Immunity Flashcards
Lectures 9 - 14
Describe streptococcus pneumonia and our immune system.
A significant human Gram-positive pathogenic bacterium. There are more than 90 different serotypes. It can cause acute sinusitis, meningitis and septic arthritis.
Describe how rapid viral evolution is a challenge to our immune system.
It’s a virulence strategy. Pathogens can mutate or recombine to avoid host immune responses, so the immune system must be able to respond.
Describe the rapid evolution of HIV by mutation.
HIV has an RNA genome associated with an RNA replicase. The mutation rate during copying is 1-10,000 bases. For eukaryotic DNA polymerases, the rate is 1-1000000000 bases.
Describe a brief history of the spanish flu and describe it too.
The 1918’s spanish flu epidemic was triggered after a bird virus crossed the species barrier. Most victims were 20-40 yrs of age and around 20-50 million people died. Average life span was reduced by 10%.
Describe the Asian flu and flu itself.
Recombination events triggered the 1957 Asian flu epidemic. It originated in China and about 2 million people died.
Describe the Hong Kong flu.
Recombination events triggered the 1968 Hong Kong flu, but this had a low death rate.
Describe how antigenic variation/shift is a challenge faced by the immune system.
Antigenic variation/shift is a virulence strategy: During initial infection, the host immune system generates and immune response that normally protects against persistent or repeat infections. Some pathogens can alter their surface proteins to avoid host immune responses.
What is the blood brain barrier?
The blood:brain barrier separated circulating blood from the brain extracellular fluid. It has tight junctions around brain capillaries.
Hence, the brain almost entirely uses the innate immune response.
Describe how the innate and adaptive arms of the immune system work with each other.
Innate: First line of defence, no memory, non-specific, encoded in the germ line. The innate arm is of ancient origin and is found in most organisms.
Adaptive: Slow to adapt, highly specific, has memory, somatic gene recombination. The adaptive arm is confined to vertebrate systems.
What are cell-mediated immunity and humoural immunity? Describe what toll-like receptors can be used for.
Cell-mediated immunity: defence provided by specialised cells in blood and tissues. It comprises a range of phagocytic cells and natural killer cells that destroy virus-infected cells.
Humoural immunity: soluble-phase defence provided by secreted proteins in body fluids. It relies on barriers and chemical warfare and makes calls for help.
Toll-like receptors provide calls for further help.
What are the three lines of innate immune system defense? Describe them.
Barriers: physical and chemical:
- Thick layer of dead cells
- Tight junctions between epithelial cells
- Mucus layers
Cell-intrinsic responses:
- Pathogen-induced phagocytosis
- Degradation of dsRNA
Specialised proteins and specialised cells:
- Professional phagocytes
- Natural killer cells
- The complement system
Describe the mucus layers of the innate immune system, including which defensins there are.
Skin and other epithelial surfaces lining respiratory, intestinal and urinary tract provide a physical barrier.
The mucus can also protect against microbial, mechanical and chemical attacks. Fish and many amphibians also produce a mucus layer on the skin. Eg. Hagfish. The mucus layer is made from secreted mucins and other glycoproteins. Most epithelial cells have beating cilia which can facilitate clearance of pathogens.
The mucus layers contain defensins: alpha-defensin, beta-defensin, insect defensin A, omega defensins.
What are defensins?
Small (12-50 amino acids length) positively charged antimicrobial peptides, which have hydrophobic or amphipathic helical domains.
Defensins have wide-antimicrobial activity and can kill or inactivate: Gram positive and Gram negative bacteria, fungi, parasites, and enveloped viruses.
Describe the mechanism of defensins.
- Their hydrophobic domains or amphipathic helices may enter into the core of the lipid membrane of the pathogen and destabilise it.
- It leads to cell lysis.
- The positive charges on the membrane may interact with negatively charged nucleic acids in the pathogen.
What are PAMPs?
Pathogen-Associate Molecular Patterns. Pathogens sometimes do breach the epithelial barriers, the innate immune system recognises molecules that are common to many pathogens but absent in the host.
Describe how complement activation targets pathogens for lysis.
Lectin pathway: mannose and fucose binding proteins.
1. The early complement components are proenzymes that activate the next member in line by cleavage, resulting in an amplified proteolytic cascade.
2. The pivotal proteolysis is the one that cleaves.
3. C3a: Calls for help. Attracts phagocytes and lymphocytes stimulating inflammation.
4. C3b. Binds covalently to the pathogen’s plasma membrane.
5. Pathogen-bound C3b stimulates a local cascade of reactions at the marked membrane.
6. C9 is inserted into the membrane.
7. A C9 pore breaches the membrane.
8. Pathogen lysis.
What is a toll receptor?
Toll is a trans-membrane protein with a large extracellular domain with repeating motifs that are versatile binding motifs for a variety of proteins.
Binding to pathogenic fungi sends a signal to the nucleus that results in expression of antifungal defensins.
Toll-like receptors have the same overall structure - and do very similar jobs.
Describe Neisseria Gonorrhoeae and its history.
1879 - The causative agent of gonorrhea was first described by A. Neisser.
1885 - The organism was grown in pure culture.
Symptoms:
- most females and low amount of males are asymptomatic.
- pelvic inflammatory disease leading to infertility in some women.
- prostatitis in males.
- conjunctivitis in newborns exposed to the disease.
Describe phagocytes including the types of phagocytes too.
Phagocytes help engulf invading microorganisms. There are 3 major classes:
- neutrophil
- eosinophil
- macrophage
Neutrophils and Eosinophils are granulocytes: named because their cytoplasm is granular. Macrophages are from an agranulocyte lineage (monocyte) but as they mature they develop granules.
What are neutrophils?
Neutrophils are the most common type of granulocyte. They are short lived, are abundant in blood and aren’t present in normal healthy tissues. They are recruited by activated macrophages, peptide fragments and by some PAMPs.
What are macrophages?
They are larger and longer-lived than neutrophils.
They recognize and remove senescent, dead, and damaged cells in many tissues. They are able to ingest large microorganisms such as protozoa.
What are eosinophils?
They help to destroy parasites which modulate allergic inflammatory responses.
Eosinophils attach schistosome larvae, but if they are coated with complement, then they can kill it.
Describe granules in immunity.
The ‘granules’ are dense membrane-bound lysosomal derivatives. They fuse with the phagosome membrane and release their contents to help digest the cell walls of pathogens. The granules also contain defensins which destabilise the pathogen’s membranes.
