introduction to the immune system

Question 1

What is Immunology?

Answer 1

Immunology is the study of our body’s sytems for preventing and treating diseases.

Question 2

How is the Immune System organized?

Answer 2

Innate Immunity - and a second, more specific defence -

Adaptive Immunity. The adaptive immunity can be humoural (ie. B cells and antibodies) or it can be cellular (ie. T cells). White Blood Cells (WBCs) are key players in the immune system.

Question 3

what are the components of innate immunity?

Answer 3

→physical barriers ( skin, mucosal surfaces)
→chemical barriers ( pH, secreted factors)
→phagocytes (monocytes/granulocytes/neutrophils)
→inflammation
→ acute phase response
→cytokines and chemokines
→complement
→natural killer cells

Question 4

what is the inflammatory response triggered by?

Answer 4

→ the release of pro-inflammatory cytokines and chemokines at the site of infection

Question 5

what is the purpose of the inflammatory response?

Answer 5

→localize and eliminate injurious agents and to remove damages tissue components

Question 6

what occurs during the inflammatory response?

Answer 6

→enhanced permeability and extravasation
→neutrophil recruitment
→enhanced cell adhesion
→ enhanced clotting

Question 7

what are cytokines and chemokines?

Answer 7

glycoprotein hormones that affect the immune response

Question 8

what do cytokines do?

Answer 8

they act to modify the behavior of cells in the immune response
most of them are called interleukins

Question 9

what do chemokines do?

Answer 9

act as chemotactic factors that create concentration gradients which attract or repel certain cell types to a site of infection or production

Question 10

how do macrophages detect microbes?

Answer 10

→Macrophages have phagocytic receptors that bind microbes and their components.

→They detect substances that are usually presented on pathogens (non-self).

Question 11

what are protein-associated molecular patterns PAMPs and give some examples?

Answer 11

→PAMPs are small molecular motifs conserved within a class of microbes.

→ glycans 
→ lipopolysaccharides 
→bacterial flagellin 
→ lipoteichoic acid 
→ peptidoglycan 
→nucleic variants normally associated with viruses, such as double-stranded RNA

Question 12

what are damage-associated molecular patterns (DAMPs) and give some examples

Answer 12

→DAMPs are molecules released by stressed cells undergoing necrosis.

→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.

Question 13

what are pattern recognition receptors? (PRR) and what are they encoded by?

Answer 13

→host factors that specifically recognize a particular type of PAMP.

→ germ-line encoded.

Question 14

what are the three types of PRR?

Answer 14

EXTRACELLULAR:
→they recognize PAMPs outside of a cell and trigger a coordinated response to the pathogen

INTRACELLULAR (CYTOPLASMIC):
→recognize PAMPs inside a cell and act to coordinate a response to the pathogen

SECRETED:
→act to tag circulation pathogens for elimination

Question 15

how does interferon work?

Answer 15

→A virus infects a cell, which then becomes known as the primary infected cell.

→ virus will multiply inside the cell, and, after the cell dies, it will release the viral progeny.

→as the primary infected cell is dying, it releases interferons.

→interferons are picked up by other healthy cells, and they induce the transcription of >400 antiviral genes.

→ healthy cells in an antiviral state so viruses cannot affect them.

Question 16

what is the ligand and outcome of lectin receptors?

Answer 16

LIGAND: terminal mannose, fucose
OUTCOME: phagocytosis

Question 17

what is the ligand and outcome of scavenger receptors?

Answer 17

LIGAND: bacterial cell walls, modified low-density lipoproteins

OUTCOME: phagocytosis

Question 18

what is the ligand and outcome of Toll like receptors?

Answer 18

LIGAND: lipopolysaccharides together with CD14 (LPS), lipoproteins, unmethylated CpG, flagellin, dsRNA and ssRNA (in endosomes)

OUTCOME: phagocytosis, inflammation,

Question 19

what is the ligand and outcome of NOD like receptors?

Answer 19

LIGAND: peptidoglycan from Gram-positive and negative bacteria, some viral DNA and
RNA

OUTCOME: inflammation, cytokine release (IL-1, IL-8)

Question 20

what is the ligand and outcome of RIG-like receptors?

Answer 20

LIGAND: dsRNA and 5’-triphosphate RNA

OUTCOME: type I interferon production

Question 21

what are complement proteins?

Answer 21

→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.

Question 22

what are the three pathways of activating complement proteins?

Answer 22

→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.

Question 23

what is the structure of natural killer cells?

Answer 23

→they are large granular lymphocytes.

→they make up about 4% of WBCs.

→ lymphocyte-like, but larger with a granular cytoplasm.

→ kill certain tumour cells and virally-infected cells.

→ Target cell destruction is caused by the cytotoxic molecules called granzymes and perforins.

Question 24

how are natural killer cells activated?

Answer 24

→Natural killer (NK) cells are activated by loss-of-self.

→An NK cell has an MHC 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.

→ with an infected cell, they do not present this ligand, so the inhibitory signal is not presented

→releases perforin and cytotoxic granules into the infected cell or engages the cell’s death receptors.

Question 25

there are specific diseases associated with innate immunity what are they?

Answer 25

→complement
→ core defects (eg. C3) linked to the development of autoimmune diseases such as lupus

complement
→ non-core defects linked to susceptibility to specific types of pathogens such as Neisseria (meningitis)

macrophage deficiencies
→ chronic granulomatous disease (CGD); no oxidative burst for bacterial killing

macrophage deficiencies
→ IRF8 (transcription factor) mutations linked to susceptibility to TB
→ Aicardi-Goutieres syndrome is associated with constitutive production of inflammatory cytokines (defect in regulation of cytokines)
→ lack of interferon-responsiveness
→ sensitivity to viral infections (eg. measles)

Question 26

compare the innate and adaptive immune system

Answer 26

→in the innate system, we have macrophages, neutrophils, dendritic cells

→ in the adaptive system, we have lymphocytes

→ the innate system acts faster than the adaptive system

→ the innate system does not hold any ‘memory’, while the adaptive system does

→the innate system is not specific, while the adaptive system is very specific

→ the innate system has a small number of microbial ligands that are highly conserved between pathogens

→ the adaptive system has billions of possible antigens

→the innate system has germ-line encoded receptors evolved by natural selection which don’t change

→the adaptive system has receptors that are generated randomly within the individual, they can’t be inherited