Neutrophils and Macrophages Flashcards
What are the primary physical and chemical barriers in the human body that prevent pathogen entry?
The primary physical barriers are the skin and mucous membranes.
Chemical barriers include stomach acid, enzymes in saliva and tears (lysozyme).
Describe the role of the skin and mucous membranes in innate immunity.
The skin acts as a physical barrier preventing the entry of pathogens. Mucous membranes line the respiratory, digestive, and urogenital tracts, trapping microbes in mucus. Cilia in respiratory tracts move trapped pathogens out of the body.
What distinguishes the innate immune response from the adaptive immune response?
The innate immune response is non-specific, rapid, and doesn’t require previous exposure to a pathogen. The adaptive immune response is specific, slower to activate, and provides long-term memory after exposure.
Explain why the innate immune response is considered non-specific.
The innate immune system does not target specific pathogens; instead, it recognizes general features common to many pathogens, such as cell wall components or viral RNA.
(PAMP)
List the types of cells involved in the innate immune response.
Functions
Macrophages- Phagocytose pathogens- Engulf and destroy pathogens, produce cytokines-Release pro-inflammatory cytokines like TNF-α, IL-1β, and present antigens- via MHC II to T cells, activating the adaptive immune response..
Neutrophils- Rapidly respond to infections by phagocytosis and degranulation.
Dendritic cells- Bridge innate and adaptive immunity by presenting antigens (APCs) to T cells.
NK cells- Destroy virus-infected and cancerous cells.
Mast cells- Release histamine and other mediators, initiating inflammation.
Describe the sequence of events that occur during an inflammatory response.
The sequence begins with tissue damage, leading to the release of histamines by mast cells and cytokines. This causes blood vessels to dilate, increasing blood flow and making vessel walls more permeable. Immune cells, like neutrophils, are then recruited to the site by chemokines to destroy pathogens.
How do cytokines and chemokines influence the progression of the innate immune response?
Cytokines promote inflammation and activate immune cells, while chemokines guide immune cells to the site of infection or injury.
How does the innate immune system trigger or link to the adaptive immune response?
Dendritic cells act as a bridge by presenting antigens from pathogens to T cells (In the lymph node), initiating the adaptive immune response.
Mast cells and their inflammatory mediators
Quick Release Histamine,
Long term- Prostaglandins
Important for vasodilation
Drive inflammation
Leukotrienes
Can act like a chemokine, especially for neutrophils
Types of macrophages
Tissue Resident- Originate during embryogenesis, First Responders, Long lived, Found everywhere, Specific to the organ, Life span depends on the tissue.
Inflammatory- Monocyte differentiate into inflammatory Macrophages, Make more cytokines and chemokines, Enhance the immune response, Express more PRR.
How do macrophages and neutrophils recognize pathogens?
They use PRRs to detect PAMPs on pathogens. Opsonization by complement proteins or antibodies also helps phagocytes recognize pathogens.
Macrophages/ Neutrophil Phagocytosis
Opsonic- Receptors on neutrophil / macrophage bind to antibody or complement which further binds to pathogen.
Non-Opsonic- PRRs such as TLR, CLR on neutrophil macrophage bind directly to PAMP on pathogen
How do macrophages contribute to the initiation of inflammation?
Macrophages recognize pathogens opsonic or non-opsonic and release pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6, which activate endothelial cells and recruit immune cells.
Cytokines
Signal through specific receptors
Pro-inflammatory
Anti-inflammatory
Help ‘direct’ an immune response
Many are called ‘interleukins’
Chemokines
Chemotaxis
Signal through G-protein coupled receptors
Mostly signal to immune cells and co-ordinate their movement in tissues
Chemokines form gradients.
Chemotaxis is the directed movement of immune cells towards the site of infection in response to chemical signals like chemokines. It ensures that immune cells reach the infected tissue.
Important cytokines
IL1-b- Activates vascular endothelium Activates lymphocytes.
IL6- Lymphocyte activation
Boost antibody production.
IL8- Boosts chemotaxis, recruits neutrophils to site of infection
TNF-a- Activates vascular endothelium; increases permeability
Extravasation
Extravasation- Chemokines released cause endothelial cells to releases selectins which form a weak bond with the carbohydrates of the leukocyte this slows them down and allows them to roll along the endothelium. Then integrins leukocytes bind to ICAMs (adhesion molecules) forming tight binding. Diapedesis, the leukocyte exits from in between the endothelial cells, and they then migrate to the site of infection guided by chemical signals.
Leukocyte Adhesion Deficiency (LAD)
Primary immunodeficiency caused by mutations in adhesion molecules
Leukocytes can’t get from blood into tissue - failure of chemotaxis
Different types depending on inherited mutation
Inability to make pus; belly- button inflammation (omphalitis) and delayed detachment.
Neutrophils
Explain the mechanisms by which neutrophils kill pathogens
1.Phagocytosis (opsonic and non opsonic)- engulf pathogens into phagosomes, which fuse with lysosomes containing digestive enzymes (phagolysosome) kill pathogen.
2.Action of granule contents (Degranulation)- Granules are either enzymes or anti-microbial factors.
Primary: Myeloperoxidase (oxidative killing), Cathepsins and Defensins (enzymes that breakdown biomolecules of bacteria
Specific: Lactoferrin (Takes nutrients away from bacteria)
Gelatinase
3.Oxidative killing
NADPH oxidase generates superoxide anions, converted into hydrogen peroxide (Superoxide dismutase) and hypochlorous acid (Myeloperoxidase), effectively killing pathogens.
4.Netosis ( Extracellular)
A type of extracellular killing for large pathogens.
Neutrophils turn themselves
inside-out
NETs are sticky and can stop pathogens moving
NETs also full of toxic molecules and enzymes; damage cell walls and membranes to burst pathogen cells
Dendritic cells
Carry the pathogen to the lymph node APC- T cells and B cells are activated by dendritic cells
