3 - Innate immunity Flashcards
Innate immune system
- First line of host defence against infections
- Starts acting immediately on encounter with infectious agents
- Instructs adaptive immune system to respond to different microbes
- Role in clearance of dead tissues and initiation of repair
- Responds in same way to repeat encounters (No memory)
4 examples of chemical and anatomic barriers that protect against pathogens
- Lysozyme in tears (dissolves cell walls)
- Mucus and cilia lining trachea (move pathogens out of body)
- Skin (barrier that produces antibacterial peptides)
- Stomach acidity (pH 2) inhibits microbial growth
3 more examples of chemical and anatomic barriers that protect against pathogens
- Normal flora (compete with pathogens in gut and on skin)
- Flushing of urinary tract prevents infection
- Mucus, antibacterial peptides and phagocytes prevent infection in lungs
3 examples of mechanical barriers
- Epithelial cells joined by tight junctions
- Longitudinal flow of air or fluid
- Movement of mucus by cilia
3 examples of chemical barriers
- Fatty acids
- Low pH
- Antibacterial peptides (defensins)
Example of microbiological barriers
Normal flora
Complement system
Includes several plasma proteins that work together to
opsonise microbes, promote phagocyte recruitment, and directly kill microbes
Opsonisation
Process by which a microorganism is coated by serum components enhancing recognition and ingestion by phagocytic cells
Outcomes of the complement system
- Direct killing of some
bacteria (Gram negative more susceptible) - Production of C3b (opsonin) leading to phagocytosis
- Release of C3a and C5a involved in inflammation
Role of complement system in inflammation
- Attract and activate neutrophils
- Activates mast cells (release of histamine and leukotriene contributes to increased vascular permeability)
Cytokines
Generic term for any soluble protein secreted by immune cells that affects the behaviour of cells bearing appropriate receptors
How many cytokines are there
More than 60, produced by many different cell types
Effects of cytokines
- Can change expression of adhesion molecules and receptors in the target membrane
- Activate cell proliferation and differentiation or modulate effector functions
- Signal cells to survive or die
Examples of cytokines
- Interleukins/Hematipoietins (IL)
- Interferons (IFN)
- Tumour Necrosis Factors (TNF)
- Colony Stimulating Factors (CSF)
- Chemokines
Granulocytes
- Neutrophil
- Eosinophil
- Basophil
Neutrophils
The most abundant population of circulating white blood cell and the principal cell type in acute inflammatory reactions
Characteristics of neutrophils
- Multilobed nuclei connected by thin chromatin bridges.
- Cytoplasmic granules have enzymes such as lysozyme, collagenase, and defensins
Functions of neutrophils
- Phagocytosis
- Degranulation and the release of neutrophil extracellular traps (NETs)
Functions of eosinophils
- Killing of antibody coated parasites
- Triggered by infectious and non infectious (allergies) processes
Characteristics of Eosinophils
bilobed nucleus with large specific granules that store cytokines, cationic proteins and enzymes
Mast cells
Release of granules containing histamine and active agents
Basophils
Found in blood, representing less than 1% of circulating white blood cells
Function of mast cells and basophils
Roles in parasitic diseases and allergic reactions
Granules of mast cells and basophils
contain vasoactive mediators (histamine, heparin, leukotrienes). have roles in vasodilation, angiogenesis and regulation of many cell types
Macrophages
Phagocytes, widely distributed in all organs and connective tissues
Two types of macrophages
- Blood circulating monocytes that migrate into tissues and mature into macrophages
- Long lived, tissue resident macrophages derived from yolk sac
Functions of macrophages
Phagocytosis (pathogens and necrotic or apoptotic host cells) and antigen presentation
Types of dendritic cells
- Conventional dendritic cells
- Plasmacytoid dendritic cells
- Follicular dendritic cells
- Tissue resident DCs (e.g., Langerhans cells)
Dendritic cells
- Most effective antigen presenting cell
- Act as bridge between innate and adaptive immune responses
- Sample antigen from throughout the body, and migrate to lymph nodes (via the draining lymphatics) to present antigen to T cells
Innate lymphoid cells
- Arise from the same common lymphoid precursor as T and B cells, but lack clonally distributed diverse receptors
