Module 31 - Innate Immunity Flashcards
Mention the principles of the immune response.
- Recognition
- Response
- Memory
- Regulation
Define antigens.
It is a unique molecule which induces an immune response in the body, especially the production of antibodies.
PRR and antigen receptors each recognize __________ and _________, respectively.
PAMPs and Antigens
Differentiate between the primary and secondary immune organs. Give examples.
The key primary lymphoid organs of the immune system are the thymus and bone marrow, and they are where the immune cells are generated.
Secondary lymphatic tissues such as the spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin and liver, contains mature immune cells.
Mention the characteristics of the innate immune system.
- Relatively non-specific
- receptor molecules on cells and in serum recognise PAMPs
- Rapid - because components already present
- Magnitude constant
- Acts as a first line defence
- Interacts with and facilitates the adaptive response
How does innate immunity recognise “non-self” antigens?
- The binding of PAMPs by pattern recognition receptors (free or cell bound) or
- When antigens are complexed with antibodies (involves the adaptive response) – detected by phagocytes
- When specialised receptors detect “altered self” glycoproteins – natural killer (NK) cells
Epithelial cells produce __________ and _________ molecules, playing a role in innate immunity.
microbicidal, inhibitory
Mention several specialised plasma factors mediating innate immunity.
They function by recognising PAMPs.
- C-reactive protein: Binds capsule of several bacteria, aids phagocytosis, triggers the complement cascade
- Mannose-binding lectin: Binds mannose residues on pathogens, triggers the complement cascade
- Complement proteins: Pro-enzymes (C1, C2 etc) which are triggered after binding a pathogen to produce a cascade of reactions which generate effector molecules against the pathogen
These and others are termed acute phase proteins - rapidly produced in infection (eg CRP, C3, C4)
Explain the complement system.
It refers to a large group of produced plasma proteins (acute phase proteins) which interact with pathogens to mark them for killing (binding to PAMP or bound-antibodies)
Proteins are activated sequentially in a cascade (multiple ways), with the breakdown of C3 protein being the critical step in the cascade. Outcomes are:
- chemotaxis and activation of phagocytes (inflammation)
- phagocytosis (opsonisation) of microorganisms
- lysis of microorganisms (MAC)
In the notation system of the complement cascade, cleaved products result in smaller and larger fragments, noted by the letter __ and __ respectively.
“a”, “b”
Mention the complement protein (cleaved from C3) that is responsible for each of the 3 outcomes of the complement system.
- Phagocytosis (Opsonisation): C3b
- Pore formation and Lysis: C5b, 6, 7, 8, 9
- Chemotaxis and inflammation: C4a, C3a, C5a
Mention the immune cells of the innate immune system.
Phagocytic cells: Neutrophil, Monocyte, Macrophage, Dendritic cell
Cytotoxic cells: Eosinophil, NK cell
Inflammatory cells: Basophil
Mention the polymorphonuclear granulocytes of the innate immune system.
Neutrophil, eosinophil, basophil
Mention the location of the PRR receptors as well as the outcome of its ligation with PAMP.
- Ligation of soluble receptors (eg MBL) -> phagocytosis
- Ligation of cell-bound receptors such as the mannose receptor, scavenger receptors -> phagocytosis
- Ligation of TLRs and NODs may result in
- expression of different cell surface receptors
- Production of chemokines and cytokines
- Production of defensins
- Ligation of RIGs associated with anti-viral immunity
All receptors can be found intracellularly on the cytosol (except for TLR - also in the plasma membrane)
What are cytokines and what is their function?
Cytokine:
- a protein secreted by cells that interacts with and affects the behaviour of nearby cell bearing the appropriate receptors
- Affect multiple functions (regulate innate immunity, adaptive immunity, haematopoiesis and more)
- Eg. IL, IFN, TNF, CSF
What are chemokines and what’s their function?
Chemokines:
- a secreted protein that attracts cells bearing the appropriate receptors (induces chemotaxis)
- two groups of receptors, both of which contain two cysteine molecules: CCR and CXCR
Describe phagocytes and their function.
- PMNs: most numerous but shortlived and found in circulation.
- Monocytes/Macrophages: long-lived cells and found in both circulation and tissues.
Their function is to enter the infection site and do the following:
- bind, engulf and kill microbes
- produce immune mediators, eg. cytokines, chemokines, which regulate the immune response
- 1st line defence
Mention the steps of phagocytosis.
- Phagocyte binds to opsonised organism
- Phagosome starts to form
- Phagolysosome formation
- Damage and digestion -> release of microbial product
Mention the function of cytotoxic cells and granulocytes.
Cytotoxic cells: target infected or altered cells, and release granules whose contents are toxic. They include:
- Natural killer (NK) cells (kill tumour, virus infected cells)
- Eosinophils (kill antibody coated parasites)
- Macrophages (release cytotoxic mediators)
Basophils and mast cells (similar to basophils, found in tissues): release granules containing inflammatory mediators to augment the action of immune cells:
- Increases inflammation,
- May mediate unwanted (hypersensitivity) reactions, eg. allergies
What occurs when the innate immune system is not successful in preventing the replication of the invading microorganism?
Resolution of infection by pathogen requires additional effector mechanisms. These are provided by the more recently evolved Adaptive Immune System.
IL-1, IL-6, TNF-alpha
IL-1 -> activate vascular endothelium adhesion, activation and recruitment of leukocytes
IL-6 -> acute phase protein production (C reactive protein, MBL, complement)
TNF-alpha -> increase cell migration
All responsible for fever and are inflammatory mediators.
IFN-alpha, IFN-gamma, IL-12
IFN-alpha -> anti-viral cytokines
IL-12 -> production of IFN-gamma
IFN-gamma -> activation of macrophages (M1)
IL-10, TGF-beta
Both are produced by M2 Macrophages and are suppressive cytokines -> inhibit inflammatory reactions
IL-4, IL-13 activates M2 Macrophages