M: Immune System and Response to Infection - Week 4 (lec 10) Flashcards
Name the 4 principles of immune responses
- Immunological recognition
- Immune effector functions (e.g. binding, death mediation)
- Immune regulation (ability to up or downregulate response)
- Immunological memory (allows faster response to known pathogens)
Explain immunological recognition. How does our body discriminate between molecules? What receptors are used?
Recognition of ‘self’ and ‘non-self’.
Microbial molecules are discriminated by:
- PAMPs (pathogen associated molecular patterns)
- Antigens
These features are recognized by PRRs (pattern recognition receptors) and Antigen receptors respectively.
Explain PAMPs, and state whether innate or adaptive responses are directed against it
PAMPs – are unique to microbes but are shared within discrete taxonomic groups (e.g. LPS) – they are directed against by INNATE responses
(adaptive is directed against antigens)
How does microbial invasion work to take over the body and produce symptoms? Explain how it’s a race between the immune system and invading microbes
The race is between microorganisms replicating vs our immune system response.
The immune system tries to reduce the number of microorganisms to prevent them from reaching a ‘multiplication threshold’, at which point the microbes then switch into a disease producing mode where they produce pathogenic factors etc.
What three kinds of barriers act as a 1st line of defense (non-specific immunity)? Are there any other 1st line defenders?
- physical barriers (e.g. skin)
- chemical barriers (e.g. mucus, saliva)
- mechanical barriers
also: cells that kill and defensive molecules
What type of cells act in specific immunity?
- cells that kill
- cells that make antibodies
- cells that help other cells
- cells that remember and prevent reinfection
What are primary lymphoid organs? Name them
are the organs where our immune cells are generated
- these include the bone marrow, and (for lymphocytes) the thalamus
– our innate immune cells are generated from progenitors in the bone marrow
Where do b-lymphocytes mature? What about t-lymphocytes?
b-lymphocytes: In the bone marrow
t-lymphocytes: in the thymus
What are secondary lymphoid organs? Name them
are where we find our lymphocytes in particular
- these include: the spleen, adenoids, tonsils, and the various lymph nodes scattered throughout our body
Compare the diversity of microbes recognised by the innate and adaptive immune systems
Innate: limited amount of microbes recognised; germline encoded
Adaptive: very large; somatic recombination of gene segments
Compare the response speed and magnitude for the innate and adaptive immune systems
Innate: rapid response, constant magnitude
Adaptive: slower response, magnitude increases with multiple exposures
Compare the cellular and chemical barriers for innate and adaptive immune systems
Innate: skin, mucosal epithelia, antimicrobial molecules
Addaptive: lymphocytes in epithelia, antibodies secreted at epithelial surfaces
Compare the blood proteins for innate and adaptive immune systems
Innate: complement, others
Adaptive: antibodies
Compare the cells found for the innate and adaptive immune systems
Innate: phagocytes, NK cells
Adaptive: lymphocytes
What is the role of lymphatic vessels?
They connect lymph nodes and are there to drain our tissues to deliver antigens to the lymph node, so that the lymphocytes are then activated.
From there they all collect and then empty into the blood stream.
What is the role of lysozyme in the immune system, and where is it found?
Lysozyme is found in tears and other secretions, and is an enzyme that acts as a 1st-line of defence by acting on the peptidogycan layer in bacteria (particularly gram +ve bacteria)
How are dendritic cells beneficial to our immune response?
They are cells that express PRRs that can recofnise foreign invaders.
AND MOST IMPORTANTLY: they are very potent cells in delivering the antigens of those foreign invaders to the lymph nodes where they can activate T- (and B-) lymphocytes
– so they act as a kind of link to the adaptive response
Explain the process of ‘colonisation’ of microbes
(Usually is the start of the infection process.)
Colonisation involves the adherence of the invading organisms and interaction with epithelial cells.
colonisation may occur to an external surface or internal surface (e.g. GI tract)
List the 4 typical steps to an invasion process,beginning with colonisation
- colonization
- invasion
- dissemination (=spread widely) and damage
- control
Once the microorganisms have entered the tissue following colonisation, what immune cells do they encounter first?
They encounter macrohpages and dendritic cells.
- the macrophages are recruited and a lot of monocytes (macrophage precursors) circulate in the blood stream
What are the fixed and induced defenders of the innate immune system?