- Stimulated by same types of stress signals that alert neutrophils, macrophages and dendritic cells
Three major subsets of innate lymphoid cells
ILC1, ILC2 and ILC 3
ILC1
Intracellular pathogen stimulus, promote macrophage activation
ILC2
Parasite stimulus, promote mucus production, vasodilation, macrophage activation and thermoregulation
ILC3
Extracellular pathogens (microbiome) stimulus, promote phagocytosis, release of antimicrobial peptides, and epithelial cell survival
Natural killer cells functions
- Kill infected (e.g., virus) and unhealthy/ tumour cells using perforin and granzymes
- Secrete cytokines
- Antibody-dependent mediated cytotoxicity (type II hypersensitivity)
Antibody dependent mediated cytotoxicity
- Antibodies bind to a malignant cell, or a host cell infected with a virus
- NK cells have a specific antibody receptors on their surface
- The antibodies bridges the infected cell with the NK cell so that the target is close enough for enzymatic activity
What are the main phagocytic cells
Neutrophils and macrophages
Steps of phagocytosis
- Pattern recognition receptors (PRRs) on phagocytic cells recognise microbe associated molecular patterns (MAMPS) on microbes
- Microbes are engulfed within a phagosome
- Lysosomes fuse with phagosome, forming phagolysosome. Respiratory burst generates toxic reactive oxygen species (ROS)
- Intracellular digestion mediated by lytic enzymes and ROS
- Microbial debris exits phagocyte by exocytosis
What causes ingestion/activation of the internalisation process of phagocytosis
Reorganisation of actin
cytoskeleton and changes in
the membrane
Phagocytosis
actin-dependent process of specifically internalising
particulate targets, which may include microorganisms, dead or dying cells or environmental debris.
Phagolysosome
contain antimicrobial agents including antimicrobial proteins (defensins),
hydrolytic enzymes (lysozyme and proteases) and low pH
Exocytosis
release of microbial
fragments
Antigen presentation
microbial fragments are united with glycoproteins (major histocompatibility [MHC] proteins) and presented at the cell surface where it is then presented to T lymphocytes, triggering adaptive immune
responses
What happens to neutrophils after phagocytosis
Continue until they become exhausted and die
What happens to macrophages and dendritic
cells after phagocytosis
they become antigen presenting cells
Pathogen recognition receptors (PRRs)
Recognise unique microbial
macromolecules by the presence of repetitive
structural proteins
Characteristics of PRRs
- PRRs are non-clonal (identical receptors
on all cells of the same lineage) - Self/non-self-discrimination (healthy host cells are not recognised)
- May be located on the cell surface or intracellularly
Types of PRRs
- Toll-like receptors (TLRs)
- NOD-like receptor (NLRs)
- RIG-like receptors (RLRs)
- C-type lectin receptors (CLRs)
- Cytosolic DNA sensors (CDSs)
What are the two principal types of reactions of the innate immune system
Inflammation and antiviral defence
What does activation of transcription factors increase
- Expression of inflammatory genes, inducing acute inflammation and stimulation of adaptive immunity
- Secretion of IFN-α and IFN-β induce an antiviral state
Innate immune system pathway
Microbial ligands (PAMPS) –> Host receptors –> Adaptor proteins –> Cytoplasmic signal transduction –> Activation of transcription factors –> Transcription and production of cytokines
Inflammatory mediators released by macrophages
TNF, IL-1, IL-6
Local effects of inflammatory mediators
- Tumour necrosis factor (TNF) and interleukin
(IL-1) act on leukocytes and endothelium to induce acute inflammation - TNF and IL-1 induce the expression of IL-6 from
leukocytes and other cell types
Systemic protective effects of inflammatory mediators
Induction of fever, acute-phase protein synthesis by the liver, and increased production of leukocytes by the bone marrow
Systemic pathologic effects of inflammatory mediators
Decreased cardiac function, shock, thrombosis and capillary leak, and metabolic abnormalities due to insulin resistance
Cardinal signs of inflammation
- redness (rubor)
- warmth (calor)
- pain (dolor)
- swelling (tumor)
- loss (altered) of function (functio laesa)
Steps of inflammation
- Injury, barrier break, microbe entry
- Sentinel cells activated
- Sentinel cells secrete inflammatory mediators
- Increased vascular permeability
- Complement, antibodies, and anti-microbial proteins kill microbes
- Adhesion molecules and chemokines cause leukocyte migration into tissue
- Phagocytosis and killing of microbes
