HD Block 1
B7 protein on APC binds to ______________ on ______________
CD28; CD4 T cells
B cell surface proteins
CD40 (binds to CD40L on T cell), MHC Class II, B7 (binds to CD28 on T cell), CD19-21
CD3 complex
found on T cells, transmits "bound" signal into cell
Chediak-Higashi syndrome pathogenesis
lysosomes fail to fuse with phagosomes --> no phagocytosis
Kupffer cells, microglia, and osteoclasts are all types of __________
macrophages
tuberculosis blocks phagocytosis by
modifies phagosome so it can't fuse with lysosome --> proliferates inside macrophages where it is protected from antibodies
why are conjugated vaccines more effective
peptide antigen is conjugated to polysaccharide antigen, so instead of just a T cell independent response, you get a (stronger) T cell dependent response
T cells only recognize ________________
peptides
neutrophil function
phagocytosis (granules are lysosomes --> bactericidal enzymes), provide extra support to macrophages
macrophage key functions
phagocytosis, cytokine production, antigen presentation
regulatory T cells
- Suppress CD4 and CD8 functions - express CD25, CD4, CD3 - produce anti-inflammatory cytokines (IL-10, TGF-beta)
Th2 cells
- activate B cells to produce IgE / IgA - "humoral" immunity
class switching
- activated B cells initially produce IgM but as they mature, they can start producing IgG / IgA / IgE - triggered by cytokines (IL-4, IL-5 in Th2 response) or T cell binding (CD40-CD40L)
Antibody-dependent cellular cytotoxicity
- antibodies coat pathogen --> pathogen destroyed by immune cells (NON phagocytic process) - classic examples: Natural Killer cells, eosinophils
IgE
- binds to mast cells and eosinophils - allergies and parasites - does not activate complement
IgG
- can cross placenta - excellent opsonin - Very important for encapsulated bacteria (opsonization --> phagocytosis)
IgA
- dimer - linked by secretory component - secreted into milk - excellent at coating mucosal pathogens
IgM
- first antibody produced - pentamer - weak opsonin - great activator of classical pathway of complement system
CD4 binds _________ while CD8 binds _____________
MHC Class II; MHC Class I
Natural Killer Cell function
- kill human cells infected by viruses - produce IFN-gamma to activate macrophages - destroy human cells with reduced MHC I
IL-1
-"endogenous pyrogen" (causes fever) -increases synthesis of endothelial adhesion molecules so neutrophils can enter tissue
MHC class II
-Binds TCR and CD4 -only on APCs -binds invariant chain in ER --> merges with lysosome so invariant chain is released --> binds with antigen and is brought to surface
Th1 cells
-activates macrophages and CD8 T cells -"cell-mediated" immune response
IL-6
-causes fever -increases CRP (C-reactive protein)
innate immunity
-fast-acting, non-specific, no memory -can be activated by free antigens
TNF-alpha
-inhibits lipoprotein lipase --> less utilization of fatty acids --> cachexia -increases synthesis of endothelial adhesion molecules so neutrophils can enter tissue -can cause intravascular coagulation --> DIC
positive selection (definition and where it happens)
-occurs in cortex of thymus -T cells tested for binding to self MHC complexes --> if binding is weak, apoptosis
negative selection (definition and where it happens)
-occurs in medulla of thymus -T-cells tested for binding to self antigens and MHC --> if binding is excessive, apoptosis
CD16
-present on Natural Killer cell surface -binds Fc of IgG -antibody-dependent cell-mediated cytotoxicity
MHC class I
-presents antigen to CD8 T cells -present on most human cells
Th17 cells
-produce IL-17 and recruit neutrophils / macrophages -important for mucosal immunity
adaptive immunity
-slow-acting, highly specific, has memory -requires antigen presentation
CD56 (aka NCAM)
-used as a marker for Natural Killer cells
How do CD8 T cells kill infected cells?
