Immune Response & Cytokines Flashcards
Can be cell-mediated (cellular) and antibody-mediated (humoral)
adaptive immunity
Involves B cell activation, production of antibodies in blood plasma and lymph
humoral immunity
About 1 to 2 weeks for a measurable amount of antibody to be observed
lag phase
Rapid increase in the concentration of antibodies observed
exponential phase
Production and degradation of antibodies are balanced
steady state
Immune system begins to shut down
decline phase
Accomplished by phagocytosis. Most injected Ag is
removed within minutes, but complete removal may take months or years
antigen elimination
After exposure to antigen, there is latent pd of
approx. 5 to 15 days before antibody appears in the serum
the primary response
Second or subsequent exposure to the same antigen elicits secondary response. there is rapid antibody response usually within 2 to 4 days after antigen exposure
the secondary response
DURATION:
Long lag phase, short plateau, and rapid decline
primary response
DURATION:
Short lag phase, long plateau, and gradual decline
secondary response
cells in primary response
plasma cells
cells in secondary response
memory cells
type of antibody in primary response
IgM
type of antibody in secondary response
IgG
antibody titer in primary response
low
antibody titer in secondary response
high
antibody affinity in primary response
low
antibody affinity in secondary response
high
antibody avidity in primary response
high (increase valence)
antibody avidity in secondary response
high
Action of T cells; produces cytokines
CELLULAR (CELL-MEDIATED) IMMUNITY
CD4 cells respond to antigen recognition
CD8 cells respond to antigen recognition
CELL-MEDIATED IMMUNE RESPONSE
Antigens that stimulate this response are mainly
intracellular
T CELLS AND CELL MEDIATED IMMUNITY
Requires constant presence of antigen to remain
effective
T CELLS AND CELL MEDIATED IMMUNITY
Unlike humoral immunity, cell mediated immunity is not transferred to the fetus
T CELLS AND CELL MEDIATED IMMUNITY
It is life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation that can be triggered by various therapies, pathogens, cancers and autoimmune conditions
cytokine storm
(T/F)
The laboratory findings in cytokine storm are
variable and influenced by the underlying cause.
true
Universally elevated and correlate with severity
C-reactive protein (CRP)
Many patients have hypertriglyceridemia and various blood-count abnormalities, such as leukocytosis, leukopenia, anemia, thrombocytopenia, and elevated ferritin and d-dimer levels
cytokine storm
key cellular component of immunity
T cells
Helper T cells activate B cells to maturity and produce antibody
CD4+
Cytotoxic T cells that directly protect from viral infection by cell lysis
CD8+
Early thymocytes lack CD4 and CD8 markers
double-negative stage
Express both CD4 and CD8 antigens
double-positive stage
The development of two distinct T-cell populations
CD4+ (helper-inducer); CD8+ (suppressor cytotoxic)
mature T cell
The loss of Tdt enzyme
mature T cell
Produce interferon and tumor necrosis factor
Th1 cells
Protect cells against intracellular pathogens
Th1 cells
Responsible for cell-mediated effector mechanism
Th1 cells
Produce a variety of interleukins, IL-4, IL-5,IL-10, and IL-13
Th2 cells
Essential role is to help B cells produce antibody against extracellular pathogens
Th2 cells
Central role in immune response
T HELPER (TH) CELLS
Most are CD4+; CD8-
T helper (TH) cells
Recognize antigen on the surface of antigen presenting cells (e.g.: macrophage)
T helper (TH) cells
Activate macrophages
T helper (TH) cells
Stimulate B cell growth and differentiation
T helper (TH) cells
50-60% in the peripheral blood
T helper (TH) cells
produces IL-2, IL-3, GM-CSF, IFN-gamma
T helper (TH) cells
Destroy target cells
cytotoxic T (Tc) cells
Most are CD4 negative (CD4 -),CD8+
cytotoxic T (Tc) cells
Recognize antigens on the surface of all cells
cytotoxic T (Tc) cells
Kill host cells that are infected with viruses or bacteria
cytotoxic T (Tc) cells
Recognize and kill cancer cells
cytotoxic T (Tc) cells
Recognize and destroy transplanted tissue
cytotoxic T (Tc) cells
Release protein called perforin which forms a pore in target cell
cytotoxic T (Tc) cells
May shut down immune response
T suppressor (Ts) cells
downregulate the actions of T & B cells
T suppressor (Ts) cells
no unique markers
T suppressor (Ts) cells
Earliest B-cell precursor – recognized by surface
molecule CD45R
Pro B cells
recognized by surface molecule CD45R
earliest B cell precursor
Distinctive markers CD19, CD45R, CD43, CD24, and c-Kit
pro B cells
Ig gene rearrangement
pre B cells
CD10 and CD19
pre B cells
Distinguished by the appearance of complete IgM molecules on the cell surface
immature B cells
CD21, CD 40, and major histocompatibility complex (MHC) class II molecules.expresses IgM on surface
immature B cells
IgM and IgD on cell surface
mature B cells
have a half-life of more than 6 weeks
mature B cells
CD25, receptor (IL-2)
activated B cells
Live for years as memory cells
activated B cells
Quickly transform to plasma cells and begin producing IgG
activated B cells
Secondary antibody response
activated B cells
End stage of B-cell differentiation
plasma cells
No further maturation
plasma cells
CD19
plasma cells
Not normally found in the circulating blood
plasma cells
Relatively short-lived
plasma cells
method for obtaining lymphocytes
Density gradient centrifugation with Ficoll-Hypaque
Layers from top to bottom:
Plasma, Mononuclear Cells, Ficoll-Hypaque, RBCs, Granulocytes
Use of labeled monoclonal antibodies against specific surface antigens
CELL FLOW CYTOMETRY
Light scattering is measured as cells flow through a laser beam
CELL FLOW CYTOMETRY
Automated
CELL FLOW CYTOMETRY
FACS meaning
