Immunology 1 Flashcards
Define “Pathogen”
Micro-organism that causes disease
Define “Chemokine”
Chemical attractant protein stimulating migration and action of cells
Define “Cytokine”
Small protein affecting the behaviour of other cells
Define “Zymogen”
Inactive form of an enzyme; must be modified before they become active
Name 4 types of pathogens:
1- Viruses e.g. HIV
2- Bacteria e.g. Perio, syphilis
3- Fungi e.g. Candida
4- Parasites e.g. Perio, Protozoa
What is the complement System
Many distinct plasma proteins that react with one another to opsonize pathogens and induce inflammatory response to help fight infection
Name 3 activation pathways:
1- Classical
2- MB-Lectin (Manose binding)
3- Alternative
What are the stages of the classical activation pathway
- C3a + C5a - enhance inflammation = mast cells release histamine
- C3b - opsonisation + cell lysis = complement proteins; C1q, C1r, C1s, C4, C2
- C1 complex = C1q, C1s + 2x C1r - activated on binding of antibody-antigen complex
- C1 cleaves C2= C2a + C2b and C4= C4a + C4b
- C2b and C4b combine- protease = C3convertase (C4bC2a)
- C3 convertase cleaves C3= C3a + C3b (C3a released)
- C3b bind to bacteria surface adjacent to C4bC2a complex and associate with it
- Forming C4bC2aC3b protease acts as C3a and C5a convertase
- C4b binds to surface of bacterium through amide/ester linkages
Stages of cell lysis:
- The C4bC2aC3b protease binds C5, C5b and C5a is formed
- C5b acts in a component in the membrane attack complex (MAC)
- C5b assembles with C6 and C7, the C7 molecule allows the complex to be inserted into the bacterial cell membrane
- C8 binds with the C5bC6C7 complex, and also inserts into the membrane
- The C5bC6C7C8 complex catalyses the assembly of many molecules of C9, this creates a cylindrical pore spanning the cell membrane
- The cylindrical pore leads to cell lysis when it disrupts ion/osmotic gradients
Stages of MB (Manose binding)-Lectin Pathway:
Complement proteins involved: (Ficolin), MASP-1, MASP-2, MBL, C4, C2 (Ficolin binds to the oligosaccharides on the bacteria surface membrane)
- Similar to the classical pathway in a sense that it also creates C3 convertase
- Ficolin binds to the oligosaccharides on the bacteria surface membrane
- MASP-1 and MASP-2 is also bound to Ficolin
- MBL (Manose binding Lectin) binds to Manose parts of the pathogen
- MASP-1 and MASP-2 (Manose associated serin protease) is also bound to MBL
- C3 convertase is made from these complexes
Stages of alternative pathway:
- Is a result of C3 convertase creating C3b
- C3b binds to the surface of the pathogen
- C3b + Factor B + Factor D = C3 convertase (C3bBb) (A different type of C3 convertase)
- C3b + Properdin = C3 convertase (C3bBb) (A different type of C3 convertase)
Stages of Opsonisation
- C3b pepper the surface of the pathogen
- The macrophage binds to the c3b protein via the CR1 receptor
- This allows the macrophage to engulf the pathogen via phagocytosis
Name 3 physical/chemical barriers:
- Epithelial layers (skin + gut lining)- involve mechanical mechanisms (cilia remove mucus + cell debris)
- Acidity + enzymes (found within gut lining)
- Healthy microflora outcompetes the pathogens
Features of the Innate immune system:
- Eliminates some virus causing micro organisms
- Controls the proliferation of microbes
- The pathogens must penetrate the physical/chemical barriers before the innate immune system is activated
- The innate immune system activates the adaptive immune system
Features of the Adaptive immune system:
- Much more potent than the innate immune system (has a larger effect)
- Can clear + destroy more virus causing diseases
- Increases the activity of the innate immune system (as they act in unison)
3 soluble immune effector molecules in saliva:
- Lysozymes (glycosidase enzyme) break down the bonds between N-acetyglucosamine and N acetylmuramic acid (Polymer of these repeating units is the peptidoglycan layer)
- Lysozymes are most against G+ bacteria (S.Mutans)
- The breakdown of the peptidoglycan layer allows for other microbial agents (of the innate immune system) to enter and destroy the pathogen G- Bacteria have an extra lipid membrane this acts as an extra protection layer from these antimicrobial agents
Antimicrobial peptides:
- Found in the blood, Saliva and other bodily fluids
- Produced by macrophages but are also secreted by the gingival epithelium
- The inactive proform of these peptides are known as zymogens
- Zymogen – An inactive form of an enzyme that becomes active by being proteolytically cleaved
- The fact that zymogens are activated when necessary means they can be present in the blood stream without causing any harm
The antimicrobial peptides in saliva:
Defensins – amphipathic (has hydrophobic and hydrophilic parts) + insert into membrane to generate pores - this causes the membrane to become leaky
- a Defensins – excreted by neutrophils
- b Defensins – excreted by epithelial cells
Cathelicidins – also amphipathic - acts in disrupting membranes
- LL-37 is the only type that is expressed in humans
Histatins - Produced by: Parotid, Sublingual, Submandibular glands.
- Histidine rich
- Active against fungal pathogens
Compare the Innate vs Adaptive immune response:
1) Response speed
2) Recognition of what is self (host) and non-self (pathogen)
3) Lasting memory/ Protection
Innate:
1)
- Acts first (mins-hours)
- Proforms are always present ready to detect pathogens
- Decrease the proliferation of pathogen, ready for adaptive arm to act
2)
- Limited range of receptors
- Receptors are unchanged during immune response
- Receptors encoded by genome (DNA is inherited from parents)
3) No lasting memory
Adaptive:
1)
- 4 days to weeks
- Activated by the innate arm of the immune system
2)
- Vast range of receptors
- Receptor recognition improves during adaptive immune response
- DNA changes from inherited form during immune response
3) Lasting immunity observed
Innate arm provides:
- Initial defences against pathogens (decrease proliferation)
- Control against virulent pathogens
- Role in inducing adaptive immune response
Adaptive arm provides:
- Increases in potent activity to control the virulent pathogens
- Takes time in raising population in number of cells to act against pathogen
- Clears away/eliminates pathogen to prevent infection
Diversity of recognition:
- Adaptive immunity increases the variety of receptors but the innate arm doesn’t
- Pathogens reproduce quicker/ increase genetic turnover/ increase rate of mutation/ take part in conjugation
- We have only 25,000 genes in our body, the adaptive immune system acts in reassembling our genome - over 25,000 receptors are observed in the body
Response speed:
- Antibodies + Igs are produced by adaptive arm
- Amount of antibody produced = antibody titre
- When a person is re-infected with pathogen A, the specific antibody is produced much quicker
- Antibodies also bind stronger to the antigen, as they are recognised quicker
