U4 L3 Innate Immune System Flashcards
What are macrophages?
Display heterogeneity (diversity)
Varying types of inflammatory cytokines produced
// pathogen recognition
Detection and phagocytosis of pathogens
Produce nitric oxides to kill phagocytoses bacteria
Toll-like receptors (TLRs)
* Bind to pathogen components for recognition
Directly to lipopolysaccharides
Antigen presentation
release TNEs
Alert immune cells of detected infection
TNF alpha initiates inflammation
Pro-inflammatory or anti-inflammatory functions
Present for all inflammation therefore neurodegenerative diseases, infections, cancers etc
Example sentence: Macrophages play a crucial role in the immune response by detecting and eliminating pathogens.
What are the four types of macrophage?
alveolar
Phagocytosis of small particles, dead cells, bacteria
Initiation and control of immunity to respiratory pathogens
Kupffer cells
In liver
Initiate immune response, hepatic tissue remodelling
microglia
Immune surveillance, phagocytosis
Splenic
In spleen marginal zone
Elimination of old damaged BC
No additional information provided.
What receptors are present on macrophages?
Antibody receptors
Cytokine receptors e.g. IL-2 and IFN
Complement receptors
Selectin and integrin
TLR
Formation of C3b (opsonin) - complement activation; covers microbe
Cell-cell adhesion receptors
What is TNF-alpha?
Pro-inflammatory cytokine released alongside IL-6 by macrophages to initiate inflammation
Chemoattractant for neutrophils
Release of prostaglandin E2 induces migratory behavior
Neutrophil migration
What is the difference between M1 and M2 phenotype macrophages?
M1:
Polarized by Th1 cytokines (TNF-alpha and LPS)
Pro-inflammatory cytokine release (IL-1, IL-6, IL-8, TNF-alpha)
M2:
Polarized by Th2 cytokines (IL-3, IL-4)
Anti-inflammatory cytokine release (IL-1)
Note that these can be kind of interchangeable
Adalimumab works by blocking TNF-alpha to treat rheumatoid arthritis - what are the contraindications?
Immunosuppression, higher risk of severe infection
What are neutrophils? What is their function?
Granulocyte from myeloid progenitor lineage - multi-lobe shape nucleus
Bone marrow stimulated to produce more neutrophils by G-CSF (granulocyte-colony stimulating factor)
First WBC to site of inflammation
In response to cytokines, chemokines e.g. IL-8 from macrophages
Phagocytosis
Phagosome, rapid maturation and granule fusion
Targeted delivery of antimicrobial via granules
Degranulation - generation of reactive oxygen species
Extrusion of nucleic acids to form NETs - neutrophil extracellular traps
Antimicrobial environment at inflammatory site, kills pathogens
Pattern recognition receptors (PRRs)
Recognizes PAMPs - pathogen-associated molecular patterns
Fc receptors or complement receptors
Recognize antibody-opsonized microbes
What are dendritic cells?
Migrate from bone marrow through blood to lymph nodes (mature)
Present in tissues in contact with external environment e.g. skin
• initiation of adaptive immune response
• Detect pathogens via PRRs and TLRs
• Antigen phagocytosis
• Migrate to T-cell zones of lymph nodes and display pathogenic antigen
• Display on Major Histocompatability Complex
Example sentence: Dendritic cells play a crucial role in activating the immune response.
How could dendritic cells be used in cancer treatment?
Cancer tumours suppress DCs by anti-inflammatory cytokine production e.g. IL-10
Leads to down regulation of CD8 T cells
• Generation of DCs possible with tumour antigens
• Reinjection into host to boost immunity against tumour cells
Additional information: Dendritic cells can be utilized in cancer immunotherapy to enhance the immune response against tumor cells.
What is the process of phagocytosis?
• chemotaxis, adherence of microbe to phagocyte
• Movement of phagocytosing cell
• Adherence via integrin etc
• Ingestion of microbe by phagocyte
° Engulfed
• Membrane activation of actin-myosin contractile network to extend pseudopodia
• Phagosome formation
• Pathogen in vacuole, pH 7
• Fusion with lysosome - phagolysosome
• PH 5
• Digestion of microbe by enzymes
• Formation of residual body containing indigestible material
• Discharge of waste materials
Example sentence: Phagocytosis is a vital process in the immune system for engulfing and digesting pathogens.
What is the complement system?
• activation via molecules acting as PRRs
• protein based
• Immune cells express and respond to complement proteins
• Synthesised in liver
• Proteolytic cascade
• Triggered by enzyme cleavage
Generates enzymes, proteolytic fragments
‘Tickover’ - constant presence of C3b able to trigger activation
• rapid response
Rapid amplification of cascade response
Cascade tightly regulated
Additional information: The complement system is an essential part of the immune response, providing rapid amplification and regulation.
