Antigens & Receptors Innate Immunity
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Describe the mammalian immune system.
The mammalian immune system is composed of two distinctly separate but intimately intertwined systems: 1) innate immune system 2) adaptive immune system. Their function and actions both depend upon and influence each other.
How do the innate and adaptive immune systems interact?
Innate can function on its own but is more effective when interacting with adaptive.Innate immune cells phagocytize items and "present" them to lymphocytes so that an adaptive immune response can be generated. Innate immune cells produce cytokine "messages" that influence lymphocyte responses. Once the adaptive immune system is up and running, the innate immune cells carry out much of their effector functions. Adaptive immune cells also produce cytokines which direct and increase, or decrease, the function of innate cells.
What are the 6 basic characteristics of innate immunity?
- 1)response is not pathogen specific, but is directed towards molecular features common to multiple pathogens.
- 2)response does not require that the patient have ever encountered the organism before.
- 3)response is very rapid->minutes to hours.
- 4)Not capable of memory
- 5)response cannot be primed or boosted
- 6)extensively interacts with and influences the adaptive immune system
What are the 5 basic characteristics of adaptive immunity?
- 1)response is antigen (pathogen) specific
- 2)response (following the first exposure to antigen) is much more slow than that of innate system->days to weeks b4 antibody response
- 3)response is capable of memory (speed and magnitude of response increases with multiple exposures)
- 4)response can be primed or boosted (vaccinations)
- 5)many of the effector mechanisms by which the adaptive immune response works are actually carried out by cells/factors of innate immune system.
What are the basic cell types of the innate immune system?
- Granule releasing cells: eosinophils, basophils, mast cells
- Phagocytes: neutrophils, macrophages, dendritic cells
- Natural Killer cells
Describe the granule releasing cells of the innate immune system.
- High density in sub-epithelial surfaces and important for protection of these surfaces.
- Characterized by dense cytoplasmic granules.
- Not phaygocytic
- Activation induces release of granules into exterior environment kill microbes and bring in more immune cells
Describe phagocytes of the innate immune system.
- Ingest and destruct particles.
- Some can "present" or "show" what the have ingested to cells of adaptive immunity
- "Antigen Presenting Cells"
- Neutrophils are polymorphonuclear with no granules
- Macrophages(tissue)/monocytes(blood) are mononuclear with clear to foamy cytoplasm
- Dendritic cells are mononuclear with long cytoplasmic "arms" (dendrites)
Describe the natural killer cells of the innate immune system.
- A variant of lymphocytes, but act more like innate immune cells.
- Not antigen specific and very rapidly activated.
- Kill "impaired self" cells (impaired self cells either lack certain surface receptors or express abnormal surface proteins)
What are the secreted components of the innate immune system?
- Complement: a series of proteins/enzymes that directly damage microbes and activate/recruit immune cells.
- Cytokines: small proteins that act as messengers between cells and help direct the immune response, they are involved in adaptive response as well.
- Chemokines: a specialized subtype of cytokines which act to recruit inflammatory cells
- Antimicrobial peptides: small proteins that kill microbes directly or target them for destruction
What are the basic cell types of the adaptive immune system?
- -B Cells: small mononuclear cells with minimal, basophilic cytoplasm. Produce antibodies.
- -T Cells: appear identical to B cells.
- -CD4 T cells
- -CD8 T cells
- -Regulatory T cells
Describe CD4 T cells of the adaptive immune system.
These are often called "helper" T cells. They interact with cells of the innate immune system as well as with other adaptive immune cells. Their major function is to direct the actions of all of the other cells in the entire immune system. (there are several functional subtypes of CD4 T cells)
Describe CD8 T cells of the adaptive immune system.
These are called "cytolytic" or "cytotoxic" T cells. They act a lot like natural killer cells in that they detect "impaired self" cells that are expressing abnormal proteins on their surface (e.g. from a viral infection) and kill them. Unlike CD4 cells, these cells do most of their own work.
Describe Regulatory T cells of the adaptive immune system.
These cells modulate or inhibit the inflammatory response to prevent an excessive response and "friendly fire" damage. ("calms")
What are the secreted components of the adaptive immune system?
Describe the structure of antibodies.
