2. Natural immunity Flashcards
What is natural immune response?
It is innate immune response which provides immediate defense
What is acquired immune response?
It is adaptive immune response which develops with time
What is the functional relationship of innate and adaptive immune response?
- Pathogen recognition and initial attack
- Transmission of Pathogen Information to Adaptive Immune System
- Specific Attack on Pathogens
What are the mechanical barriers for first line defense?
skin, mucous membranes, cough, sneeze
What are the chemical barriers for first line defense?
skin pH: ~5,5
stomach pH: 1,2-3
What are the biological barriers for first line defense?
in the mouth saliva contains antibacterial agents
- defensin (also in toothpaste)
- lysozyme (also in toothpaste)
- lactoperoxidase (also in toothpaste)
- lactoferrin (also in toothpaste)
- antibody – natural IgM ; IgA
What are the molecules for first line defense?
Complement system
IgA
What are the cells for first line defense?
Innate lymphoid cells
First line barrier:
-> What does the The SKIN / MUCOUS MEMBRANES contain?
Mucus contains antimicrobial secretions
First line barrier:
In general defensins are expressed along the first line barriers which are ___ (3)
- In salivary gland
- In Paneth cells of the small intestine
- In many leukocytes (e.g. neutrophils)
What are defensins? What do they form?
Most defensins are amphipathic molecules (positively charged and hydrophobic parts), and form holes in the membrane.
2 examples of defensins of the saliva
Alpha-defensins HNP 1- 4
Beta-defensins hBD1 hBD2 hBD3
What is the origin of Alpha-defensins HNP 1- 4?
- Neutrophils
- Gingival sulcus
- Sites of inflammation
- Salivary duct cells
What is the origin of Beta-defensins hBD1 hBD2 hBD3?
Epithelia, salivary ducts
What is lysozyme?
peptidoglycan N-acetylmuramoyl hydrolase that destroys bacterial cell wall by breaking glycosidil bonds between peptidoglycan components
What are 2 types of phagocytes?
- Neutrophils
- Macrophages
Which phagocytes are the most abundant leukocytes in the circulation appear first at site of infection?
Neutrophils
Macrophages mature from ___ in tissue
circulating momocytes
Characteristics of MPS (mononuclear phagocyte system)
Contain tissue-resident macrophages and recruited macrophages
Overview of phagocytosis and intracellular killing
I. Recognition and attachment - microbes bind to phagocyte receptors
II. Engulfment
- Phagocyte membrane zips up around microbe
- Fusion of phagosome with lysosome
III. Killing and degradation
- Killing of microbes by by ROS
- Degradation of microbes by lysosomal enzymes in phagolysosome
(ROS: highly reactive oxidizing agents
NO combines with superoxide to produce highly reactive peroxynitrite radicals(
What is the cause of CGD (Chronic granulomatous disease)?
Failure of phagocyte oxidase: Defective production of reactive oxygen species results in a failure to kill phagocytosed microbes.
What is granular formation?
Composed of activated macrophages, which try to eliminate the microbes
2 activation types of recruited macrophages
Elimination of apoptotic cells by macrophages
What are the 3 important granulocytes?
- Neutrophil
- Eosinophil
- Basophil
What is the function of neutrophil?
Phagocytosis
What is the function of eosinophil?
Degranulation against parasites
What is the function of basophil?
Degranulation against extracellular bacteria
What are the 3 Neutrophil effector functions (killing mechanism)
- Intravesical killing as in macrophages
- Frustrated phagocytosis
- Extracellular DNA trap
What is the role of immature Dendritic cells?
Antigen uptake
Antigen processing
What is the role of mature Dendritic cells?
Antigen presentation
Constimulation
T cell activation
- Lymphocytes and lymph return to blood via ____
thoracic duct
Naive lymphocytes enter ___ from blood
lymph nodes
How antigens reach lymph node? (dendritic cells)
What are Innate lymphoid cells (ILCs)?
Subsets of bone marrow–derived cells with lymphoid morphology and effector functions similar to those of T cells:
- early first line defense against pathogens – mostly in mucosal tissue
no T cell receptors
3 types of Innate lymphoid cells (ILCs)
NK CELLS has dual receptor system
-> What does it mean?
Killer-activating receptor
Killer-inhibitory receptor - MCHI inhibits killing activity
Innate immune response has limited specificity
-> What are 3 strategies in recognition?
