L03: Innate immunity overview Flashcards
Layers of immunity (3)
- Barrier defence: epithelium and host defence
- Innate immunity: cellular mediators of innate immunity, connectedness with adaptive immunity, leukocyte recruitment, soluble mediators of innate immunity
- Adaptive immunity
Pathogen
Biological agent causing disease or an organism that breaches the host innate immune system
Innate immunity danger senses (2)
Through cellular mediators and soluble mediators
Sensing something not present on self
- Pattern recognition receptors detect PAMPs (cellular mediators)
- Classical and MBL complement activation (soluble mediators)
- Activating signal allows microbial destruction
Sensing absence of something normally present on self
- NK cell activation (cellular medaitors)
- Alternative complement activation (soluble mediators)
- Inhibitor signal prevents host destruction
Barrier layer
First line and non specific: microbes encounter external coverings and their secretions
Innate layer
Second line and non specific: microbes penetrating barriers encounter phagocytes and inflammation
Adaptive (acquired) layer
Third line and specific: surviving microbes encounter cell-mediated and humoral responses
Differences in innate VS adaptive
Timing
Specificity
Memory
Epithelium
Tissue containing layers of cells lining outside (skin) and inside cavities and structures in the body. Functions for exchange of nutrients, gas water products, and in immune response: physical barrier to prevent microbial entry; mechanical function; chemical; microbiological; express PRRs
Cellular and soluble mediators
Cellular and soluble mediators destroy the microbe and trigger inflammation, acting in synergy
Soluble mediators can be made or performed by cellular mediators in response to infection
PRRs and PAMPs
Pattern recognition receptors to recognise microbial structures = pathogen-associated molecular patterns; initiate inflammatory response
Myeloid cells (6)
- Neutrophil - phagocytosis and activation of bactericidal mechanisms
- Eosinophil - killing of antibody-coated parasites
- Basophil
- Mast cell - release of granules containing histamine and other active agents
- Macropage - phagocytosis and activation of bactericidal mechanisms
- DCs - antigen uptake in peripheral sites, antigen presentation in LN
Lymphoid cells
NK cells - relelase lytic granules that kill some virus-infected cell
Innate lymphoid cells (ILCs): lymphoid-derived cells, roles in pathogen clearance and inflammation
Mechanisms of leukocyte recruitment (4)
- Rolling adhesion
- Firm adhesion
- Diapedesis
- Migration
Rolling adhesion
Infection triggers chemokine release and upregulation of selectins on endothelial cells. Selectins are receptors which bind carbohydrates on leukocytes and are part of the initial adhesion step
Firm adheson
Other molecules interact to enable leukocytes to tightly bind:
1) ICAM-1 (intracellular adhesion molecule) on endothelial cell weakly binds to LFA-1 (leukocyte functional antigen) on leukocyte
2. Chemokine on endothelial cell binds to chemokine receptor on leukocyte strengthening the bind
Soluble mediators of innate immunity:
- Anti microbial peptides: primarily produced by epithelial cells; direct anti-microbial action
- Complement: system of plasma proteins; activated by alternative, lectin and classical pathways; direct anti-microbial activity, opsonins and chemoattractants
- Cytokines and chemokines: secreted proteins from range of cell types that act locally and systemically; increase vascular permeability, leukocyte recruitment, acute phase response, body temperature, antigen presentation; enables recruitment and activation of leukocytes; chemokines are able to induce directed chemotaxis in nearby responsive cells
- Other proteins: lysozyme (degrades peptidoglycan), calgranulins (anti-bacterial property neutrophil products); pentraxins (many functions)
Complement system
Series of pre-formed proteins present in an inactive state in body fluids and tissues and enhances pathogen clearance. Important for cell recruitment, opsonisation, and direct killing of pathogen. 3 pathways of activation (classical, MB-lectin and alternative)
Classical pathway
Ag/Ab provides trigger: Ab recognise Ag present on surface of microbes and cluster around
Mannose-binding lectin pathway (MB-Lectin)
Sugars on pathogen surface provide the trigger: sense something that shouldn’t be there and trigger activation
Alternative pathway
Slow tick-over of C3 enables binding of complex to cells: regulatory proteins on host cell prevent complement activation, inhibitory signal is lost so immune activation is triggered
Key effectors in the complement system (3)
C5a - cell recruitment (chemoattractant)
C3b - opsonisation (reactive component which binds covalently to the pathogen surface, tagging it for macrophages and other immune cells)
C9 - pore of membrane-attack complex for direct killing of pathogen, forms pore in membrane of pathogen for lysis
