lecture 8 exam 2 Flashcards
SubQ or intramuscular immunization routes
antigen drains to nearest LN and stimulates SYSTEMIC immunity NOT mucosal immunity
peripheral immune system & draining lymph nodes
facial retropharyngeal submandibular superficial cervical axillary iliac superficial inguinal femoral popliteal
innate protection mechanisms on body surfaces
vomiting/saliva
turbulence/sneezing
tears/blinking
mucus/cilia/coughin
dessication/desqamation/fatty acids/normal flora
acid pH/vomiting
normal flora/anaerobiasis/lysozyme/defensins/proteases/diarrhea
mucosa-associated lymphoid tissues (MALT)
MALT cellular mass: excess total lymphoid cells in bone marrow, thymus, spleen and LN
ex: NALT, GALT, BALT
NALT
type of MALT
nasal associated lymphoid tissue - tonsils
GALT
type of MALT
gut associated lymphoid tissue - peyers patches
BALT
type of MALT
bronchus associated lympoid tissue
epithelial barrier
mucosal epithelium in lumen
peyeres patches dense with lymphocytes in ileum
lamina propria has lymphocytes, lymphatic systems
intestinal lumen
commensal bacteria
IgA from antibody (blood borne)
mucosal epithelium
mucus goblet cell M cell intestinal epithelial cell dendritic cell crypt intraepithelial lymphocytes vilus paneth cells defensins
lamina propria
plasma cell - IgA peyers patch follicle macrophage mast cell T cell B cell LYMPH DRAINAGE VIA AFFERENT LYMPHATIC dendritic cell
mesentary
mesenteric LN
- homing of lymphocytes to intestinal mucosa
- priming of antigen specific responses taking place here
properties of MALT
large lymphoid areas
-continuously exposed to microorganisms and food antigens
-mucous membranes largest organ
partially separate from the peripheral immune system
epithelial barrier (innate immunity)
produces T cell and B cell effectors and memory cells:
-generated in one location then circulate to distant sites
provides tolerance to food antigens
epithelial barrier immune functions
epithelial tight junctions
mucus: mucins, lipids & bicarbonate fluid
- secreted by goblet cells
- neutral pH at epithelial layer
- adhere to luminal surface of epithelium: allow nutrients but not macromolecules to pass
defensins: antimicrobial peptides secreted by paneth cells
- disrupt bacterial membranes
epithelial cells produce cytokines and chemokines
IL10/TGFB - immunosuppressive (inflammation) TNFalpha - Th1 differnetiation CXCL1 - neutrophils CCL2 - eosinophils CXCL10 - lymphocytes recruitment
compartments of MALT
inductive sites
effector sites distant from inductive sites
inductive sites of MALT
antigen is process and T and B cells are activated antibody class switching occurs
effector sites of MALT
sites where antibody and cell mediated responses are generated against pathogens:
antibody is released by plasma cells
CTLs kill virus infected cells
inductive site examples
tonsils - most mammals except rodents pharynx, NALT BALT appendix peyers patches (discrete in jejunum) mesenteric LN
anigen transport across mucosal epithelium
M cells - take bacteria into epithelium and give to DC, located w/in epithelial cells
intestinal mucosa DCs - read or let in antigen to find DC, CDs CXs TGFb to t cell or treg
discrete peyers patches in jejunum
dome region: CD4 T cells, DCs, macrophages germinal center: B cells (class switching) parafollicular region: CD4, CD8, DCs and macrophages
antigen transfer by M cells into lymphoid follicle
model for T cell differentiation in inductive sites
M cell brings antigens in and presents to DC resulting in a. IL10/TGFB expression response to low dose antigen (food)
b. IL4 expression response to extracellular pathogen parasites
c. IL12 expression response to intracellular pathogen
d. IL23 expression response to endogenous flora
IL10/TGFbeta response to low does antigen “food” results in
Treg w default IL10 and TGFbeta
IL4 response to extracellular pathogen parasites results in
Th2 w default IL4, 5, 10
IL12 response to intracellular pathogen results in
Th1 w default IFNgamma
IL23 response to endogenous flora results in
Th17 w default IL17, 6
intestinal villi components
intraepithelial lymphocytes (IEL) - gamma delta T cells, CD8+ alpha beta T cells lamina propria + lymphocytes - CD4 tcells activating B cells crypt epithelium paneth cells - lysozyme and defensins
homing properties of intestinal lymphocytes
Mcell call in antigen and HEV brings in DC/naive T cell, and B cell to interact and go through mesenteric LN to lymph to heart to blood to chemokines direct homing of effector lymphocytes (CD4, CTLs, and B cells)
secretory IgA is the
main mucosal immunoglobulin in most animal species
except: cattle - igG is most important mucosal
T dependent IgA class switching in gut - antigen
done by plasma cell through interactions of antigen w DC and B cell
DC to naive CD4+ tcell then activated Thelp w B cell receiving NO and TGFb from DC to become plasma cell and leave the peyers patch into lamina propria
T independent IgA class switching in gut - bacteria/PAMP
DC TLR interacts w bacteria and APRIL, TGFB, BAFF released to IgM+ b cell to travel as plasma cell to lamina propria and release IgA
APRIL
A proliferation inducing ligand
released by DC in response to bacteria/PAMP
BAFF
bcell activating factor of the TNF family
released by DC in response to bacteria/PAMP
transport of IgA across epithelial cells
Jchain is released and hold dimeric IgA in lamina propria
attaches to polyIg receptor - bound IgA and enter mucosal epithelial cell
endocytosed complex of IgA and polyIg receptor and proteolytic cleavage occurs on apical side to secrete IgA
immune elimination of intestinal round worms
when worm gets to tissue eosinophils (IL5, IL13 signal) attack and B cell reads antigens and bind to Th2 in submucosa, releasing IL4 IL4 activates class switching from IgM to IgE in plasma cell IgE on mast cell releases histamine which leads to vascular permeability leading to smooth muscle contraction which brings more fluid into the lumen IgG + C =MAC and attacks on luminal side causing expulsion
ADCC of parasites by eosinophils
helminths are vulnerable to :
ADCCA involving eosinophils, neutrophils and macrophages
eosinophil degranulation releases: major basic protein (MBP) eosinophil cationic protein (ECP) eosinophil peroxidase (EP) eosinophil neurotoxin (EN) phospholipase D lysophospholipase all these are toxic to helminths
IgE is antibody for eosinophils and helminths
treg functions at mucosal surfaces
inhibit th2, th1, th17 to regulate immune system
