Immunology 3 and 4 Flashcards
What are the 2 distinct mechanisms of communication in the immune system?
Direct contact (receptor: lingered interactions)Indirect (production and secretion of cytokines)
Do immune cells have receptors or ligands on them?
Receptors
What cells tend to produce and secrete cytokines?
Injured tissue cellsActivated immune cells
What is an autocrine signal?
A signal that acts back on the same cell that produced it
What are the physiological symptoms of acute inflammation? (4)
RuborCalorTumorDolor
What are the 3 phases involved in innate immune cells recognising and responding to pathogens?
RecognitionActivationEffector
What happens in the recognition phase of innate immune cells recognising and responding to pathogens?
Pathogens express signature molecules not found on human cells called |”pathogen associated molecular patterns” -PAMPS (common to many different types of pathogens)innate immune cells (and some other cell types) express specific receptors for these PAMPS called “pattern-recognition receptors” (PRRs) - found on cell surface and intracellular (detect extra- and intra- cellular pathogens)
Example of PAMPs and PRRs on gram negative bacteria?
PAMPs = lipopolysaccharide (LPS)PRRs = Toll-like receptor 4 (TLR4) - extracellular
Example of PAMPs and PRRs for fungi?
PAMPs = beta-glucansPRRs = dectin 1 (extracellular)
Example of PAMP and PRR for TB?
PAMP = muramyl dipeptidePRR = NOD2 (intracellular)
Example of PAMP and PRR for viruses?
PAMP = ssRNAPRR = toll-like receptor 7 (intracellular)
What role do macrophages play in the homeostasis of the skin?
Induction of programmed cell death (apoptosis)Specific recognition and removal of dying cells by phagocytes e.g. macrophages
How are apoptotic cells cleared by tissue-resident macrophages? (5)
Apoptotic cells release “find-me” signals to attract and activate macrophagesMacrophages recognise specific “eat-me” signals expressed on the surface of apoptotic cellsMacrophages rearrange their cytoskeleton to internalise apoptotic cellsDigestion of the ingested “cargo”Secretion of anti-inflammatory mediators e.g. IL-10
What happens when physical barriers are breached by pathogens?
PAMPs of pathogens are recognised and injured tissue cells release “danger” signalsThis activates macrophages, mast cells and NK cellsThis causes the pathogens to be killed, infected tissue cells killed, production of inflammatory mediators
What happens when macrophages digest a pathogen compared to apoptotic cell debris?
Pro-inflammatory mediators are released compared to anti-inflammatory mediators
How do macrophages kill pathogens? (2)What enhances its killing ability?
Phagolysosome (acidification, lysosomal hydrolases)Production of toxic reactive oxygen and nitrogen species(killing ability (and other functions) are enhanced by pro-inflammatory cytokines e.g. IFN gamma
How do pro-inflammatory cytokines enhance macrophages pathogen killing? (3)
Produced by NK cell (and some T cells) e.g. IFN gammaIncreased production of toxic reactive oxygen and nitrogen speciesIncrease microbicidal activityBoost antigen presentation capability
How do mast cells aid in the killing of pathogens?
They produce inflammatory mediators that enhance killing response
Where do mast cells reside?
In tissues and protect mucosal surfaces (play a key role in defence against parasites)
What happens when a pathogen binds to a PRR on a mast cell?
Degranulation occurs (release of pre-formed pro-inflammatory mediators)Gene expression = production of new pro-inflammatory mediators
What is the purpose of NK cells?
They specifically kill virally infected cells and abnormal cancer cells
How do NK cells recognise cells infect with intracellular pathogens or cancer cells?
If they have an MHC class 1 then the NK cells binds and doesnt attackIf there is no MHC class 1 (virus or cancer cell), the NK cell attacks it and releases pro-inflammatory mediators
What 3 cells produce inflammatory mediators as part of the innate immune response?
Macrophagesmast cellsMK cells
What are some examples of inflammatory mediators produced by macrophages, mast cells and NK cells?
NOProstaglandins/ leukotrienesHistaminesCytokines e.g. TNFalpha, IL-1, IL-6, IFNgammaChemokines
What systemic effect do cytokines have (IL-1, IL-6, TNFalpha)? (3)
Cause the release of prostaglandins from the hypothalamus causing feverCause the release of acute phase response proteins from the liverCause creased neutrophil production (leukocytosis) in the bone marrow)
What is the acute phase response?
A group of physiological processes that occur soon after the onset of infection due to the release of a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation (this is stimulated by IL-2, IL-6 and TNFalpha) causing the alteration in protein synthesis in the liver
What are examples of acute phase proteins? (7)
CRPSerum amyloid protein (SAP)Complement proteinsFibrinogenHaptoglobinManganese superoxidase dismutaseProteinase inhibitors
What biological role does CRP, SAP and complement proteins have?
Preventing the spread of infectionDiagnostic marker
What role does fibrinogen have?
CoagulationWound healing
What role does CRP, haptoglobin, manganese superoxidase dismutase and proteinase inhibitors have?
Preventing systemic inflammation
How many subunits is CRP made up of?
5 identical subunits
What does high levels of CRP mean?
There is inflammation/ infeciton
How does CRP enhance phagocytosis?
CRP opsonises bacteria, facilitating their clearance by phagocytes