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innate immune response
- protection we are born with
- vary amount of cells and chemicals, but we can't change the mechanisms
-
first line defenses
- obstacles to MO invasion
- includes physical barriers, antimicrobial substances, normal flora
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physical barriers
intact skin and mucous membranes
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antimicrobial substances
- in sweat or mucous
- lysozyme: lyce cell walls
- peroxidase: create free radicals
- lactoferrin: hides iron from MO
- defensins: destroy target cell
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normal flora
protect their "turf"
-
communication as an immune response
- surface receptors: self/non-self
- cytokines: chemical messengers
- adhesion molecules: allow damaged tissue to flag for help. ex: interferons
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sensor systems
- recognize breach of 1st line of defense
- ex: TLRs (toll-like receptors) and compliment
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TLRs
- toll-like receptors
- on host cell surface
- recognize and bind to certain molecules that are unique to MO's
- recognize LPS to bind and enfulf and destroy
-
compliment
- group of 20 serum proteins
- when activated it triggers inflammation and MAC (membrane attack complex) on the target (pokes hole in MO)
- classical path to activate- requires Ab's
- non-classical - repeating surface molecules like LPS on gram negative cell wall
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phagocytes
- enfulf and digest invaders
- includes macrophages, dendritic cells, and neutrophils
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macrophages
- derived from monocytes
- surveillance and clean up
-
dendritic cells
in tissues, when they encounter antigen, they migrate to lymph nodes
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neutrophil
first responders to SOS signal
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natural killer cells
- NK
- not phago cytes
- lyse cancer cells (abnormal and foreign)
- lyse viral infected cells
- respond to interferon
-
inflammation
triggered by injury, infection and irritation
-
cardinal signs of inflammation
- erythema
- edema
- heat
- pain (from injury or pressure)
-
function of inflammation
- prevent the spread of damage
- set the stage for repair
- disposes of debris
- alerts adaptive response
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interferon
- alpha and beta IFN are anti-viral and they attract NK cells; produced by viral infected cells
- gamma IFN - secreted by lymphocytes to attract macrophages
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fever
- elevated temp
- controlled by hypothalamus
-
function of fever
- activate and accelerate immune response
- pyrogens - chemicals that induce fever. including lipid A and interleukin 1 (IL-1) which is released by activated macrophages
- sequesters iron and zinc
- speeds up repair
-
origin of immune system cells
- red bone marrow
- hematopoiesis: blood cell formation
- leukopoiesis: white blood cell formation
- stem cells: where all blood cells originate from; pluripotent (they give rise to different types of blood cells)
- colony stimulating factors - dictate what cells are produced
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leukocytes
- granulocytes - named for dark staining granules; multi-lobed nucleus
- agranulocytes - no dark staining granules, single nucleus with no lobes
-
3 granulocytes
- neutrophils
- basophils
- eosinophils
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neutrophils
- 3-6 lobes
- polymorphonucleur neutrophillic leukocytes (PMN)
- phagocytosis
- lyse target with defensins and hydrolytic enzymes
-
basophils
- dark blue granules
- 2 lobed nucleus
- allergic reactions and inflammation
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eosinophils
- reddish/orange granules
- 2 lobed nucleus
- fight parasitic worms
- modulators of immune response
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2 agranulocytes
- mononuclear phagocytes (monocytes, macrophages, dendritic cells)
- lymphocytes (T and B)
-
monocytes
- in blood
- precursor to macrophages
- mononuclear phagocytes
- agranulocyte
-
macrophages
- abundant in spleen, liver, lymph nodes, lungs, and abdominal cavity
- antigen presentation
-
dendritic cells
- highly branched
- go between for the innate and adaptive response
- antigens activate and they migrate to nodes
- antigen presentation
-
lymphocytes
- responsible for adaptive response
- nucleus almost as large as cell
- T lymphocyte: cell mediated immunity and coordinate response
- B lymphocyte: antibody mediated (hemoral) response
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antigen
any substance that triggers an immune response
-
characteristics of adaptive defenses
- specific: recognize and target a particular antigen
- systemic: not restricted to initial site; part of blood and lymph
- memory: recognize and mount a stronger and faster response
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self antigens
MHC proteins on cell surface
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MHC
- major histo compatability complex
- set of genes unique to individual
- code for surface (self) proteins
- MHC proteins - glycoproteins
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2 classes of MHC
- MHC I: all cells except RBC, "window" into cells activity; present endogenous Ag
- MHC II: activated immune cells; macrophages and B cells; presents exogenous Ag
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cells of adaptive response - maturation
- immunocompetent - able to recognize and bind to a specific Ag; must have a surface receptor for this (B cell or T cell receptor)
- self-tolerance: recognize self but are unresponsive, don't attack self
- naive: haven't "seen" real Ag yet but they are ready
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B lymphocytes
- origin: bone marrow
- maturation: bone marrow
- receptor: IgD molecule (Ab)
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T Lymphocyte
- origin: bone marrow
- maturation: in thymus gland
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maturation for T lymphocytes
- positive selection: does it recognize MHCI? If yes then it goes on to the next step, if no then it goes through apoptosis (cell death).