- barriers (physical, chemical, cellular)
- specialised proteins (complement, chemokines, cytokines)
- specialised cells (neutrophils, macrophages, NK cells, etc.)
What 3 specialized plasma factors are together involved in triggering the complement cascade? What do these factors do?
- c-reactive protein: binds capsule of several bacteria
- mannose binding lectin: binds mannose residues on pathogens
- complement proteins: pro-enzymes triggered after binding a pathogen to produce a cascade of reactions
What are complement proteins? Where are they produced and present? In what way do they activate?
A group of about 30 different proteins that are produced mainly by the liver and are present in our plasma and body tissue fluids
- they are a set of pro-enzymes whose activation happens in a cascade fashion (one after the other)
How can c-reactive protein (C-RP) activate the complement cascade?
By coating the microorganisms with it (it = C-RP). Note: this coating also facilitates phagocytosis
List the outcomes of complement activation (3)
- migration of phagocytes to site of infection
- phagocytosis of microorganisms
- lysis of microorganisms
T/F: activation of the complement cascade usually results in the cleavage of complement proteins into fragments
True
(e.g. C3 becomes C3a and C3b)
What is the common pathway involved in the complement cascade and what 3 pathways lead into it? What does this mean
The common pathway is the: cleavage of C3
pathways leading into it are: classical pathway, lectin pathway, alternative pathway
– this means that you can use different complement proteins and different triggers to activate the cascade, but it will always result in the cleavage of C3 and subsequent effects
After the cleavage of C3, what effects might we see result from the complement cascade? (4)
- recruitment of inflammatory cells
- stimulation or adaptive immune responses
- pore formation and lysis
- coating of microbes and induction of phagocytosis and opsonisation (C3b)
What 4 leukocytes engulf extracellular material (i.e. are phagocytic)
- neutrophil 2. monocyte 3. macrophage 4. dendritic cell
What 2 leukocytes kill eukaryotic parasites or altered cells?
- eosinophil 2. NK cell
What leukocyte releases immuno-modulatory compounds and is important in allergic reactions?
Basophil
Where are neutrophils, eosinophils and basophils derived?
from pluripotent stem cells in the bone marrow
Do neutrophils, eosinophils and basophils express one or many PRRs? What does this mean?
Many. This means they can be activated by multiple PAMPs and therefore multiple microbes
Which leukocytes are found in blood vs which are found predominantly in tissues?
blood: neutrophil, eosinophil, basophil, monocyte, NK cell
tissues: macrophage, dendritic cell
Provide 3 examples of Pattern Recognition Receptors (PRRs)?
- TLR (Toll-like receptors)
- NOD (nucleotide binding oligomerisation domain)
- RIG (retinoic acid inducible gene)
What are DAMPs? What binds them?
Danger associated molecular patterns. They are binded to by some/certain PRRs
T/F: Different PRRs can be found either on the cell surface or within the cytosol
True
What does TL-4 recognise?
The conserved portion of LPS (i.e. the lipid A portion that embeds into the bacterial membrane)
[PRR-PAMP ligation] What 2 types of PRR-PAMP ligation result in phagocytosis?
- ligation of soluble receptors (e.g. M.B.L)
- ligation of cell bound receptors (e.g. mannose receptors, scavenger receptors)
[PRR-PAMP ligation] What can ligation of TLRs and NODs result in? (3)
- ligation of TLRs and NODs may result in:
—— expression of difference cell surface receptors
—– production of chemokines and cytokines
—– production of defensins
T/F: to respond to a cytokine, a cell must have the receptor for that cytokine
True
Name the 2 groups of receptors that respond to chemokines
- CCR
- CXCR
note: they both contain 2 cysteine molecules
How do chemokines interact with cells containing chemokine receptors?
They attract these cells to the site of infection or to a particular site in the lymph node where cells need to interact
Name 3 functions of phaycotyes
- bind, engulf, kill microbial agents
- produce immunomodulatory substances (e.g. cytokines, chemokines)
- act as 1st-line defence against infection
Describe the steps involved in ingesting and killing of bacteria by phagocytes (5)
- Pseudopod engulf bacterium
- phagosome formation and acidification
- phagolysosome formation
- lysosomal proteins kill bacterium (degradative enzymes, defensins, myeloperoxidase)
- Release of bacterial fragments
What antimicrobial peptides are involved in phagocytic mechanisms?
defensins, cationic proteins
What pH is involved with acidification?
3.5-4.0
