Innate Immune System Flashcards
Describe the barriers present in the innate immune system
- physical barriers against invasion e.g., epidermis of skin, eyelids, earwax
- inhospitable environments e.g., stomach acid, mucous, cilia
- microbiome - competes with pathogens for resources
Describe the anti-microbials present in tears and saliva
- lyzosomes attack peptido-glycans in gram-positive bacterial cell walls
- leads to holes in the walls
Describe defensins
- small proteins
- present in lungs, skin, gut, tears
- attacks lipid bilayers
- effective against viruses, bacteria, fungi
- can be induced after activation
How do defensins attack lipid bilayers?
- defensins are positively charged molecules
- form pores in bilayer
What are PRRs?
Pattern Recognition Receptors
- innate cell receptors that recognise non-self molecules e.g., lipopolysaccharides are only in gram-negative bacteria
- collectively called Pathogen-Associated Molecular Patterns (PAMPs)
- important in identifying pathogens
- recognise conserved PAMPs
- different PRRs interact with different PAMPs - different responses
Describe PAMPs
highly conserved so hard for pathogens to evade recognition
Give 4 different PRRs
- Toll-Like Receptors (TLRs)
- NOD-like receptors
- Lectins
- RIG-like receptors
Describe Toll-like receptors
- multiple receptors in family
- recognise range of PAMPs
- TLR4-LPS recognise gram negative
- TLR9-CpG DNA recognise viral/bacterial
- some occur at cell surface, some within endosomes
Describe the activation of TLRs
- TLRs dimerize and induce signalling via adaptor proteins e.g., TRIF or Myd88
- TLR-initiated signalling activates transcription factors e.g., IRFs or Nf κβ
- these mediate transcription of specific cytokines, activating immune system
Describe how TLRs within endosomes are different
recognise nucleic acid structures
Describe NOD-like receptors
- NOD 1 & 2 are cytoplasmic receptors
- recognise peptidoglycans from bacteria
Describe Lectins
- surface receptors
- mannose receptor recognises terminal mannose - glycan unique to microorganisms
Describe RIG-like receptors
- cytoplasmic receptors
- MDA5 recognises dsRNA from viruses
What are the 7 major innate immune cell types?
- dendritic cells
- macrophages
- neutrophils
- eosinophils
- basophils
- mast cells
- natural killer cells
Describe dendritic cells
- present in skin, lungs, gut etc
- major function mediating immune response
- innate and adaptive
- not an effector cell
- activation leads to inflammation
- pathogen molecules shed/dead internalised via phagocytosis or macropinocytosis
- release of immune molecules
Which PRRs are expressed in dendritic cells?
TLR1, TLR2, TLR3, TLR4, NOD1, NOD2, MDA5
What is the activated function of dendritic cells?
- antigen uptake in peripheral sites
- antigen presentation
Which immune molecules are released from dendritic cells?
- cytokines
- chemokines
Describe cytokines
- small, soluble proteins - peptides and glycoproteins
- intercellular messengers of immune system
- binds to specific membrane receptors
Describe chemokines
- subset of cytokines
- specialised function - chemoattractants
- mobilise immune cells to move to tissues or within tissues
Describe macrophages
- PRR activation on macrophages initiates phagocytosis
- critical for adaptive response
- can kill pathogens
What are the activated functions of macrophages?
- phagocytosis
- activation of bactericidal mechanisms
- antigen presentation
Which PAMPs are expressed from macrophages?
TLR1, TLR2, TLR3, TLR4, NOD1, NOD2, MDA5
Describe the process of inflammation
- bacteria trigger macrophages to release cytokines and chemokines
- vasodilation and increased vascular permeability cause redness, heat, swelling
- inflammatory cells migrate into tissue, release inflammatory mediators that cause pain
Describe immune evasion in relation to phagocytosis
- deliberate modulation of a host system to benefit infectious agent
- can prevent phagocytosis on specific bacteria
- can prevent lysosome fusion
- can escape endosome
Describe the process of phagocytosis
- PRRs and other receptors bind micro-pathogen
- Transported by phagosomes-
- Fuse with lysosomes
- Pathogen destroyed by lysosome products
- destroyed pathogen used to aid adaptive immune response
Describe neutrophils
- earliest responders to any infection
- largest % WBCs in blood of most species
- formed in bone marrow & moves from blood to tissue site of infection
- NETosis
Describe the activated function of neutrophils
- phagocytosis
- activation of bactericidal mechanisms
Describe NETosis
- neutrophils kill extracellular bacteria, fungi after LPS or CXCR8 activation
- release nuclear antimicrobial contents
What are the other effector mechanisms of the innate immune system?
- NK cell killing
- complement
- degranulation
