Gullo Exam 1 Flashcards
Antigen Definition?
A substance that interacts specifically with any product of the immune system- not always productively
Pathogen definition?
living organisms (usually) that has the ability to cause disease- often has many potential antigens
Immunogen Definition?
an antigen that is recognized by the immune systems and leads to a productive response
What cell type is the largest proportion of leukocytes?
Neutrophils
Humoral Immunity refers to what broadly?
B Cells and their products (antibodies)
Cell-Mediated Immunity refers to what broadly?
CD8+ and CD4+ T Cells
Cytotoxic and Helper, respectively
Infants and Geriatrics share what in common about immune system?
Both weak immune systems
infants have no adaptive immunity, elderly have no new T cells
Explain Recognition Phase of Adaptive Immunity
involves processing of antigen by macrophages/dendritic cells
along with additional cellular interactions which lead to lymphocyte activation.
Explain Activation phase of Adaptive Immunity
involves proliferation and differentiation of lymphocytes
resulting in the expression of specific humoral and cell mediated immune effector functions.
Explain Effector phase of Adaptive Immunity
interaction of immune effector cells and molecules with antigen resulting in the elimination of antigen at the site of the infection.
Antigenic Determinant / Epitope Definition?
exact area of the recognition by B and T lymphocytes on the antigen
Most common antigen type?
proteins
T Cells can only ‘see’ what type of antigen?
peptides
B Cells can ‘see’ what type of antigens?
Chemicals Nucleic Acids Carbohydrates Lipids Peptides
Immunodominant Epitopes definition?
A single Pathogen can contain hundreds of antigens and a large number of immungens
only a set of them will be immundominant
Immunodominant epitopes are defined as those that dominate over others eliciting immune responses
Cross Reactivity and Penicillin
B-lactam ring of penicillin, cephalosporin, and carbapenems
some patients with a previous drug allergy to penicillin can develop drug allergy to cephalosporin
Penicillin can act as a hapten (non immunogenic) and can interact with RBC surface proteins. The combination of both can lead to the recognition of the new immunogen by B cells
Passive Immunization
Homologous hyper immune globulin (e.g. rabies)
Maternal to fetal transmission
Active Immunization
can be live or inactivated/killed. can be whole-cell, polysaccharides, or a subunit.
Explain Antigenic Sin
This process occurs with pathogens that have frequent variation in their antigen structures such as influenza
Immunodominant epitope dominate the response and often mask the new epitopes that on their own might otherwise elicit a response
Happens can only elicit an immune response when?
only capable of stimulating an immune response when bound to a carrier.
B-Cell Receptors are made up of what?
Membrane Bound Abs
Function of Secreted Abs
Neutralize toxins
Prevent the entry and spread of pathogens
Eliminate microbes
General Structural Properties of Ab
two heavy and two light chains held together by disulfide bonds with a ‘hinge’ region
Light Chains of Ab specific structural properties
constant (C) domain at the carboxyl half of the protein
variable (V) domain at the amino terminal half of the protein
Within the variable domain there are three sections with very high variability from protein to protein. Each section is called a complementarity determining regions (CDR) or hypervariable region.
Heavy Chains of Ab specific structural properties
variable (V) domain at the amino terminal end of the protein
Within the variable domain the heavy chain has 3 CDRs or hypervariable regions.
The remainder of the protein chain is divided into several constant domains
Antigen Bindings occurs where on an Ab
Vh and Vl Domains. CDRs function is to bind Antigens
Where is the hinge region found on an Ab?
H chain
Fab region of Ab structure and function?
consists of one light chain and amino terminal half of
one heavy chain
can bind antigen
Fc fragment of Ab structure and function?
consists of the carboxy terminal half of the 2 H
chains
region responsible for most of the common functions of immunoglobulins
F(ab’)2 fragment of Ab function?
can bind antigen bivalently
Function of Hinge Region
Important in activation of B cells (e.g. need to be cross-linked)
Function of Constant Region
Little genetic variation
Imparts function of antibody to the molecule
Define the isotype (E.g. IgG)
Antibody Affinity definition?
Strength of binding between a single Ab arm and an Ag epitope (dissociation constant)
Antibody Avidity definition?
The overall strength of attachment and is much greater than the affinity of any one antigen-binding site
Ratio of human kappa to lamda isotypes of Ab light chains
2:1 (κ to λ)
Agglutination Definition?
