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Immunity (Introduction (Innate Immunity - non specific response
1st…
Immunity
Introduction
Role of immune system
- Defence against pathogens
- Maintain memory
- Kill and remove microbes, cancer transformed cells, virus infected cells, rogue leukocytes
- Tolerate self and untransformed self
Pathogenicity
- Pathogens may enter host cells, attach to host tissues and proliferate while evading host defences
- Damage may be caused by:
a. excessive host response induced by pathogen
b. virulence factors: molecules produced by bacteria, fungi, protozoa that add to their effectiveness and enable them to achieve colonisation in host, evade host's immune response, suppress host's immune response, gain entry and exit obtain nutrition from host
c. genetic predisposition e.g. susceptibility
Host Immune Response
- Differs due to genetic and environmental factors
- Is lowered with age, disease, medication , malnutrition
- Can prevent invasion, colonisation, excessive immune response
- may cause collateral damage e.g. autoimmune diseases
- must be down regulated after threat is over
- immune tolerance exists
a. can be self-tolerance
b. induced tolerance, tolerance to external antigens
Innate Immunity - non specific response
- 1st line of defence
- skin
- mucous membranes and secretions
- normal flora
- 2nd line of defence
- innate immune cells: phagocytic cells, NK cells
- inflammation
- complement
- antimicrobial proteins
- Three classification of function
- cells and cell products for physical barriers and effector cells
- receptor recognition to sense microbe presence and initiate host defence response
- proteins: enzymes, inflammatory proteins, CRP, lectins, antimicrobial
- Provides early defence against infections
- instructs adaptive immune system by directing specific behaviours effective for specific microbes
- constant bi-directional cross-talk occurs between innate and adaptive immunity
Acquired Immunity - slower responses to specific microbes
- humoral response via antibodies
- cell-mediated response e.g. cytotoxic lymphocytes
a. b-lymphocytes/ b cells produce antibodies
b. t cells --> helper t cells, killer t cells
- specifically recognise single type of threat
- immunity is upon 2nd exposure
Dental Clinic
- pt may have immuno-deficiencies
a. pt will have excess umber and severity of infections
b. relatively common infection may be persistent
c. will be prone to malignancy
- pt with autoimmune diseases will have loss of regulatory and surveillance cells
- pt may have history of allergies
Innate Immunity
Cell and Cell Products
- Barriers protects from microbe entry, can be physical, mechanical or chemical barriers
- continuous lining
- antimicrobial peptides
- pH
- secretions such as mucous, saliva, tears, sebum, urine
- nasal hairs
- muco-ciliary escalators
Cells of Innate Immunity
Neutrophils
- most abundant WBC with a short cell life, will be rapidly deployed to inflammatory sites while also constantly surveying, locating and destroying threats while creating chemotactic gradients
- have different types of granules with different properties; myeloperoxidase, lactoferrin, metalloperoxidase9
- acts via phagocytosis; degranulation and neutrophil extracellular traps (extracellular fibres composed of DNA from neutrophils that bind to pathogens)
Macrophages
- phagocyte
- antigen presenting
- more long lived than neutrophil
Natural Killer Cells
- granular lymphocytes with n antigen receptors
- granules contain proteins such as perforin and proteases which induce apoptosis of neighbouring cells
- activated in response to interferons or macrophage derived cytokines
Receptor Recognition
Recognition Receptors
- 2 categories of patterns stimulate the innate response: exogenous pathogen-associated molecular patterns (PAMPS) and endogenous damage-associated molecular patterns (DAMPS)
- innate cells such as phagocytes, dendritic cells, epithelial cells, lymphocytes and endothelial cells have pattern recognition receptors which are called toll-like receptors
Antimicrobial Peptides
- Found on skin and mucosa for protection, secreted on site
- WIll kill phagocytosed organisms
- prevent microbe attachment and invasion
- Can disrupt membrane integrity
Specificity of Innate Immunity
- structures shared by microbe classes/molecular patterns (PAMPS)
- Receptors are encoded by germline and so has limited diversity
- Distribution of receptors, identical receptors on all cells of same lineage
- discrimination of self and non self
- there are approx. 12 different TLRs each of which recognise a different specific set of molecular patterns
Proteins
Interferons
- group of 3 related cytokines is released from virus-infected cells, provides brief nonspecific resistance o viral infections
- virus infected cell synthesizes and secretes interferon when exposed to viral nucleic acid
- when interferon is released into ECF, it binds with receptors on plasma membrans of healthy neighbouring cells thus signalling surrounding cells to prepare for possible viral attack
- interferon triggers production of virus-blocking enzymes which remain inactive until coming into contact with a virus
- interferon enhances macrophage activity, stimulated production of antibodies and boosts power of killer cells
Complement
- serves as chemotaxins which attract and guide professional phagocytes to site of complement activation
- acting as opsonins by binding with microbes and enhancing their phagocytosis
- promoting vasodialtion and increased vascular permeability increasing blood flow to invaded rea
- stimulating release of histamine from mast cells which enhances local vascular changes characteristic of inflammation
- activating kinins which further reinforce inflammatory reactions
- opsonisation = foreign particle marked for phagocytosis, requires antigen signal
- chemotaxis = attraction and movement of macrophages and neutrophils after release of cytokines and chemokines (released from eosinophils, neutrophils, dendritic cells, NK cells and mast cells, used for communication)
- lysis = destruction of cell membrane, proteins destroy integrity of pathogen
- agglutination = use of antibodies to cluster and bind pathogens together so immune cells can attack and weaken infection
Microcidal molecules
- defensins = created by neutrophils & macrophages, act against bacteria, fungi, viruses by binding to membrane and increasing their permeability
- lysozyme = enzyme catalyses destruction of cell walls in bacteria
- dnases = enzyme causing hydrolysis of DNA
Inflamation
1) isolate, destroy or inactivate invaders
2) remove debris
3) prepare for subsequent healing and repair
Defence by resident tissue macrophages
- when bacteria inavde through break in barrier, macrophages in area begin phagocytosis
- macrophages also secrete chemotaxins and cytokines
Localised vasodilation
- immediately arterioles within area will dilate, increasing bloos flow to site of injury
- localised vasodilation is induced by histamine released from mast cells
Increased capillary permeability
- released histamine increases capillaries permeability by enlargin capillary pores, allowing plasma proteins to excape to inflamed tissue
Localised Oedema
- accumulation of plasma proteins in interstitial fluid raises local interstitial fluid-colloid osmotic pressure therefore pressuring fluid to move out of the capillaries