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IMM250H1 Study Guide - Midterm Guide: V(D)J Recombination, Clostridium Difficile Infection, Inflammatory Bowel Disease


Department
Immunology
Course Code
IMM250H1
Professor
Michael Ratcliffe
Study Guide
Midterm

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IMM250 MIDTERM REVIEW
Immunity the ability to resist infection
Immune system the tissues, cells and molecules involved in protecting the host and responding to foreign antigens
primary defence against pathogens
Variolation the inoculation of scab material into the skin of individuals
Thucydides
- Reported the concept of immunity after exposure to disease during a plague outbreak
Ar-Razi
- Diagnosed smallpox versus measles
- Recognized the epidemic force of smallpox
- Described allergic asthma
- Understand that fever is a mechanism for fighting infection
Avicenna
- Father of modern medicine
- How to run a clinical trial
- Experimental medicine
- Evidence-based medicine
- Contagious nature of infectious disease
- Acquired immunity
Francastoro
- Suggested contagious particles transmitted disease by direct or indirect contact or even without
contact over long distances
Pasteur
- The first production of attenuated chicken cholera vaccine
Tyndall
- Discovery of penicillin
Mechnikov
- Discovered role of phagocytes in invertebrates (star fish)
- White blood cells could engulf and destroy harmful bodies such as bacteria
Behring
- Developed a serum-based therapy for diphtheria and tetanus
Ehrlich
- Proposed the side-chain theory was that antibodies are naturally occurring macromolecules
within the body whose specificity for antigen and complement depends on the presence of
certain sterio-chemical configurations
- Discovered mast cells
Koch
- Described the delayed-type hypersensitivity (DHT) response
- An animal previously infected with tuberculosis organisms is re-infected intra-cutaneously, a
local inflammatory reaction marked by necrotic lesions will develop rapidly and heal quickly
Landsteiner
- Discovery of human blood groups
Medawar
- Described the discrimination of self versus non-self
- Cells acquire the ability to distinguish between their own tissue substances on the one hand and
unwanted cells and foreign material on the other
Burnet
- Proposed the clonal selection hypothesis
- Each lymphocyte bears on its surface specific immunoglobulins reflecting the specificity of the
antibody that will later be synthesized once the cell is activated by an antigen
- The antigen serves as a selective stimulus, causing preferential proliferation and differentiation
of the clones that have receptors for that antigen
- Proposed the theory tolerance to self-antigens
Edelman
- Discovered the structure between antigen and antibody
Tonegawa
- Discovery of V(D)J recombination to form the vast array of available antibodies
Milstein
- Antibodies undergo hypermutation/selection to neutralize pathogens
Bretscher and
Cohn
- Two signals are delivered to T cells before they may be activated
Davis and
Mak
- Cloned the TCR
Zinkernagel
and Doherty
- Responses to virus occur by MHC restriction
Steinman
- Dendritic cells present antigen in the context of MHC
Janeway
- Recognition of exogenous microbial products
Matzinger
- Recognition of endogenous danger signals (dead or dying cells)

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Marshall
- Infects himself to prove Koch’s postulates for Helicobacter pylori
Volhard
- Drosophila Toll receptor involved in embryonic neural tube development
Gay
- Cytoplasmic domain of Toll receptor related to human IL-1 receptor called TIR domain
Lemaitre and
Hoffmann
- Drosophila Toll receptor involved in adult immunity to fungus
Medzhitov
and Janeway
- Discovery of human Toll receptor (TLR4)
Rock and
Bazan
- Identified five human TLR
Beutler
- TLR4 activated by LPS
- Mutation in C3H/HeJ mice affecting cytoplasmic domain of TLR4 making them resistant to
LPS
- C57/Bl6 mice undergoes cytokine storm and inflammatory response
Tschopp and
McDermott
- Link between NLRP3 and associated diseases
Innate barriers
Anatomical barriers (physical barriers)
o Mechanical factors
System or organ
Cell type
Mechanism
Skin
Squamous epithelium
Physical barrier
Desquamation
Mucous
membranes
Non-ciliated epithelium
(GI tract)
Peristalsis
Rapid cell turnover
Ciliated epithelium
(respiratory tract)
Mucociliary escalator
Epithelium (nasopharynx)
Flushing action of tears, saliva, mucus, urine
The epithelium
Most commensal bacteria are maintained at the top of villi
Crypts of villi produce antimicrobial products
Antimicrobial products kill commensal bacteria or pathogens
Microvilli increases surface area of intestine to increase absorption of nutrients
Tight junctions enhance tightness
Play an active in host defence
o Function within seconds of detecting pathogen
o Produce mucins
o Produce cytokines
o Produce chemokines
o Produce antimicrobial peptides (defensins and cathelicidins)
Antimicrobial peptides are positive
Bacterial cell membrane is negative
Interaction causes conformational change within bacterial membrane
forms pore
Huge osmotic gradient of water bursts bacteria
o Transport antibodies from inside (blood) to outside (epithelial cells)
o Chemical factors
System or organ
Cell type
Mechanism
Skin
Sweat
Antimicrobial fatty acids
Mucous
membranes
HCl (parietal cells in
stomach)
Tears
Saliva
Low pH
Lysozyme
Phospholipase A
Defensins (respiratory
tract and GI tract)
Cationic anti-microbial peptides
Surfactants (lung)
Opsonin (enhances uptake by phagocytes)

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o Biological factors
System or organ
Cell type
Mechanism
Skin and mucous
membranes
Normal flora
Antimicrobial substances
Competition for nutrients and colonization
The normal microbiota
More bacterial cells (1014) in the human body than human cells (1013)
Found on skin and mucosal surfaces exposed to external environment
Composition of normal flora varies
Harmful effects
o Antibiotic use perturbs normal flora
Overgrowth of less common and more resistant bacteria
Clostridium difficile diarrhea (pseudomembraneous colitis),
ulcer
Candida albicans vaginitis, thrush (oral cavity)
o Re-establishing normal proportions of flora
Use of probiotics and prebiotics
o Possible implication in other diseases
Obesity
Inflammatory bowel disease
Allergy
The “core” gut microbiota
Highly variable between individuals
Family members have more similar microbiota
Early environmental exposure is the key determinant
Metabolic outputs seem to remain constant
Factors that impact establishment of the “core” gut microbiota
o Host genetics
o Life style
o Early colonization
o Medical practices
o Disease
o Health
Beneficial effects
o Protective functions
Pathogen displacement
Nutrient competition
Receptor competition
Production of antimicrobial factors
o Structural functions
Barrier fortification
Induction of IgA
Tightening of tight junctions between epithelial cells
Immune system development
o Metabolic functions
Synthesize vitamins
Salvage energy
Ion absorption
Control differentiation and proliferation
Harmful effects
o Escape of normal flora to abnormal sites
Perforated appendix leads to peritonitis
Urinary tract infections
E. coli found in abundance in the intestinal tract
o A link between gut microbiota and obesity
Less microbial diversity in guts
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