Cells of the Immune System Flashcards
2 types of viral infections
- non-envolope (single layer)
- enveloped (double layer)
3 different types of nucleic acids that a virus can contain
- dsDNA
- dsRNA
- ssRNA
Actinobacteria
- gram +
- aerobic
- e.g. Bififobacterium
An example of a protein that can be incorporated into the envelope
Spike protein on SARS-CoV2
Anaerobes vs Aerobes in GIT
- SI - aerobes
- LI - anaerobes, faculative aerobes
APC examples
- Monocytes & Macrophages
- DCs
- Langerhan cells
APCs
Recognise foreign antigens and present them to T cells
Bacteria associated with malnourishment
Proteobacteria
Bacteria that affects LRT
- M.tuberculosis - massive infiltration of macrophages under lining of alveolar sacs -> chronic inflamm nodules
- Influenza A
- COVID-19 - earlier strains
Bacteria that colonise the URT
- Staphylococcus
- Streptococcus - meningitis
Bacteroidetes
- Gram -
- non spore forming
- an and aerobic
- rod shaped
Basic mechansim of pathogens
Basophils & MCs
- Mast cells not found in circulation - mucosal and connective tissue
- Mast cell activated and degranulates
CD3, CD19, CD1
- CD3: found on T-cells
- CD19: found on B-cells
- CD1: maturation marker on T cells in thymus - not when they leave thymus
Cells that line the GIT
Single epi cells
Composition of the intestinal mucosal surface
Enterocytes - nutrient absorbing, monolayer
Dendritic cells
- professional APCs
- originate in bone marrow
- constitutively present in epi and most tissues
Describe how flurochrome-labelled molecules can be used to analyise cell pops?
e.g. FITC
- fluoro-labelled abs are usually monoclonal abs with a fluorochrome conjugated to the ab
- direct immunofluorescence - fluorescence is chemically linked to ab (usually Fc portion)
- usually emits a green colour
Difference between Viral TLRs and Bacteria and Fungi TLRs
TLRs detect Bacteria and Fungi via cell surface
Enveloped viruses
- contain an extra layer of protection in addition to capsid
- envelope - lipid bilayer which is acquired from the plasma membrane of an infected cell as the virus buds away
Eosinophils
- Bilobed nucleus with many granules
- Main target - parasitic worms
- Binds worm larvae coated with IgG and IgE antibodies
- Degranulates - release of toxin
- Major basic protein
Examples of monocytes/macrophages important locations
- blood
- liver - Kupffer cells
- lungs (alveoli)
- serosal
- brain microglia
- spleen
- lymph nodes
Examples of TCRs unique to T-cells
- Th cells - CD3 and CD4
- CTL cells - CD3 and CD8
Eye Function
- mucus secreting epi cells
- inner surface of eyelids - tears (contains lysozyme)
Firmicute examples
Lactobacillis
Enterococcus
Flow Cytometry
Fluorescence-Activated Cell Sorter (FACS)
- characterisation of cell populations into
- cell lineages
- maturation state
- activation status
purification of cell subtypes
- CD34+ haemopoetic stem cells
Function & Contents of NETS
- both kill the bacteria and serves as a physical barrier preventing the spread of the pathogen
- contain antimicrobial proteins
- NF elastase
- cathepsin G
- histones/DNA
Function of lymphatic system
- removal of interstital fluid from tissues
- monitor for infection and tissue damage
Functions of Respiratory tract to expel pathogens
- cilia in nasal cavity and lungs - beat out microbes to pharynx
- coughing and sneezing
- low pH in stomach
Granules and their associated hydrolytic enzymes
- azurophilic - myeloperoxidase, NF elastase, proteinase 3
- specific - NGAL
- gelatinase - MMPs
- secretory - CR1NF
Hematopoietic Stem Cell Transplantation
- CD34 present on the surface of stem cells
How are N2 and O2 radicals produced?
Enzymes on the inner membrane of phagozomes/lysosomes from O2 and N2
How are pathogens killed via phagocytosis?
Monocytes/macrophages, NFs, DCs
- free radicals react with AAs in active sites and the binding sites of proteins including enzymes - leads to death of microbe
How do immune cells recognise pathogens?
Pathogen Recognition Receptors (PRRs) - on DC and macrophages
e.g. TLR
How many leukocytes must be produced to maintain homeostasis
4x1011
How to DCs present processed antigens?