- Pathogen - non-self
- Missing - self
- Altered-self
Innate immune response has limited specificity
=> Thus, they have 3 strategies in recognition
-> What is the characteristics of missing-self strategy?
Immunreaction is blocked in case of self markers
(missing in microorganisms)
Innate immune response has limited specificity
=> Thus, they have 3 strategies in recognition
-> What is the characteristics of altered-self strategy?
Non healthy self markers
Innate immune response has limited specificity
=> Thus, they have 3 strategies in recognition
-> What is the characteristics of pathogen-nonself strategy?
Characteristic markers of pathogens
(missing in the host)
Phagocytes have two types of receptors on their surfaces
-> What are they?
- Opsonic receptors - Fc receptors and complement receptors
- pathogen recognition receptors (PRRs)
What is Opsonization?
Facilitation of phagocytosis
What is Opsonization?
Facilitation of phagocytosis
What is happening here?
OPSONIZATION
What is happening here?
OPSONIZATION
The structure of Fc receptors
The role of Fcγ receptors
- bind IgG
- facilitate phagocytosis (regulate B-cell activation)
The role of Fcε receptors
1/ Bind IgE
2/ High affinity receptor is expressed on mast cells and basophils – have role in immunity against parasites and allergy (low affinity receptor has regulatory function)
What is happening here?
Fc receptor mediated phagocytosis
Name 4 Secreted pattern recognition receptors
List 2 Intracellular cytoplasmatic Pathogen recognition receptors (PRRs) with their roles
- RIG-I-like Helikases (RLHs, RLR) - recognize virus
- Nod-like Receptors (NLRs) - recognize intracellular bacteria
List 3 membrane Pathogen recognition receptors (PRRs)
I. Scavenger receptors
(CD14: LPS receptor)
II. Lectin receptors
(macrophage mannose receptor)
III. Toll like receptors: carbohydrates, lipids, nucleic acid
membrane Pathogen recognition receptors (PRRs)
-> What are 2 types of TOLL-LIKE RECEPTORS (TLR)
- Plasmamembrane receptors
- Intravesicular receptors
membrane Pathogen recognition receptors (PRRs) - TOLL-LIKE RECEPTORS (TLR)
-> Characteristics of Plasmamembrane receptors
Lipid or protein TLR ligands are recognized on the plasma membrane
- e.g. LPS, flagellin
membrane Pathogen recognition receptors (PRRs) - TOLL-LIKE RECEPTORS (TLR)
-> Characteristics of Intravesicular receptors
Nucleic acids are recognized by TLRs in the endosome
Ligand binding to TOLL-LIKE RECEPTORS (TLR) trigger ____
the activation of a signal cascade
EVEN WITHOUT PHAGOCYTOSIS IL-1, TNF-alfa, IL-6
-> How do pathogen recognition occur?
- Macrophage expresses receptors for many bacterial constituents
- Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
- Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
What type of inflammation is happening here?
Local inflammation
How many signal(s) does activation of the natural immune cells require?
What are DAMPs?
molecules released upon necrosis, that trigger the generation of extracellular pro-inflammatory molecules
4 examples of DAMPs?
- HMGB1: intracellular nucleosome stabilizing DNA- binding protein
- Heat-shock proteins
- uric acid
- Genomic double-stranded DNA
Components of the inflammasome
NLRP3
ASC
pro-caspase-I
What does the inflammasome activate?
Common feature of Autoinflammatory disorders (inflammasomopathies)
increasing IL-1 beta secretion (due to the defective regulation of the pro- IL-1 beta
-> active IL-1 beta transition)
What is Aphthous-like ulceration?
manifestation in some of the auto-inflammatory syndromes
What do PAMP and DAMP stands for?
PAMP: Pathogen associated molecular pattern
DAMP: Damage associated molecular pattern
What is happening in Danger model
Necrotic cell death releases DAMPs which will bind to DAMP receptor
-> DC maturation
-> CD80 and/or CD86 co-stimulatory molecule
-> Migration to lymph node
What is happening in Stranger model
Pathogen releases PAMPs which will bind to PPR receptor
-> DC maturation
-> CD80 and/or CD86 co-stimulatory molecule
-> Migration to lymph node
Why is COSTIMULATION required in immune response?
COSTIMULATION required for initial activation of T cells
Natural (innate) immune system
-> Toll-like receptors based CONNECTION between ___ and ___
natural and adaptive immunity