General Flashcards
Neutrophils recognize bacterial components through
CD14, MR, CR3, CR4, GR
enhances phagocytosis of bacteria
chemotactic agents
C5a, LTB4, chemokines (IL-8/CXCL8, MIP, MCP)
TCR
Ag peptide/MHC
TCR coreceptors
CD4, CD8
MHC class I expressed by
all cells in the body besides RBCs
for comprehensive surveillance by CD8 T cells
occurs at old age
thymic involution and immunological senescence
CD8 binds
MHC class I
CD4 binds
MHC class II
superantigens
SEB (staphylococcal enterotoxin)
SEC-2
SEE
TSST-1
co-stimulatory receptor required for full activation
CD28/B7
T cell receptors for B7 molecules on APC
CD28 and CTLA4
expressed by all T cells
CD28
expressed by activated T cells
CTLA4
interaction negatively regulates T cell activation, shutting down immune response
CTLA4:B7
Lck and ZAP-70
involved in the intracellular signaling events during T cell activation
immature effector T cells to Th1
IL-12 from DCs
IFN-gamma from Th1 and NK cells
immature effector T cells to Th2
IL-4 from mast cells, B cells and Th2 cells
Th1 cells
macrophage activation
B cell activation and production of opsonizing antibodies such as IgG1
cell-mediated
IFN-gamma
suppresses Th2 cells
Th2 cells
general activation of B cells to make neutralizing IgG antibodies eosinophil activation suppression of macrophage activation production of IgE humoral
Six phases of B cell development
- repertoire assembly (generation in bone marrow)
- negative selection (alteration/elimination/inactivation of B cells that bind to self-antigens)
- positive selection (promotion of a fraction of immature B cells to become mature in secondary lymphoid tissue)
- searching for infection (recirculation of mature B cells)
- finding infection (activation/clonal expansion activated by pathogen antigens in secondary lymphoid tissue)
- attacking infection (differentiation in antibody secreting plasma cells and memory B cells)
Two signals required for B cell activation
- antigen
2. T cell
T-independent antigens
TI-1
TI-2
TI-1
activates B cells via co-receptor other than Ig
polyclonal activation of B lymphocytes
ex) lipopolysaccharide
TI-2
repetitive epitopes
polysaccharides or proteins
activate B-1 and B-2 cells
inadequate response in children
Innate Immunity response
antigen independent, immediate, neutrophils, NK cells, Macrophages (DCs and TLRs)
Adaptive Immunity response
Antigen-dependent, slower, T cells, B cells
First immune cells to arrive at sites of infection from blood
neutrophils
constitute 50% of white blood cells in blood
neutrophils
short-lived, forms “pus”
neutrophils
kills ingested bacteria by respiratory burst and bactericidal agents
neutrophils
Steps of leukocyte migration/infiltration
- Rolling adhesion (L-selectin)
- Tight binding (adhesion triggered by cytokines)
- Diapedesis (firm adhesion through LFA-1:CR3)
- Migration (chemotaxis to infection sites)
primary lymphoid follicle
mostly B cells
secondary lymphoid follicle
has germinal center
paracortical area
mostly T cells
differentiation sites for effector T and B cells
lymph nodes
Three ways for NK cells to recognize target cells
- binding of NK cell to antibody-coated target cell
- binding of NK cell to adhesion molecules on target cell
- activation of NK cell by absence of class I MHC
Which antigens activate MHC class II?
extracellular:
extracellular bacteria, protein vaccine, fungi, tumor antigens
Which antigens activate MHC class I?
intracellular:
virus, DNA vaccine, tumor antigens
cells that express high levels of MHC II and MHC I
B cells, macrophages, DCs and thymic epithelial cells
professional antigen-presenting cells
B cells, macrophages, DCs
increases the expression of MHC I/II in APC and induces their expression in non-APC cells at the sites of infection
IFN-gamma
uncommitted T cell progenitor cells express
CD34
committed double-negative T-cell progenitor cells express
CD2
Uncommitted double-positive thymocytes express?
CD8 and CD4
T cell positive selection
interaction of a double-positive T cell with a self-peptide:self-MHC complex determines whether the T cell will become a CD4 or a CD8 T cell
T cell negative selection
deletes T cells whose antigen receptors bind too strongly to the complexes of self peptides and self-MHC molecules presented by the cells in the thymus
alpha subunit of CD8 binds to
alpha3 subunit of the MHC complex
What do superantigens bind?
they link the MHC complexes with the TCRs
function of TCRs
specific recognition of antigen
function of CD3, CD4/CD8, CD28
signal transduction
function of integrin
adhesion
ligand for L-selectin
CD34, GlyCAM-1, MAdCAM-1, SIaly Lewie
ligands for P-selectin and E-selectin
Sialyl Lewis
how do IFN-alpha and IFN-beta fight viral infections?
- inhibit viral replication
- increase MHC class I expression and antigen presenting in all cells (promote recognition by cytotoxic T cells)
- Active NK cells to kill virus-infected cells
inflammatory cytokines
IL-1, IL-6, TNF-alpha
role of IL-6
promote phagocytosis through the production of opsonins in the liver
down regulators
- IL-10, TGF-beta
- killing of activated lymphocytes by FAS-FASL
- CTLA4-B7 interaction
- Regulatory T cells (FoxP3+)
- Activation-induced cell death
Pathogens’ immune-evasion strategies
- hide or disguise
- change Ag
- suppress Ag presentation
- suppress immune response
Immunology of pregnancy (important points)
- Mucosal immunity (IgA) of the female genitalia tract
- Trophoblasts don’t express MHC I and MHC II
- Active immune supression bysecretion of immunosuppressive factors (alphafetoprotein, IL-10, TGF-beta)
- inhibition of immune cells by T-regulatory/suppressor cells ad progesterone
Uses of antibodies for diagnosis and research
- blocking by neutralization of cytokines (steric hindrance)
- complement fixation and cytolysis or depletion of target cells
- agonistic antibodies (activate cells)
- simple binding (ELISA, Flow cytometry)
- cross-reaction (Coombs test)
Coombs’ test
to detect the presence of cell-surface binding antibody
direct and indirect
Direct Coombs’ test
commonly used for hemolytic anemia
cells are coated with primary Abs
Indirect Coombs test
to screen pregnant women for anti-RhD antibodies that may cause hemolytic disease of the newborn
cells and primary Abs are from different persons