INNATE IMMUNSE SYSTEM

What are the 3 levels of immunity

1.  physical and chemical barriers, skin and mucous membranes

2. Innate (nonspecific)

Adaptive (Specific)

 What are the characteristics of innate immunity?

Innate, present at birth, fast, non-specific, no memory

skin (physical) barriers/components in innate immunity

Skin

• Many layers thick/keratinized 

• Top layer = dry (dead skin)

• Keratin

• Sloughing removes microbes

• Oil glands: acids & oils

• Sweat: lysozyme (enzyme in almost all body fluids, clips peptidoglycan → Gm+ are more vulnerable to this enzyme) & salt

Mucous membrane (innate physical barrier)

Mucous membranes

• Generally one cell layer thick

• has goblet cells that makes it difficult for microbs to adhere (coated in sugars)

• Line: respiratory, GI, genitourinary tract

Eyes (physical barrier)

Lacrimal glands- constant motion makes it hard for bacterial colonization

Salivary Glands (innate physical)

• Secrete saliva

• Prevents colonization

Nasal cavity:(innate physical)

• Turbinates (wind tunnel)

• Nasal hairs

• Mucous membranes

Ciliary-mucus escalator in lower respiratory tract (physical barrier)

• Sneezing: clears mucous from upper respiratory tract

• Coughing: clears mucus/particles from throat/trachea

• Urethra: cleansed by urine

• bodily secretions inhibit growth of pathogens

Digestive (physical barriers)

• Peristalsis

• Vomiting

• Defacation 

Skin (chemical barrier)

• Sebaceous gland: sebum, unsaturated FA, pH 3-5

• Sweat glands: lysozyme & salt

Mouth (chemical)

• Saliva: lysozyme, urea, uric acid, pH 6.5-6.85, IgA

Stomach chemical

• Gastric juice

• pH 1.2-3

• Enzymes

• Staph aureus toxin

• H. pylori neutralizes stomach acid

Vagina (chemical)

• Glycogen in vagina

• Fermented by lactobacillus acidophilus

• Low pH

• Cervical mucus

Bladder (chemical)

Bladder: 

• Urine contains lysozyme

• pH 6

• Urea

Normal microbiota

 inhibit colonization of other microbes

What are the different types of blood cells?

• Erythrocytes (RBCs): transports oxygen & CO2 (gas exchange)

• Leukocytes (WBCs): defense/immunity

• Platelets: blood clotting

Where do the blood cells originate?

bone marrow

How do blood cells differ?

function, hormones, cytokines

monocytes

• blood phagocytes that rapidly leave circulation; mature into macrophages/dendritic cells

Macrophage

• largest phagocytes that ingest/kill foreign cells; strategic participants in certain specific immune reactions

Dendritic cells:

•  relative of macrophage, reside in tissues, responsible for processing foreign matter and presenting it to lymphocytes

• Common: all from macrophage

What do monocytes, macrophages, and dendritic cells have in common?

• all come from bone maerrow stem cells, activate cytokines

1. Describe the process of phagocytosis.

• adherence or microbe to phagocyte

• Ingestion of microbe by phagocyte

• Formation of a phagosome

• Fusion of phagosome with a lysosome = phagolysosome

• Digestion of ingested microbe by enzymes

• Formation of residual body containing indigestible material

• Discharge of waste materials

What are neutrophils?

• one of the first wbcs to respond, phagocytes in blood, active engulfers/killers of bacteria

• Make NETs

NETs:

neutrophil extracellular traps, release chromatin (DNA + histones), eject web-like structure to stop pathogen

Describe inflammation: the process and outcome

basal and mast cells release histamine, vasodilation at site of i injury = increased bf and redness/heat, constriction at other site (fluid build up of clotting factors) capillary permeability increases to release clotting factors to injury

outcome: inflammation, pus (build up of neutrophil, macrophage and pathogen) everything killed

Chemical mediators and cellular response for inflammation

Chemical mediators: Histamine, complements, neutrophils, secreted lactoferrin, wbcs, macrophages

• Cellular response: capillary permeability inceases: blood vessels dialiate at injury site, diapedisis: neutrophils and macrophages move from bloodstream to tissue, phagocytosis occurs to remove damaged tissues and debris

 Describe the pyrogenic response: the process, the chemical mediators, the outcome

•  LPS enters body, macrophages release IL1 and TNF, causes pyrogenic response (causes a fever), travels from blood stream to hypothalamus 

• Process: peripheral tissue: 1) noradrenaline: activation of brown adipose tissue (uncoupling tissue) increases heat, vasoconstriction or vessels in extremities → done to trap heat 2) acetylcholine: activation of muscles (skeletal) for shivering

Pyrogenic response outcomes and chemical mediators:

• Contraction of skeletal muscles (shivering)- ACh

• Vasoconstriction at extremities (noadrenaline)

• Uncoupling protein in brown adipose tissue- releases heat (norepinephrine)

• = Fever develops to slow bacterial growth

• Outcome: shivering (smooth muscle and skeletal muscle contraction), vasodilation at injury site/vasoconstriction at extremities, uncoupling proteins release heat= fever, fatigue

 interferon and its role in immunity

• Secreted protein/cytokines , non-specific immune response to viron

• Stimulates antiviral proteins (AVP) & increased MHC in neighboring cells

• Role: naked virus triggers release of cytokines, binds neighboring cells, acts as warning for neighboring cells, stimulates immunse defense

  
  

Interferon AVPs:

• RNAse enzymes (destroys RNA to stop virus)

• Inactivation of elF2 (slows down protein synthesis)

Describe complement

• nonspecific, inactive in blood and are waiting for a trigger (pathogen)

Compliment activation:

• When triggered, create cascade = complement proteins activate each other and increase phagocytic response: 

• 1. 3a releases histamine

• 2. 3b binds to pathogen surfaces and coats w/ complement (opsinization)

• 5a= creates inflammation= capillaries become leaky → allows fluids out, causes low BP and shock due to inflammation

1. 5b: attracts 5-9 compliment proteins =Come tg/, land, and extend → creates MAC/pore

Compliment outcomes:

MAC: creates pore, causes cell lysis/death of pathogen, can lead to edema

Describe antimicrobial peptides (AMPs). What is their role in immunity?

Small: 12-50 amino acids/proteins

insert themselfs into microbial cell membranes and punch holes in them.

• works better on Gm- due to being positively charged

What are antigen-presenting cells?

3 kinds: macrophages, dendritic cells, b-cells

• recognized by PRRS

• capture antigens, process them, and present pieces of them on their surface to activate T cells.

 What are PAMPs

Pathogen associated molecular patterns (LPS, peptidoglycan, DNA/RNA virus)

• found on pathogens, immune system recognizes as “foreign.”

• activate APCS and PRRs, signal infection

DAMPS

Damage-associated molecular patterns

molecules released by damaged or dying body cells, signal tissue injury

TLRs

• Toll-like Receptors: pathogen recognition receptor

• receptors on immune cells that recognize PAMPs and DAMP

What are eosinophils?

• active in worm/fungal infections, allergy, & inflammatory reactions (granules contain enzymes to pop holes in worms)

What are basophils?

primary response for allergen, releases histamine

What are Natural Killer Cells

• Destroys any body cell not showing MHC type 1

• Cells are active against cancerous/virally-infected cells