Neutralization can occur in solution (e.g. with toxins) or on the surface of a cell through a process called agglutination
Mechanism of Agglutination?
Agglutination often caused toxin or infected cell to be phagocytized or removed from circulation
Opsonization Definition?
Opsonization is the process of coating a surface with antibody and also often leads to phagocytosis
phagocytosis or removal of antibody bound material happens through what type of event?
happens through receptor mediated event on the phagocyte (FcR)
Antibody Maturation Process Explained
Antibodies change from IgM initially to IgG
Requires recognition of same antigen (from primary to secondary response)
Increased concentration, time to produce Ab, and affinity of Ab to antigen in the secondary response
Happens in normal exposure and vaccination
Xenogeneic
non-human Ab treatment
Chimeric Ab
66% Human Ab treatment
Humanized Ab
90-95% human Ab treatment
Fully Humanized Ab
100% human Ab treatment
Isotype defined how?
defined by epitopes on the constant region (H or L chain) and show no variation by member of the same species
Allotype defined how?
defined by epitopes on the constant region (H or L chain) and show variation by members of the same species
Idiotype defined how?
defined by epitopes on the variable regions (H or L chains) and show variation even within the same individual (Bob’s IgM against Polio and his IgM against Varicella Zoster)
What are Fc Receptors?
receptors for Ig on various cell types
What Ig crosses the placenta?
IgG
What Ig crosses the epithelium?
IgA dimer
What Ig activates the Complement system?
IgG and IgM
What Ig diffuses across extravascular space?
IgG and IgA monomer
What Ig sensitizes mast cells?
IgE
What Ig passes to baby from breast milk?
IgA
What Ig sensitizes NK cells?
IgG through ADCC
What Ig is able to opsonize?
IgG
What Ig is able to neutralize?
IgG and IgA
Ratio of kappa to lambda light chains in Ab?
2:1
IgA dimer can cross mucosal epithelial membranes via what?
an accessory chain called Poly Ig receptor
How does IgE sensitize mast cells?
coat mast cells allow for the release of their granules (allergic reaction) upon allergen binding
What Ig is stabilized by the J chain?
IgM (pentamer) and IgA (dimer)
Ig maturation causes what isotypes to change?
IgM to IgG
What are the anaphlatoxins from the complement system?
C3a C4a C5a
All complement pathways result in what opsonizing molecule?
All produce C3b which is recognized by receptor on phagocytes and material to be removed (cell or soluble)
What happens to the pathogen at the end of the complement pathway?
lysis
Components/fragments of complement system with protein binding activity?
C1q, C4b, C3b
Components/fragments of complement system with enzymatic activity?
C1r, C1s, C2a, Bb and D
Components/fragments of complement system with inflammatory activity?
C4a, C3a, C5a
Membrane attack components/fragments?
C5b, C6, C7, C8, C9
All pathways of complement converge on what?
C3
Anaphlatoxins do what?
Stimulate cellular degranulation
Chemotactic for neutrophils
C3 convertase in classical pathway makeup?
C4b2a
C5 Convertase in classical pathway makeup?
C4b2a3b
How does C3 convertase get formed in classical pathway?
C1s cleaves C4 to C4a/b. C4b binds to microbe C4b binds to C2 C1s cleaves C2 to C2a/b C4b2a complex forms - C3 convertase
function of C3 Convertase
cleaves C3 to produce C3a/b and C3b binds to microbe as opsonin
How is C5 converts formed in classical pathway?
C3b binds to C3 convertase to make C4b2a3b - C5 convertase
function of C5 convertase?
cleaves C5 to C5a and C5b. C5b then helps form MAC
How is MAC formed?
C5b binds with C6,7,8,9
How does MAC function to lyse microbe?
C9 polymerizes to form pore in microbe membrane
What acts like C1 in the Lectin Binding Pathway?
Mannose-binding lectin
What cleaves C2 and C4 in Lectin Binding Pathway?
MBL-Associated Serine Protease (MASP) 1 and 2
Which complement pathway is constitutively active and how?
Alternative Pathway
C3 convertase can be activated spontaneously on cell surfaces
What does C3 convertase not require in Alternative Pathway?
Does not require C1 or MBP
What stabilizes the C3 Convertase in Alternative Pathway
Properdin
What makes up C3 Convertase in Alternative Pathway?
