CIS: Immunizations And Complement Flashcards
An immunization (vaccination) mimics a natural infection. A normal immune response is invoked to destroy and clear the components of the vaccine.
The primary immune response that results in immunological memory is called __________.
Each subsequent immunization results in increased __________ and __________ of response.
______________ is when repetitive challenge with antigen achieves a heightened state of immunity.
Priming
Intensity; magnitude
Hyperimmunization
_________ immunity is acquired when a critical number of individuals in a population are vaccinated which results in the reduction in the transmission of disease which effectively protects unimmunized individuals
Herd
Why can’t all individuals in a population be vaccinated?
Certain individuals within a population will be immunocompromised or immunosuppressed
Vaccination would be potentially harmful or ineffective in this portion of the population
__________ immunization gives immediate but transient immunity, and uses preformed antibodies
Passive
What type of immunization might be used to prevent disease after a known exposure or ameliorate symptoms of an ongoing disease?
Passive
What kind of immunization protects immunosuppressd patients and blocks the action of bacterial toxins and prevent diseases they cause?
Passive
What are some examples of passive immunization?
Snake bite antivenom
Passive transfer of Ig from mother to child
_________ immunizations provide delayed immunity but more permanent, and produce immunological memory
Active
What are some examples of active immunization?
Natural exposure to pathogens
Vaccines
What type of immunization was designed to give both immediate, transient protection as well as slowly developing durable protection?
Combined passive-active immunization
What are some examples of combined passive-active immunization?
Tetanus
Rabies
Considerations to make in the development of an immunization schedule include:
Timing of likely __________
Immunological _________ of the child
Passively transferred Abs may interfere with the immune response to a vaccine
Interference
Exposure
Maturity
After birth, the mother is no longer capable of supplying the baby with _____, so the remaining maternally derived ____ is broken down.
Eventually, the infant will begin to produce its own antibody.
_______ is produced around birth, _____ and _____ lag 6-12 months, leaving a vulnerable period when a baby is not immunocompetent.
IgG; IgG
IgM; IgG, IgA
What are the 2 types of live vaccines?
Live viruses from a different species
Live, attenuated viruses
What are the 4 types of inactivated vaccines?
Killed
Subunit/component
Toxoid
Conjugate
What are the 2 types of experimental vaccines?
DNA
Recombinant vector
What are some potential problems with vaccines?
Clinically important epitopes may not be intact in vaccine
Individual genetics may effect efficacy
Some individuals may be genetically predisposed to adverse events
Often work poorly in very young infants or the elderly
Many do not induce CMI; Ab may not be sufficient
Allergies to vaccine components
___________ are used to heighten the effectiveness of a vaccination
Adjuvants
Adjuvants are normally composed of __________ components or other substances suspended in a medium such as ______
Bacterial
Oil
What is the benefit to using oil as an adjuvant
Prolongs dispersal in tissues
Adjuvants invoke a mild inflammation that attracts ___________ and accelerates _____ activation and antigen presentation to T cells
Phagocytes; APC
_________ vaccines utilize capsular polysaccharides from pathogenic bacteria that elicit TI responses
They do this via linkage of a polysaccharide to either an antigen or ______, forming an _______________
This stimulates a _____ T cell response
Conjugate
Toxoid; immunogen
CD4+
[TI responses are weak in children under the age of 18 months and in the elderly]
___________ ___________ refers to the unresponsiveness of adaptive immune system to antigens as a result of inactivation or death of antigen-specific lymphocytes, induced by exposure to the antigens
Immunological tolerance
_________ is a collection of circulating and cell membrane proteins that play important roles in host defense
It does this through a coordinated, sequential, proteolytic cleavage of C’ proteins aka _______
Complement
Zymogens
C’ functions to:
Trigger and amplify __________ reactions.
Attraction of ___________ by chemotaxis.
Clearance of immune __________.
Cellular activation and direct microbial _______
Development of _________ responses
Inflammation Phagocytes Complexes Killing Humoral
When a convertase cleaves a complement component, which fragment is larger?
Larger fragment is “b”
Smaller fragment is “a”
Which fragment of the complement system is the active component?
“b” fragment which binds to the target near the site of activation
Which complement fragment is the anaphylatoxin?
The “a” fragment, which diffuses from the site and plays a role in localized inflammatory response
How is the classical complement pathway activated?
IgM (or IgG) binds Ag (functions in adaptive immunity)
Which complement pathway is always on guard due to constant trickle of an activated component?
Alternative
Which complement pathway is activated by binding of a serum mannose binding protein to bacteria initiating the cascade?
Lectin
What are the serine proteases associated with each complement pathway?
