Immunology 2 Flashcards
What proviides the first line of defence?
Epithelial Surfaces e.g. skin, gut, bronchi
In the skin epidermis, what do keratinocytes do in the stratum spinosum?
Produce a waterproof antimicrobial layer
In respiratory epithelium, what do goblet cells secrete and what does it do? (2 marks)
- Secrete mucins
- Mucus layer traps foreign particles which are cleared by the muco-ciliary escalator - allows for FLOW
In the gut epithelium, how does peristalsis work to reduce bacterial infection and what do paneth cells do? And urinary tract?
(3 marks)
- Peristalsis will move food and infectious agents creating a nice FLOW
- Paneth cells produce several types of antimicrobial proteins
- Urinary tract also maintains the FLOW and prevents kidney infections
What are the humoral components of the innate immune system?
- Complement system
- Defensive chemicals
- Peptides
- Enzymes
Where are microbicidal and microbiostatic chemicals found? GIve examples of these. (3 marks)
-
Digestive tract:
- stomach acid
- digestive enzymes
- bile salts
Acidic and create a bad environment for bacteria
Where can antibacterial enzymes that are secreted be found? Give an example of these. (3 marks)
- Found in tears, saliva and paneth cells:
- Lysozyme (breaks down cell wall)
- Secretory phospholipase A2 (breaks down plasma membrane)
What are antimicrobial peptides (AMP) and where can they be found? (3 marks)
- Secreted by epithelial cells into mucosal fluid to produce antimicrobial peptides
- Secreted by phagocytes into tissues
- E.g. defensins, cathelicidins, histatins
What are defensins and how do they work? (4 marks)
- Short peptide with hydrophobic and hydrophilic regions - this allows them to disrupt the membrane very quickly
- Attracted first to phospholipids on bilayer
- Slips through bilayer and creates a pore which allows fluid to come out of bacteria
- Loss of fluid in bacteria means can no longer maintain its pH
- Thus causing death of bacteria
What are cathelicidins and what do they do? (4 marks)
- amphipathic peptide with hydrophobic and hydrophilic region
- Bind to plasma membrane and wrap it up into little balls
- Break down bilayer by dissolving into little balls
Where are catheliciins:
A. Constitutively expressed
B. Induced expression
(2 marks)
A. Myeloid progenitor cells
B. Induced during bacterial infection
Explain the process of the function of the complement system (6 marks)
- Small proteins circulate in plasma found in interstitial fluid - whilst here are inactive. Proteins able to leave with plasma
- Bind directly to surface of pathogen or complement protein can bind to carbohydrate sequences and initiate activation of other complement proteins
- Once bound = protelytically active. Can split themselves in 2 (A,B). Some parts biologically active to kill pathogen and others can cleave themselves in 2.
- B part combined with another b can turn into another proteolytically active enzyme which can cleave another protein into 2 Ca and a Cb.
- Ca will go off to kill and Cb will re-join with another b so you will get a cascade of proteins that create either Ca and b and so forth
This is known as amplification of production of portions of complements
What is the role of C3 and C5 in the complement system? (6 marks)
C3:
- can bind directly to surface of pathogen and then enzymatically split itself in 2 to 3b and 3a
- 3a has role in inflammation, 3b activates opsonisation (assisting phagocytosis) also has role in converting c5 to c5a and c5b
- 3b binds with another 3b to split c5
C5:
- 5a involved in inflammation
- 5b involved in creating membrane attack complex - which is a type of pore that kills pathogen inside of it by leaking fluid out of pore
Binding of 2 complement proteins to surface of pathogen will also induce enzymatic splitting of c3 into b which will create a cascade to create other c protein parts
How does vascular permeability occur in an infected capillary? (3 marks)
- C3a and 5a bind to part of endothelial cells and tells them to pull a part to allow more plasma to come out = VASCULAR PERMEABILITY
- This increases fluid in tissue and induces expression adhesion molecules inside of capillary
- More plasma in tissue = more complement proteins
What is the effect of pore formation from terminal complement proteins C5b and C6-9?
- Pore is formed in lipid bilayer of membrane which destroys proton gradient as - unstable pH, so no drive to proton pump, no voltage and no energy
- Pore destroys membrane integrity and fluid in bacteria floods out causing pore destruction
What happens after the activation of the complement system by C3 binding to the surface pathogen? (6 marks)
- Cleavage of 5a into 5b
- After 5b inserted inot membrane, C7 undergoes conformational change recruiting C8
- C8 undergoes another conformational change recruiting C9 which inserts all th way across lipid bilayer
- This combination of complement genes induces polymerisation of C9 which adds to pore and causes hydrophilic tunnel
- Allowing bacteria to flood out
What is opsonisation?
