Diseases of the Immune System I Flashcards
innate immunity
inflammation - phagocytes
anti-viral defenses - NK cells
PAMPs
microbial structures recognized
DAMPs
molecules released by injured or necrotic cells for signaling to leukocytes
pattern recognition receptors
recognize PAMPs and DAMPs
-ex/ TLRs
NF-kappa-beta
way the pattern recognition receptors signal
-transcription factor
stimulate microbicidal activities
epithelia
mechanical barrier
and produce defensins
phagocytes in blood
monocytes and neutrophils
innate activation of complement
alternative and lectin pathways
adaptive activation of complement
classical pathway (antibodies)
humoral immunity
extracellular microbes and their toxins
-B lymphocytes
cell-mediated immunity
intracellular microbes
-T lymphocytes
CD4 T cells
helper T cells
-activate macrophages, inflammation, and stimulate B cells
CD8 T cells
cytotoxic T cells
-kill infected cells
thymus
development of T cells
MHC restriction
T cells only recognize antigen presented by MHC on APCs
T cell receptor
alpha and beta polypeptide
RAG1 and RAG2
enzyme in developing lymphocytes that mediates rearrangements of receptor genes
monoclonal vs. polyclonal T cell populations
monoclonal - neoplastic
analysis of antigen receptor gene arrangements is a valuable assay for detecting lymphoid tumors
TCR complex
alpha and beta protein receptor
zeta and CD3
gamma-delta TCR
no requirement for MHC
-at epithelial surfaces
NK-T cells
recognize glycolipids displayed by MHC-like CD1
function not known
MHC class II
binds CD4
MHC class I
binds CD8
rule of 8
MHC and CD binding multiplies to 8
2 x 4 = 8
1 x 8 = 8
IgM and IgD
membrane bound antibodies - on all mature naive B cells
-antigen binding component
identifying B-cell tumors
look for monoclonal gene rearrangement of B cell receptor
B cell receptor complex
IgG and IgD
Ig-alpha and Ig-beta
receptor for EBV
type 2 complement receptor on B cells
-this is why this virus infects B cells
langerhans cells
immature dendritic cells in epidermis
dendritic cells
APCs for initiating T cell responses
- located under epithelia
- have TLRs and mannose receptors
- recruited to T-cell zones of lymphoid organs
follicular dendritic cells
in germinal center of lymphoid follicles
-spleen and lymph nodes
-present antigens to B cells and select highest affinity B cells
macrophages
function as APCs to T cells
T cells activate them back
phagocytose opsonized molecules - IgG or C3b
NK cells
abundant azurophilic granules
- can kill without prior exposure (innate)
- CD16 - receptor for IgG
- CD56 also used to identify NK cells
ADCC
antibody-dependent cell mediated cytotoxicity
NK cells recognizing IgG coated microbes and killing them
-by CD 16
activity of NK cells
balance of + and - signaling
- activating - NKG2D
- inhibiting - recognized MHC class I
inhibitory signals prevent from killing normal cells
viruses and neoplastic growth
induces expression of NK activators -also reduce MHC class I expression
activates NK cells
IFN-gamma
secreted by NK cells
-activates Macrophages
IL-2 and IL-15
stimulate proliferation of NK cells
IL12
stimulates NK release of IFN-gamma and killing
generative lymphoid organs
bone marrow and thymus
peripheral lymphoid organs
nodes, spleen, mucosal, and cutaneous tissue
lymph nodes
receive lymph vessel flow
spleen
receives blood-borne antigens
network of sinusoids
peyers patch
peripheral lymph organ
-in intestine
lymph node organization
B cells - in follicles around cortex
- have follicular dendritic cells
- germinal center - B cells activated
T cells - in parafollicular regions
-has dendritic cells
once activated, chemokine expression brings them together at edge of follicle
spleen organization
T cells in periarteriolar lymphoid sheath
B cells in follicles
lymphocyte recirculation
naive traverse peripheral lymph organs
activated go to sites of infection and inflammation
plasma cells - stay in lymph organs
naive T lymphocytes
enter T-cell zone through HEVs
MHC gene
segment of chromosome 6
class I MHC
all nucleated cells and platelets
- present cytoplasmic protein antigens
- recognized by CD8 T cells - viruses or tumors
HLA A, B C
Class II MHC
present vesicle bound antigens from extracellular microbes
- recognized by CD4
- on cells that present ingested antigens - M0, B cells, dendritic cells
HLA DP, DQ, DR
HLA haplotype
combination of HLA (MHC) genes
-important in organ transplant and grafts
role of MHC
regulate T cell response
- CTLs to cytoplasmic microbes
- helper T cells to extracellular microbes
HLA-B27
associated with ankylosing spondylitis
-chronic inflammation of axial skeleton
CD8 cell association
HLA and diseases
inflammatory - HLA-B27
autoimmune - HLA-DR
inherited errors of metabolism - HLA-BW47 (21-hydroxylase deficiency) and HLA-A (hereditary hemochromatosis)
interleukins
mediate communication between leukocytes
innate immunity ILs
TNF IL-1 IL-12 type I IFNs IFN-gamma chemokines
adaptive immunity ILs
IL-2 IL-4 IL-5 IL-17 IFN-gamma
colony-stimulating factors
stimulate hematopoiesis
-cytokines
clonal selection hypothesis
lymphocytes specific for larger number of antigens select single antigen
the recognizing lymphocytes is selected and develops clones
immunization
antigen presented
-initiates innate response
costimulators
expressed by APCs
- required to activate lymphocytes
- ensures that harmless substances don’t elicit response
B7 proteins
costimulator for T cells
-CD80/CD86
IL-2
secreted by CD4 helper T cells
-acts on T cells proliferation
CD40L
expressed by CD4 helper T cells
-engages CD40 on M0 and B cells to activate them
Th1
subset of CD4 helper T cells
- secrete IFN-gamma
- activates M0s
Th2
subset of CD4 helper T cells
-secretes IL-4 (stimulates B cells to produce IgE) and IL-5 (eosinophils activation)
Th17
subset of CD4 helper T cells
- secrete IL-17
- recruit neutrophils and monocytes
B cell activity
ingest protein antigens and display them with MHC to bind helper T cells
isotype switching
in B cells - secrete variable antibodies
stimulated by IFN-gamma and IL-4
affinity maturation
production of antibodies with higher affinity in B cells
IgG
opsonize
IgG and IgM
activate complement
IgA
secreted from mucosal epithelium
IgG
secreted across placenta and protects newborn
IgE
activates eosinophils
-response to helminthes
from Th2 cell stimulation
naive B cells
has IgM and IgD
