Innate Myeloid and Lymphoid Cells Flashcards
What are the two types of macrophages?
There are two types of these - tissue resident macrophages and recruitment macrophages
What do tissue resident macrophages do?
- They capture and destroy pathgoenic intruders and are found in every tissue of the body.
- They also recruit other innate effector cells through chemokines and are essential for wound healing and tissue remodelling.
- They are also needed for development e.g. making fingers.
- They also maintain tissue homeostatis by removing apoptitic cells and maintain tissue resident T cells.
What growth factor do macrophages rely on?
Colony stimulating factor 1 or Il-34 or GM-CSF
In health what do macrophages do?
They mainly remove apoptosed cells
What are recruited macrophages?
They are derived from classical blood monocytes and recruited in response to inflammation. They are short lived
What do recruited macrophages do?
They are highly phagocytic and bactericidal and produce pro-inflammatory cytokines and chemokines
They also present T cells with any antigens on MHC class 2
What is dysregulation of macrophages a feature of?
Severe covid19 - this is because recruitment of monocytes with an aggressive inflammatory phenotype are disregulated in the lungs
What do macrophages do when activated?
They are activated by DAMPS and can become different macrophages and respond to specific infections. Monocytes come into the cell via chemokine receptors which are highly pro-inflammatory.
What are neutrophils?
They are polymorphonuclear phagocytes that are short lived in the blood.
What do neutrophils rely on for development?
GM-CSF and G-CSF
How are neutrophils recruited to the infection site early?
With chemokines CXCL1, CXCL2, IL-8 or fMLP, leutrienes
Do neutrophils die at the site of infection?
Yes and are cleared up by tissue resident macrophages
How do neutrophils kill?
Phagocytosis
Degranulation (these can be released to kill - are toxic)
NETS
How do neutrophils kill via phagocytosis?
Pathogens are coated in antibodies and complement and neutrophils take up these particles into vesicles where they are broken down by things such as toxic nitrogen products, toxic-oxygen derived products, anti-microbial peptides, emzymes or via competition e.g. starving the pathogens of iron
What are the different kinds of granules that neutrophils can release?
Primary
Secondary
Tertiary
Antimicrobial but can help them navigate through tissue
What do NETS do?
Release of histone proteins and anti-microbial peptides to catch the microbes and destroy them
What is chronic granulomatous disease?
A disease which occurs when you have issues with neutrophils because of defects in NADPH.
You become infected with opportunistic pathogens which causes accummulation of chronically infected phagosytes and formation of granulomas.
What are eosinophils?
These circulate in low numbers in the blood and are short lived. You can find them via staining with acidophilic dyes.
What is needed for eosinophil development?
IL-5 and IL-3 and CSF2
How are eosinophils recruited?
Recruited via the CCR3 in response to chemokines CCL11, CCL24, CCL26
What type of receptors do eosinophils have?
Cytokine, lipid mediators, Fc, PRRs
What do eosinophil granules rapidly release?
Major basic protein (MBP)
Eosinophil cationic protin (ECP)
Eosinophil peroxidase
Eosinophil derived neurotoxin (EDN)
What do eosinophils direcly target?
Anti-parasite action, tissue repair and remodelling
What do eosinophils cause?
Type 2 immune response encourages macrophages to site of infection.
When disregulated what do eosinophils cause?
Allergies etc.
What are mast cells and what groups can they be split into?
Tissue resident cells and can be split into mucosal mast cells and connective tissue mast cells. These are relatively long lived.
What do mast cells depend on for development?
Stem cell factor and IL3
What do basophils depend on and what do they do?
Depend on IL3 and TSLP and are short lived molecules which circle in the blood
What do mast cells and basophils have?
Receptors and granules which can be released when infection occur.
What is found in mast cell and basophil granules?
Histamine, serotonin, heparin, leukotrienes, prostaglandins, several proteases and degranulation induced by IgE or IgG.
What do mast cells and basophils cause?
These cause vasodilation, vascular permeability, smooth muscle contraction, remodel connective tissue and leukocyte migration.
Triggers weep and sweep response to get rid of helminths.
What happens in mast cell disfunction?
Goblet cell hyperplasia and also hypersensitivity such as allergies.
What do Dendritic cells do?
They phagoctye and preserve antigens to show to T cells (they are APC)
Where are dendritic cells from and what do they rely on?
From pre-DC progenitors in BM and rely on growth factors FIt3L and CSF2
How are dendritic cells activated and what do they do then?
Danger via PRR, they then pick up the antigen and migrate to lymph node following CCR7.
In the lymph nodes what happens to T-cells?
The T cells notice the presented Ag and are primed. They then clonally expand and specilise into subsets best suited to deal with pathogen.
How do T-cells then know how to get to where the dendritic cell found the infection?
Chemokine receptors
Do dendritic cells show T-cells all antigens even harmless ones?
Yes but you shouldn’t respond and this leads you to have tolerance.
What happens if the dendritic cells fail at tolerance?
Autoimmunity, chronic autoinflammatory diseases, allergy
What happens if dendritic cells fail at causing protective immunity?
Chronic or overwhelming infection
What are the three steps of Dendritic Cell interacting with a T cell?
1 - presentation of peptides on MHC class 1 or 2. MHC 1 presents to CD8+ T cells (mainly cytostolic antigens) and MHC2 presents to CD4+ T cells (mainly exogenous antigens).
2 - costimulatroy molecule expression - CD40, CD80, CD86 by DC must bind to CD28, CTLA by T cells which gives an activation signal if there or an inhibitory signal if not there.
3 - cytokine produced by DC directs the nature of the T cell either Th1, Th2, Th17, Treg (you only want this if the antigen picked up is something from the microbiota) or CTL
How do we know DC are needed in tolerance?
Delete the cytokine FIt3L in mice leading to reduce Treg and autoimmunity
Knockout CCR7 leads to mice failing to develop oral tolerance
If you delete MHC2 on DC in mice this prevents Treg from priming
If you delete integrins and molecules needed for migration back to site of infection you do not get tolerance.
If you delete Tregs after they have been produced you dont get oral tolerance.
How do we know DC’s are needed in protective immunity?
If you knockout FIt3L mice fail to induce effector T cell response to pathogen
Lymphocyte deficient mice are highly immunocompromised e.g. SCID
Mice unable to generate specific effector T cells are susceptible to distinct pathogen
In humans what leads to abnormal monocyte and DC development?
IRF8 deficiency
What are Innate lymphoid cells (ILC’s)?
These are similar to T cells but have a dedicated ILC progenitor in BM and their role is to be present in tissue, detect things early and ellicit a response.
How are ILC’s different from T-cells?
1 - lymphoid morphology
2 - no myeloid markers
3 - No Rag-dependent rearranged AgRs
4 - relatively rare in lymphoid tissue (high numbers in lymphoid cells)
What roles do ILC’s play in health and disease?
Inflammtion due to cytokine release
Do ILC subsets perform distinct functions?
Yes, there is at least 3 which lines up with their T cells.
What do group 1 ILC’s do?
These include NK cells and are characterised by needing IL-15, IL-7 and IL-15 and produce cytokines IFN gamma and TNF
What do group 2 ILC’s do?
These are like Th2 cells and rely on IL-7 for development. They release IL-4 (in humans), IL-5, Il-13 and AREG
What do group 3 ILCs?
These are developed from IL-7 and release IL-17A, IL-17 and IL-22
How are ILC’s good?
They are early respondants to infection and release cytokines to help control the invasion
Why can ILC’s be bad?
They can react innapropriately and increase the amount of proinflammatory cytokines in the body leading to diseases such as IBD and allergic asthma