Coating of surface of pathogen by antibody and/or complement protiens to aid process of PHAGOCYTOSIS and destruction of pathogen
Outline the process of phagocytosis.
- Recognition of pathogen by receptor on surface of phagocyte
- Pathogen brought to surface of P cell and internalised and cell ingests pathogen inot phagosome
- Phagosome binds with lysosome - have chemicals that can induce oxidative stress in bacteria
- Bacteria releases lots of nitric oxide inot phagolysosome and hydrogen peroxide
- Bacteria can’t cope and dies
What complement protein is the major opsonising complement component?
C3b is and requires C5a binding
What is the process of complement related phagocytosis? (3 marks)
- Bacterium coated with C3b
- When only C3b binds to CR1 bacteria will not be phagocytosed
- C5a can activate macrophages to phagocytose via CR1
What are the different phagocytic cells? (3 marks)
- MAcrophage
- Granulocytes - neutrophils main phagocyte
- Dendritic cell
What kind of cell is recruited from blood to tissue to become a macrophage?
Monocytes
When do macrophages ‘mature’?
Development occurs in the bone marrow - it enters the bloodstream as a monocyte which isnt mature. So only mature once they have entered the tissue.
What kind of cells does TISSUE macrophages arise from?
Progenitor cells in embryonic development
(self renew in situ as needed in the body)
What are the main characteristics of a dendritic cell?
(3 marks)
- A part of myleoid or lymphoid lineage
- Arise from bone marrow progenitors
- In lymphnoid organs and peripheral tissues
What does the dendritic cell do? (3 marks)
- Patrols vulnerable parts of body e.g. tissues exposed to outside
- Undergoes phagocytosis
- Uses its long protrusions to display parts of pathogen on surface to communicate with the immune system
What is a neutrophil and what does it do?
A granulocyte that only undergoes one round of phagocytosis and then dies.
What do PAMPs and DAMPs recognise respectively?
PAMPs recognise pathogen infiltration
DAMPs recognise tissue injury
What immune system are PAMPs and DAMPs a part of ?
Humoral and cell-mediate innate immune system
What are PAMPs and what do they recognise specifically?
Pathogen Associated Molecular Patterns:
pathogen surfaces patterns of carbo and polysaccharide and recognise friendly bacteria e.g. bacterial flagelin, bacterial lipopolysaccharides (LPSs)
What are DAMPs and what do they recognise specifcally?
Damage Associated Molecular Patterns
- Recognises cell and tissue injury
e. g. components of damaged plasma membrane, oxidised nuclear and cytosolic proteins
What are the 3 receptor types that cells use to recognise PAMPs and DAMPs?
(3 marks)
- Membrane bound phagocytic receptors - if bind to DAMP will undergo phagocytosis
- Membrane bound signalling receptors- Toll-like receptor (TLR) - cell will signal commnunicate between innate immune system cells
- Cytoplasmic signalling receptors - NOD if there’s an infection within cell will alert cell that there’s a pathogen in the cytoplasm
What are teh 3 kinds of phagocytic receptors? (6 marks)
-
C-type lectin like family receptors:
- Bind to carbohydrate and induce phagocytosis in cell.
- e.g. dectin-1, mannose receptor
-
Scavenger receptors:
- Induce phagocytosis and bind to anionic polymers on surface of pathogens
- Important in atherosclerosis and recognises low density proteins
- e.g. SR-AI, SR-AII, CD36
-
Complement receptors:
- bind to complement proteins on opsonised pathogens
- Integrin in opsonised pathogen recognise complement protein bound to surfce of pathogen - induce phagocytosis in cell
What is the function of Toll like receptors?
- Induce cytokine expression upon binding to pathogen
- ligand binding cuases dimerisation and coformational changes
Where are toll like receptors expressed?
- Macrophages, DCs, B-cells, Stromal and epithelial cells
- Located on cell surface intracellularly
What happens after dimerisation of toll like receptors?
(3 marks)
- Happens after a common pattern is recognised
- Induces cell signalling by TRIF and TRAM
- Induces expression of cytokines IL-1 and TNF-α (both involved in inflammation)