- MHC I to cytotoxic T cells (CTL)
- MHC II to Helper T cells (Th)
Innate Immune System Cells
Phagocytes
- NF
- Macrophages
- DCs
Large Intestine
- absorbs water from waste
- huge pop of anaerobic bacteria
Lymphocyte examples
- B cells
- T cells
- Natural Killer Cells
Macrophage chemoattractant
Azurocidin (CAP 37)
- a cationic antimicrobial protein (CAP)
Main functions of monocytes
- remove particulate antigens such as pathogens and dead/dying cells
- APCs - present pathogen antigen to T cells
Main types of TCR on Th & CTLs
- alpha-beta TCR
- found on maj of T-lymphocytes
- gamma-delta
- found on min of circ T cells
- found in maj of intestinal intraepi T cells
Method used to isolate and purify Lymphocytes
- density-gradient centrifugation - “buffy coat” of lymphocytes
- fluorescence-labelled markers bound to magnetic beads (CD8+ - yellow green while nuclues stains blue)
Monocyte differentation
- myeloid progenitors differentiate into pro-monocytes in bone marrow and then into blood monocytes
- When monocytes migrate into tissues they become macrophages
Most common bacteria in microbiome
Firmicutes
- gram +
- anaerobes and obligate or faculative aerobes
Mucus
- made up of glycolipids and glycoproteins
- secreted onto epi cell surface
- produced by goblet and mucin- secreting cells
- composed of mucin (alpha gp), lipids and electrolytes
Name an ab produced by B lymphocytes
- IgM (always the inital ab produced)
- IgD
Name types of lymphocytes
- B
- T (Th, CD4+) & (CTL, CD8+)
- NK - no TCR, derived from bone marrow
Natural Killer Cells
- lymphocytes without a TCR
- have cytotoxic activities - similar to CTLs
- circulate in blood and lymphoid tissues
- kill cells that don’t express MHC molecules on their surface e.g. cancer cells or virus-infected cells
NETs
Neutrophil extracellular traps
- secreted extracellular fibres - composed of DNA of NF and granule
- suicidal NETosis - release of NETs result in NF death (differs from apoptosis or necrosis)
Non-enveloped viruses
- contain a capsid surrounding the DNA/RNA
- capsid composed of several protein types
e.g - Norovirus causes gastroenteritis
pH of GIT
- stomach - 2
- SI - 4/5
- LI - 7
Phagocyte examples
- NF & MC - polymorphonuclear
- Monocytes & Macrophages - mononuclear
- Dendritic cells
Phagosome
Once the microbe is phagocytosed within the vacuole it is referred to as a phagosome
- fuse with lysosomes or granules to form phagolysosomes
Polymorphonuclear Cells
- also known as granulocytes
- produced by bone marrow
- short lived (2-3 days)
- migrate to peripheral tissues
- multi-lobed nucleus
- 60-70% of normal WBCs
main role - phagocytosis of invading micro-organsisms and cellular debris
Protection against pathogens in stomach
- IgA - protects against exposure to pathogen for a 2nd time
- Commensals or probiotic bacteria
Proteobacteria
- gram -
- faculative or obligately anaerobes
- e.g. salmonella
Role of DCs
- recognition of invading microbes by PPRs on DCs leading to the destruction of pathogen and production of pro-inflamm cytokines, chemokines and INFs
- presentation of short peptides (bits) of the pathogens antigens to T cells
- B cell memory - DCs play a role in maintenance of B cell recall responses
- immune tolerance - T cells that respond to DCs carrying peptides are destroyed in thymus by negative selection
Skin & Mucous Membrane
effective mechanical barrier
- keratinized cells
- undergoes shedding
- dry
- acidic (pH 5 to 6) - FAs (toxic to bacteria)
- normal skin microflora - antagonistic to pathogens
Small Intestine
- Duodenum, Jejunum, Ileum
- absorbs nutrients
- pathogens destroyed by pancreatic enzymes, bile and ab (IgA)
Stomach
- gastic juices - HCl ( pH 2) - kills pathogens
- salmonella is resistant to acidity
T lymphocytes
- each has a TCR - only see antigens presented to them on MHC molecules on APC surface
- role is to eliminate microbes that survive inside cells (mainly viruses but some bacteria - M.tuberculosis)
Types of B lymphocytes
- naive B cells - surface ab (BCR)
- plasma cells - secrete ab into circulation
*each B cell has its own BCR
Types of granules
- azurophilic - primary
- specific - secondary
- gelatinase - teritary
- secretory
*contents mainly composed of hydrolytic enzymes
Ways in which macrophages have the innate ability to recognize bacteria, fungi and viruses
- PPRs
- mannosyl-fucose receptors - bind sugars on surface of microbes
- CD14r - remove microbes coated with LPS
- Fcr - bind abs bound to pathogen (IgG, IgM, IgA)
- Complement receptor - CR1/CD35 - binds complement coated microbes - can directly lyse bacteria
What acts as the bridge between Adaptive and Innate immune system?
macrophages and DCs
- act as APCs - present processed antigens which have been killed by pathogens to T cells
What are APCs?
- Heterogeneous pop of cells that present processed antigen to T cells
- links innate and adaptive immune responses
What are the main APCs?
- DCs
- tissue macrophages
- langerhans cell - skin
- B lymphocytes
What bacteria disappears with age?
Bifidobacteria
What cells have high expression of PRRs?
Macrophages and DCs
What detect bacteria and viruses in the cytoplasm?
NLRs and RLRs
What detects viruses in the endosomes?
TLRs
What do antibodies and T-cells see?
Proteins and Peptides
*carbs and lipids at a lesser extent
- T cells cna only see these antigens when a peptide is presented to its TCR by an APC (MHC I or II)
What do NODs recognise?
bacterial peptidoglycan in the cytoplasm of cell
What do PRRs activate?
TFs
- NFk-beta
- IRF3
- IRF7
What do PRRs identify?
Danger signals or Pathogen-Associated Molecular Patterns (PAMPs)
e.g. LPS (PAMP) recognises TLR4 (PPR)
What do TLR3, TLR7, TLR9 dectect?
- located in endosome membrane
- detects viral genomes (DNA or RNA)
What does activation of TFs lead to?
Cytokines and IFNs
What does TLR4 recognise?
LPS on surface of gram - bacteria
What does TLR5 recognise?
flagellin on motile bacteria
What does TLR7 detect?
ssRNA
e.g. influenza A
What influences the flora composition
- diet
- maternal colonisation
- environmental exposure
- antimicrobial treatments
What occurs once PAMP is recognised by PRR?
secretion of regulatory cytokines and IFs
Where are APCs found?
- skin
- lymph nodes
- spleen
- mucousal surfaces
- thymus
Where does lymph drain back into?
Left Subclavian Vein via thoracic duct
Where is bacteria found in regards to cells?
Not within the cell - tend to adhere to body surface layers and are “free floating” in bodily fluids
- PRRs makes immune system aware of their presence
exception - M.tuberculosis in macrophages in lung of TB patient
FITC emission and excitation wavelengths
Excitation - 495nm
Emission - 519nm
