Acute Immunology Flashcards
(20 cards)
Describe the phases of wound healing
- Inflam. phase: wound sterilisation + clearance
- phagocytosis
- removal of infection + damaged tissue - Prolif. phase: wound closure
- angiogenesis
- granulation tissue
- fibroblast prolif
- collagen synthesis
- ECM reorganisation
- early epithelialisation - Remodelling phase: returns tissue to normal function
- full epithelialisation
- ECM remodelling
- increase in tensile strength
- apoptosis + removal prolif cells
- scar maturation
Name the cardinal signs of inflammation
- Redness
- Heat
- Swelling
- Pain
- Loss of function
Name the cells of innate immunity
- macrophage
- neutrophil
- complement
- basophil
- mast cell
- eosinophil
- NKC
Name the cells of adaptive immunity
- T cell
- CTC
- HTC
- B cell
What is the function of dendritic cells?
Switch on adaptive immunity
What is non-self and how is it recognised?
- microbes
- triggers inflam response
- IS recognises PAMPs
- adaptive immune response to eliminate infection
What is altered self and how is it recognised?
- damaged/necrotic tissue
- inflam response to remove necrotic cells + debris
- IS recognises DAMPs = released by damaged/necrotic tissue
- does not typically lead to adaptive immune response
Describe how the complement system is activated and initiates inflammatory responses
Detection - classical, lectin and alternative pathway
Detection/disposal - opsonisation
Disposal - lysis
Communication - inflammation
How does pathogen recognition by macrophages initiate inflammatory responses?
- Bacteria trigger macrophage to release cytokines + chemokines (TNF alpha + CXL8) + lipid mediators of inflam
- Vasodilation + increased vasc. perm = redness, heat + swelling
- Inflam. cells migrate into tissue releasing inflam. mediators that cause pain
Describe local inflammatory responses
- Inactive WBC’s recruited + activated
- WBC production from bone marrow progenitors increases
- Specific B+T cells activated + expand in LN’s - travel to site
- Increased production of complement molecules by liver hepatocytes
- Cytokines co-ordinate these responses + turn off system once infection cleared
What are cytokines?
Umbrella term - describes
- Interleukins (-IL)
- Interferons (-IFN)
- Tumour necrosis factor family (-TNF)
- Chemokines
- Colony stimulating factors (-CSF)
Majority = soluble
Name the function of cytokines
- Cellular diff
- Cellular prolif
- Leukocyte mobilisation
- Cellular activation
- Cell death
- Cell survival
How do cytokines achieve specificity and regulate activity?
- Bind to specific receptors
- Expression of cytokine receptors can be regulated by altering responsiveness of cells to cytokines
- Cytokine secretion = brief + self-limited
- Limited range of activity - typically local cellular enviro
- Cytokines influence synthesis + action of other cytokines - effects can be propagated + amplified
Name to 2 main inflammatory processes regulated by cytokines
- Inflammation e.g. TNF alpha- proinflam cytokine
2. Movement of cells e.g. CXL8 - chemokine
Describe the role of TNF alpha
- Mobilises body pathogen defence
- activates endothelial cells to allow leukocytes to enter tissue - Induces acute phase response
- diffuses via blood stream to liver + upregulates expression of proteins (inc. complement)
- increases body temp
- mobilises energy stores from fat + muscle - Encourages clotting of small damaged BV’s to prevent systemic spread
Overall: increased inflam, cell recruitment, angiogenesis + complement expression
What is the effect of TNF-alpha expression in sepsis?
- Increases system wide vasc. permeability
- Reduces BP
= SHOCK
What is the effect of TNF-alpha expression in arthritis?
- Increased inflam in joints drives TNF expression
- Increased metalloproteinase synthesis
= loss of CT in joints
What is the role of CLX8?
- 1st chemokine to be cloned + characterised
- Recruits neutrophils to site of infection
- Directs neutrophils along chemotactic gradient
- Induced by PAMPs, TNF + other pro-inflam cytokines
Describe the process of neutrophil migration during inflammation
- Local TNF alpha = increases selection expression of BV to slow down passing neutrophils + make BV’s more permeable
- Secreted IL-8 tethers to cell surfaces + ECM
- Interaction of IL-8 with IL-8 receptors on neutrophils activates adhesion molecules = tight binding of cells to BV ready for migration
- Sub-endothelial space - neutrophils follow gradient of IL-8 tethered to ECM towards infected site
How is CLX-8 receptor expression in neutrophils induced?
By other cytokines or recognition of PAMPs by TLR’s or other PRR’s
