Flashcards in Immunity to infection 1+2 Deck (69)
What are the general features of microbial immunity?
There is innate immunity which is the first line of defence with immediate action this is not enhanced by previous exposure and functions based on pattern recognition and uses features such as complement, anti microbial peptides and NK cells
Adaptive immunity however will only start 4-7 days after infection and involves the response of antigen specific lymphocytes and has immunological memory
What are the specific interactions which may occur between a bacteria and a phagocyte?
There may be interactions between lectins and oligosaccharides on the surface of either of the cells
Alternatively several compounds may be deposited on the bacteria and recognized by the phagocyte such as antibodies (recognized by an Fc receptor), Mannose-Binding lectin (recognized by C1qR), iC3b (recognized by both p150,95 and CR3) and C3b (recognized by CR1)
What is the key difference between immunity to extracellular gram negative and gram positive bacteria?
Gram positive bacteria are not as effectively killed by complement
What is the early immune response to bacteria?
There is increased vascular permeability, Chemotaxis, activation of phagocytes and activation of the endothelium so that phagocytes can better and adhere to it
How does the increased vascular permeability seen in the early immune response to bacteria occur?
The bacteria leads to the activation of complement which can lead to the activation of Mast cells which produce histamine leading to increased vascular permeability
How does the chemotaxis seen in the early immune response to bacteria occur?
Bacteria can activate complement which will result in the production of anaphylotoxins to induce chemotaxis as well as activate mast cells to produce IL-8 to mediate chemotaxis
Bacterial components are also capable of activating macrophages to produce IL-8
How are phagocytes activated in the initial immune response to bacteria?
Bacteria activate complement which will result in the production of components which will activate phagocytes
Bacteria may also activate NK cells to produce IFN-gamma which activates phagocytes
Bacterial components may activate macrophages to produce IL-12 and TNF which can activate NK cells to produce IFN-gamma activating phagocytes
How do phagocytes have increased adhesion and endothelial cells become activated in the early immune response to bacteria?
Bacterial components activate macrophages to produce Il-1 and TNF-alpha cause increased adhesion of phagocytes as well as activating endothelium which itself also causes increased adhesion of phagocytes
What is the acute phase response seen in the early immune response to bacterial infection?
Bacterial components activate macrophages to produce IL-1, IL-6 and TNF-alpha (IL-6 being the major player here) which induce the liver to produce acute phase proteins including mannose-binding lectin, surfactants SP-A andSP-D as well as C-reactive protein
How can the immune response against pathogens lead to shock and death?
Certain bacterial compounds like LPS can activate macrophages to produce IL-1, IL-6, TNFalpha and other endogenous pyrogens which can lead to endotoxic shock
Alternatvely superantigens can non-discriminately activate T cell subpopulations leading to production of IL-1, TNFalpha from macrophages and IL-2 from the T cell inducing toxic shock
What are the features of endotoxic shock?
There is a significant change in vascular permeability, loss of fluid into the tissue and a fall in blood pressure
The symptoms include fever, circulatory collapse, diffuse intravascular coagulation, haemorrhagic necrosis and multiple organ failure
How cod bacteria avoid complement mediated damage?
They may have an outer capsule or coat which prevents complement activation
Long side chains such as the O antigen on bacterial LPS may prevent the binding of Cb3 to the complement receptor
Surface structures on the microbe divert attachment of lytic complex to the membrane
Membrane bound enzyme degrades fixed complement or causes it to be shed (such as Pseudomonas elastase which cleaves C1q and IgG)
There is a resistant outer membrane (containing large amounts of sialic acid)
Secretion of decoy proteins that bind complement (like SIC protein of S. Pyogenes)
What is the unique feature of the S. Pyogenes capsule?
It is made of hyaluronic acid which is a host protein and can therefore facilitate immune evasion
What is the oxygen dependent mechanism of phagocytosis?
Inside the phagosome a respiratory burst occurs this involves reactive oxygen intermediates such as the hydroxyl free radical, super oxide and peroxide which may directly kill the pathogen through the peroxidase independent pathway or myeloperoxidase/catalase can also act on peroxide to produce hypochlorous acid which may kill the pathogen in the peroxidase dependent pathway
What is the nitric oxide pathway of bacteria killing?
