What do toll like receptors respond to?
PAMPs - Pathogen
DAMPs - Damage
Associated Molecular Patterns
Important TLRs (apparently)
2,4,5,7,9
2- G+ and TB (extracellular)
4 - lipopolysaccharides (G-) (extracellular)
5 - Flagellin (extracellular)
7 - Single strand RNA (intracellular)
9 - unmethylated CPG DNA (intracellular)
Which TLRs are intracellular
3,7,8,9
All TLRs (1-11) and what they recognise
*2 - gram positive + TB
3 - viral dsRNA
*4 - Lipopolysaccharides (G-)
*5 - Flagellin
6 - Lipoteichoic acid (G+)
*7 - single stranded RNA
8 - DSRNA (G+)
*9 - CPG (non methylated) DNA (bacteria)
11 - bacteria (urogenital pathogens)
1,2,6 - bacterial cell wall components
3 - dsRNA
4 - G- LPS
5 - flagellin
7 - ssRNA
9 - unmethylated CpG
Innate vs adaptive immunity
Innate
- Non specific
- Resistance not improved by reinfection
- Instinctive
- Rapid response
- Phagocytes and natural killer cell
- No memory
Adaptive
- Specific “acquired” immunity
- Resistance improved by repeat infection
- Slower response
- Requires lymphocytes (T&B)
- Memory
Clinical indications of an allergic reaction
(Skin, Airways, GI)
Skin - Swelling, itching, reddening
Airways - Excessive mucus production, bronchoconstriction
GI - Abdominal bloating, vomiting, diarrhoea
What stem cell do blood cells originate from
Haematopoietic pluripotent stem cell
What are the 3 ways the complement system destroys pathogens
Innate immunity
Neutrophil properties
65% of blood
Lifespan: 6 hours - 12 days
Contain primary lysosomes and secondary granules which secrete toxic substances to kill microbes
Key role in innate immunity and inflammation
Monocyte properties
Lifespan: months
Innate (phagocytosis) and adaptive (antigen presentation) roles
Differentiate into macrophages in tissue
Macrophage properties
Lifespan: Months/years
Kupffer cells in liver, microglia in brain
innate (phagocytosis) and adaptive (antigen presenting) role
First line non self recognition
Macrophage properties
Lifespan: Months/years
Kupffer cells in liver, microglia in brain
innate (phagocytosis) and adaptive (antigen presenting) role
First line non self recognition
Eosinophil properties
Lifespan: 8-12 days
Contain major basic protein (MBP) toxin, which activates neutrophils and induces histamine release
Granules stain using eosin (red/pink)
Often seen in parasitic infection
Basophil properties
Lifespan: 2 days
Express high affinity IgE receptors, which cause degranulation and release of histamine.
Similar to mast cells (mast cells fixed, basophils circulate in blood)
Granules stain using haemotoxylin (blue/violet)
T lymphocyte (t cell) properties
Hours-years
Originate in bone marrow but mature in thymus
Recognise antigens displayed by antigen presenting cells, which they bind to with t cell receptors.
Produce cyotkines
Found in blood, lymph nodes, spleen
T helper 1&2 (CD4)
Cytotoxic T cell (CD8)
T reg
Natural killer cells
Express CD56
Recognise and kill virus infected cells and tumour cells by apoptosis
Primary vs secondary lymphoid organs
Primary - Bone marrow (immune cell origin, b cell maturation site), thymus (t cell maturation site)
Secondary - Lymph nodes, spleen (Removal site of RBC and antibody coated bacteria)
Physical and chemical barriers in innate immunity
Physical - skin, mucus, cilia
Chemical - Lysozyme in tears, stomach acid
What are antigen presenting cells and 2 functions?
E.g. dendritic cells
Present foreign antigens to T helper cells.
Stimulates Th proliferation
or B cell production
Explain TLR 4
TLR activated by LPS on gram negative bacteria (endotoxin)
Trigger immune response (activate complement, cytokine release (TNFa, IL1,6), phagocytosis)
Explain Thymic tolerance
Thymic tolerance/selection used to see if immature T cells are functional. Any failed selection results in apoptosis.
+ selection (self recognition) - CD8 (Tc) binds to MHC-I, CD4 (Th) binds to MHC-II with moderate strength; recognise self. Allowed to survive.
allocation - If immature T cell interacts with MHC-1: CD8 upregulated and becomes Tc cell
If reacts with MHC-2: CD4 upregulated, becomes Th cell
CD8 T cell function
Cytotoxic T cells interact with MHC-I
Direct killers - Secrete Perforin or express FAS to trigger apoptosis
CD4 T cell function
T Helper cells that interact with MHC-II
TH1 - IFNy - Activate NK cells and macrophages (innate immunity)
TH2 - IL4 - Activate B cells to differentiate into plasma cells (adaptive immunity)
Where are B cells produced and where do they mature
Both in bone marrow