C3bBb
C5a stimulates phagocytosis via what receptor on what cells?
via CR1 on macrophages
What complement receptors are found on most phagocytic cells and which one stimulates the phagocytosis of complexes containing C3b
CR1, CR3, and CR4
CR1
RBC express what complement receptor that serves an important role in clearing immune complexes
CR1
Decay Accelerating Factor (DAF) functions how?
dissociates C3b and C4b from C3 and C5 convertase complexes.
Membrane Cofactor Protein (MCP) functions how?
binds to C3b and C4b and promotes their cleavage by Factor I.
C1 INH functions how?
Prevents the C1r2s2 from becoming proteolytically active
Membrane CD59 (protectin) functions how?
CD59 blocking prevents the assembly of the C9 polymers around C8. (S protein acts in a similar fashion.)
Leukocytes of the innate immune system do not express what type of receptors?
clonally distributed antigen receptors
Macrophage activated function and location?
Phagocytosis
Bactericidal mechanisms
antigen presentation
Tissue
Dendritic Cell activated function and location?
Antigen uptake in peripheral sites
Antigen presentation
Tissue
Neutrophil activated function and location?
phagocytosis
bactericidal mechanisms
Blood
Eosinophils activated function and location?
killing antibody coated parasites
Blood
Basophil location
Blood
Mast Cell activated function and location?
release of histamine granules
allergies
Tissue
During inflammation after tissue injury, what is exudate and what makes it up?
permeable capillaries allow for fluid to enter affected area.
includes complement, antibody, and C-Reactive Protein
Pattern Recognition Receptors recognize what?
PAMPS and DAMPS
Virus is recognized by what ‘signatures’?
dsRNA
ssRNA
Fungi are recognized by what ‘signatures’?
mannoproteins
B-glucans
Bacteria are recognized by what ‘signature’?
LPS (G-)
LTA (G+)
Proteoglycan
Flagellin
Toll-Like Receptors are expressed where and signal how?
Expressed on cell surface or in endosomes
MyD88 adapter protein
Activate NFκB and interferon response factors (IRFs)
What receptor recognizes LPS (g-)
TLR-4
What receptor recognizes Viral RNA?
RIG-like receptor
Where is NOD-like receptor found?
cytoplasm
What 3 cytokines together lead to Septic Shock?
IL-1
IL-6
TNF-alpha
NK Cells attack what type of infected cell?
virally infected cell
Explain Missing Self Hypothesis
NK cells usually kill cells, but virally infected cells. MHC protein goes down when cell is infected, marker for T-cells (for self). Remove self from surface. MHC is a strong negative regulator of NK cells. NK cells recognize the lack of MHC cells in virally infected cells.
3 Major effects of innate antiviral immune response?
Resistance to viral replication
Increased MHC Class I expression
Activation of NK responses
IFN Type 1 protects against what?
viral infections, protective against viral machinery from taking hold
Timeline of antiviral response including players?
production of IFN alpha/beta, TNF-alpha, IL-12
NK cell mediated killing of infected cells
T-cell mediated killing of infected cells
Mast Cell/Basophil characteristics
covered with PRRs and IgE receptors
Rapidly release pre-synthesized factors (TNFα, histamine, IL-4)
DC activation
Smooth Muscle contraction
Endothelial activation, Vasodilation & increased vascular permeability, edema
Neutrophil characteristics
short half life
Destroy the pathogens themselves and respond to macrophage products (e.g. IL-8 , INF-γ and C5a)
Contain granules with MPO, lactoferrin, and defensins
Release of anti-bacterial peptides (defensins)
Ways that Macrophages and Neutrophils cause intracellular death of pathogens?
Oxidative Burst
ROS
O2-independent - iNOS
Attraction of neutrophils to an acutely inflamed site requires endothelial cell expression of what?
new selectins and chemokines
Stepwise recruitment of leukocytes - specific players (chemokines, selectins, etc)
First attachment via selectins and Chemokines (CXCL8/IL-8) More firmer attachment via LFA-1 Leukocyte diapedesis via CD31 or PECAM -1 Cells respond to infection in tissue and follow chemokine gradient
Eosinophils characteristics
fight parasites
Parasites coated with antibody can be recognized and targeted for destruction via Eosinophils via their FcR
What can produce products that trigger muscle cell contraction and help to expel parasite – vomiting and defecation
Mast Cells
