L2&3 Cells of the Immune System Flashcards
What are the physical barriers in the immune system?
Skin & mucous membranes, Eye
What are the special characteristics of the skin?
Keratinised cells, shedding of cells, dryness, acidity (pH 5-6) & fatty acids (anti-bacterial function), normal skin microflora antagonistic to pathogens
What do epithelial cells in the eye secrete?
Mucus
What enzyme is present in tears, and what does it do?
Lysozyme - attacks the peptidoglycan layer in bacterial cell wall
Does the Omicron variant of COVID-19 tend to affect the upper or lower respiratory tract more?
Upper
What bacteria typically colonise the URT?
Staphylococcus, Streptococcus
What bacteria/viruses commonly infect the LRT?
Mycobacterium tuberculosis, Influenza A, COVID-19
What is the pH of the stomach?
pH 2
What are examples of food poisoning associated pathogens that can survive the acidity of the stomach?
Salmonella, Listeria
Which part of the GIT would you find Immunoglobulin A?
Small intestine
Does the large intestine mainly contain aerobic or anaerobic bacteria?
Anaerobic
What cells produce mucus, and what glycoprotein is found in mucus?
Goblet and mucus-secreting cells.
Mucin - glycoprotein
What is the function of enterocytes?
Absorb nutrients
Is the small intestine primarily an aerobic or anaerobic environment?
Aerobic
What are the 4 major Phyla in the human GIT?
Firmicutes (by far the most common) G+ e.g. Lactobacillus & Enterococcus
Bacteriodetes G- e.g. Bacteroides
Actinobacteria G+ e.g. Bifidobacterium spp.
Proteobacteria G- e.g. Escherichia, Salmonella, Vibrio
Does Streptococcus pneumoniae have a high, moderate or low virulence?
High
Examples of phagocytes in the innate immune system
Neutrophils, macrophages, dendritic cells
What are PRRs? Give an example
Pathogen Recognition Receptors
e.g. Toll-like receptors (TLRs)
What do PRRs recognise?
PAMPs = pathogen associated molecular patterns on pathogens (danger signals)
What PRR recognises LPS (a PAMP)?
Toll-like receptor 4 (TLR4)
What happens when a PRR is triggered?
Regulatory cytokines and Interferons are secreted
How do cells such as macrophages and DCs connect the innate to the adaptive immune system?
They act as Antigen Presenting Cells (APCs) - present processed antigens from killed pathogens to T cells (adaptive)
Are bacteria generally found within our cells?
No - they tend to adhere to body surface layers or are ‘free-floating’ in body fluids. An exception is M. tuberculosis in lung macrophages of TB patients!
Viruses are either…
Naked or enveloped
Naked (non-enveloped) viruses have a…
Capsid that surrounds the DNA/RNA
What is an example of a naked virus?
Norovirus (winter vomiting bug) - causes gastroenteritis
What is the envelope in enveloped viruses?
A lipid bilayer - acquired from the plasma membrane of an infected cell as the virus ‘buds’ away
What do innate immunity PRRs recognise?
The nucleic acid in either DNA or RNA
What type of virus is Rotavirus?
dsRNA
What are the vast majority of viruses?
dsDNA
How do viruses enter cells? (in one word)
Endocytosis
What do cell surface TLRs mainly detect?
Bacteria and fungi
How are bacteria & viruses in cytoplasm detected?
NLRs and RLRs
How are viruses in endosomes detected?
TLRs
What are the 2 main roles of the lymphatic system?
- Removal of interstitial fluid from tissues
2. Monitor for infection/tissue damage
What is lymph?
Clear to white fluid that contains leukocytes (WBCs)
How does lymph drain back into the bloodstream?
Left subclavian vein via the thoracic duct
How much lymph is returned to blood circulation per day?
4 litres!
How many leukocytes are produced per day?
Around 4x10¹¹
What make up 95% of circulating granulocytes?
Neutrophils
Are granulocytes short or long-lived?
Short lived (continuously produced), 2-3 days
Main role of polymorphonuclear cells (PMNs) or granulocytes?
Phagocytosis of invading microorganisms and cellular debris
Phagosomes (phagocytosed microbes contained within vacuoles) fuse with __ to form __
fuse with LYSOSOMES/GRANULES to form PHAGOLYSOSOMES
What is CAP and what can it do?
CAP = cationic anti-microbial protein - can lyse & kill bacteria
What are the 4 types of granules?
- Azurophilic (primary)
- Specific (secondary)
- Gelatinase (tertiary)
- Secretory
What is the main target of eosinophils?
Parasitic worms
bind worm larvae coated with IgG and IgE antibodies
Are mast cells found in circulation?
No
What is released when mast cells degranulate?
Histamine and other inflammatory mediators
When do monocytes become macrophages?
When they migrate into tissues
What are the 2 main functions of macrophages?
- ‘Professional’ phagocytic macrophages, role to remove particulate antigens such as pathogens & dead/dying cells
- APCs present pathogen antigens to T cells
VERY IMPORTANT IN IMMUNOSURVEILLANCE
What is the shape of a monocyte nucleus?
