Innate Immunity 5 Flashcards
what is the size of cytokines? is this big or small?
25 kD, small
are cytokines heterogeneous or homogeneous? what does this mean?
heterogeneous –> has many components so allows for many combinations with many diff functions
what type of molecule is a cytokine?
glycoprotein
are most cytokines soluble or membrane-bound?
most are soluble but some have membrane-bound forms
what regulates the production of cytokines?
post-transcription/translational modifications
what is the main general role of cytokines?
cellular communication
what are 3 cells that cytokines can affect? and the name for each mechanism?
- the producing cell –> autocrine
- adjacent cells –> paracrine
- distant cells –> endocrine
how does endocrine mechanism of cytokine activity work?
cytokines must go thru blood
what are the 4 biological functions of cytokines on target cells?
- activation
- proliferation
- differentiation
- survival/death
how do cytokines affect diapedesis?
change expression of adhesion molecules
how do cytokines affect enzymes?
increase/decrease activity of enzymes to change transcriptional program and change its function
how do cytokines affect B and T cells?
activate B and T cells to determine what type of cell and signal the naive T cell will get (signal 3)
how do cytokines cause a cytokine induction?
action of 1 cytokine induces that cell to produce 1 or more additional cytokines
what are the 5 groups of cytokines?
- interleukins (IL)
- interferons (IFN)
- tumour necrosis factors (TNF)
- Hematopeoitins/growth factors
- Chemokines
how many types of interleukins have been discovered so far?
1-37
what are the 3 interferons?
Type I:
1. IFN-alpha
2. IFN-beta
Type II:
3. IFN-gamma
what are the 2 types of tumour necrosis factors?
- TNF-alpha
- TNF-beta
what are 2 examples of hematopeoitins/growth factors?
- GM-CSF
- G-CSF
What are the 4 ways that cytokines can exert their effects?
- Pleiotropy
- Redundancy
- Synergy
- Antagonism
what is pleiotropy?
one cytokine produces many effects
what is redundancy?
more than 1 cytokine induces the same effect
what is synergy?
2 or more cytokines work together to induce an effect
what is antagonism?
1 cytokine can inactivate the effect of another
describe the network of complex cytokine interactions
multiple cells can produce the same cytokine and each cell type can produce multiple cytokines
specific cytokines are produced at different times in different locations
ultimately, what determines the type of adaptive response that is produced?
cytokines
when does cell-mediated vs humoral immunity occur?
usually both occur, but 1 type is usually more complementary to the pathogen
what are 2 types of pathogens where cell-mediated immunity is favoured?
- viruses
- intracellular pathogens
what is cell-mediated immunity characterized by? (2)
- macrophage activation
- cytotoxic T lymphocyte activation
when is humoral immunity favoured?
extracellular bacteria/pathogens
what is humoral immunity characterized by? (2)
- predominant B cell activation
- predominant antibody production
what type of cell secretes TNF-alpha?
mainly macrophages
what 2 things does TNF-a stimulate?
- migration of innate cells (diapedesis)
- dilates blood vessels and increases clotting
why does TNF-a increase clotting?
to prevent pathogen from entering the bloodstream
what type of diseases is TNF-a involved in?
autoimmune disease –> Rheumatoid arthritis and Crohn’s disease
why do therapies for autoimmune diseases target TNF-a?
to reduce inflammation
describe the effects of TNF-a in local infection (4 steps)
- bacteria infects local tissue site
- macrophages activated to secrete TNF-alpha in local tissue
- increased diapedesis and blood migration at local site
- phagocytosis
describe the effects of TNF-a in systemic infection (5 steps)
- bacteria infects systemically (multiple organs)
- macrophages in all infected organs secrete TNF-a
- multiple areas dilate and undergo diapedesis
- BP decreases as blood leaves so it is hard to clot blood and vessels collapse
- multiple organ failure
what is sepsis?
systemic infection and inflammation
what induces the acute phase response?
proinflammatory cytokines
what are 3 proinflammatory cytokines involved in the acute phase response?
- IL-1
- TNF-alpha
- IL-6
when does the acute phase response occur?
early on in infection
what occurs during acute phase response?
increased production and secretion of antimicrobial proteins from the liver, as well as other activating other processes for eliminating pathogens
what are 3 types of antimicrobial proteins released during the acute phase response?
- mannose-binding lectin
- complement components
- C-reactive protein
what is the role of C-reactive protein? (2)
- allows C1q to bind for the classical pathway in the complement system
- opsonize bacteria
what are the 3 main roles of IL-1B, IL-6, TNF-a?
PRO-INFLAMMATORY against pathogen
- Acute phase response
- Mobilizing cells
- Fever
what is the role of IL-1B, IL-6, TNF-a in the liver?
activate acute-phase proteins for A) activation of complement and B) opsonization
what is the role of IL-1B, IL-6, TNF-a in the bone marrow endothelium?
mobilize neutrophils for phagocytosis
what is the role of IL-1B, IL-6, TNF-a in the hypothalamus?
increased body temp for fever
what is the role of IL-1B, IL-6, TNF-a in fat and muscle?
protein + energy mobilization for increased body temp for fever
what is the role of IL-1B, IL-6, TNF-a in hypothalamus and fat+muscle? (3)
- reduce viral and bacterial replication
- increase antigen processing
- increase specific immune response
what is the role of IL-1B, IL-6, TNF-a in dendritic cells?
TNF-a stimulates migration to lymph nodes + dendritic cell maturation to initiate adaptive immune response
why does fever/increased body temp kill pathogen? (2)
- pathogens need 37degC so anything high is bad
- possible evidence that high temp increases efficiency of immune cells