The basic structure of an antibody is 4 polypeptide chains arranged in a "Y" shape. Some types consist of 2 or more of these "Y" units linked together. The 2 "arms" of the Y bind target substances. The "tail" of the Y interacts with antibody receptors on host cells.
What is an antigen? (be able to recognize one if described to you)
- An antigen is a substance that is bound by specific lymphocyte receptors. If that substance also triggers an immune response it can be further defined as an immunogen.
- -This response may be positive (e.g. generate an immune response)-OR-
- -The response may be negative (an immune response is suppressed or tolerance is induced)
What is an epitope? (be able to recognize one if described to you)
The portion of an antigen that is actually bound by any individual lymphocyte receptor. Any given antigen may have many epitopes on it. It may have multiple copies of the same epitope or it may have different epitopes. (soccer ball)
What is a hapten? (be able to recognize one if described to you)
A small protein that becomes antigenic by binding to a larger protein, the carrier. This makes small proteins appear to be large and become more "effective".
What are the 5 characteristics of a "good" (effective, immunogenic) antigen? (be able to determine if a substance is likely to be a good antigen (or not) if it is described to you)
- 1) foreign
- 2) large size
- 3) complexity
- 4) structural stability
- 5) moderate degradibility or digestibility
Overview of processes in inflammation.
- Initial insult ->
- Engagement of "sentinel cells" ->
- Initial local inflammatory response ->
- Local and systemic vascular and cellular responses ->
- Sequelae and resolution of insult
How does the innate immune system recognize its targets?
Pathogen associated molecular patterns, aka PAMPs
What is a PAMP?
- Pathogen Associated Molecular Patterns
- PAMPs are a part of the initial insult process in inflammation and is how the innate immune system recognizes its targets.
How do PAMPs allow the innate immune system recognize a broad category of non-self agents (e.g. what type of features of the agents allow it to do this)?
- 1) They correspond to molecules or structures that are highly conserved between many different organisms-(they are highly conserved because they usually represent structures that are critical for survival of the pathogen, e.g. cell wall components)
- 2) They are NOT found in normal "host" tissues.
- 3) recognized by (sentinel) cells of the innate immune system.
What are some examples of PAMPs?
- 1) Gram Negative (GN) bacteria: lipopolysaccharide/endotoxin--critical component of cell membranes.
- 2) Gram Positive (GP) bacteria: peptidoglycans, lipoteichoic acids--critical component of cell walls
- 3) Acid fast bacteria: glycolipids and carbohydrates--components of cell walls
- 4) Fungi: Carbs, especially mannose and zymosan--components of cell walls
- 5)Viruses: nucleic acids, especially single or double stranded RNA
What are PRRs?
- Pattern Recognition Receptors
- They recognize and bind PAMPs
Why are PAMPs and PRRs important to a productive immune response?
- The PAMP-PRR interactions are the signal for the innate immune system.
- The circumstances under which an innate immune cell encounters an antigen will determine how it responds-whether it does nothing or becomes activated and initiates an active immune response.
- This response will in turn dictate much of the future immune response to that insult, including the nature of the adaptive response.
What are alarmins/DAMPs?
- Damage Associated Molecular Patterns
- These are substances produced by the host's own body, which are released by dying or damaged cells. They may also be released intentionally by sentinel cells.
What functions do alarmins/DAMPs serve?
Purpose is to recruit and activate inflammatory cells: especially innate immune cells, but the indirectly promote adaptive responses as well - promotes tissue repair
What are the cardinal signs of acute inflammation?
- local accumulation of fluid, plasma proteins and white blood cells that is initiated by physical injury, infection or a local immune response.
- 1)redness (rubor)
- 2)swelling (tumor)
- 3)heat (calor)
- 4)pain (dolor)
- 5)loss of function
What is the purpose of inflammation?
To recruit elements of the immune system to a damaged/infected area to address the issue. (Contain, destroy or remove foreign substances)
What are some examples of alarmins/DAMPs?
- Defensins and cathelicidins: small antimicrobial peptides, especially near body surfaces - disrupts microbial membranes.
- Fibrinogen, heparan sulfate: increased by injury, activates macrophages by TLR4
- Heat shock proteins: bind TLR2 and TLR4
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