Immunology Part 2 Flashcards
Where are the cells of the immune system derived from?
From precursors in bone marrow
Where do lymphocytes mature?
In bone marrow or the thymus and then continually circulate in blood, seconday lymphoid tissues and lymph during life
Name the secondary lymphoid tissues
Lymph Nodes – stations for monitoring tissues infections
Spleen – monitoring blood-borne infections
Mucosal-associated lymphoid tissues
What is the lymphatic system?
Vessels draining fluid from body tissues
Where are lymph nodes?
Regularly along lymph vessels
- trap pathogens and anitgens in lymph
Where does lymph drain to?
drains back to bloodstream via lymphatic vessels and the right subclavian vein
How does lymph move?
moves via valves and the movement of muscles
What are the causes of lymphoedema?
Inherited
Cancer treatments
Parasitic infections
What are the two arms of the immune system?
Innate immune system
Adaptive immune system
What is the inate immune system responsible for?
Rapid response within minutes-hours
Same generic response to different pathogens
What is the adaptive immune response responsible for?
Unique response to each individual pathogen within days.
Generating immunological memory
What mediates the adaptive immune response?
B cells and T cells
Describe acute, limited infection
Rapidly cleared by the immune sysrem
Lasting immunological memory
Descibe latent infection?
Controlled by the immune system
Periodic episoes of pathogen reactivation and replication
Describe chronic infection?
Immune response fails‘immunodeficiency’
On-going pathogen replication
What are the two mechanisms of communication between the innate and adaptive arms?
- direct contact
* receptor:ligand interactions - Indirect
* production and secretion of cytokines
Give examples of receptor ligand interactions in direct contact?
Peptide/MHC : TCR
PAMP : PRR
What cells can produce and secrete cytokines?
Injured tissue cells and activated immune cells
Give examples of mechanisma of indirect communication?
- Interleukins
- Interferons (aplha, ß, gamma)
- Tumour necrosis factor a (TNFa)
Autocrine, paracrine and endocrine signalling
Descibe the characeristics of interferons?
Produced by virally infected cells
Host specific but not virus specific: general anto-viral protection
Describe the role of IFNs?
- prevent virus replication, stop them replicating within an infected cell
- signal to allow infected cells to warn nearby cells of virus, signalling makes neighbouring cells increase MHC I molecules so T cells and NK cells can identify and eliminate infection
What are the three stages of innate immune cells recognising and responding to pathogens?
- recognition phase
- activation phase
- effector phase
What is involved in the recognition phase?
- pathogens express signature molecules not found on human cells
- PAMPs
- Innate immune cells express receptors for PAMPs
- Pattern recognition receptors (PRRs)
Name some PRRs and the pathogens related to them
Toll like receptor 4 (cell surface) : Lipopolysaccharide LPS
(gram negative bacteria)
Dectin 1 (cell surface) : B-glucans
(fungi)
Toll like receptor 7 (intracellular) : ssRNA
(viruses)
What happens when a cell initiated the apoptotic programme?
Releases soluble ‘find-me’ signals that attract phagocytes
What does an activated macrophage release?
Interleukins (antiinflammatory cytokines)
Which cells are capable of phagocytosis?
Macrophages
Neutrophils
Dendritic Cells
What happens in phagocytosis?
- Receptor binding to ‘eat-me’ signals on apoptotic cell - formation of a phagocytic cup
- Cup extends around the target and pinches off, forming a phagosome
- Fusion with lysosomes to form a phagolysosome - degradation of contents (acidification, lysosomal hydrolases)
- Debris (including antigens) is released into extracellular fluid
How is phagocytosis different in response to a pathogen and pro-inflammatory stimuli (LPS, IFNgamma) as opposed to an apoptotic body?
The macrohpage will kill the pathogen and them present its antigen on its surface
It will release proinflammatory mediators
What is present inside the phagolysosome?
Acidification, lysosomal hydrolases, proteases
Which bacteria can evade phagolysosomal killing?
Salmonella
Staph aureus
Mycobacteria
What is the pathway of viral infection?
- virus infects host cells
- direct activation (loss of MHC-I), indirect activation IFNa/B
- NK cells activated
- Infected host cells killed
What is the pathway of bacterial infection?
Extracellular bacterium phagocytosed by macrophages and undergo pathogen killing
What does interferon gamma released from NK cells do to macrophages?
Increased pathogen killing
Increased antigen presentation
What are the inflammatory mediators produced?
- NO
- prostaglandins/leuktrienes
- histamines
- pro-inflammatory cytokines (TNFa)
What does the acute phase response involve?
Changes in plasma concentration of specific proteins in response to inflammation
- driven by cytokines produced during localised inflammation
- changes are due to altered protein synthesis in the liver
What does increased
- CRP
- SAP
- complement
indicate?
Biological prevention of spread of infection
Diagnostic marker
What does increased
Fibrinogen
indicate?
Wound healing
Coagulation
What does increased
- CRP
- Haptoglobin
- Manganese superoxidase dismutase
- proteinase inhibitors
indicate?
Preventing systemic inflammation
What is the normal levels of CRP?
<10mg/L
What levels of CRP indicate mild inflammation or viral infection?
10-40mg/L
What CRP concentrations indicate active inflammation or bacterial infection?
40-200mg/L
What concentration of CRP indicated severe bacterial infection or burn?
>200mg/L
What is the biological role of CRP?
Enhance phagocytosis
Complement system activation
