Immunity = resistance, the bodys ability to ward off infectous diseases
Susceltibility = no immunity - vulnerable to a disease
Difference between innate & adaptive immunity
Innate immunity = nonspecific defenses against any pathogen - present at birth
- Adaptive immunity = resistance to a specific microbe - memory involoved - recognition of a specific microbe
- -acquired over a lifetime
1st line of defese
1st = skin & mucous membranes, normal microbiota
2nd = NK cell (nonspecific), inflammation, fever, antimicrobial substances
3rd = T & B lymphocytes, Ab (specific immunity)
How is skin protective?
Skin is structural barrier - 2 layers - dermis & epidermis
- Epidermis - tighly packed cells w/ cell junctions plus keratin - protien that form dense outer layer
- - hard to get thourgh unless broken
- Physical factors:
- 1. Keratin
- 2. Shedding - removes microbes
- 3. dryness - dosent support life
- Chemical Factors:
- 1. Sebum - lactic acid = pH 3
- 2. Lysozyme -breaks down peptidoglycan cell wall -Gram (+) bacteria - found in sweat, tears, saliva
How are mucous membrane protective?
- mucous membranes line the respiratory, GI & GU
- - thinner - less physical resistance than skin
- - produce mucous (goblet cells)
1. muco/ ciliary escalator - microbes are trapped in mucous and moved via cilia - moved away from lungs where they can be spit out or swallowed
2. lactomial apparatus - tears - contain lysozyme (eats peptidoglycan) and dilutes & washes away microbes
3. Dilution - flow of fluids prevents colonization - saliva, urine, vaginal secreations, defication & vomiting
- 4. Chemicals -
- -HCl in stomach
- -lysozyme (sweat, tears, salvia)- breaks chemical bonds in pepdidoglycan
What part does normal flora play in defense?
- Normal flora prevents the overgrowth of pathogens.
- Nomal flora is a result of competitive exclusion:
- - compete with pathogens for nutrients
- - produce toxins that kill other pathogens
- - change condtions to kill other pathogens -pH, O2
What is transferrin?
Transferrin - binds & transports Fe - keeps it away from microbes that need it
2nd line of defense - 7 parts
- 1. Phagocytosis - PMN, macrophages, dendritic cells
- 2. Inflammation - from tissue damage
- 3. Fever
- 4. The complement system
- 5. Interferon - blocks viral replication
- 6. Transferrins
- 7. Antimicrobial peptides - lysis
What are granulocytes? List 4 & function
Granulocytes are leukocytes (WBCs) that have large granules in their cytoplasm - can be seen under microscope
- 1. Neutrophils (PMNs) 70% - phagocyte- first to attack - leave blood to move into tissue
- 2. Basophils (1%)- histamine → vasodilator/ increases permeability
- 3. Eosinophils (3%)- release histamine - seen in allergic reactions
- 4. Dendritic cells - APC (Ag presenting cell) - phagotize cell & present parts to T cells (initiate specific immunity)
PMN - polymorphonuclear leukocyte
What are agranulocytes? 2 & function
- 1. Lymphocytes
- a. T cells - specific immunity
- b. B cells - specific immunity
- c. NK cells - non-specific
- 2. Monocytes → macrophages
- monocytes in blood mature into macrophages in tissue
- (kidney bean shaped nucleus)
What is a CBC w/ differential?
- CBC = complete blood count
- Differential = % of each type of WBC out of 100 WBCs
- -diagnostic hospital test
- Normal %:
- 1. Neutrophils - 60-70%
- 2. Lymphocytes - 20-25%
- 3. Monocytes 3-8%
- 4. Eosinophils 2-4%
- 5. Basophils .5-1%
What is phagocytosis?
- - Ingestion of microbes
- - Activated by cytokins (immune mediators released by WBCs)
PMNs, Eosinophils, macrophages, dendritic cells (APC)
What cell is a macrophage derived from?
Where are fixed & wandering macrophages?
- phagocytic - derived from monocytes once they leave the blood stream
- Fixed macrophages
- Dust cells - lungs
- Kupffer cells - liver
- microglial cells - nervous system
Wandering macrophages - roam through tissue and gather at sites of infection
What are the functions of eosinophils, basophils, & dendritic cells?