Horseshoe-shaped nucleus
Macrophages have prominent__ membrane-bound __
prominent ELECTRON-DENSE membrane-bound LYSOSOMES
What do mannosyl-fucose receptors bind?
Sugars on surface of microbes
What do Fc receptors bind?
Antibodies bound to pathogen - IgG, IgM, IgA
What can CD14 receptors bind?
LPS
What are Neutrophil Extracellular Traps (NETs)?
Networks of secreted extracellular fibres, composed of DNA & granule contents
What anti-microbial proteins do NETs contain?
Neutrophil elastase, cathepsin G, histones/DNA
What are the 2 main functions of NETs?
- Kill the bacteria
2. Act as a physical barrier that prevents the spread of the pathogen
What is Suicidal NETosis?
The release of NETs result in neutrophil death, different to apoptosis or necrosis
Free radicals react with __ in active sites and binding sites of __, including __, leading to the death of the microbe.
amino acids
proteins
enzymes
What is one of the only pathogens known to survive the really tough environment formed by free radicals, and how?
M. tuberculosis - due to its thick cell wall
What does TLR4 recognise?
LPS on the surface of Gram negative bacteria
What does TLR5 recognise?
Flagellin on motile bacteria
What do NODs recognise?
Bacterial peptidoglycan in cytoplasm of a cell
TLR3, TLR7 and TLR9 are in the endosome - what do they recognise?
Viral genomes (DNA and RNA) in cells
What does TLR7 detect?
ssRNA e.g. Influenza A virus
What type of virus is Influenza A?
ssRNA
What are the 2 main types of T cells involved in immunity?
T helper cells and cytotoxic T cells
How does the adaptive immune system ‘see’ antigens?
In the form of short peptides from proteins (& carbohydrates/lipids to a lesser extent)
T cells can only ‘see’ antigens when…
When a peptide is presented to its TCR by an APC (MHC I and II)
What is the classical APC in skin?
Langerhans cell
Where do DCs originate?
Bone marrow, then migrate throughout the body
What are the 2 principal roles of DCs?
- Recognition of invading microbes by PPRs on DCs, leading to destruction of pathogen & production of proinflammatory cytokines, chemokines & Interferons
- Presentation of ‘bits’ (usually short peptides) of the pathogens ‘antigens’ to T cells
What is a unique characteristic of dendritic cells?
They can cross-present
To which cells do MHC 1 present?
CTLs (CD8+)
To which cells do MHC 2 present?
Th cells (CD4+)
What is the role of DCs in immune tolerance?
T cells that respond to DCs carrying self-peptides are destroyed in the thymus by negative selection
What is the role of DCs in B cell memory?
DCs play a role in the maintenance of B cell recall responses
What are plasmocytoid DCs (pDCs) a major source of?
Anti-viral cytokines and interferons
Where are NK cells derived from, and what do they do?
Derived from lymphoid precursors in the bone marrow
Kill tumour cells & virus-infected cells
Do NK cells possess a TCR?
No
What do naive B cells have?
A surface antibody (BCR)
What do plasma B cells do?
Secrete Ab into circulation
What do antibodies mainly recognise?
Peptides & intact folded proteins
Around how many BCRs are in a cell?
10⁵
What are the two isotypes of BCR?
IgM (mainly) and IgD
What happens to the B cell when its surface Ab detects its antigen?
The B cell differentiates into an antibody-secreting plasma cell
Where is secretory IgA (sIgA) secreted?
onto mucosal surfaces
What are the 5 antibody subclasses?
IgA, IgG, IgM, IgE, IgD
Cell-lineage specific cell surface markers:
CD3 found on all T cells, CD19 found on B cells
For what is CD19 being used as a potential target for monoclonal antibodies?
In certain leukaemias
Maturation marker cell surface marker:
CD1 on T cells in thymus, not on T cells in circulation
What can cells with different densities be separated by?
Density-gradient centrifugation
RBCs go down to the bottom
All lymphocytes in white area “buffy coat”
Using antibodies attached to magnetic beads
What is FACS in Flow Cytometry?
Fluorescence-activated cell sorter
What is the aim of haematopoietic stem cell transplantation?
To re-establish a patient’s immune system following cancer-related therapy
What is CD34?
A transmembrane phospho-glycoprotein
What is the main role of T cells?
To eliminate microbes that survive inside cells - mainly viruses but some bacteria like M. tuberculosis. Therefore, T cells recognise cell-associated but not ‘free’ antigens
What cells are CD3 and CD4 positive?
T helper cells
What cells are CD3 and CD8 positive?
Cytotoxic T cells (CTLs)
What are the 2 main types of TCR on Th and CTLs?
αβTCR - on majority of T cells
γδTCR - on a minor population of circulating T cells, mainly on intestinal intraepithelial T cells
What cells do NK cells kill?
Cells that do not express MHC molecules on their surface i.e. virus-infected cells, cancer cells
Give examples of duality in the immune system
- innate and adaptive
- innate: phagocytes & APCs
- adaptive: B cells & T cells
- T cells: Th cells & CTLs
- BCRs: heavy & light chain
- TCRs: alpha-beta & gamma-delta
- immunity to bacteria/fungi & immunity to viruses/cancer
- recognition of ‘self’ and ‘non-self’
