Innate Immunity Flashcards
What is innate immunity and what makes it up in the human immune system?
Innate immunity is the first stage of an immune response. It is often non-specific with no antigen recognition
Involves:
- Physical barriers like Skin, mucosal surfaces (huge system)
- Chemical barriers e.g. pH, secreted factors
- Phagocytes such as Monocytes/granulocytes
- Inflammation; acute phase response
- Complement
- Cytokines/chemokines
What types of immune cells are essential to the innate immune system?
Monocytes:
- Macrophages
- Dendritic Cells
Granulocytes:
- Neutrophils
- Eosinophils
- Basophils
What are neutrophils?
- Large cells (10-20 microns); only live about 2-3 days – majority of peripheral blood
- 90% of granulocytes are neutrophils
- Neutral staining cytoplasmic granules containing enzymes e.g. lysozyme
- Phagocytic, kill bacteria by microbicidal mechanisms
- Most important cell in non-viral infections -> septic pus = neutrophils as they are scavenging lots of cells
What are Eosinophils?
- Contain prominent granules, which stain red with eosin
- Granules contain a crystalline core cytotoxic for parasites; EOSINOPHIL BASIC PROTEIN (EBP)
- Important in immunity to helminth infections
- Phagocytic, though this is not a major function
What are Basophils?
- <0.2% white blood cells, only go into tissues during inflammation
- When stimulated, release substances that promote inflammation
- Important in allergy
- Don’t phagocytose
What are monocytes and macrophages?
Monocytes • Produced in BM then in blood 1-2 days • Mononuclear leukocytes • Phagocytic • Derive out to become DCs
Macrophages
• MCs in tissues = macrophages (MF)
• Up to 10x larger than MCs
• can live months or years
• Characteristics of macrophages depend on tissue e.g. Kupffer cells in liver, microglia of brain
• Phagocytic (like neutrophils and eosinophils), adherent
Innate cells need some pathogen specificity . How do they get this specificity?
• Specificity from host molecule
– e.g. IgG, complement components, chemokines
• Inherent specificity (pattern recognition)
– germline-encoded receptors for conserved molecular patterns
– detects foreign invaders or aged/damaged host cells (apoptotic)
What types of receptors determine specificity?
Non-opsonic Pattern recognition receptors (PRRs):
a. Recognise parts of bacteria in a pattern dependent manner
Opsonic receptors:
a. FC and complement receptors (Fc can be induced on various cells)
b. 7- Transmembrane g-protein coupled receptors (chemokine receptors)
c. Host produces Ab or complement against the pathogen. Cytokine and chemokine are also produced aswell as lipid mediator such as prostaglandins
Give some examples of opsonic receptors, their ligands and what the outcome of the interaction is.
Fc receptors:
- these are receptors for the Fc region of Ig on located on host cells.
- Many different types including FcgR/aR or eR which correspond with different Ig
- Binding results in the internalisation of Ab-coated Ab
- If located on a macrophage, it results in the activation and production of reactive oxygen species
Complement Receptors:
- CR1-5, diverse structures which are endocytic and activator
- CR1,3 and 4, bind C3 cleavage products which are bound to pathogens, immune complexes or other complement activators
Chemokine Receptors:
- 7- Transmembrane receptors which are G-protein coupled
- They recognise host chemokines, complement fragments and lipid mediators such as prostaglandins.
- This results in cell migration so immune cells are where they need to be
What are the general properties of PAMPs (Pathogen- Associated molecular patterns)
- They are invariant structures present only on pathogens, specific for pathogen and not on host cells
- Essential for survival of pathogens
- Cell wall peptidogylcans are an important pattern because bacteria cant survive without a cell wall
Examples include:
- terminal mannose and fructose, bacterial cells walls, LPS, flagellin, pathogenic genetic material ect.
Give examples of the main pattern recognition receptors (PRRs)
Lectin Receptors (Mannose receptors)
- bind terminal mannose and fucose sugars
- also links to the lectin complement pathway which use mannose-binding lectin (MBL)
- Interaction results in phagocytosis
- Lectin domains -> multimeric binding sites which can be associated with Fcg chain ITAM, allowing a signal to be transported to host cells.
Scavenger Receptors
- Membrane-bound PRRs which bind to apoptotic cells, modified self molecules or bacterial cell walls
- They clear up after an immune response and may effect the TH1/TH2 response
- They can mediate endocytosis and can also fine-tune TLRs using class A (C-lectin domains) and class B (CD36 domain) receptors
Toll-like Receptors:
- the main PPR for bacterial and viral ligands
- TLR1-9
- Results in cytokine release (IL-1, IL-12) and inflammation
RIG-1/MDA-5:
- recognise dsRNA and 5’tri-phospho RNA
- Causes IFN-1 production via mitochondria and IRF-3 and NFkB
- Particularly for viral pathogens
NOD-like Receptors (NLRs):
- bind dsRNA and peptidoglycan (Gram + and -) which indirectly produces NFkB for cytokine production
- Some can form an inflammasome and activate caspases via IL-1B , releasing IL-1 and IL-18
What are the other types of cells involved in innate immunity:
NK cells NKT cells Dendritic cells gd T cells Innate lymphoid cells
What are NKT cells?
Natural Killer T cells are innate immune cells which express NK (NK1.1) and T cell markers (TCR). However they have restricted usage of TCR a-chain.
The recognise non-protonated molecule related to CD1 such as lipids, glycolipids and hyprophobic peptides which are recognised by CD1d - related to non-classical MHC-1
They can produce TH1 and TH2 differential cytokines
What are gd T cells?
gd T cells are a type of T cell with a distinct TCR. They are less common than ab T cells but are highly abundant in gut mucosa. They don’t need MHC antigenic presentation. Hiowever they do recognise some bacterial proteins and lipid antigens swell as some small aliphatic molecules (isoprenoid pyrophosphates and amines) which are produced when bacteria get into a cell. They may be triggered by heat shock proteins
What are the different types of innate lymphoid cells?
Grouped into 3 categories which are determined by the cytokines they produce. They come from a ID2-ILC precursor and are expressed at barrier surfaces, influenced by DC and endothelial/epithelial cells. This cytokine production may influence Th1 and Th2 development
Group 1 ILCs:
- They constitutively express transcription factor T-bet
- Influence both NK cells and ILCD1 cells and can produce Th1 cytokines ( IFNγ and TNF) after stimulation with IL-12 or IL-18
- They are weakly cytotoxic cells closely related to Group 3 ILCs, from which they can arise.
Group 2 ILCs
- Also known as natural helper cells or innate helper 2 cells
- Play crutial role in secreting type 2 cytokines in response to helminth infection -> IL-4, IL-5, IL-9, IL-13.
- For their development, they need IL-7, which activates two transcription factors —RORα and GATA3 to develop the precursor.
- The mature ILC2 cells are then stimulated by Th2 polarising cytokines e.g. IL-25, IL-33, TSLP)
- ILC2s are abundant in tissues of skin, lungs, livers and gut
Group 3 ILCs
- They are dependent on RORyt TF for development via IL-7 stimulation
- They produce 2 different cells: Lymphoid tissue-inducer (LTi) cells and NCR-ILC3 cells
- These are then stimulated by IL-23 and IL-1B to produce IL-17 and IL-22
- They are the innate counterpart to Th17 cells and are heavily involved in intestinal homeostasis as they are found mainly in mucosal tissues and particularly in the GI tract
