Innate immunity Flashcards
Why do we need both the innate and adaptive immune systems?
- We need the innate immune system as it provides immediate and early protection.
- We need the adaptive immune system as it provides ‘memory’ of an infection, making recovery faster the next time we’re faced with the same challenge.
- The innate system alone may not be strong enough to protect us from certain pathogens, and the adaptive immune response alone is too slow to protect us from a new pathogen.
List some components of innate immunity.
- PHYSICAL BARRIERS - skin, mucosal surfaces
- CHEMICAL BARRIERS - pH, secreted factors
- PHAGOCYTES - monocytes / granulocytes / neutrophils
- INFLAMMATION
- ACUTE PHASE RESPONSE
- CYTOKINES/CHEMOKINES
- COMPLEMENT PROTEINS
- NATURAL KILLER CELLS (NK CELLS)
Describe cytokines and chemokines.
Both of them are glycoprotein hormones that affect the immune response.
- CYTOKINES - act to modify the behaviour of cells in the immune response - most (not all) of them are called interleukins (eg. IL-1).
- CHEMOKINES - act as chemotactic factors, ie. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection.
What is the inflammatory response? How does it take place?
It is a generic defence mechansim whose purpose is to localize ane eliminate injurious agents and to remove damaged tissue components.
- Enhanced permeability and extravasation.
- Neutrophil recruitment.
- Enhanced cell adhesion.
- Enhanced clotting.
- Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection.
What are some of the cytokines secreated by macrophages and dendritic cells?
How do macrophages ‘see’ microbes?
- Macrophages have phagocytic receptors that bind microbes and their components.
- They detect substances that are usually presented on pathogens (non-self).
Describe protein-associated molecular patterns (PAMPs).
- In order to protect against infection, one of the first things the body must do is detect the presence of microorganisms.
- The body initially does this by recognizing molecules unique to groups of related microorganisms and are not associated with human cells. (They are not present on human cells)
- These unique microbial molecules are called pathogen-associated molecular patterns or PAMPs.
What do gram negetive bacteria have?
- The Gram-negative cell wall is composed of a thin, inner layer of peptidoglycan and an outer membrane consisting of molecules of phospholipids, lipopolysaccharides (LPS), lipoproteins and surface proteins.
What do gram positive bacteria have?
- The Gram-positive cell wall appears as dense layer typically composed of numerous rows of peptidoglycan.
- They have small peptide chains sticking off the peptidoglycan (3 - 5 amino acids).
Describe damage-associated molecular patterns (DAMPs).
- DAMPs are molecules released by stressed cells undergoing necrosis.
- They vary greatly depending on the type of cell and injured tissue.
- Some of these endogenous danger signals are proteins - heat-shock proteins and cytokines. Non-protein DAMPs include ATP, heparin sulfate and DNA.
Necrosis - the death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply.
Describe Pattern Recognition Receptors (PRRs).
- They are host factors that specifically recognise a particular type of PAMP and DAMP.
- They are germ-line encoded.
- There are several classes of PRR, but functionally they are either: -
- EXTRACELLULAR PRRs- they recognise PAMPs outside of a cell and trigger a coordinated response to the pathogen.
- INTRACELLULAR (CYTOPLASMIC) PRRs- they recognise PAMPs inside a cell and act to coordinate a response to the pathogen.
- SECRETED PRRs- they act to tag circulation pathogens for elimination.
Describe how the interferon system works.
- A virus infects a cell, which then becomes known as the primary infected cell.
- The virus will multiply inside the cell, and, after the cell dies, it will release the viral progeny.
- However, as the primary infected cell is dying, it releases interferons.
- These interferons are picked up by other healthy cells, and they induce the transcription of >400 antiviral genes.
- These put the healthy cells in an antiviral state, meaning that now, viruses cannot affect them.
Interferon meaning - a protein released by animal cells, usually in response to the entry of a virus, which has the property of inhibiting virus replication.
Describe complement proteins.
- A system of secreted proteins made in the liver that recognise PAMPs on the surface of microbes and ‘decorate’ or ‘tag’ them.
- The microbes are then cleared by phagocytosis, “opsonised” (C3 sticks to pathogen membranes) or they have holes punched in them.
- There are three ways of activating them: -
- Recognition of LPS and other PAMPs by the C1q component of the ‘classical’ pathway.
- Non-host glycosylation is recognised by MBP (mannan/mannose-binding protein) and other lectins to activate the ‘lectin’ pathway.
- Membranes that are recognised as “non-self” activate the ‘alternative’ pathway.
- Complement activation involves a proteolytic cascade.
Lectin meaning - any of a class of proteins, chiefly of plant origin, which bind specifically to certain sugars and so cause agglutination of particular cell types.
Describe the structure of natural killer (NK) cells.
- They are large granular lymphocytes.
- They make up about 4% of WBCs.
- They are lymphocyte-like, but larger with a granular cytoplasm.
- They kill certain tumour cells and virally-infected cells.
- Target cell destruction is caused by the cytotoxic molecules that are injected into the target.
- These cytotoxic molecules are called granzymes and perforins.
How are NK cells activated?
- Natural killer (NK) cells are activated by loss-of-self.
- NK cells possess the ability to recognise and lyse virally-infected cells and certain tumour cells.
- An NK cell has an MHC (major histocompatibility complex) receptor on its surface.
- With an uninfected cell, it will present the ligand for the MHC receptor, stimulating an inhibitory signal that stops the NK cell from killing it.
- However, with an infected cell, they do not present this ligand, so the inhibitory signal is not presented, thus the NK cell stimulates cell death in two ways.
- The first way is that it releases perforin and cytotoxic granules into the infected cell, and the second way is that it engages the cell’s death receptors.
Compare aspects of the innate and adaptive immune system.
