lec 2- immediate innate response Flashcards
(43 cards)
what are the two categories for the innate immune response?
-immediate
-induced
what is commensal bacteria?
bacteria that reside on epithelia (skin and gut) without causing harm
what does commensal bacteria protect us from?
it protects us from pathogens by acting as a barrier that inhibits them from crossing through
if a pathogen gets past the commensal barriers, what kicks in to protect us?
the innate immune response system takes over and if the innate immune system cannot clear the organism, the adaptive immune system comes into play
what are examples of mechanical barriers?
epithelial cells joined by tight junction, mucus, tears
what is the difference between innate and adaptive immune response?
innate: rapid, fixed, limited number of specificities, constant during response
adaptive: slow response, variable, numerously highly selective specificities, improve during response
explain the steps that occur once a foreign organism enters the skin ?
-surface wound introduces the bacteria, which activate resident effector cells to secrete cytokines
-vascular permeability is increased to allow protein, fluid, and inflammatory cells to leave the bloodstream and enter the tissue
-inflammation, swelling, redness, heat, and pain occur at the infected tissue
explain how the immediate innate response activates the induced innate response, and then the adaptive response:
immediate: pathogen invades tissue, causing it to be recognized by the effector cells and effector molecules already present at the site of infection, infection is not gone so induced innate response is activated
induced: more cells in the resident area are activated and more effector cells are recruited which move to to the infected area from other places, inflammation occurs, infection is not gone so adaptive response
adaptive: effector B and T cells are identified, become mature, and antibodies are released to halt the infection
what must the immune system kill?
cells infected with intracellular pathogen, which leads to the pathogen then accessing soluble secreted molecules (extracellular pathogen)
what is the complement system?
-a part of the innate immune system that consists of small proteins
-found in blood, lymph, and extracellular fluids
-over 30 proteins in the complement cascade including the products of cleavage of other complement proteins
how many pathways are there to activate complement?
3
what activates the complement system?
the cleavage of proteins in the cascade
what is the ultimate goal of the complement system?
to destroy pathogen in the innate immune response
what are the three ways the complement system destroys pathogen?
- by coating pathogen (opsonization) with complement protein making it easier for neutrophils and macrophages to phagocytose using specific complement receptors on these cells
- by forming a membrane attack complex on a pathogen resulting in cell lysis
- by recruiting cells of the innate immune response to the site of injury
where do all three pathways of the complement system converge?
they all converge at C3 (complement protein 3) and generate C3 convertase that will cleave C3 into C3a and C3b
what is C3?
a glycoprotein with a high energy thioester sequestered within the hydrophobic interior that is protected from hydrolysis
what is the first pathway to be activated in the complement system?
alternative pathway
is the alternative pathway the oldest evolutionary pathway of complement activation?
yes, but discovered after classical pathway
explain the alternate pathways steps to form C3 convertase:
-C3, which is secreted from the liver, circulates the bloodstream where it spontaneously changes its conformation into iC3 (C3H2O)
-factor B binds to iC3, causing factor B to be susceptible to cleavage by factor D
-factor D cleaves factor B into Ba, which is released, and Bb, which stays bound to iC3 (Bb has protease activity)
-this forms iC3Bb which is a soluble C3 convertase
-when a molecule of C3 binds to the iC3Bb, it becomes cleaved into C3a and C3b
-C3b can now bind to an amino group or a hydroxyl on the pathogen membrane, where it acts as a complement receptors for phagocytosis
what happens to C3a in the alternate pathways?
it will be recruiting other components of the immune system
explain the alternate pathways steps to form more C3b onto the pathogen surface?
-C3b is bound to pathogen surface
-factor B binds to C3b, allowing it to be susceptible to factor D cleavage
-factor D cleaves factor B into Ba and Bb (which is bound to C3b)
-C3bBb is an insoluble convertase
-C3 binds to C3bBb and becomes cleaved into C3a and C3b which can now bind to the pathogens surface, increasing its numbers
what regulates C3 to help prevent it from being used up too much on one single pathogen?
complement control proteins which stabilize or degrade C3b at the cell surface
what does properdin (factor P) do?
prevents degradation of the alternative C3 convertase (C3bBb) on pathogen surface, stabilizing the complex
what do the two RCAs (regulators of complement activity) factor H and factor I do?
factor H: binds to C3b changing its conformation so factor I can bind
factor I: cleaves C3b into iC3b
-iC3b is still attached to the pathogen surface but cant bind to Bb, preventing the formation of C3bBb and spares circulating C3
