CH1&3

to distinguish between self and oneself and recognize pathogens

innate immune system and adaptive immune system

antigen-specific receptors

1. recognition of foreign and dangerous material
2. early innate response to recognition
3. slower specific response to particular antigen (adaptive response)

memory of specific immune responses

provides a quicker and larger response when that particular antigen is encountered a second time

skin
mucous membranes & secretions
sweat (which contains lactic acid)
cilia
urine
normal flora

innate immune cells
inflammation
complement
antimicrobial substances

B cells
T cells

immediate response to pathogen
promoting phagocytosis
very efficient
always present
constitutively expressed

ability of the host to resist infection by means of normally present body functions

no prior exposure is required; nonadaptive or nonspecific

identical response for all pathogens or foreign substances (no memory!)

same response every time

physical barriers
phagocytic cells
protective chemicals
enzymes
recruitment of other inflammatory cells

acid pH, surface lipids

saliva, digestive tract enzymes

complement

anatomic barriers
physiologic barriers
phagocytic barriers
inflammatory barriers

unbroken skin
psoriasin
lactic acid
respiratory tract
flushing action of urine
keratinocytes
stomach
tears (antibacterial enzymes)

unbroken skin

small protein produced by skin cells that has antibacterial effects

make skin impermeable to most infectious agents

skin and mucosal membranes
prevent pathogen entry into the body's interior

expel microbes

produces lysozymes

mucus (trapping microbes) and cilia (expelling mucus)

colicins

protein produced by normal flora that binds to surface of bacterial (to kill them)

PMN
eosinophils
baso
mono
lymphs
macrophages
mast cells
dendritic cells

covered with long extensions
most effective Antigen Presenting Cell (APC)

-contains cells for phagocytosis and soluble factors
-recognizes microbiota molecules unique to infectious organisms
-enhances phagocytosis
-enhanced by acute phase reactive (soluble factors)
-mechanism to distinguish pathogens from normal using PRR on immune cells

facilitate contact with microbe and or clean up after phagocytosis

present on macrophages, dendritic cells, neutrophil, eos, mono, mast cell, epithelial cells, cells binding pathogens

to recognize pathogen if they escape first line of defense by binding pathogen and phagocytic cells to being phagocytosis
(although part of the innate response, it is slightly more specific)

Toll-like Receptors (TLR) on certain human cells

membrane-spanning glycoproteins that share a common structural element called leucine-rich repeats (LRRs) found in endosomal compartment or cell surface
-recognizes a different pathogenic product

mono, macrophages, and PMN

PRR distinguish self from oneself b pathogen-associated molecular patterns (PAMPS)

only on microorganisms

TLRs on cell surface tend to form dimers to increase changes of binding to foreign substance

on macrophages and neutrophils

part of internal defense of innate

increases with infection, trauma or injury, stimulated by cytokines causing phagocytosis or proteolytic enzyme release

primarily produced by hepatocytes in response to IL-1, TNF and IL-6
(cytokines released from monos and macrophages during inflammation)

C-Reactive protein (CRP)

hsCRP

CRP, hsCRP, the complement system, mannose-binding protein

-pathogen breaches outer barriers of innate immunity
-body's reaction to injury or infectious agent-cell and humoral mechanisms

redness
swelling
heat
pain

neutrophils

neutrophils proportional to level of chemotactic factors present in the area

24 to 48 hrs

16 to 48 hrs

macrophages attempt to clear involved area through phagocytosis

tissue damage and loss of function

1. mq and mast cells release chemokines that cause vasodilation and induce selectins
2. selectins bind to circulating leukocytes, roll to vascular wall
3. chemokine-induced integrins bind to endothelial cells
4. integrins enable leukocytes to crawl between endothelial cells (diapedesis)
5. leukocytes follow chemokine concentration gradient to the site of infection (chemotaxis)

loosely bind circulating leukocytes and cause them to roll along the vascular wall

induced integrins on the leukocytes that bind firmly to endothelial cells

integrins enable the leukocytes to crawl between endothelial cells (diapedesis)

when leukocytes crawl between endothelial cells

1. physical contact between WBC and foreign particle
2. formation of phagosome
3. fusion with cytoplasmic granules to form a phagolysosome
4. digestion and release of debris to the outside

anaerobic glycolysis

when phagocytosis is triggered by oxygen dependent process
-produces greater energy than oxidative metabolism

HMP shunt is used to change nicotinamide adenine dinucleotide phosphate (NADP) to its reduced form (NADPH)

hexose monophosphate

NADPH reduces oxygen to superoxide (2O2-) when NADPH oxidase complex (NOC) is assembled in membrane of phagolysosome

catalyzes the conversion of superoxide to hydrogen peroxide (H2O2)

MPO catalyzes formation of hypochlorite (OCl-), a strong oxidizing agent

strong oxidizing agent

taken into phagosomes (and fused with lysosomes or granules)

enzyme degradation
antimicrobial proteins
toxic effects of reactive oxygen and reactive nitrogen species (ROS and RNS)

NADPH donates electron to oxygen to NADPH oxidase, which is only activated by conformational change triggered by microbes

superoxide (O2-) is formed

converts superoxide to hydrogen peroxide or the hydroxyl radical OH

effect is potentiated (increased) by the formation of hypochlorite ions

by PMNs marginating along blood vessel walls, allows them to move from blood vessel into interstitial space

messengers that attract PMN to site of inflammation

complement components, PAF, etc

enhances phagocytosis

serum proteins that attach to a foreign substance and help prepare it for phagocytosis

C-reactive protein
complement components
antibodies

action of myeloid cells

neutrophils, basophils, eosinophils, monocytes & macrophages, mast cells, dendritic cells

involved in inflammatory and allergy reactions
leave capillaries and enter connective tissue as mast cells
release heparin, histamine & serotonin

heighten the inflammatory response and acct for hypersensitivity (allergic) reaction

can enhance and suppress the adaptive immune response

mast cells

play a role in allergic reactions

mast cells

tissue-derived monocytes, name based on tissue location

microbial killing
anti-tumor activity
intracellular parasite eradication
phagocytosis
secretion of cell mediators-cytokines

macrophages

dendritic cells

first line against viral/tumor cells

no prior exposure needed to recognize and eliminate these cells

stimulated by IL-12, interferon- alpha (IFN) and IFN-beta, localizes in tissue where inflammation is occurring

in 3 days

produces IFN-gamma and tumor necrosis factor (TNF-alpha)

helps to recruit T cells

Natural killer (NK) cells

monitors for class I MHC protein presence and no foreign or stress protein

send inhibitory signal sent to NK cell; no killing and normal cell is released

lose ability to produce MHC proteins

no inhibitory signal is given by NK cells, granzymes and perforins are released, infected cell is eliminated by apoptosis

create pores

enzymes the mediate lysis

infected cells may express foreign proteins on surface that are recognized by antibody

NK cells express CD16-receptors that bind the immobilized antibody and activate the release of perforins and granzymes (antibody dependent cell-mediated cytotoxicity)

antibody dependent cellular cytotoxicity

binds to antibody coating the target cell in Ab (NK cell will lyse cell coated with Ab)

monos, macrophages, and PMN

serious viral infections and incidence of tumors