Innate Immunity Flashcards
Spit some facts about bacteria in the gut
GI tract has on average 1kg of bacteria. Over 400 species. You excrete your own body weight in bacteria every year. 1 gramme of feces contains around 100,000,000,000 bacteria. Access to bloodstream would therefore not be ideal!
What are the two types of immunity a pathogen must face?
- The innate immune system is your first line of defence against pathogens. It is not specific.
- Followed by adaptive immunity, which is specific and can involve memory.
What is the associated mode of transmission of pathogens entering through the mucosal surfaces of the airway and some examples of pathogens and associated diseases that transmit in this method
Mode of transmission:
Inhaled droplets
Pathogen:
Influenza virus
Neisseria meningiditis
Disease:
Influenza
Meningococcal meningitis
What is the associated mode of transmission of pathogens entering through the mucosal surfaces of the GI tract and some examples of pathogens and associated diseases that transmit in this method
Mode of transmission:
Contaminated food or water
Pathogen:
Salmonella typhi
Rotavirus
Disease:
Typhoid fever
Diarrhea
What is the associated mode of transmission of pathogens entering through the mucosal surfaces of the genitourinary system (GU) and an example of a pathogens and associated disease that transmit in this method
Mode of transmission:
Physical contact
Pathogen:
Treponoma pallidum
Disease:
Syphilis
What is the associated mode of transmission of pathogens entering through the epithelia of the external surface and an example of a pathogens and associated disease that transmit in this method
Mode of transmission:
Physical contact
Pathogen:
Tinea pedis
Disease:
Athlete’s foot
What is the associated mode of transmission of pathogens entering through the epithelia around wounds and abrasions and an example of a pathogens and associated disease that transmit in this method
Mode of transmission:
Minor skin abrasions
Punctures
Pathogen:
Bacillus anthracis
Clostridium tetani
Disease:
Anthrax
Tetanus
What is the associated mode of transmission of pathogens entering through the epithelia through insect bites and an example of a pathogens and associated disease that transmit in this method
Mode of transmission:
Mosquito
Mosquito Ticks
Pathogen:
Flavivirus
Plasmodium
Borrelia burgdorferi
Disease:
Yellow fever
Malaria
Lyme disease
What are the three phases of response to initial infection?
Innate Immunity.
Immediate: 0-4 hours
Early induced response.
Early: 4-96 hours
Adaptive Immune Response
Late: >96 hours
Discuss the events of innate immunity in infection.
Immediate: 0-4 hours
Infection
Recognition by preformed, nonspecific effectors
Removal of infectious agent
Discuss the events of early induced response in infection.
Early: 4-96 hours
Infection
Recruitment of effector cells
Recognition and activation of effector cells
Removal of infectious agent
Discuss the events of adaptive immune response in infection.
Late: >96 hours
Infection
Transport of antigen to lymphoid organs
Recognition by naive B and T cells
Clonal expansion of effector cells
Removal of infectious agent
What are the mechanical barriers to infection?
Tight junctions between cells prevents access
Air and fluid flow across epithelium
Movement of mucus by cilia
What are the chemical barriers to infection?
Fatty acids on skin
Enzymes: lysozyme in saliva, sweat and tears.
Low pH in stomach
Antibacterial peptides: defensins (skin and gut) cryptidins (gut)
What are the microbiological barriers to infection?
Normal flora compete for nutrients and attachment (biofilms), and also produce antibacterial substances (colicins).
Provide a summary of the action of the innate immunity
• Once across an epithelial
barrier, in most cases microorganisms are recognised and ingested by mononuclear phagocytes, or macrophages.
What receptors are found on cells within the innate immune system?
• Receptors include:
Mannose receptor, glucan receptor, scavenger receptor, CD14 (LPS), CD11b/CD18 (CR3)
What bactericidal effects and agents are produced by phagocytes in the innate immune system?
- Acidification: pH 3-4, bactericidal
- Toxic oxygen derived products: superoxide, hydrogen peroxide, hydroxyl radical
- Toxic nitrogen oxides: Nitric Oxide
- Peptides: defensins and other cationic proteins
- Enzymes: Lysosyme, acid hydrolases
- Competitors: Lactoferrin, vitamin B12 binding protein.
What cell is the progenitor to all cellular elements of blood, rbc, platelets and white cells?
hematopoietic stem cell
What are monocytes?
