Humoral Immunity I (Lecture 3) Flashcards
Effector Functions of Antibodies
Now we’re going to focus on interactions with accessory cells
YEA
Fc Receptors
macrophages have large numbers of ____ receptors; upon binding of antibody to receptor it can enhance ____ of macrophage recognizing the bacteria
either scenario can happen, Ab can bind ____ and then cell is activated, or the Ab can bind to the antigen and then the ____ can bind to the macrophage
Fc gamma
efficiency
first
whole complex
Fc Receptors
appreciate each Fc receptor uniquely interacts with a particular class of Ab
he will tell us which ones to remember
engagement of an Fc receptor does not induce the same ____ in every receptor, in addition to the ____ that is expressing the receptor; some can ____ the cell, some receptors can ____ the cell
receptors are ____ expressed on different cell types, and some are only expressed ____
response
cell type
activate
inactive
differentially
intracellularly
Phagocytosis
most important cells involved w/ phagocytosis: \_\_\_\_ \_\_\_\_ (which give rise to macrophages) \_\_\_\_ \_\_\_\_ cells
extracellular bacterial infections –> ____ + ____ are v v v v v important
macrophages monocytes neutrophils dendritic neutrophils macrophages
Phagocytosis
macrophages can distinguish bt our own cell and microbial cells, but they cannot distinguish one ____ cell type from another
can recognize that it’s a ____ cell and not a ____ cell
macrophage can phagocytose ____ cells, a case where it can eat up our own cells
macrophage is acting as an ____ mediator of immunity; cannot distinguish a gram positive from a gram negative, can only tell that what it has engaged doesn’t belong here and it must get rid of it (the basal level of phagocytic activity)
once engaged by receptor, internalized via RM ____ > phagosome > interacts with lysosome and fuses > gives rise to a ____
bacterial prokaryotic eukaryotic apoptotic innate endocytosis phagolysosome
Phagocytosis
on surface of phagocytic cells exists ____ receptors > interact with IgG molecules
different subclasses have different affinities to Fc gamma receptors
conceptually, a macrophage can ave a Fc gamma receptor and can then interact with IgG > so now this cell can be coated by ____ molecules > now it becomes more ____ and less innate > specificity is dictated by the ____ regions of the light and heavy chains of the Ab molecule
FcR’s are ____ expressed on macrophages
lvl of expression can go up if macrophages is stimulated but just know it’s constitutively expressed
Fcgamma
antibody
specific
variable
constitutively
Fc receptors
Fc-gammaR1 (CD____)
expressed on ____, ____, ____, dendritic cells, mast cells
____ expressed on most potent ____ cells
64 neutrophils monocytes macrophages uniformly phagocytic
Opsonization
Opsonization – enhancement of the efficiency of ____ mediated by molecules that bind to receptors on the surfaces of phagocytic cells; “targets” ____ for phagocytosis.
Opsonization mediated by antibody is a classic example of ____ between innate and adaptive forms of immunity.
opsonization > think of Fc gamma receptors and interaction with Ab; but there are other examples that he will explain (not simply Ab-receptor binding)
cell interacts with IgG (specificity for epitopes); Ab now coating the surface of bacterial cell can interact with Fc receptors on surface of phagocytic cell > once this interaction takes place > signal transduction initiated that activates the phagocytic cell > gives it a level of ____ stronger than the generic receptors in innate immunity
bacteria, Ab and receptor is ____, into a phagosome, interaction with lysosome forming a phagolysosome (all agents involved in the PL is upregulated following activation)
phagocytosis
microbes
synergism
efficiency
endocytosed
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
NK ells > mediators of ____ immunity; ability to interact with microbes and tumor cells (receptors normally found are nowhere near as ____ as other mediators)
important in eliminating ____, and elimination of ____ infected cells
tumor develops, humoral immune system will be asked to respond to create Ab against tumor-specific antigens > tumor cells becomes coated with ____ (IgG here), and they also bind to the Fc receptor (____ *REMEMBER THIS FC RECEPTOR) on NK cells
once Ab engages Fc receptor > signal transduction occurs that activates NK cells > the cytoplasm of the NK cells has cytoplasmic ____ (purple), these granules move to plasma membrane upon activation, fuse and release contents in the ____ bt the NK cell and target cells > molecules exist that form ____ in the target cells, and others that enter the cytoplasm of the target cell and induce it to undergo ____
innate
specific
tumors
virally
Ab
FcgammaRIII, CD16
granules
space
pores
apoptosis
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) - Killing of Helminth
involves ____ molecules that interact with Fc epsilon receptors on surface of ____ (derived from bone marrow)
eosinophil has a large number of ____ (some of the same granules as NK cells, some unique contents that are directed towarding killing ____)
contents released upon binding of Ab and receptor > will be ____
molecules within the granules: ____ proteins (major basic protein); and a number of enzymes that can degrade ____ molecules on surface of worm, and can also undergo ____ (____, can degrade the connective tissue, causing the worm to be ____, and the worm is expulsed in the next bowel movement)
IgE
eosinophils
granules
helminth
localized cationic superficial tissue remodeling eosinophil peroxidase detached
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
Eosinophils attacking a schistosome larva in the presence of serum from an infected individual.
schistosome (____)
entirely surrounded by eosinophils, in all likelihood this organism will be killed by activation of eosinophils
____ can be killed by this mechanism, but larger things (like tapeworms) will not directly be killed
multicellular parasite
small parasites
Mast Cells
- Granulocytic cells derived from myeloid stem cells in the ____.
- Similar in appearance and biology to ____.
- Found in most tissues in close proximity to ____ and ____ but are most prominent in connective tissue underlying ____ and ____.
- Have roles in a number of physiologic (sentinels to presence of ____, ____ healing) as well as pathologic processes.
- Can be activated by a number of distinct stimuli.
bone marrow basophils nerves blood vessels skin mucosal surfaces microbes wound
Mast Cells
mast cells > extremely ____ number of cytoplasmic granules
large list of bioactive molecules contained within the granules
on surface of mast cells > large # of molecules that have potential to act as receptors (some for microbes) > ____ (many different types that recognize different molecules)
mast cells also express ____ receptors (interact with IgG molecules) > high level of expression of ____ on surface of mast cells
when these cells are activated: release contents of granules into extracell space, induction of expression of ____ and ____ (potent inducers of inflammatory rxns), and the upregulation of lipid mediators (____ and ____ - also inducers of inflammation)
large
toll-like receptors
Fcgamma
Fcepsilon
pro-inflam cytokines
chemokines
prostaglandins
leukotrienes
IgE-Mediated Activation of Mast Cells
mast cell becomes pre-coated with ____ molecules (slightly different from previous examples, in opso and ADCC the Ab bound to target first, in this molecule, Ab binds ____ and then interacts with the antigen that they are specific for)
microbe/antigen that the Ab is specific for binds to multiple Ab molecules; must crosslink at least ____ Ab molecules in order to induce activation of the mast cell > activation signal that leads to ____ of mast cell
IgE
first
two
degranulation
Mediators Released by Mast Cells
can affect ____, can affect ____ (bronchoconstriction) and the ____ by biogenic amines
cytokines and lipid mediators are potent mediators in the induction of ____ > vasodilation, chemotaxis of WBC
enzymes found in granules of mast cells can result in ____
one of the major fxns of mast cells is a ____ to infection; cut arm and get infected; bacteria bypass physical barrier of skin > first thing that happens, they activate mast cells in dermis (engaging ____ receptors) > induce an inflammatory reaction and attract WBC
vascularization respiratory GI hypermobility inflammation tissue damage
sentinel
toll-like