FLUORESCENCE-ACTIVATED CELL SORTER
Old method; manual
rosette technique
T lymphocytes form rosettes with sheep’s RBC
rosette technique
Use of labeled monoclonal antibodies against specific surface antigens. Slides are read with a fluorescent microscope
direct or indirect immunofluorescence
Immunoenzymatic method to demonstrate immunoglobulins on B cells
surface immunoglobulins
Example of chemotaxins
C5a, C5b, C6, C7
Cell surface receptors
Fc receptor, complement receptor
Humoral and cell-mediated
immune response
Involves Ig production by B lymphocytes and complement
humoral immunity
3 phases of humoral immunity
antigen elimination
primary response
secondary response
Phagocytosis
antigen elimination
Latent period (5-15 days) before the antibody appears in the serum; IgM is the first Ig to appear and is the majority Ig produced
primary response
days in primary response
5-15 days
Second or any subsequent exposure to same antigen; rapid antibody response (2-4 days); IgG is the predominant Ig; circulating antibody titer is much higher and lasts longer than in primary response
secondary response
days in secondary response
2-4 days
Especially important in viral and fungal infections
and in infections caused by acid-fast bacilli
cellular immunity
______, _______, and ______ play a role in cell-mediated immunity
Macrophages, Tc, and NK cells
cells with cytolytic activity and Fc receptors, especially NK cells, are able to directly lyse antibody-coated (usually IgG) target cells
Antibody Dependent Cell-Mediated Cytotoxicity (ADCC)
are protein messengers produced by cells. Many play a role in cell-mediated immunity
cytokines
Are responsible for cell-mediated immune responses
T lymphocyte
_______ are CD4 positive and produce the lymphokines interleukin-2 (IL-2), interleukin-3 (IL-3), granulocyte-monocyte colony stimulating factor (GM-CSF), and gamma interferon (IFN-γ). They aid in B Cell differentiation, and they stimulate other T-cell populations
T helper cells (Th)
_______ are CD8 positive and produce factors that inhibit the action of other T cells
T suppressor cells (Ts)
Most ______ are CD8 positive. They secrete lymphotoxins and release perforins, which destroy cells recognized as foreign
cytotoxic T cells (Tc)
_______ are CD4 positive. They secrete macrophage chemotaxin and macrophage migration inhibition factor (MIF)
Delayed-type hypersensitivity T cells (TDTH)
Produce interferon gamma (IFN-γ), interleukin-2
(IL-2), and tumor necrosis factor-β (TNF-β), which
protect cells against intracellular pathogens by activating cytotoxic lymphocytes and macrophages
Th1
Produce a variety of interleukins, including IL-4,
IL-5, IL-6, IL-9, IL-10, and IL-13; help B cells produce antibodies against extracellular pathogens and to generally regulate B-cell activity
Th2
Regulatory, possess the CD4 antigen as well as
CD25; comprise approximately 5% of all CD4+ T
cells; inhibit proliferation of other T-cell populations by secreting inhibitory cytokines and the response is antigen specific
Treg
Produce interleukin-9 (IL-9) and appear to have a
proinflammatory effect; they stimulate growth of
hematopoietic cells, especially mast cells which may they promote autoimmune inflammation
Th9
Produce interleukin-17 (IL-17) and interleukin-22
(IL-22). Both of these cytokines can increase inflammation and joint destruction. They have been associated with autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease
Th17
Chemical messengers that regulate the immune
system, orchestrating both innate and adaptive
response to infection
cytokines
Chemical messengers that regulate the immune
system - small proteins produced by several
different types of cells that influence the
hematopoietic and immune systems through
activation of cell-bound receptors
cytokines
Are induced in response to the binding of stimuli,
such as bacterial lipopolysaccharides, flagellin, or
other bacterial products, to specific cell receptors or through the recognition of foreign antigens by host lymphocytes
cytokines
It includes regulation of growth, differentiation, and gene expression by many different cell types, including leukocytes
cytokines
Responsible for many of the physical symptoms attributed to inflammation, such as fever, swelling, pain, and cellular infiltrates into damaged tissues
cytokines
cytokines families:
Tumor necrosis factor (TNF)
Interferon (IFN), chemokine
Transforming growth factor (TGF)
Colony-stimulating factor (CSF)
first isolated from lymphocytes and macrophages and was so named because it induced lysis in tumor cells; causes vasodilation and increased vasopermeability; trigger for TNF-α production
is the presence of lipopolysaccharide, which is
found in gram-negative bacteria; in excess may
lead to septic shock
Tumor necrosis factor (TNF)
enhance motility and promote migration of many types of white blood cells (WBCs) toward the
chemokine source via a process known as chemotaxis
Interferon (IFN), chemokine
a regulator of cell growth, differentiation,
apoptosis, migration, and the inflammatory
response
Transforming growth factor (TGF)
proliferation and differentiation of cell types
Colony-stimulating factor (CSF)
Interleukins
Interleukins (IL)
Is produced by macrophages, B cells, and other cell
types. IL-1 activates T helper cells, increases the number of B cells, activates vascular endothelium, causes fever and acute-phase protein synthesis, and induces T cells to produce lymphokines
INTERLEUKIN 1 (IL-1)
Is produced by T helper cells
IL-2
causes proliferation of activated T and B cells
IL-2
Is produced by activated T cells
IL-3
increases the number of mast cells in the skin, spleen, and liver
IL-3
Is produced by activated T cells. IL-4 induces the
proliferation of T cells and class switching from IgM
to IgGl and IgE
IL-4