Monocytes: one of the three types of
phagocytic cell of the immune system. Circulate in bloodstream, differentiate into macrophages in tissue
(looks kinda like a heart)
What are granulocytes?
- Also called polymorphonuclear (PMN) leucocytes due to shape of nuclei
- Neutrophils
- Eosinophils
What are neutrophils?
also phagocytic, most numerous and important cell of innate immunity. Neutrophil deficiency leads to overwhelming bacterial infections.
What are eosinophils?
evolutionarily important in parasite defence. Kill antibody coated parasites through release of granule contents
Put out a shit ton of additional facts about neutrophils
- Most common PMN (polymorphonuclear leucocytes), around 99% of all circulating PMN’s
- Overall represents around 70% of all ciculating white blood cells.
- Short time spent in circulation, around 12 hours, once in tissue survive for maybe only 2 days.
- Active phagocytes , but probably only one round. Possible adaptation to prevent growth of parasites that can live in phagocytic cells. Alternatively since antimicrobial products damage host tissues, short lifespan may limit host damage
- Neutropenia = low numbers, may be genetic or the result of medication including chemotherapy
- Chronic granulomatous disease - failure in respiratory burst, superoxide production limited, antibacterial activity impaired
- Alpha 1-antitrypsin deficiency, elastase from neutrophils not adequately inhibited, excessive tissue damage during inflammation- pulmonary emphysema
How long fo neutrophils live?
Short time spent in circulation, around 12 hours, once in tissue survive for maybe only 2 days.
What are three conditions relating to neutrophils?
- Neutropenia, low numbers, may be genetic or the result of medication including chemotherapy
- Chronic granulomatous disease - failure in respiratory burst, superoxide production limited, antibacterial activity impaired
- Alpha 1-antitrypsin deficiency, elastase from neutrophils not adequately inhibited, excessive tissue damage during inflammation- pulmonary emphysema
Put out a shit ton of additional facts about eosinophils
- Granules contain histamine, peroxidase, RNase, DNases, lipase, plasminogen, Major Basic Protein
- Circulate for 12 hours, survive in tissues for 3 days
- Eosinophilia (increase, more than 500 per microlitre blood) seen in parasitic infections of gut, some vascular diseases, Hodgkin’s Disease, Addison’s Disease
- Eosinopenia often seen when glutocorticoids used.
- Eosinophilia-myalgia syndrome (EMS) - potentially fatal condition - neurological - but eosinophils increased in blood. Identified in 1989 when a batch of tryptophan food supplement was incorrectly prepared. Potential interference with histamine metabolism
What are basophils
also a granuloctye, function probably similar and complementary to eosinophils and mast cells.
What are mast cells?
when activated release a number of substances that effect vascular systems. Most well known due to IgE mediated triggering in allergies. Can cause expulsion of parasites from the body through release of granules containing histamine and other active agents
Spit some additional facts about basophils
- Least common PMN
- Upon activation secrete histamine, proteoglycans, leucotrienes, some cytokines including IL-4 (potentially important for IgE and allergy)
What is found within the population of B or T cells?
The adaptive immune response - B cells producing antibody, T cells becoming cytotoxic T cells (CD8) or helper T cells (CD4).
What are plasma cells?
Fully differentiated form of B cell that secretes antibodies
What are natural killer (NK) cells?
large granular lymphocytes that can recognise virally infected cells non- specifically
What are dendritic cells?
potentially the most important immune cell, bridges the innate and adaptive immune responses. Specialised in antigen uptake and antigen presentation
Responsible for activation of T cells and initiation of adaptive immune responses
What chemical do virus infected cells give off to warn the body?
IFN-(alpha) + IFN-(beta)
What do IFN-(alpha) + IFN-(beta) do?
Induce resistance to viral replication in all cells
Increase MHC class I expression and antigen presentation in all cells
Activate NK cells to kill virus infected cells
At what point of the immune response do NK cells play a role?
• NK cells appear to play an early defence role against viral infection
What is the difference between NK and CD8 T cells?
The key difference between NK and CD8 T cells is that NK cells are not antigen specific. Also they do not require to undergo the lengthy clonal expansion of T cells in lymph nodes when virus is detected
What occurs when a NK cell interacts with a healthy cell?
