Immunity - D W Sexton Flashcards
Name 4 types of receptor in innate immunity
Toll-like receptor
Mannose receptor
Scavenger receptor
Formyl-peptide receptor
Innate immune system consists of which two main reactions
Inflammatory and antiviral defence
Inflamm involves the process of leukocyte and plasma protein recruitment from the blood and their accumulation in tissues and their activation to destroy microbes- these often involve cytokines that are produced by macrophages and other types of cells during innate immune reactions.
Major leukocytes recruited are PHAGOCYTES AND NEUTROPHILS- phagocytes ingest microbes and destroy these in intracellular vesicles
Antiviral involves a cytokine- mediated reaction where cells acquire resistance to viral infection and the killing of virus infected cells by NK cells.
Explain phagocytosis
- Chemotaxis and adherence of microbes to phagocyte
- Ingestion of microbe by phagocyte
- Formation of phagosome
- Fusion of phagosome with a lysosome to form a phagolysosome
- Digestion of ingested microbe by enzymes
- Formation of residual body containing ingestible material
- Discharge of waste materials
What is adaptive immunity
Adaptive immunity involves the ability to different substances- therefore the ability to be specific.
For example there are unique components such as lymphocytes with specific antibodies that can be adapted and secreted for certain antigens
Give the 6 phases of adaptive immune response
- Recognition of the antigen
- Activation of lymphocytes eg T and B cells
- Elimination of the antigen (effector phase) - through production of specific antibodies produced by B-cells
- The response decreases as antigen-stimulated lymphocytes die by apoptosis
- Homeostasis is restored
- Antigen specific cells that survive are then responsible for memory
4 signs of inflammation
Rubor-redness
Dolor- pain
Heat
Swelling
These are due to increased blood flow and vascular permeability; the release of mediators
3 functions of the innate immune system
- Prevents and controls/eliminates infection of the host by pathogens
- Mechanisms eliminate damaged cells and initiate the process of of tissue repair
- Stimulates the adaptive immune response
Defence mechanisms of the innate immune system
Mucous, saliva, gastric acid, sweat and tears
Discuss the 4 stages of leukocyte recruitment in innate immunity
- ROLLING
endothelial cells lining the post-capillary venules are activated in response to microbes
Cytokines produced by microphages and other cells may be produced also
Cytokines stimulate expression of cell mediators which induce surface expression of P-selectin
Blood vessels dilate and blood flow slows
Leukocytes move closer to the vessel lining =MARGINATION
allows ligands on leukocyte to bind to selections on endothelial cells
These interactions are weak and detach easily
Therefore they attach and detach causing a ROLLING action along the endothelial surface which slows the leukocyte down to facilitate the next step in the process - INTEGRIN ACTIVATION BY CHEMOKINES
chemokines displayed by endothelial cells at the infection site bind to the receptors on the rolling leukocytes meaning they’re bound more strongly to the endothelial surface - ADHESION
the activation of intigrins increases the expression of ligands on endothelial cells
The ligand VCAM-1 causes the intergrins VLA-4 and ICAM-1 to bind and also LFA-1 and Mac-1 to bind
The leukocytes attach firmly to the endothelium and causes the leukocyte to spread out along the endothelium - MIGRATION
Leukocyte migrates through the boarder of the endothelial cells- this requires a transient and reversible disruption of adherens junction proteins
THIS ALLOWS THE LEUKOCYTE TO MOVE OUT OF THE BLOOD AND INTO THE TISSUES
Name circulating cell types in innate immunity (effector cells)
- Neutrophils- carry out early phagocytosis and kill microbes
- Macrophages- secrete cytokines that stimulate inflammation- carry out efficient phagocytosis
- NK CELLS - cause lysis of infected cells and activate macrophages
Name circulating effector proteins
- Complement
Causes killing of bacteria
The opsonisation of microbes and activation of leukocytes - Mannose- binding lectin
Causes the opsonization of microbes and activation of complement (the lectin pathway) - Pentraxin
Causes the opsonization of microbes and activation of complement
What is a PRR (pattern recognition receptor)
These work to immobilise pathogen and start phagocytosis and to activate the host cell
These recognise pathogen associated molecular patterns (PAMPS) and damage associated molecular patterns (DAMPS)
What is a PAMP
A pathogen associated molecular pattern
Eg
LPS- a specific component of the gram- bacteria and recognised by TLR-4
MANNOSE receptor (CD206) is involves in the phagocytosis of microbes - recognises terminal sugars on the microbial surface of carbohydrates
Fmlp- is a PAMP as it is the only molecule that comes from bacteria cells
Discuss the use of pattern recognition receptors
Inflammation triggered when innate immune cells detect infection or tissue injury.
Mechanisms to detect this include the use of PRR’s on the cell surface and and in the cytoplasm. These respond to PAMPS eg LPS, carbohydrates or microbial nuclei acids or DAMPS which are released from injured cells.
The activated PRR’s then oligomerize and initiate signalling cascades that trigger the release of factors that promote recruitment of leukocytes to the area of infection.
Examples of PRR’s are;
TOLL - like receptors …… LPS will bind to TLR’s
Responds to endogenous molecules whose location or expression indicates cell damage
Eg heat shock proteins
SCAVENGER RECEPTORS
Collection of cell surface proteins originally involved in the uptake of oxidised lipoproteins into cells
Involved in binding lipoproteins, some polysaccharides and some nucleic acids
Internalisation if bacteria and apoptopic cells
Eg SR-A and CD36 expressed in macrophages
OPSONINS
Substances that coat particles for enhanced phagocytosis = OPSONIZATION
EG. antibodies and complement proteins
Opsonin receptors and should the microbe be coated with the complement then phagocytosis will be more efficient
Discuss the complement cascade in inflammation
The complement system consists of several plasma proteins and cell surface receptors that work together to opsonize microbes which promotes the recruitment of phagocytes to the site of infection and may directly kill microbes.
It is activated by proteolytic cascades where an enzyme is altered to because an active protease which cleaves and then induces the proteolytic activity of the next complement protein in the cascade.
The cascade results in a large amount of proteolytic products being generated and these products perform effector functions of the complement system.
There’s 3 pathways of complement activation ;
Classical which is triggered by the antigen-antibody complex, the alternative which is triggered by foreign surfaces and the lectin pathway which is triggered by carbohydrates.
Recognition of microbes by any of these pathways = sequential recruitment and additional complement proteins into protease complexes
