- toll-like receptors (TLRs), pattern recognition molecules (PRR), PMNs, monocytes, macrophages, eosinophils, Natural Killer cells (NK)

Innate Immunity Cells

- play an essential role in both innate AND adaptive immune respones

Cytokines

- does NOT generate specific immunologic memory

- present at birth

- not learned

- not triggered by any specific antigenic recognition

- rapid defense against invading microbes (within hours)

Innate Immunity

- innate immune system recognizes these microbial structures via PRRs and TLRs

- expressed by microbes and NOT by host

- Example: LPS, viral double-stranded RNA

Pathogen-associated molecular patterns (PAMPs)

- PRR and TLR activiation mobilizes the innate immune response, leading to up-regulation of these co-stimulatory molecules

- leads to priming of T cells

Inflammatory cytokines

- LPS and TLR ligands activate pathways that activate and/or express these

transcription factor NF-kB, tumor necrosis factor-alpha (TNFa), and interleukin-1 (IL-1)

- nuclear transcription factor regulating the expression of a large number of genes involved in apoptosis, viral replication, inflammation, and autoimmune disease

- in active form, found in the cytoplasm

- activated by stress, growth factors, cytokines, drugs

NF-kB

- has a pH of 4.5-5.5

- consists of sebum and sweat

- found on intact epithelial (first line of defense)

'Acid Mantle'

- MALT tissue/Mucosa traps microbes and passes them onto this structure for excretion

respiratory escalator

- acidity of stomach (pH 1-2) from KCl and HCl

- Lysozyme found in saliva, tears, sweat, human milk, cytoplasmic granules of PMNs, and mucus (hydrolytics carbohydrase -->peptidoglycan breakdown [Gram +])

- acidity of vagina (pH 3.8-4.5)

- Proteolytic enzymes and bile in GI tract

Biochemical Immune Defenses

- when an antibody or component of complement cascade (C3B) coats the enemy and augments phagocytic activity

Opsonization

- major phagocytic cells that migrate into tissue

- short-lived and possess proteolytics-rich lysosomes

- first cell to arrive at sites of injury because of chemotactic factor attraction (chemokines)

- does not present antigen

Polymorphonucleated neutrophils (PMNs)

- enables the binding of PMNs

- induced by cytokines (inflammatory mediators from adhesion molecule interaction) which are produced as a result of infection

Selectin

- many different cell-surface receptors

- WBCs engulf particles and/or microbes and destroy them

- Kupffer cells (liver), alveolar/splenic/peritoneal macrophages, microgial cells (brain), Langerhands cells (skin), DENDRITIC CELLS (APC)

- Example: mannose receptor or scavenger receptors

Monocytes/Macrophages

- has polysaccharide capsule that inhibits phagocytic engulfment

- can survive inside of phagosomes (prevent discharge of lysosomal contents)

- can survive inside the phagolysosome

Pathogenic (mutated) bacteria

- couples the innate and adaptive immune systems

- phagocytize and present epitopes to TcR

- macrophages, dendritic cells, B-lymphocytes

- professional and non-professional

-express MHC Class I (and II)

APCs

- macrophages, dendritic cells, B-lymphocytes

- activate T helper cells

- express MHC Class I & II

Professional APCs

- fibroblasts, thymic epithelial, glial, pancreatic, and vascular epithelial cells

- express only MHC Class I

Non-professional APCs

- formed during chronic inflammation from macrophages

- predominant cell that froms progressive plaque lesions associated with atherosclerosis

Granulomas (inflammation lesions)

- compromised during sepsis or septic shock (severe bleeding)

- Streptococcus secretes an exoenzyme called streptokinase that lyses fibrin clot

- protects host from microbial infections

- PMNs degrade an inhibitor of coagulation that locally "traps" bacteria

Coagulation

- delivers vasoactive proinflammatory mediator bradykinin (BK)

- poorly delineated system of blood proteins that play a role in inflammation, blood pressure, coagulation, and pain

- exert significant effect in various surface-mediated defense reactions

Kallikrein-Kinin system

- biochemical cascade that helps the ability of antibodies to clear pathogens via inflammation

- proteins/fragments make up system including serum and serosum proteins

- account for 5% of globulin fraction of blood serum

Complement System

- enhances phagocytosis of microbes

Complement fragment C3b

- large family of small protein molecules that have a specific effect on the interactions that occur between cells (communication & behavior)

- interleukins, lymphokines, TNFa, interferon

Cytokines

- small cysteine-rich cationic proteins

- active against bacteria, fungi, viruses

- found in PMNs and most epithelial cells

- bind to microbial cell membrane, form pore-like membrane defects

Defensins

- primarily expressed in PMNs and NK cells

- Paneth cells in the gut express these

Alpha defensins

- most widely distributed defensin

- secreted by leucocytes and epithelial cells

- found on tongue, skin, kidneys, esophagus, and respiratory tract

- an imbalance may cause acne

Beta defensins

- proteins that respond to inflammation by increasing or decreasing levels

Acute-phase proteins

- granulocytes and macrophages secrete these cytokines into the blood stream following injury

- 'Fantasic Four' of inflammatory response

- incite fever

interleukins (IL-1, IL-6, IL-8 and TNF-a)

- common measurement of acute-phase proteins that indicates inflammation

C-reactive protein

- concentrates immune competent cells at the site of injury

- blood supply increases to that area

- capillary permeability increases

- WBCs migrate out of venules attracted by chemotactic factors (cytokines/chemokines) and the complement cascade

Inflammation

- four words to describe inflammation

- swelling, redness, heat and pain

Tumor, Rubor, Calor, Dolor

- complement cascade component primarily associated with optonization

C3b

- complement cascade component primarily associated with chemostasis

C3a

- complement cascade component primarily associated with inflammation

C5a

- large granular lymphocytes, 'front line of defense'

- deficiency --> persistent viral infection (herpes)

- 5-25% of blood lymphocytes

- kill certain virus-infected cells and tumor cells without prior stimulation (lack antigen-specific receptors)

- kills by 'hand-to-hand' combat

Natural Killer (NK)

- checks for MHC Class I surface markers (all nucleated cells possess them)

- if it can't bind with killer-cell inhibitory receptors (KIR), it kills

Natural Killer Cell (NK)

- principal cytokine released by NK cells

IFNy

- protein that allows the NK cells to kill non Class I MHC bearing cells via the MAC

- creates pores in the plasma membrane

Perforin