The healthy cell has MHC class I proteins on its membrane which binds to the inhibitory receptor on the membrane of the NK cell. A ligand on the healthy cell also binds to the activating receptor on the NK cell but as the inhibitory receptor is activated lytic granules remain in the NK cell
What happens when a NK cell interacts with a target cell in which MHC class I expression is lost (normally virus infected cell)
The inhibitory receptor on the membrane of the NK cell remains unbound, while a ligand on the membrane of the target cell binds to the activating receptor on the membrane of the NK cell, thus lytic granules are released to kill the target cell
What happens when a NK cell interacts with a healthy cell in the presence of an anti-MHC class I antibody?
The anti-MHC class I antibody binds to the MHC class I protein, thus preventing the binding between the MHC class I protein and the inhibitory receptor of the NK cell. The anti-MHC class I antibody has no effect on the ligand on the membrane of the healthy cell that binds to the activating receptor of the NK cell however, so the NK cell releases lytic enzymes to kill the healthy cell
What are the inhibitory receptors of NK cell and their MHC class I ligands?
CD94 and NKG2A -> HLA-E
KIR3DL -> HLA-B
KIR2DL -> HLA-C
What is the compliment?
• Heat labile component of plasma that act in concert with
antibodies to kill some bacteria
• Comprises a large number of distinct plasma proteins
• Three distinct activation pathways exist that trigger the complement cascade.
What are the three distinct activation pathways exist that trigger the complement cascade?
Classical pathway
- Antibody binds to specific antigen on pathogen surface
Lectin pathway
- Mannose-binding protein binds to pathogen surface
Alternative pathway
- Pathogen surface creates local environment conductive to compliment activation
What does compliment activation do?
Recruitment of inflammatory cells
Organisation of pathogens, facilitating uptake and killing by phagocytic cells
Lysis and death of pathogens
What are the functionally distinct classes of compliment protein?
Binding to antigen:antibody complexes - C1q
Activating enzymes - C1r, C1s, C2b, Bb, D
Membrane-binding proteins and opsonins - C4b, C3b
Peptide mediators of inflammation - C5a, C3a, C4a
Membrane attack proteins - C5b, C6, C7, C8, C9
How is the classical pathway of compliment activation initiated?
by activation of the C1 complex
How is the alternative pathway of compliment activation initiated?
The alternative pathway is caused by spontaneous hydrolysis (tickover) of serum C3, which then bind factor B allowing cleavage by factor D into Ba and Bb. The resulting soluble C3 convertase cleaves C3 to C3b, which binds to membranes.
What does C3b do when bound to a cell surface?
C3b bound to cell surface acts to increase phagocytosis, for example by complement receptor CR1 (CD35), expressed on macrophages and PMNs
Describe the formation of C5 convertases
C3b binds both the C4b, C2b an to C3b CBb forming the active C5 converses C4b, C2b, C3b and C3b2 and CBb
C5 binds to the C3b component of the C5 convertase
C5 is cleaved to form C5b and C5a
What are C5 and C3a?
C5a and C3a are inflammatory mediators, and C5a assists in the phagocytosis of C3b covered bacteria
Describe assembly of the membrane attack complex
C5b binds C6 and C7
C5b C6 + C7 complexes bind to membrane via C7
C6 binds to the complex and inserts into the cell membrane
C9 molecules bind to the complex and polymerise
10-16 molecules of C9 bind to form a pore in the membrane
Why is compliment activation regulated?
To protect host cells from damage
What is a DAF?
Decay accelerating factor
What is a MCP?
membrane cofactor protein
What is CR1?
Compliment receptor 1
What is CD59?
A protectin
What does CD59 do?
The terminal components of compliment form a membrane pore (the membrane-attack complex); CD59 prevents final assembly of the membrane attack complex at th eC8 to C9 stage
What occurs in C1q, C1r, C4 deficiency?
inflammatory disease, similar to autoimmune condition systemic lupus erythematosus (SLE). Glomerulonephritis (70%), bacterial infections (20%), healthy (<20%)
What occurs in C2 deficiency?
inflammatory disease, SLE-like (35-75%) bacterial infections (35-65%), healthy (<20%)
What occurs in C3 deficiency?
recurrent bacterial infections (70%) glomerulonephritis (80%), healthy (0%)
What occurs in C6 deficiency?
recurrent neisserial infections (>50%)
What occurs in C9 deficiency?
possible neisserial increase
What the fuck are neisserial infections?
Bacteria called Neisseria meningitidis cause meningococcal disease
