What is primary lymphoid tissue
Site of production for B cells and T cells
- Bone marrow and thymus
What is secondary lymphoid tissue
sites where B and T cells become activated by antigen
- Lymph nodes
- Pyers patch
- Adenoid tonsils
What is lymphoedma
- Lymphatic obstruction
- Inherited
- Cancer treatment
- Parasitic infections
- Tissues with lyphodema are at are higher risk of infection
Describe the features of the innate immune system
-
Rapid responce - mins to hrs
- The same responce is produced to a many different pathogens
Describe the adaptive immune systems
- Slow responce - days
- Unique responce to each individual pathogen
- Mediated by T cells and B lymphocytes
- Immunological memory
Define acute inflammation
- Rapidly cleared by the immune system
- Lasting immunological memory
Describe latent infection
-
Controlled by the immune system
- Periodic episode of pathogen reactivation and replication
Decribe Chronic infection
- Immune system fails
- On-going pathogen replication
How do the two system act in responce to an infection
How do the two systems communicate with each other
-
Direct communication - Via receptor ligand interactions
-
Indirect communication - production and secretion of cytokines
Describe the direct contact between the arms of the immund system
Via receptor ligand interactions
Examples
- Peptide: MHC or TCR
- PAMP: PRR
Decribe the indirect contact between the two arms
synthesis and secrtion of cytokines by activated immune cells or injured tissue cells
Give some examples of cytokines
- Interferones
- TNF
- leukoriences
What do virally-infected cells produce
Interferons - INF
What is the function of Interferons
- Signals neighboring uninfected cells to destroy RNA and reduce proteins synthesis
- Signaling neighboring infected cells to undergo Apoptosis
- Activates immune cells - natural killer cells
What are the early innate immune responces
- Acute inflammation
- Macrophages
- Mast cells
- NK cells
How does the innate immune system recognise and respond to pathogens
- Recognition phase
- Activation phase
- Effector phase
Describe the Recognition phase
Pathogens express Pathogen associated Molecular Patterns - PAMPs
- These are common to many different species of pathogen
- Innate immune cells express Receptors for these PAMPs
- Pattern-recognition receptors - PRR
- PRR - are found on cell surface and intracellularly - for extra and intracellular pathogens
Give examples of PAMP:PRRS
-
Toll-like receptor 4 : Lypopolysaccharide LSP (gram -ve bacteria)
-
Dectin 1 : B - Glucans (fungi)
-
Toll like receptor 7 : ssRNA (viruses)
What are all the innate immune cells that are tissue-resinant
- Macrophages
- Mast cells
- Natural killer cells
- Dendritic cells
How do apoptotic cells get cleared from the body
- When a cell undergoing apoptosis it releases Eat me signals
- Binds to engulfment receptors on apoptotic body and is cleared
Decribe the process of phagocytosis
- Apoptotic cell will release eat me signals which will bind to engulfment receptors on phagocyte
- Formation of phagocytic cup
- The cup will extend around the and pinch off forming a phagosome
- Phagosome will fuse with a lysosome inside the macrophage
- Formation of phagolysosome causes lysis its contents
- Debris are released into the Extra-cellular fluid
- at the same time cytokins like IL-10 are being released to dampen down any unwanted responces
What happens when this is injury or infeciton to the tissue
- Early innate immune responces are triggered
- Macrophages
- NK cells
-
mast cell
2. Pathogens and infected tissue cells are killed
3. Production of inflammatory mediators
What is the difference between macrophages phagocytosing pathogens and tissue cells
- Phagocytosing tissue cells - will released anti-inflammatory cytokines - IL-10
- phagocytosing Pathogens - will released Pro-inflammatory cytokines + antigen presentation
What is contained within the phagolysosome
- Lysozyme
- Hydrolases
- Proteases
- Acidification
Which bacteria can invade phagocytotic killing
- Salmonella
- Staph- aurous
- Mycobacteria - TB
How do macrophages deal such pathogens
- Enhancement of phagocytosis by pro-inflammatory cytokines - e.g IFNy (NK cells)
- Leads to production of toxic Reactive oxygen and nitrogen species ROS/RNS
- Now can present antigen on surface
What is the function of Natural killer cells
Kill virally infected and tumour cells and ignore normal cells
How can NK cell differentiate between the normal cells and abdnormal cells
- Normal cells present MHC Class 1 on their cell surface which allows them to termed normal
- Where as an infected cell will not present MHC Class one - production of pro-inflammatory mediators
Describe how NK cells kill pathogens and enhance phagocytosis
-
Virus infectes cell - which will result in altered or absent MHC CLass 1 - This will allow the infected cell to be detected and killed by the NK cells
-
At same time indirect activation of IFNa/b - pro-inflamatory cytokines
-
Release of IFNy - allows enhancement of macrophages - activation of ROS/RNS
- Increased pathogen killing and antigen presentation by macrophage
What are some inflammatory Mediators that are produced during the innate responce
- Nitric oxide
- pro-inflammatory cytokines - TNFa
- Prostaglandins/ leukotriens
- Histamine
What does production of inflammatory mediators cause
localised aute inflammation
What are the clinical features of acute inflammation
What is the acute phase responce
- Changes in concentration of plasma proteins in repsonce to inflammation
- This is driven by cytokines produced during localised inflammatory responces
- Changes due to altered protein synthesis in the liver
What are the acute phase proteins and whats their function
What is the role of CRP and how is it produced
- Used as marker for inflammation
- Prevents spread of inflammation and prevents systemic inflammation
- produced in the liver in responce to production of - IL6 and IL-1b
