Week 103 Swollen finger Flashcards
What are signs of acute inflammation?
- Redness
- Swelling
- Pain
- Heat
- Loss of function
Describe the 1st layer of immune defense (1/3)
External barriers e.g. skin and mucous membranes
Describe the 2nd layer of immune defense (2/3)
Innate immune system: cellular components e.g. phagocytes, degranulating cells and NK cells
Soluble components e.g. complement, cytokines, antimicrobial peptides and acute phase proteins.
All of this leads to non-self recognition, inflammation, phagocytosis and killing of microbes
Describe the 3rd layer of immune defense (3/3)
Adaptive immune system:
Soluble components: Antibodies
Cellular components: B and T cells
These all leads to non-self recognition (Ag specific), block microbial adhesion, neutralising toxins, chronic inflammation and killing of microbes
How is a pathogen phagocytosed?
The pathogen is phagocytosed or taken up by the macrophage. This internalised vacuole is known as a phagosome. Lysosomes, that contain digestive enzymes and sit in the cytoplasm of the cell, fuse with the phagosome to form a phagolysosome and the pathogen is broken into waste material. The vacuole then fuses with the plasma membrane to expel the waste material from the cell
What do dendritic cells help do?
Antigen presentation: phagocytosis occurs followed by degradation of the microbe
The Ag is then presented on the surface of the dendritic cell
Describe mast cell degranulation
Mast cells are found in connective tissues around our external barriers (e.g.
skin, respiratory tract , GI tract etc) and contain lots of granules that discharge
their contents externally upon detection of a ‘foreign’ substance. The granules
contain a number of different substances, such as histamine, that under normal
circumstances are protective; upon degranulation they chemically attract other
immune cells to the area under attack and thus contribute to the inflammatory
response. However, in certain individuals, these cells can also contribute to
allergic and inflammatory diseases
What is the name of a clump of pus?
An abscess
How does an abscess form?
1. The pathogen is deposited in the tissue. 2. Blood vessels dilate and leukocytes migrate to the multiplying pathogens. 3. This results in pus formation and clotting occurs in blood vessels adjacent to infection. 4. Build-up of pressure causes abscess to expand in direction of least resistance; if it reaches a body surface, it may rupture discharging pus
Describe features of cytokines
They are integral to inflammation, innate and adaptive immunity.
They are:
- secreted proteins
- have many cell sources
- structurally diverse
- diverse functions
- small peptides, folded 3D structure (~100-150 amino acids)
- produced at very low concs
- usually act over small distances (cell-cell: paracrine)
What are major functions of cytokines?
Major Cytokine Functions:
cause growth/ differentiation of immune cells
stimulate an effector response (immunity)
stimulate directed migration of immune cells
regulate the immune response (e.g. suppression)
What do cytokines bind to?
Cognate cellular receptors
Extracellular domain= cytokine binding
cytoplasmic domain= intracellular binding
Name examples of cytokines and their receptor
IL-1Beta –> IL-1R
TNF-alpha (homo-trimer)
Name and describe 3 structurally diverse cytokine receptor families that induce different intracellular events
Hematopoietin family:
- 2 distinct peptide chains
- activates Jak-STAT proteins
Chemokine family:
- single peptide chain
- activates G proteins
TNF family
- 3 identical chains
- activates NF-kappa beta
Describe what’s present in infected pus
Extracellular fluid
Lymph
Neutrophils
Name examples of inflammatory mediators
Cytokines: TNF-alpha, IL-8, IL1-beta, IL-6 (early tissue response 24-48 hrs)
Prostaglandins
Leukotrienes
What are the effects of major cytokines during tissue inflammation and immune activation?
- macrophage activation (microbial killing)
- tissue inflammation, innate immunity
- Ag presentation (T-cell activation)
- Adaptive immunity (delayed response)
What does TNF-alpha do?
Plasma leakage–> vasodilation
What does IL1-beta do?
(PGE2)—> fever response
What does IL-6 do?
acute phase response - fibrinogen, CRP, MBL
What does IL-8 do?
Neutorphil chemotaxis
What chemicals activate antibody synthesis?
IL-4 and Th2-type
What chemicals activate macrophages?
IFN-gamma and Th1-type
What 3 ways can the complement system be activated?
1 - Classical (with Abs)
2- Alternative (spontaneous generation of active C3b complement fragments)
3- Lectin (with mannose binding lectin) pathway activation
What are three ways the complement cascade helps defend against microbes?
(1) formation of the
smaller or minor fragments that contribute to inflammation (e.g. C3a, C5a)
(2) formation of the larger or major fragments (C3b) which function as opsonins (which leads to phagocytosis)
(3) formation of the
membrane attack complex (C5b678poly9) that ultimately causes lysis of the microbe
What does C1 inhibitor (C1 INB) do?
This plasma protein is a proteolytic enzyme (protease). As the name suggests it de-activates antibodybound
C1 of the classical pathway, stripping it of the components that activate C4 and C2. As C1 INB is a
plasma component, it regulates the overall amount of activity in the classical pathway.
