2.1 - Innate Immunity Flashcards
What are the mechanisms of defence?
1) 1st Line - Innate
- always active
- includes barriers
- provides immediate protection, but short-term immunity
2) 2nd Line - Inflammation
3) 3rd Line - Adaptive
- evolves over time
- targets pathogens through a tailored response
- slower acting, provides longer-lasting immunity
Physical Barriers in the 1st Line of Defence
- skin and the linings of tracts within the body
1) shedding of cells - expulsion of cells removes invaders
2) coughing and sneezing expel pathogens from the resp tract
3) vomiting expels pathogens from the stomach
4) Peeing clears pathogens from urinary tract
5) Cilia moves mucous out of the lungs
What are the 2 chemical barriers in the 1st line of defence?
1) Epithelial Cells
- epithelial cells secrete fluids - tears, ear wax, saliva, sweat, mucous - which contain antimicrobial peptides
- antimicrobial peptides inhibit growth/kill bacteria
2) Microbiome
- contains bacteria that outcompetes other harmful organisms trying to invade
What is the 2nd line of defence?
- inflammatory response
- triggered by ischemia, trauma, necrosis, injury, foriegn bodies
Process of Inflammation
1) Vasodilation - increases blood flow to the area; causing redness and heat
2) Vasodilation increases vascular permeability; more fluid and immune cells leak into tissue; causing inflammation
3) Immune cells (leukocytes) adhere to vessel walls and travel to site of injury
- the vascular response is need to recruit immune cells to the effected site
What are the goals of inflammation?
1) Prevent further damage: isolate harmful agents
2) Control inflammatory process
3) Initiates adaptive response
4) Initiates healing
What are the 3 Plasma Protein Systems
- plasma protein are formed in plasma of liver cells
1) Complement
2)Clotting
3) Kinin
Role of the Complement System
PHAGOCYTES
- produces fragments that recruit phagocytes and destroy pathogens
Role of the Clotting System
FIBRIN
- forms the fibrin mesh at site of injury
Function of The Mesh
1) Prevents spread of infection
2) Localizes bacteria
3) Forms a clot to stop bleeding
4) Provides framework for healing
Role of Kinin System
BRADYKININ
- assists inflammatory cells
- Bradykinin: causes vasodilation and increases vascular permeability
What are the 4 Types of Cytokines
Cytokines - intracellular signalling molecules that activate the inflammatory response
1) Chemokine’s
- made by many cells
- guides immune cells to the site of injury (induces chemotaxis) (allows phagocytosis)
2) Interleukins
- produced by macrophages and lymphocytes in response to stimuli
3) Tumour necrosis factor alpha
- secreted by macrophages in response to a pathogen
- in excess, can cause muscle wasting and thrombosis
4) Interferon
- produced and releases by virus infected cells
- induce antiviral state in neighbouring cells to limit spread of infection
Blood Cell Types and Functions
Erythrocytes - RBC’s
Platelets - aid in clotting
Leukocytes (BEN)
1) neutrophils - early responders
2) eosinophils - combat parasitic infxns
3) basophils - release histamine
Monocytes
- differentiate into macrophages and dendritic cells
- macrophages: engulf pathogens
- dendritic cells: antigen presentation
Lymphocytes
- T cells -
- B cells - produce antibodies that target pathogens
- Natural Killer cells - directly attack infected cells
Mast Cells
- mast cells are immune cells
- found in loose connective tissue (skin, resp tract, blood vessels)
- contain granules which are packed with histamine, cytokines, and chemotoxic factors (recruit immune cells)
- basophils also release histamine
Degranulation
- process by which immune cells (mast cells) release the contents within their granules into surrounding tissue to fight infection
Function of Histamine
1) constricts large blood vessels and dilates small blood vessels
- increases blood flow to area
2) increases permeability of endothelial cells
- creates gaps b/w endothelial cells allowing fluid and immune cells into surrounding tissues
- helps immune cells reach site of infection
Role of the Endothelium
Endothelial cells
- line the surface of blood vessels
- adhere to connective tissue
- interact with circulating platelets
Damage to endothelial cells
- when endothelial cells are damaged, platelets leak out of exposed vessels and adhere to tissue to start forming a clot
- endothelial cells control ho many cells and proteins enter/exit the tissue to regulate inflammation
Function of Platelets
- platelets are activated by tissue destruction and inflammation
- once activated, platelets interact w coagulation cascade and undergo degranulation
- plts release serotonin - promotes vasodilation and increases vascular permeability
Difference in Function of the 3 types of Leukocytes
Neutrophils
- most abundant
- early responders
- ingest bacteria and dead cells via phagocytosis
- short-lived and eventually become part of the pus
Eosinophils
- defend against parasitic infections
- mildly phagocytic
Basophils
- least abundant
- releases histamine (and other mediators)
- often associated w allergic rxns
How do monocytes contribute to inflammation?