1. insert perforin 2. insert granzyme 3. produce Fas ligand 4. insert granulysin
steps of neutrophils exiting blood stream
1. rolling (bind selectins on endothelial cell surface) 2. crawling (neutrophils express integrin, which binds ICAM on endothelial cells) 3. transmigration (bind PECAM-1 between endothelial cells) 4. migrate to inflammation site (chemokines C5a and IL-8)
superantigens
Activate many more T cells than normal --> can cause massive vasodilation and shock (Toxic Shock Syndrome)
____________ on ____________ binds to CD28 on CD4 T cells
B7 protein; APC
protein A
Binds Fc region of IgG. Prevents opsonization and phagocytosis. Expressed by S. aureus.
macrophages attracted by
C5a
macrophage cytokines
IL-1, TNF-alpha, IL-6, IL-8, IL-12
__________________ drives Th1 production
IL-12 (macrophages)
Th1 cytokines and their functions
IL-2 (T cell growth factor and activates B cells/NK cells) and IFN-gamma (activates Th1, suppresses Th2, activates macrophages)
Th1 cytokines and their functions
IL-4 (activates Th2, suppresses Th1, promotes IgE production), IL-5 (activates eosinophils, promotes IgA production), IL-10 (inhibits Th1 production)
eosinophils are stimulated by
IL-5 from Th2 cells
eosinophil antibody-dependent cellular cytotoxicity
IgE binds to pathogen --> eosinophil binds Fc of IgE --> release toxic enzymes onto parasite
which antibodies bind neutrophils?
IgG
NK cell antibody-dependent cellular cytotoxicity
IgG binds to pathogen-infected cells --> CD16 on NK binds to Fc of IgG --> cell death
CD8 T cells (cytotoxic T cells)
Kill virus-infected cells (also tumor cells)
macrophages activated by
LPS (bacteria), peptidoglycan, bacterial DNA (because no methylation), IFN-gamma (from T cells and NK cells)
superoxides are produced by ________________
NADPH oxidase
How does the PPD test work?
TB protein injected --> memory Th1 cells activated --> IFN-gamma secreted --> activate skin macrophages --> local skin swelling/redness
how are there more unique B cell receptors than genes
VDJ rearrangement
mannose
binds mannose-binding lectin (MBL) from liver --> activates lectin pathway of complement activation
LTA on gram (+) bacteria, double stranded RNA, unmethylated DNA
all recognized in innate immunity
chemokine
attracts immune cells (chemotaxis)
IL-8
attracts neutrophils
mast cells and basophils mechanism
bind Fc of IgE --> IgE molecules crosslink --> degranulation --> release histamine (vasodilation) and enzymes (peroxidase/hydrolase)
LPS
binds CD14 on macrophages --> triggers TLR4 --> cytokine production (IL-1, IL-6, IL-8, TNF)
peptidoglycan cell wall
binds NOD receptors --> cytokine expression
TNF
can cause tumor death
IgA protease
cleaves IgA on mucosal surfaces --> allows colonization of mucosal surfaces
opsonization
coating antigen with antibody enhances phagocytosis
B cell structure
comprised of two light chains, two heavy chains, two antigen binding sites; variable vs constant regions
what cells are APCs?
dendritic cells, macrophages, B cells
B cell function
each recognizes a specific antigen and synthesizes antibodies --> antibodies attach to pathogen --> pathogen is killed
phagocytosis
engulf pathogens into phagosome --> merge with lysosome --> lysosomal enzymes kill pathogen
are NK cells part of adaptive or innate immunity?
innate
interferons
interfere with viral replication
Th1 is important for what type of infection
intracellular (ex: M. Tuberculosis, Listeria)
IL-12
promotes Th1 development (cell-mediated response)
TLRs (toll-like receptors)
recognize PAMPs (pathogen associated molecular patterns) --> secrete cytokines
CD4 T cells (helper T cells)
secrete cytokines and help activate CD8 T cells and B cells and macrophages