What does Factor H with Factor I do?
These two plasma proteins are both proteases that work together. Factor H (FH) binds to C3b breaking
the bond between C3b and Bb, then Factor I (FI) breaks C3b de-activating it. They are important in
causing the breakdown of C3 convertases of the alternative pathway. As they are both plasma
components, they regulate the overall amount of activity in the alternative pathway.
What does C4 binding protein (C4BP) with Factor I do?
These two plasma proteins work together to de-activate C3 convertases in the lectin and classical
pathways. C4BP binds to C4b displacing C2b, then Factor I (FI) breaks C4b deactivating it. As C4BP and
FI are both plasma components, they regulate the overall amount of activity of the lectin and classical
pathways.
What does Membrane cofactor protein (MCP
) with factor I do?
MCP is found on host cells specifically the membranes of leukocytes, epithelial cells and endothelial
cells. When either C3 or C4 attach to cells that contain this protein, it will bind to them, factor I (FI) is
then able to cleave the fragment, deactivating it and preventing the formation of C3 convertase in all
three pathways. As MCP is found on host cell membranes, it minimises the damage to host cells, and,
thus, directs the activity of the complement system.
What does Decay-accelerating factor (DAF) with factor I do?
DAF is found on host cells specifically the membranes of blood cells, epithelial cells and endothelial cells.
DAF binds to C4b displacing C2b in the classical pathway (Fig 5) or C3b displacing Bb in the alternative
pathway (Fig 6) then Factor I (FI) break the C4b or C3b proteins deactivating them. Thus, DAF is
important in causing the breakdown of C3 convertases of all complement pathways. As DAF is found on
host cell membranes, it minimises the damage to host cells, and, thus, directs the activity of the
complement system.
What does CD59 do?
CD59 is found on host cells specifically the membranes of blood cells, epithelial cells and endothelial
cells. During the formation of the MAC, it attaches to the C5b component of the C5bC6C7 preventing
the C9 fragments assembling. As CD59 is found on host cell membranes, it minimises the damage to
host cells, and, thus, restricts the formation of the MAC to foreign cells.
What does S protein do?
S protein (SP) is found in plasma. It binds to the C7 component as the MAC is forming. This binding prevents the C5bC6C7 complex from inserting into the plasma membrane and inhibits the formation of the MAC. As the protein is found in plasma, it regulates the overall activity of MAC formation.
When does the complement system cause us problems?
sorry dis one long
1) Complement deficiencies
Genetic deficiencies or defects in any of the protein components can lead to abnormal patterns of
complement activation/regulation. This can be the result of :-
Deficiencies in any of the early pathway components (C1, C2, C3, C4, Factor B, Factor D,
Properdin, MBL). This can cause failure to clear immune complexes
or an increased
susceptibility to infection.
Deficiencies in any of the terminal complement components i.e. those that make up the MAC (C5,
C6, C7, C8, C9). This tends to cause an increased susceptibility to disseminated infections by
Neisseria bacteria.
Deficiencies in the complement regulatory proteins (C1 IHB, Factor I, Factor H, C4 BP and S
protein, MCP, DAF, CR1, CD59). This causes problems from excess inflammation and cell lysis.
Deficiencies in complement receptors (type 1-4). These receptors are vital in mediating the
biological activities between complement fragments and various cell types (e.g. Phagocytic cells
use CR1 to recognise, bind to and internalise C3b or C4b coated particles)
2) Pathological effects of a normal functioning complement system.
Despite being properly regulated and appropriated activated the complement system can cause
significant damage to tissues. This might come about when you:
Have a chronic infection (i.e. infectious organisms that persist in the body)
Make antibodies to components of your own cells (autoimmune conditions)
Have immune complexes deposited in tissues (immune complex disease)
Name cellular examples of anatomical and physical barriers of the IS
Cilliary clearance
Low stomach pH
Skin, intestinal movement, oscillation of broncho-pulmonary cilia etc – prevent pathogens from entering and/or establishing in the body
Name innate immunity cells
NLRs TLRs Complement Neutrophils Host defence peptides Dendritic cells
Name adaptive immunity cells
T cells
B cells
Name secreted molecules (anti-microbials) of our body
Chemical: Organic acids in skin secretions; lysozyme in oro-nasopharyngeal and lacrimal secretions; bile acids in the GI tract; transferrin; interferons; complement; cytokines (e.g. TNFa); chemokines
Name innate immunity surface barriers
Tears (lysozyme) Skin Acidic pH Sweat, oil, fatty acid secretions Large intestine normal flora Saliva washes microbes from teeth Respiratory tract (mucus and cilia) Bladder (urine washes microbes from urethra)
What do microbes express?
Evolutionary conserved patterns of molecules termed
PAMPS (pathogen associated molecular patterns)
that are recognied by PRRs (pattern recognition receptors) expressed by cells of the innate immune system
