2001). Innate immunity: Self-defence is a sweaty business, Nature Reviews Immunology (1, 174). Retrieved
from http://www.nature.com/nri/journal/v1/n3/full/nri1201-174b.html
[4] Delves, P.J., Roitt, I. (2001) Essentials of Immunology. Retrieved from http://www.uib.
cat/depart/dba/microbiologia/ADSenfcomI/material_archivos/Essentials%20of%20immunology%20Roitt%20chap01.
pdf
[5] Nordqvist, C. (2015). Impetigo (Infantigo): Causes, Symptoms and Treatments. Retrieved from http://www.
medicalnewstoday.com/articles/162945.php#causes_of_impetigo
References
[6] MedlinePlus. Impetigo. Retrieved from https://www.nlm.nih.gov/medlineplus/impetigo.html
[7] Fisher, P. Principal cells and tissues of the immune system. Retrieved from http://missinglink.ucsf.
edu/lm/immunology_module/prologue/objectives/obj04.html
[8] MedlinePlus. Impetigo. Retrieved from https://www.nlm.nih.gov/medlineplus/ency/article/000860.htm
[9] DermNet. (2015). Impetigo. Retrieved from http://www.dermnetnz.org/bacterial/impetigo.html
[10] Fisher, P. Humoral immunity: How B cells recognize and respond to foreign antigens. Retrieved from http:
//missinglink.ucsf.edu/lm/immunology_module/prologue/objectives/obj05.html
[11] Todar, K. (2012). Immune Defenses against Bacterial Pathogens: Adaptive or Acquired Immunity. Retrieved from
http://textbookofbacteriology.net/adaptive_3.html
References
[12] Henderson, B. Oyston, P. (2003). Bacterial Evasion of Host Immune Responses. Retrieved from http://site.ebrary.
com/lib/ubc/reader.action?docID=10070373
[13] Mak, T.W. Saunders, M.E. (2005). The Immune Response: Basic and Clinical Principles. Retrieved from https:
//books.google.ca/books?
id=2AaJqNl1QIYC&pg=PA644&lpg=PA644&dq=host+damage+from+immune+response&source=bl&ots=AHqezC2Y7&sig=dni2SdfaNISTid9sf4qUMXWMDA&hl=en&sa=X&ved=0ahUKEwiNrM3n6q_KAhXHMGMKHah3CXsQ6AEIUjAI#v=onepage&
q=host%20damage%20from%20immune%20response&f=false
[14] (2006). Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial
Therapies. Retrieved from https://books.google.ca/books?
id=6NuWZyFVuZsC&pg=PA39&lpg=PA39&dq=host+damage+from+immune+response&source=bl&ots=fT7SrtDgWv&s
ig=jiRvXSGtXbRU0bXBHOYVedrvwM&hl=en&sa=X&ved=0ahUKEwiNrM3n6q_KAhXHMGMKHah3CXsQ6AEIPjAF#v=onepage&q=host%20damage%
20from%20immune%20response&f=false
[15] Todar, K. (2012). Mechanisms of Bacterial Pathogenesis. Retrieved from http://textbookofbacteriology.