- Eosinophils = phagocytic - can leave the blood
- - produce toxins to kill helminths & other paracytes
- - release histamine - involved in hypersensitivity reactions
- produce histamine - called Mast cells
if in tissue
- look like dendrites of neurons - phagotize microbes & initiate specific immunity by presenting to T cells - APC = Ag presenting cells
5 stages of phagocytosis
- 1. Chemotaxis - chemical attraction of WBCs to the microbes location
- - chemotactic factors: leukotrienes, complement, cytokins
- microbe is opsonized
(coated with complement or host Abs) phagocyte then adheres
- in vesicle called a phagosome
- lysosomes attach & secrete lysozyme - called a phagolysosome
5. Residual body
- digested remains (unusable parts) are discarded from the phagocyte (exocytosis)
How can microbes evade phagocytosis?
1. block adherance - M protein on cell wall and capsules
2. Kill phagocytes - once inside hold cell, bacteria uses leukocidins to release lysozyme into host cell cytoplasm
3. Lyse phagocyte - MAC - membrane attack complex
4. Escape from phagosome - leave vesicle
5. Live inside phagocyte
What are the clinical signs of inflammation?
- 1. Redness - increased blood flow
- 2. Heat - increased blood flow
- 3. Edema - swelling- from increased vascular permeability
- 4. Pain - PGs, kinins - mediators released from cells
3 phases of inflammation
- 1. Vasodilation and increased vascular permeability - caused by histamine, kinins, PGs, and leukotrienes cause
- - edema (increased interstitial fluid)
- - hyperemia (increased blood flow)
- 2. Pagocytosis - phagocytes migrate to site of infeciton then:
- margination - sick to blood vessel
- emigration - exit blood vessel to tissue
- 3. Tissue repair - removal of microbes & debris
- repairs by parenchymal cells (functioning part of tissue)= near perfect reconstruction of tissue
- repair by stroma cells (supporting CT) = scar tissue
What mediators are vasodilators & ↑ vascular permeability?
histamine, kinins, Pg's, Leukotrienes
Is compliment an acute phase protein system?
Acute phase proteins = proteins are present in the blood in an inactive form and are converted to an active form during inflammation.
Compliment is an acute phase protien system becuase Compliment proteins are present in the blood but are inactive until they are split into fragments.
What is complement?
- Defensive system of 30 serum proteins - made in liver
- C1 - C9 - fragments created with activation
cascade effect - each reaction triggers another
How does complement destroy mictrobes?
1. Cytolysis - MAC - membrane attack complex (cell lysis)
- 2. Inflammation -
- - Mast cells (Mature basophil in CT) release huistamine
- - some complement are chemotactic factors
3. Phagocytosis - complement opsonizes microbes
3 complment pathways
1. Classical - Ab/Ag complex activates complement cascade (each reaction triggers another)
2. Alternative - Pathogen directly activates the complement cascade
3. Lectin - Macrophages release cytokins when they injest a microbe → cytokins stimulate liver to realese lectins (proteins that bind carbs) → lectins activate complement
all three pathways lead to opsonization, inflammation, & cytolysis
What is a mast cell?
A mature basophil that is found in connective tissue
What is chemotaxis? What are chemotactic factors?
Chemotaxis is the chemical attraction of phagocytes to microorganisms
- Chemotactic fators - chemicals that draw phagocytes
- - Cytokins
- - complement
- - WBC compontnts
- - damaged tissue cell components
- Fever can be beneficial - ↑rate of tissue repair
- -↑ T cell production (IL-1)
- -↑ interferon effect (block replication)
- -↑ transferrins (hog Fe)
- Triggers are called pyrogens (cytokins, PGs, complement)
- Cytokins (released from damaged cell)→ hypothalamus releases PGs→ PGs reset hypothalamus thermostat to higher temp
- ↑ thermostat setting causes body to increase temp by
- - constiricing blood vessels
- - ↑ metabolism
- - shivering
- When temp reaches thermostat setting the chill subsides - when thermostat setting returns to normal body looses heat:
- - vasodilation
How does aspirin work?
Aspirin works by inhibiting PG synthesis
- made by virus infected host cells (often lymphocytes, macrophages, fibroblasts (CT))
- stimulates normal cells to make "antiviral protein"
- nonspecific - block viral replication - any virus
- used as Rx - Hep B, influenza, viral cancers
- Innate Immunity - Made in liver
- -act as broad spectrum (kills most bacteria & viursus) bactericidal (kills bac) antibiotics
- - can kill some cancers & enveloped viruses
- - can kill some microbes that are resistant to antibiotics