Innate immunity

Question	Answer
List five characteristics of the innate immune system that differ from the adaptive immune system.	The innate immune system is: non-specific, short-lived, and immediate, and it is the first response to an immune threat, and has no memory, so that the reaction to the stimulus is the same each time it is encountered.
List three physical barrier to immune challenges that the body has.	The skin and its tight epithelial junctions, the mucous membranes and their tight mucous cell junctions, and the microbiota of the skin which outcompetes pathogenic microorganisms.
What is the general term for the receptors that distinguish non-self from self?	Pattern recognition receptors.
What are the molecular patterns recognised as non-self, comprised of combinations of sugars, some lipid-bearing molecules, or some nucleic acid motifs, called?	Pathogen-associated molecular patterns (PAMPs).
What does the innate immune system's accurate tendency to recognise PAMPs prevent?	Recognition of and reaction to non-self but non-pathogenic substances such as artificial hip joints, and the development of recognition of self antigens which produce autoimmune disorders (this occurs in the adaptive immune response).
What are the two main functions of the innate immune system?	To help prevent or limit infection of the host (i.e. by killing invading microbes), and to stimulate and direct the adaptive immune response (so that the response is dependent on the stimulus).
How many microbes are present in the skin microbiota?	10^14. They are predominately protective and non-pathogenic.
What is the epidermis?	The thin outer layer of the skin which consists of tightly packed dead epithelial cells and water-proofing keratin.
What is the dermis?	The thick, deeper layer of skin composed of connective tissue containing vasculature, hair follicles, sebaceous glands, and sweat glands. It produces antimicrobial peptides and proteins.
What is psoriasin?	An antibacterial peptide produced by the dermis which is bacteriocidal for E coli.
What are the antimicrobial biochemical properties of the skin useful for?	For protecting the host against infection in events of skin breaks such as scratches, wounds, abrasions, and bites (animal/human/insect).
Which three bodily tracts and which organs use mucous membranes for physical protection against infection?	The alimentary, urogenital, and respiratory tracts, and the eyes.
Which two layers of tissue does a mucous membrane consist of?	An outer epithelial cells layer and a deeper connective tissue layer.
How does saliva protect against infection?	It contains antibacterial and antiviral substances.
Other than saliva, what other protection does the alimentary tract offer against infection?	Mucous is viscous and entraps microorganisms, as well as containing antibacterial and antiviral substances, while the hostile mix of HCl and digestive enzyme in the stomach breaks them down.
How is the lower respiratory tract protected against infection/colonisation?	The synchronous movement of cilia propels mucus-entrapped microorganisms from the lower respiratory tract, resulting in them being swallowed and digested or coughed out of the host.
How has influenza virus evolved to evade the defences of mucous membranes?	It has a surface molecule that enables it to attach firmly to cells in mucous membranes of the respiratory tract, preventing it from being swept out by the ciliated epithelial cells.
How has Neisseria gonorrhae evolved to evade the defences of the urogenital mucous membrane?	It has surface projections that bind to epithelial cells and adhere it to them.
Give the general mechanism of adherence of bacteria to mucous membranes.	It is generally mediated by hairlike protrusions (fimbriae, pili) which interact with certain glycoproteins or glycolipids only expressed by epithelial cells of the mucous membrane of particular tissues, making these tissues susceptible to invasion by particular pathogens.
Name two initiators of the complement system that opsonise pathogens, stimulating both the complement pathway and phagocytosis.	Mannose-binding lectin (MBL) and C-reactive protein (CRP).
Once a single phagocytic cell has phagocytosed a pathogen (having bound PAMPs to its PRR), what happens to recruit more immune cells?	It secretes inflammation-promoting cytokines and chemokines such as IL-8 which recruits macrophages, and C3 which breaks down to C3a (increases vascular permeability) and C3b (opsonises microbe/antigen to increase immune response).
What is the role of the dendritic cell in the immune response?	Dendritic cells link the innate and adaptive responses. They internalise microbial components, mature, and present microbial peptides on MHC molecules. They then migrate through lymphatic vessels to nearby lymph nodes, where they present antigen to T cells, which initiate adaptive immune responses against the pathogen.
Generally speaking, what is complement?	The complement system consists of at least 20 liver-derived proteins which circulate in an inactivate pro-form and are activated directly by pathogens during an innate response. The three complement activating pathways are the classical, the alternative, and the lectin pathway. Their functions include lysis by the formation of a membrane attack complex, opsonisation (C3b primarily does this, and this 'flags' the innate immune cells to the pathogen), and chemotaxis (the binding of complement to pathogens creates a chemical gradient up which innate immune cells can travel towards the infectious/damaged tissue.
Which two auxillary cell types are activated by complement to increase the immune response?	Circulatory basophils and tissue mast cells.
In the absence of C5, the convertase required for the formation of the membrane attack complex at the end of the complement cascade, which blood protein may substitute, creating an 'alternative' to the three existing complement activation pathways?	Thrombin http://www.lambris.com/pdf/GenerationofC5aintheabsenceofC3anewcomplementactivationpathway.pdf
What are the three types of auxillary immune cells? Which is activated by neutrophils in an innate immune response?	Circulatory basophils, tissue mast cells, and circulatory platelets. Platelets are activated by neutrophils.
Which inflammatory mediators are secreted by the auxillary innate immunity cells?	Mast cells, basophils, and platelets all secrete leukotrienes and prostaglandins, which cause vasodilation and activate immune cells in order to draw them to the site of infection/damage. Mast cells also rapidly degranulate to release histamine and platelets release serotonin.