IFN-gamma can activate inducible nitric oxide synthase resulting in Nitric oxide synthase with its tetrahydrobiopterin cofactor being able to use O2 and L-arginine to produce citrulline and the toxic Nitric oxide
This process may be enhanced by the actions of TNF and crosslinking of CD23
What are the escape mechanisms bacteria have from phagolysis?
They may inhibit chemotaxis through secretion of repellents or toxins preventing the phagocyte from taking up the bacteria
They may also have capsules or outer coats which prevent attachement and uptake by phagocytes
Release of factors which block the triggering of killing mechanisms such as blocking lysosome fusion, inhibiting the proton pump or the release of catalase
There may be blocking of the IFNgamma signal through compounds such as lipoarabinomannan
There may be a resistant outer coat which scavenges free radicals like phenolic glycoprotein
What is toxic shock syndrome?
This is something which may occur as a result of S. Pyogenes or S. Aureus infection where superantigens act of case hypotension, fever, rash, vomitnng and shock
What is Whooping cough?
This is something which may occur as a result of Bordetella pertussis, where pertussis toxins act to cause ADP-Ribosylation of G-proteins and induce lymphoproliferation
What is tetanus?
This is something which may occur as a result of Clostridium tetani which produces tetanus toxin which blocks inhibitory neuron action and induces muscle cramps
What is diphtheria?
This is something which may occur as a result of Corneybacteria diphtheria which produces diphtheria toxin which inhibits protein synthesis leading to epithelial cell damage
What is cholera?
This is something which may occur as a result of vibrio cholera which produces cholera toxin which activates adenylate cyclase leading to an increase in cAMP
What is Botulism?
This is something which may occur as a result of clostridium botulinum which produces botulinum toxin which blocks the release of acetylcholine triggering paralysis
What is Anthrax?
This is something which may occur as a result of Bacillus anthracis which produces anthrax toxin which increases vascular permeability leading to edema and haemorrhage
How can the immune system neutralise bacterial toxins?
Through high affinity IgG and IgA which prevents the toxin from binding to its receptor
What is the role of antibodies in microbial immunity?
Antibodies to fimbriae, lipoteichoic acid and some capsules and adhesins can block bacterial attachement
Antibodies can trigger complement mediated damage to the bacteria or block transport mechanisms and receptors preventing bacterial proliferation
Antibodies to capsules can lead to opsonisation via Fc and C3 receptors or they may neutralise immune repleelents prevent the bacterias ability to avoid phagocytosis
Antibodies to toxins can prevent bacterial toxin mediated damage
Antibodies can neutralise spreading factoes like hyaluronidase preventing the bacteria from becoming invasive
How do microbes counteract the activity of antibodies?
They have rapid cell division
Host like coat (Hyaluronic acid or fibrin deposits)
Soluble antigen release as a decoys
Antibody specific proteases
What is antigenic variation?
Due to genetic or allelic variation microorganisms are often able to change epitopes in prtoeins or carbohydrates
What is the difference between Th1 and Th2 responses to infection?
Th1 cells drive cell mediated immunity with the production of TNF and IFNgamma which lead to macrophage activation (as well as IL-2 production to drive more Th1 production) Th1 cells also respond to IL-12 from the macrophages
Th2 cells however drive humoral immunity with production of IL-4 prevent macrophage activation by IFN-gamma and IL-10 preventing Th1 proliferation
How do Th1 and Th2 response differ in the host response to mycobacterium leprae?
If a Th1 response predominates then the tuberculoid form of the disease will develop as this will induce a vigorous host cellular response with many immune cells in the lesions, there may also be tissue damage as a result of type IV hypersensitivity, there will only be a few bacteria visible microscopically and disease progress is slow with the patient typically surviving
If a Th2 response predominates then the lepromatous form of the disease will predominate with humoral response, there will be an adequate antibody response but this will be unable to access the intracellular bacteria, this results in there being many bacteria in the lesions, the patients being highly infectious along with gross tissue destruction and the disease typically being fatal