Monocytes - produced in the bone marrow, enter circulation, travel to effected site where they mature into macrophages
1) Macrophages - arrive at site quickly
2) DendritIc Cells - migrate through lymphatic system and interact with T cells to initiate adaptive immune response
Function of Phagocytosis
- to ingest and eliminate foreign/harmful material
- when inflammation occurs, blood vessel walls and immune cells produce adhesion molecules; helps immune cells stick to blood vessels
What is Diapedesis?
- how white blood cells squeeze through gaps of endothelial cells to move out of the bloodstream into surrounding tissues
Steps/Process of Phagocytosis
1) Adherence
- immune cells stick to receptor on surface of target
2) Engulfment
- cell wraps itself around the target
- cell eats the target and pulls it inside itself
3) Phagosome formation
- once target is inside cell, cell uses its own membrane to enclose the target
4) Fusion with lysosomal granulation
- phagosome fuses with lysosome which contains digestive enzymes
5) Traget Destruction
- digestive enzymes break down and destroy target
Function of Natural Killer Cells
- recognize and eliminate infected cells
- produce cytokines and toxic molecules to directly kill cells
How do NK cells differentiate bw normal and abnormal cells?
- healthy cells send inhibitory signals to NK cells so they do not attack
1) when cell sends inhibitory signals, NK cell knows not to kill it
2) If cell does not send inhibitory signals, NK cells knows it needs to destroy it
Acute Inflammation
- resolves once the harmful stimulus is removed
- immediate response to injury
Local manifestations
- heat
- swelling
- redness
- pain
- exudative fluid accumulation
4 Types of Exudative Fluids
1) Serous
- watery
- indicates early inflammation
2) Fibrinous
- thick, clotted
- contains fibrin
- indicates advanced stages of inflammation
3) Purulent
- pus
- indicates infection
4) Hemorrhagic
- contains blood
- indicates bleeding
- results from severe injury/damage
Systemic Manifestations of Acute Inflammation
1) Fever
- causes by pyrogens that act on hypothalamus (which regulates body temp)
- fever create less favourable environment for pathogens
2) Leukocytosis
- increased WBC count to fight off infection
3) Increased Plasma Protein Synthesis
- during inflammation, liver increases production of plasma proteins (aid in healing)
Lab Tests for Inflammation
1) Fibrinogen
- protein that aids in clotting
- increased if inflammation ouccrs
2) ESR
- measures how quickly RBC’s settle to bottom of test tube
- faster rate indicates inflammation
3) C-reactive protein (CRP)
- higher levels indicate inflammation
What is Chronic Inflammation
- inflammation lasting > 2 weeks
Results from:
1) pathogens were not phagocytosed
2) microorganisms w high lipid content - harder to break down
3) continuous exposure to toxins, irritants
Characteristics
- pus (purulent exudate)
- accumulation of lymphocytes and macrophages
- granuloma formation (groups of macrophages)
- giant cell formation (macrophages fuse together)
3 Steps of Wound Healing
1) Resolution
- tissue can be restored to original structure and function
- damage was minimal
2) Repair
- damaged tissue is replaced with scar tissue
- scar tissue restores tissue strength, but does not restore function
3) Healing
1. Fill - tissue covers wound
2. Seal - epithelial cells grow over
3. Shrink - cell contract + pull edges
together
2 Types of Wound Healing
1) Primary (assistance)
- wound heals with minimal tissue loss
- wound is restored with sutures, glue, staples
2) Secondary (no assistance)
- wound is allowed to heal naturally
- when wound is either TOO small or too large/complex
Phases of Wound Healing
1) Inflammation
- coagulation: blood clot occurs
- infiltration: cells move into wound
- angiogenesis: new blood vessels form ( to supply nutrients to healing wound)
2) Proliferation
- granulation: new tissue forms
- epithelialization - epithelial cells cover the wound
- fibroblast proliferation and collagen formation: provides structural support
3) Remodelling
- cell differentiation: cells adapt to diff roles in healing
- scar tissue forms
- scar remodelling: overtime, it reorganizes and becomes stronger
Dysfunctional Wound Healing
Occurs due to:
1) ischemia - not enough blood supply
2) excessive bleeding - disrupts clot formation
3) excessive fibrin -
4) predisposing disorders: diabetes, obesity, inadequate nutrition, meds, tobacco
Dysfunction during reconstructive phase is due to:
1) dysfunctional collagen synthesis
- keloid: raised scar
- hypertrophic scars
2) wound disruption
- dehiscence: wound edges separate
3) Impaired contraction
- contracture