- negative selection: checks for self tolerance. If yes then it leaves the thymus, if no then apoptosis.
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2 populations of T lymphocytes
- 1. cytotoxic T cells - Tc cells
- effector cell - take action, "killer" T cells
- receptor - MHCI + Ag restricted; recognize foreign, abnormal and infected cells
- CD8+
- 2. Helper T cells - Th cells
- coordinator
- CD4+
- TCR - restricted to MHCII + Ag (presented Ag)
- TCR
-
cell mediated immune response
- 1) infected or abnormal cell - present Ag with the MHCI
- 2) Tc Cell - make contact with target cell; release granules to destroy the target
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antibody mediated response
- 1) B lymphocyte
- a) bind to Ag (IgD)
- b) engulfs Ag and processes it
- c) presents Ag w/ MHCII
- 2) APC
- a) engulf Ag
- b) process Ag
- c) presents Ag with MHCII
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antibodies
immunoglobulins
-
structure of antibodies
- four polypeptides; 2 light and 2 heavy chains
- Fab: variable region; binds Ag
- Fc: constant region; can bind complement; host cells
-
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IgM
- pentamer
- large
- mop
- 10 Ag binding site
- First Ab produced
- remain in blood
- agglutination - clumping Ag/ Ab
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IgA
- secretory Ab
- dimer
- secretions - milk, tears, sweat, saliva, and intestinal juices
- protects the "tracts", epithelial surfaces
-
IgD
- B cell receptors
- typical Y structure
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IgG
- gamma globulinds
- typical Y structure
- in blood and tissues
- can cross placenta (maternal)
- fixes complement
- late primary and first in secondary response
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IgE
- Fc region binds to mast cells and basophils to sensitize them
- inflammation and allergic reactions
-
amnestic response
- secondary response
- memory response
- no lag
- higher titer
- lasts longer
- memory b cells
- occurs at 2nd challenge
-
function of Ab's
- neutralization - block Ag from binding
- agglutination
- precipitation - fall out of solution
- activate complement
- opsinization - increased phagocytosis
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natural immunity
- acquired via normal life experience, no medical intervention
- either active or passive
-
active natural immunity
- exposed to microbe and you mount immune response
- if pathogen, you will probably get sick
-
passive natural immunity
- receive antibodies
- maternal Ab's - transplacental or by breastfeeding
-
artificial immunity
- purposefully exposed to Ag or receive immunity
- vaccination - shows Ag in an inactivated or attenuated or acellular for. mount own immune response
- preformed Ab's - gamma globulin shot
-
live vaccines
attenuated - weakened strain
-
inactive or killed vaccine
dead, not capable of infection
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acellular vaccine
- polysaccharides - capsule, LPS
- proteins - viral spikes or receptors
- show you a piece of the virus
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DNA and recombinant vaccines
- DNA - load genes on gold beads and shoot skeletal muscle; muscle cells express gene and show it to immune system
- recombination - package pathogen genes into one MO
-
adjuvant
- increase the efficacy of the vaccine
- boosts immune response
- contains oils
- extends exposure
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