1-Innate Immunity Flashcards
immunology
study of host defenses vs infectoius disease and neoplasm and the undesirable consequences of immune interactions
innate immunity
definition
1st line of defense vs microorgs
defense mechanisms that are always present and ready to combat microbes, stand by
keep person alive long enough for more potent response to dev (adaptive immunity)
characteristics
- NOT antigen specific
- exist prior to antigen exposure
- not enhanced following exposure
- always available bc not depend on clonal expansion of antigen specific cells
components
- phagocytes
- natural killer cells
- complement proteins
- interferons
- acute phase proteins
phagocytes
neutrophils
macrophages
dendritic cells
first line of defense after physical barrier
neutrophils
-polymorphonuclear cells/neutrophils (PMN)
-small granules
-either circulating pool or marginal pool of blood and will stay there until recruited
marginal loosely bound to endothelial cells
macrophages
primary functions are NOT immune
1. remove dead cells (wound healing)/inhaled particles/aged RBCs
2. secrete hormones to reg granulocyte and erythrocyte pools
dendritic cells
involved in antigen presentation
-connect innate and adaptive immunity
pattern recognition receptors
- PAMP-pathogen associated molecular pattern molecular structures syn by microbial pathogens i.e. LPS (gram neg) or peptioglycan (gram pos)
- DAMP- damage associated molecular pattern endogenous molecules syn or released from damaged or dying cells i.e. heat shock proteins
toll like receptors
TLR
bind to PAMPs to recognize bacterial or viral products
TLR2 = bacterial peptidoglycan
TLR4 = LPS
-both @ plasma membrane
phagocytosis steps
- attachment- nonspecific antigens, if encapsulated in sugar/polysacc coating then must be opsonized
- ingestion- pseudopods/plasma membrane wraps around particle until fuse together/zip = phagosome once internalized
- digestion- lysosomes fuse with phagosomes = phagolysosome to degrade microbial components
opsonization
coating of a microbe with antibody (IgG) or complement (C3b) to facilitate phagocytosis bc phagocytic cells have receptors for IgG and C3b
respiratory burst
-inc consumption of oxygen during phagocytosis bc NADPH oxidase = superoxide anion
-also hydroxyl radical, singlet oxygen, hypochlorite are toxic just not made by NADPH
damage membranes, proteins, nucleic acids
chemotaxis
directed movement up a chemical gradient of a chemotactic factor
so phagocytic cell can find target microbe
chemotactic factors
- C5a
- leukotriene B4 (from arachidonic acid)
- chemokines (from macrophages @ site of infection)
- bacterial lipids and proteins
natural killer cells
characteristics
- large granular lymphocytes
- not specifically recognize antigens
- kill virus infected cells and tumor cells via perforin that forms pores in plasma membranes of target cells
- mediate antibody-dependent cell mediated cytotoxicity (ADCC)
- highly activated when exposed to interleukin-2 or interferons
either target cell itself or antibodies
complement cascades
sequentially activated soluble serum proteins to make pores in cell surface and opsonize antigens
pores lead to osmotic lysis
complement pathways
- alternative- initiation @ microbe
- classical- initation @ antibody
- lectin- mannose binding lectin, dont need to know
all paths end with membrane attack complex (MAC) that makes pores
classical pathway
complement
activation requires 2 IgGs spaced apart OR 1 IgM pentamer for antigen to bind and start complement, free antibody will not work
IgM more efficient than IgG at activating
alternative pathways
complement
don’t need antibody to initiate can just bc directly on microbial surface
important as host defense vs infectious pathogens
lysis
function of complement proteins
C5-9 = membrane attack complex aka MAC > osmotic lysis via pores
opsonize
function of complement proteins
via C3b to promote phagocytosis
anaphylatoxins
functions of complement proteins
C3a, C4a, C5a
all bind to receptors on mast cells and basophils to release histamine
chemoattractants
functio of complement proteins
by C3a and C5a to stimulate chemotaxis of neutrophils to site of production
immune complex removal
function of complement proteins
antigen-antibody complexes coated by C3b to bind to erythrocytes and be removed by phagocytic cells in liver and spleen
regulation of complement
DAF (decay accelerating factor) compete with C3b to prevent formation of convertases
CD59 prevent binding of C9 to complete MAC
if not have either then proxysmal nocturnal hemoglobinuria aka lysis of RBCs by complement
low yield
meningitis
if deficient in any of C5-9 then 10,000x inc chance of infection with N. meningitidis that gives you meningitis
complement deficiencies
C2 most common but also have C3-4, C1q-s
inc incidence of pyogenic infections aka pus producing
immune complex diseases like lupus
C1 inhibitor
results in hereditary angioedema (HAE) so when emotional stress or trauma complement activated + bradykinin
edema in skin and larynx (life threatening)
restricts spontaneous activated of C1 in plasma and regs hageman factor that gives rise to HAE if no inhibitor
interferons
type 1 interferon = alpha + beta IFN
-inhibits viral replication via paracrine action
-enhance cytolytic capability of NK cells
-inc cellular expression of class I MHC molecules
acute phase proteins
syn by liver in response to interleukin 6 from macrophages after infection into bloodstream
C-reactive protein, mannose binding lectin = opsonins
-CRP also activate classical complement by C1q
fibrinogen, serum amyloid A protein too
