301 Immunology Flashcards
What is inflammation?
When blood vessels dilate,
Leading to local swelling and accumulation of components
So TLR activation in epithelium
And activated macrophages contribute by secreting cytokines/chemo lines that attract neutrophils and other cells
Steps on how inflammation takes place
- Bacteria invades tissue
- Bacteria trigger macrophages
- Release cytokines & chemokines
- Bacteria phagocytosed by macrophages
- Chemokines & cytokines move into local blood vessels
- Stimulate vasodilation & increase vascular permeability
- Cause redness, heat & swelling due to blood movement from vessels to peripheral tissue
- Inflammatory cells migrate into tissue and causes pain
What is c5a and what does it do?
Part of innate immune system
Activated again when there is infectious agent
Complement binds to bacterial cell wall & punches hole into cell membrane to kill infecting agent
What are chemokines known as and produced by?
IL8 (interleukin 8)
Monocytes, macrophages, fibroblasts, epithelium and endothelial cells
What are the 2 receptors of chemokines?
CXY R1 and R2
What does CXY R1 and R2 do?
Attract neutrophils and naïve T cells (involved in secondary response)
What is a major effect of IL8?
Mobilises, activates and degranulates neutrophils
Involved in angiogenesis (new blood vessels forming form existing ones)
What is CCL5 released by and what does it attract?
T cells, endothelium and platelets
Monocytes, natural killer cells and T cells, basophuls, neutrophils and dendritic cells
What does CCL5 degranulate and activate?
Basophils
T cells
What is autoimmunity or inflammatory disease (most the time)?
Overproduction of cytokines and chemokines
Triggers/causes of inflammatory disease
Pathogen
Tumours
Autoimmunity
Atherosclerosis (fat build up on artery walls)
Heart disease
Obesity
Any tissue damage (especially chronic)
Why does tissue damage cause inflammatory disease?
Brings immune cells to damage site
Releasing chemokines which bring more immune cells and follow the cycle
Why are Crohn’s and ulcerative colitis ‘technically’ not autoimmune?
Immune cells are attacking commensal gut bacteria instead of own or host cells
Cannot survive without gut bacteria
Cryonic reaction is constant so always inflammatory response
Symptoms of inflammation
Dolor - pain
Rubor - redness
Calor - heat
Turgor - swelling
Monocytes at infection site
- Monocyte binds adhesion molecules on vascular endothelium near infection site, receiving chemokine signal
- Monocyte migrates into surrounding tissue
- Monocyte differentiates into inflammatory monocyte at infection site
Examples of cytokines and chemokines
TNF-α and chemokines
Prostaglandins
Leukotrienes - leukocytes
Platelet activating factor
C5a - complement components + promotion of inflammation
What are cytokines and chemokines?
Messenger molecules that control inflammation, tell immune cells what to do and where to go
Subset of cytokines that direct immune cells to damaged/infected site
Ulcerative colitis
Long term IBD causing colon and rectal inflammation
Crohn’s disease
Chronic IBD can affect entire GI tract from mouth to anus
Describe the molecular inflammatory pathway of Crohn’s disease
- Phagocytes take in bacteria that normally cause no harm but introduce them to macrophages
- Phagocytic cell and macrophage show them as harmful
- Cytokines & chemokines are produced
- Producing Th 1 & Th 17 cells
- Antigen processed by tissue macrophages
- Stimulates helper cells to produce cytokines, chemokines, cytotoxins (cause damage themselves)
Which cytokines & chemokines are produced in immune response to Crohn’s?
IL12, IL6, EGF beta, IL1 beta and IL23
When an antigen is processed by tissue macrophages and Th1 cells are stimulated, what is recruited?
Chemokines - recruit macrophages at antigen site
IFN-γ - induces vascular adhesion molecule expression, activates macrophages, releasing inflammatory mediators
TNF-α and LT - local tissue destruction, adhesion molecule expression in local blood vessels
IL3/GM-CSF - monocyte production by bone marrow stem cells
What does coeliac disease lead to and what response is it?
B cell activation and IgA release
CD4+ cell mediated response
Coeliac disease body’s response
- Gliadin enters epithelial cells
- Attaches to tissue transglutaminase (TTG)
- Creates deamidated gliadin
- Body reacts to TTG binding, activating antigen presenting cell
- Genetics of MHC binds amino acid sequence
- Activating T cell when bound to T cell receptor
- Releasing INF-γ causing inflammation
- Damaging epithelial cells
- Producing B cells producing IgA to gliadin endomysium & TTG
- Antibodies bind to complex deamidated gliadin and TTG causing damage and release of factors
- T cells activate natural killer cells damaging epithelium cells, flattening GI so lack of nutrients and villi
- So inflammatory response
When coeliac disease occurs and antigen presenting cell is activated, which types are most common?
HLA or MHC molecules DQ2 or DQ8
What is rheumatoid arthritis?
Autoimmune disease which is chronic inflammation of gut
What systems can rheumatoid arthritis affect?
