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