8. Early events of immunology Flashcards
(Preparation and innate immunity)
Structure of lecture (i.e., components of early immune response)
- Pattern Recognition Receptors
- Interferons
- ‘Tolerate and Kill’
- Differentation of cells
- Spatial organisation of immune system
- Integrin receptors
- Chemokin proteins
- Unique cell subsets
What are PRRs?
1.1
PRR stands for Pattern Recognition Receptors. They are highly conserved proteins within vertebrates with many orthologues. Each vertebrate genome contains roughly 100-200 different PRRs
Where are PRRs found (+ examples)?
1.2
- Tissue fluids (Mannose-Binding Protein C3b)
- Body Surface (SpA/D)
- Cell Surface (TLRs, Mannose-Receptors, Dectin 1/2)
- Cytoplasm (Nod-Like Receptors, RIG-1, PKRs)
What are the consequences of PRR activation?
1.3
- Soluble activation: surveying and protecting tissue fluids, activation of extracellular cascades and coordinate cellular responses
- Cell-associated activation: Surveying and protecting intracellular compartments, activating cell signalling cascades, changing cell behaviour, inducing cytokines, chemokines and interferons
Example: Comparative biology of TLRs in rodents
1.4
Different TLRs are present across different species of vertebrates. Most mammals have 10 TLRs, but some rodents have no TLR10, and non-functional TLR8. In their place, they have TLR11 and TLR13. These are important to consider during the creation of vaccine adjuvants.
Example: Comparative biology of RIG-1 in birds
1.5
RIG-1 is a PRR involved in the cytoplasm. It is absent in most galliform birds (i.e., chickens), but is present in most anseriform birds (i.e., ducks). RIG-1 is key in the susceptibility of different birds to influenza, and the development of avian influenza epidemic
Example: Comparative biology of NLRP3 in bats
1.6
Nod-Like Receptor family. Reduced activity in bats, meaning lowered production of IL1β.
What is the first class of interferons?
2.1
Type I Interferons: Produced by all nucleated cells. Mostly ‘off’ and requires PRR activation to be active. Important in conditioning different parts of the immune response (like macrophages). Important in early viral infections. Includes IFNα and IFNβ
What is the second class of interferons?
2.2
Type II Interferons: Produced by lymphocytes (including T-cells and NK-cells). Important in inductin of anti-pathogenic states. Includes IFNγ.
What is the third class of interferons?
2.3
Type III: Produced by any nucleated cell, but only in specific organisms. Important in early viral infections
What are the pros/cons of the ‘tolerate’ response?
3.1
Pros: Low-energy. Low chance of autoimmunity.
Cons: Limited clearance. Risk of infection getting out of hand.
Give an example of interferon use in the animal kingdom
2.4
Bats. Have unique Type I Interferons, which are always switched ‘on’, and do not require PRR activation. Type I IFNs are always activating RNAse L, which cleaves viral RNA and leads to low viral replication and limited activation of adaptive immune response
What are the pros/cons of the ‘kill’ response?
3.2
Pros: Strong response to infection. Rapid infection control. Efficient clearance.
Cons: High energy. High chance of autoimmunity.
Example of the ‘tolerate’ or ‘kill’ response in the animal kingdom
3.3
Bats. Constitutive expressive of Type I IFN, and expanded IFn locus, with direct RNAse L activation. Leads to immediate viral cleavage, and increased autophagy. Viruses cannot get stronghold easily. However, this tolerant response leads to greater carriage and persistent, and higher chance of zoonoses
What are the two classes of early immune cell subsets?
4.1
- Myeloid progenitor cells: Innate
- Lymphoid progenitor cells: Mostly adaptive (aside from NK-cells)
Formed from pluripotent hematopoietic stem cells
What are Polymorphonuclear cells?
4.2
- Eosinophils: Involved in helminth infections
- Neutrophils: Rapid phagocytosis
- Basophils: Involved in allergies
- Mast cells: Involved in intestinal helminths
What are phagocytic cells?
4.3
- Macrophages (Tissue residents that can ‘call in’ other cells
- Neutrophils (Rapid phagocytosis, then death, and casting out of toxic DNA net)
- Dendritic cells (Report to the lymph nodes and activate naive T-cells)
What are the professional Antigen-Presenting Cells (pAPCs)?
4.4
- Macrophages: Direct interaction with CD4+ T-cells
- Dendritic Cells: Only cell that can activate naive T-cells
- B-cells: Direct interaction with CD4+ T-cells to inform antibody production
All body cells contain MHC Class I. Only pAPCs contain MHC Class II
What are the two spatial levels of the immune system?
5.1
Resting. Inflamed.
What are the 3 major clues given to cells to exit the blood?
5.2
- Trauma and infection
- Induction of adhesive molecules
- Deposition of chemokines
What are integrins?
6.1
Cell-surface receptors that comprise 18 α-chains, and 8 β-chains that associate in pairs to create a variety of different combinations
Example: What are some common forms of integrin?
6.2
- Addressins: Act like cellular postcodes
- LFA-1: Bind at intercellular sites called ICAMs
- VLA-4:: Binds to vascular adhesion molecules called VCAMs
What is outside-in signalling in integrins?
6.4
Signalling via integrin-binding to the ligand. Leads to intracellular-signalling cascades inside the cell. Can lead to actin polymerisation and changes in transcription
What is inside-out signalling in integrins?
6.3
Signalling to the intracellular component of integrins, causing inversion (a form of maturation), allowing it to stick to its partner.