Haematologic, cardiovascular and respiratory
Describe the molecular inflammatory pathway of rheumatoid arthritis
Produce antibodies that react to Fc region (bottom of Y shape) of IgG
IgM-IgG complexes deposit in joints
Agglutination due to antibodies binding and clump together
Complexes activate complement cascade
Type III sensitivity (body reacts to IgG)
Describe the bacterial glycocalyx
Gel-like, polysaccharide-based layer coats outside of a gram negative bacterial cell’s membrane or peptidoglycan layer of gram positive
Function of the glycocalyx
Protects bacteria from toxic compounds and desiccation and helps them adhere to surfaces and evade the host’s immune system
How do bacteria attach to cell surfaces?
Pili: made of protein & protrude from bacterial surface
Adhesins: on bacterial surface bind to host surface receptors
Flagella: help bacteria stick to surfaces, especially hydrophobic surfaces
EPS: made of polysaccharides, proteins, DNAs, lipids & other polymeric compounds, role in surface adhesion, biofilm formation and more
Sortase A: enzyme that covalently attaching surface-exposed proteins to cell wall envelope
Describe the differences between a pathogen and a commensal bacteria
CB coexist peacefully with their host, while P cause disease
CB don’t usually have aggressive tools that P use to invade
What is biofilm?
A slimy community of microbes growing on a surface
What does antagonistic mean in terms of microorganisms?
Harms other organism
What does synergistic mean in terms of microorganisms?
Organisms cooperate to gain equal advantages
What does symbiotic mean in terms of microorganisms?
Organisms are interdependent and rarely live outside relationship
What does biofilm mean in terms of microorganisms?
Complex relationships among numerous microorganisms, often different species
Examples of biofilms:
Dental plaque
Soap scum on baths
Slime on rocks in streams
Implanted medical devices
Mucous membranes of digestive system
Steps of biofilm development
- Free living microbes settle & attach to surface
- Cells produce extracellular matrix (DNA, proteins, polysaccharides from glycocalyx)
- Matrix aids in adherence to other cells creating microenvironment
- Secrete QS molecules
- QS molecules trigger changes in biochemistry & shape - cells take on differing roles in film
- New cells arrive to join biofilm & others leave
Time frames of biofilm development stages
- Reversible adsorption of bacteria (seconds)
- Irreversible attachment of bacteria (seconds-mins)
- Growth & division of bacteria (hrs-days)
- Exopolymer production & biofilm formation (hrs-days)
- Attachment of organisms to biofilm (days-months)
What is quorum sensing?
Chemical produced by bacteria communicate with other bacterial cells
Steps of quorum sensing
- Chemical produced by bacteria communicate with other bacterial cells
- Bacterial cells have receptors for the chemicals
- As cell no. increases, conc. of QS molecules increases
- Once QS chemicals bind to receptors exceeds limit, gene expression triggered
- Enzymes produced, cell shape change, maintenance of biofilm
Examples of quorum sensing responses
Virulence
Bioluminescence
Other group behaviours
Quorum sensing in psuedomonas aeruginosa
Synthesises harmful toxins during infection
Leads to bacteria recognition in body
Secretes QS chemicals to determine cell density
Bacterial cells only secrete toxin once reached certain density
What can drug targets cause in quorum sensing?
Disruption of QS can inhibit biofilm formation
By decreasing cell communication, become “blind”
Amplify QS before biofilm formation can inhibit infection
Increase in QS reveals bacteria to host immune system before infection takes hold
Biofilms in infection
Instead of requiring adhesion for infection, bacteria form biofilms to “stick” to surface
Biofilms and how they affect antibiotic resistance?
Layer on top of film may block antibiotic activity
Increased mutational activity in biofilms
Cells in biofilm centre get signals from QS to stimulate SOS response
Dormant cells in nutrient poor section have decreased metabolic activity but increase doubling time
What are the roles of intestinal microflora?
- Aids digestion & nutrient absorption
- Supports immune system
- Regulates metabolism
- Protects against pathogens
- Influences mental health via gut-brain axis
- Modulates inflammation
What are consequences in microflora changes?
- Digestive issues (IBS, bloating)
- Weakened immune function
- Increased risk of obesity, diabetes
- Triggering inflammatory & autoimmune diseases
- Mental health impacts (anxiety, depression)
- Allergies & heightened immune sensitivity
How do intestinal bacteria aid in digestion?
Ferment fiber, producing energy-rich short-chain fatty acids
Break down complex carbs into simpler sugars
Synthesise essential vitamins (K & B)
Aid in fat digestion by processing bile acids
How do probiotics protect against disease?
- Strengthen immune system
- Compete with harmful bacteria, preventing infections
- Reduce inflammation
- Support gut barrier to block pathogens
- Produce antimicrobial substances
What are some disadvantages of using probiotics for certain diseases?
- May cause gas, bloating or infections in vulnerable individuals
- Risk of antibiotic resistance transfer
- May interfere with immune responses
- Effectiveness varies by strain & individual
Describe the synthesis, recognition & response of quorum sensing
- S: Bacteria synthesize & release signalling molecules, known as autoinducers
- R: As the conc. of these molecules increases, bacteria detect them through receptors
- R: Bacteria coordinate group behaviours, such as bioluminescence, virulence & other community actions