Why is the production of prostaglandins a delayed process?	Because they are formed from membrane lipids so are not readily available in their intact form.
What are chemokines?	Small cytokines which induce chemotaxis for immune cells.
Where are macrophages found?	All tissues have resident macrophages which detect 'distress' from infected cells in the form of soluble mediators and cell debris as well as PAMPs, and which escalate the signals to other immune cells by producing cytokines.
Which soluble mediators are not very common but involved in antiviral protection?	Interferons α and β
Which is the main chemokine? HINT: It mainly recruits neutrophils	Interleukin 8
Which fever-inducing cytokines are released by macropages, dendritic cells, and infected/damaged tissues?	IL-6 (which induces activate phase proteins and is one of the earliest innate indicators of infection; it is produced quickly and maintained at a high level, and is clinically diagnostic) and 1L-1 β and TNF α (these encourage leukocytes to migrate from the circulation into infected tissues - they are pro-inflammatory cytokines). TNF-α also helps cells to proliferate.
Which soluble mediator encourages leukocytes out of the blood? Which then directs them to the infected site?	TNF-α then IL-8.
Give a rough description of acute phase protein function.	When IL-1 and IL-6 are released (these are also fever-inducing and act on the hypothalamus), they reach the liver in the circulation and trigger the release of acute phase proteins, which are elevated very early during infection. These proteins, such as C-reactive protein (CRP) activate complement in order to generate further opsonins (e.g. C3b) and this results in pathogens being phagocytosed as quickly as possible to avoid further spread of infection and further development of symptoms.
Invariably, the innate response is not quick or specific enough to completely avoid further spread of infection or development of symptoms - but what does it do?	'Buys time' for the generation of the acquired immune response to develop in order to direct a specific attack against the pathogen.
A phagocyte will struggle to engulf an entire self cell (i.e. in the event of an intracellular infection such as a virus, or a cancer), or a pathogenic cell that is too big, so a different mechanism, cytotoxic cells, is required. Which are the two main innate immune cells involved?	Eosinophils and natural killer cells, which both kill their target cells by the release of toxic granules.
Why are eosinophils only triggered in close proximity to their target cell?	Because their granule contents is highly toxic and capable of causing significant tissue damage if triggered inappropriately i.e. in anaphylaxis.
What is the main target of eosinophils?	Helminths
What are the main targets of natural killer cells?	Intracellular pathogens such as viruses, and cancers.
Name a mononuclear, long-lived phagocyte.	Macrophages.
Name a polymorphonuclear, short-lived phagocyte.	Neutrophils.
Why are phagocytes important alongside cytotoxic cells?	Because it is important to remove the pathogens/cell debris as well as to kill the pathogen.
What are the three main stages of phagocytic function?	Engulf, internalise, and destroy.
What happens to form a phagosome around a pathogen?	Phagocytic pseudopodia extend around the pathogen and fuse when they meet to form a vesicle.
What may happen to fragments of phagocytosed pathogens after digestion?	Macrophages (not neutrophils) may either present these fragments to T cells via MHC molecules, or exocytose them.
Why is acidification important for phagocytes?	Because enzymes require a low pH for their structure and function, and this low pH is also toxic.
Name 4 substances that phagocytes produce in order to kill pathogens (other than acid and enzymes).	Toxic oxygen-derived products for the respiratory burst, toxic nitrogen oxides, antimicrobial peptides, and competitors.
Which three components of immune attack or response to phagocytes have receptors for in order to activate them?	PAMPs (e.g. flagella or Gram negative capsules), antibody (acts as an opsonin), and activated complement (which also acts as an opsonin).
Is phagocytosis enhanced if more than one type of activator (antibody, PAMPs, complement) binds to a phagocyte, or is it a constant process?	The activity can be enhanced with increased binding of activators, meaning that opsonins and receptors are important for determining the rate of clearance of an infection.
What are PAMPs?	Pathogen-associated molecular patterns (PAMPs) are invariant structures needed for survival of the organism, such as lipopolysaccharides in bacterial cell walls, which are detected by toll-like receptors on phagocytes and most other leukocytes.
Are these TLR-PAMP interactions strain-specific?	No, they are shared by groups of microbes e.g. Gram positive/Gram negative bacteria, viral RNA, bacterial DNA.
What happens when a toll-like receptor recognises PAMPs?	The PAMP binds to TLR-4 (for instance; the most commonly studied toll-like receptor because it binds bacteria lipopolysaccharide which causes sepsis, and, despite how much research has gone into this area, still has a high mortality rate) and cell signalling activates the transcription factor NFK-β, which transcribes pro-inflammatory cytokines.
Which toll-like receptors detect the following: peptidoglycan, lipopolysaccharide, RNA, flagella, DNA?	Peptidoglycan: TLR-1, TLR-2, and TLR-6. Lipopolysaccharide: CD14 and TLR-4. RNA: TLR-3. Flagella: TLR-5. DNA: TLR-9.
B cells are primed and activated by...	...complement.
T helper 1 cell differentiation is determined by...	...different cytokines produced.
Innate immunity primes adaptive immunity and innate immunity does what in a positive feedback loop?	Enhances innate immunity.
In enhancing the innate immune response, what do Th1 cells do?	Promote macrophage phagocytosis and neutrophil killing by releasing cytokines.
In enhancing the innate immune response, antibodies...	...act as opsonins and some activate complement and thus help focus the innate response and make it more specific.

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