Classical: C1r and C1s
Lectin: MASPs
Alternative: Bb
What is the enzymatically active complex that begins the complement cascade in the classical pathway?
C1qrs
Which complement component is responsible for the distinction between self and nonself?
C3
What is the main amplification step of the complement cascade?
Cleavage of C3
Which complement component forms the pore of the MAC?
C9
What component of complement acts as an antibody independent surveillance system by identifying and binding to non-self membranes?
Alternative pathway
Self membranes have ______ levels of sialic acid, which rapidly ____________ bound C3b molecules on host cells
High; inactivates
Non-self membranes have _____ levels of sialic acid, so bound C3b will remain active longer
Low
MBL is a member of the _________ family
Collectin
______ deficiencies lead to life-threatening problems associated with severe, recurrent infections that begin soon after birth due to the central role that ____ plays in opsonin.
C3; C3b
Deficiencies in ________ and ________ mimic C3 deficiencies as unregulated C3b generation completely exhausts C3 from the serum
Factor H; Factor I
Those with _______ deficiencies are generally healthy other than an increase in infection by Neisseria gonorrhoeae and meningitidis.
MAC
What is the most commonly identified form of complement deficiency?
C2 deficiency
A _______ deficiency results in a high degree of systemic lupus erythematosus and may arise from failure to efficiently clear circulating immune complexes (which deposit in blood vessel walls and tissues, activating the alternative complement cascade)
C2
[may lead to autoimmunity]
What are the primary mechanisms of regulation of the complement system?
Regulation occurs primarily during activation, amplification, and membrane attack.
The two main functions are binding with dissociation and proteolytic digestion
What is the first level of control of convertases?
Decay acceleration
Generation of _____ is a major amplification step in the complement cascade; rapid hydrolysis limits deposition on nearby cells, limiting formation of the _____ convertase
The same mechanism is used by C4b to regulate formation of the _____ convertase; the majority of C4b formed reacts with water and is inactivated
C3b; C5
C3
What is the effect of C1 inhibitors on complement regulation?
Binds C1r and C1s and dissociates them from C1q
Removes MASP enzymes from MBL complex
[Control of classical and lectin events]
What type of complement deficiency results in hereditary angioneurotic edema?
C1inh deficiency
With C1inh deficiency, C1 is not regulated properly, leading to chronically low levels of ____ and ____
C4; C2
Treatment with _________ has caused some patients to produce near normal levels of C1inh
Androgens
_________ is also known as a C3b inactivator due to its ability to cleave C4b or C3b; requires presence of a cofactor and prevents formation of convertases
Factor I
______ promotes dissociation of the C3 convertase, affecting the classical and alternative pathways
DAF (decay-accelerating factor)
What is the acquired hemolytic disorder with spontaneous episodes of RBC lysis, and patient presentation includes morning hematuria?
Paroxysmal nocturnal hemoglobinuria
What is the treatment for paroxysmal nocturnal hemoglobinuria?
Erythropoietin
_________ regulates the MAC by blocking C9 binding to C5bC678 complex on the cell surface
CD59
____________ regulates the MAC by binding to the fluid phase form of C5b67, preventing its ability to bind membranes but does not prevent association with C8 and 9 proteins
Vitronectin (S protein)
[since it is not in the membrane the MAC has no effect, although it still fully forms]
______ is the major opsonin in the complement system
C3b; C4b can also function as an opsonin
Opsonins such as C4b and C3b bind complement receptors on phagocytic cells like —-?
CR1, CR2, CR3, etc.
How does C5a act to increase inflammatory response?
As an anaphylatoxin, it increases the numbers of complement receptors on the cell surface and greatly facilitates their phagocytosis of C3b-coated antigen
How are immune complexes with bound C3b removed from tissues and circulation?
Monocytes and other phagocytes
Erythrocytes
Usually transported to spleen and liver
Immune complexes normally bind complement and are removed by the liver and spleen after binding CR1 on RBCs. What pathologic condition is characterized by an issue in this process, leading to increases in blood pressure, vascular turbulence, and complex deposition?
Type III Hypersensitivity
How many MACs are required to lyse an RBC?
One
What type of cells are most resistant to complement mediated lysis?
Nucleated cells
What are the primary functions of anaphylatoxins?
Bind receptors on mast cells and blood basophils –> induce degranulation with release of histamine and othe active mediators
Induce smooth muscle contraction
Induce monocytes and neutrophils to adhere to vascular endothelial cells
Which complement fragment is cleaved by plasmin to yield kinin, which results in edema?
C2b: Prokinin
Normal complement components can enhance infectivity of what viruses?
EBV - uses CR2 as a receptor for attachment
Measles uses MCP as a receptor
West Nile gains entry via CR3 receptor
