In centrifuged blood, what layer may factors of the humoral response be found in? What are these factors?
What layer contains factors of the cellular immune response? What are these factors?
Humoral immune response (plasma)
Cellular immune response (buffy coat)
- Natural killer cells
According to first aid and chart pn pg 41 of course notes, B-lymphocytes are part of the humoral response : /
When does innate immunity become active?
What are the functions of innate immunity?
Explain the response of innate immunity to repeated exposure of a pathogen.
How do mediators of the innnate immune response recognize pathogens vs tissue of the organism?
What are the effectors of innate immunity?
Characteristics of Innate immunity
• Active upon first exposure to a pathogen
• Possesses host cell receptors to distinguish non-self
(“foreign to the host”) and self
• Similar degree of response whether it is the first exposure to a pathogen/tumor cells or several exposures
• Response occurs quickly (within hours)
• Are necessary for triggering adaptive immune responses (i.e., antigen presentation)
• The innate immune response typically slows the spread of infection while it recruits lymphocytes (i.e., T-cells and B-cells) that increase the potency and focus of the immune response.
Effectors of innate immunity: epithelial barriers, phagocytes, NK cells, complement, dendritic cells, chemical barriers, cytokines
What is the first line of defense to a pathogen? Describe the passive and active functions it.
Epithelial layers are the first line of defense to pathogens.
Passive: physical barrier
Active: killing of microbes by locally produced "antibiotics". Examples: epithelial cells secrete peptides that lyse bacteria. can also take up things like iron, chelate them, and prevent pathogens from thriving
Which part of the immune system initiates inflammation? (innate or adaptive)
Innate immunity initiates inflammation. Adaptive immunity can prolong inflammation but innate immunity iniates it!
see slides 11-14 of PP
Once a pathogen gets past passive barriers of infection (epithelial cells), what are the first responders to the pathogen? How do they recognize the pathogen?
After these first responders recognize the pathogen, what is their reponse?
Innate Immunity and inflammation
Once the pathogen gets past (e.g., through tissue injury) the passive barriers they begin to grown and release noxious substances. Inflammation is a complex response within vascularized tissue which includes changes to blood vessels within inflamed tissue and accumulation as well as activation of leukocytes and plasma proteins at the site of infection or exposure to noxious agents.
The first responders to the pathogen are tissue resident phagocytes (i.e., macrophages and dendritic cells).
- Phagocytes recognize common structural features found on pathogens. These common structural features on pathogens are completely different from the host (e.g., lipopolysaccharides of gram negative bacteria).
- All phagocytes have evolved to express receptors, to common structural features found on pathogens, which trigger a vigorous cellular response to pathogens.
- The recognition receptors of the common structural features found on pathogens are non-clonal (i.e., every phagocyte expresses them). This response is nonspecific in nature and recognizes all pathogens that posses the common structural feature.
Once a phagocyte recognizes the pathogen it initiates destruction of the pathogen. Moreover, when pathogen components trigger receptors on phagocytes, the phagocyte begins to make and secrete soluble mediators, known as cytokines (e.g., tumor necrosis factor). These cytokines produced by the innate immune system are able to activate cells in the inflamed site.
- A specialized cytokine known as a chemokine will begin to recruit specialized cells to the infectious site, which are very efficient in destroying the pathogens.
- Some cytokines lead to blood vessel dilation and vascular leakage.
- Although inflammation is meant to serve as a means to control infection and promote wound healing, prolonged inflammation also lead to tissue damage and in some cases disease if it is persist. It is critical that the initiator of the inflammatory response and its noxious substance be removed from the body as quickly as possible.
What are the effectors of the adaptive immune response?
What kind of receptors are present on these cells? What do these receptors recognize?
Adaptive responses primarily involve T-cells and B-cells. These lymphocytes recognize specific “foreign” molecules (antigens) using receptors known as T-cell antigen Receptors (TCR) and immunoglobulins (Ig). TCR are present on T-cells and Ig are found on B-cells.
T-cells: possess T-cell receptors. T-CELLS ONLY RECOGNIZE PEPTIDES! (these peptides are typically 15-20 aa long)
B-cells: possess immunoglobulins that recognize epitopes on “foreign” proteins, carbohydrates, lipids and nucleic acids. epitopes are specific regions of the above listed macromolecules.
see slides 15-16
Note that immunoglobulins and T-cell receptors recognize very specific components made by the pathogens. The lymphocytes adapt to the infecting agent so it can provide a highly specialized defense, which will clear the pathogens and/or and the pathogen’s noxious agent efficiently.
We know that TCRs only recognize peptide sequences. What must present these peptides to TCRs for them to be recognized and activate the T-cell? Explain in detail how this process works.
Explain what occurs during immune activation.
The TCR only recognizes specific peptide sequences presented by scaffolding proteins called major histocompatibility (MHC) molecules found on the surface of antigen presenting cells (e.g., dendritic cells).
The adaptive immune responses develop when soluble antigens (float into lymph nodes via circulation) and antigen presenting cells [e.g., dendritic cell (DC)] travel though the lymphatic ducts into specialized aggregates of naïve T and B-cells known as lymph nodes (LN). Within the LN, macrophages and B-cells also engulf soluble antigens that travel from the inflamed site to the LN via the lymphatic ducts. Then DCs, B-cells and macrophages present the antigen to TCR on T cells. Ig on B-cells will also interact with soluble or particulate antigen and respond accordingly (see below). Within the mucosal layer, beneath epithelial layers, are aggregates of lymphocytes (e.g., gut associated lymphoid tissues), which function similar to LNs.
Interaction of Ig and/or TCR with specific epitopes on antigens leads to immune activation. During activation, the cells increase their expression of genes necessary to generate a response or the release of substances that aid in the elimination of the pathogen. Activation also subsequently leads to proliferation by mitosis and expansion of cells recognizing the antigens.
see figure on top of pg 47 of course notes, slide 18 of pp
What lymphocytes prolfierate as a part of immune activation? What 2 things does proliferation of lymphoctyes result in?
Following proliferation, the responding naive replicating lymphocyte develops into specialized ____ ____.
What is the antigen elimination stage?
Only lymphocytes that recognize the specific antigen will expand. About 1/10^5 naïve lymphocytes will be specific for an antigen.
Clonal expansion (proliferation) allows for both increased breadth and specificity in the responding lymphocyte population.
Following proliferation, the responding naïve replicating lymphocyte develops into specialized effector cells (e.g., Ig expressing B-cells differentiates into an antibody secreting-plasma cell).
Specialization allows for optimal response to different types of microbes. This is known as the “antigen elimination stage” since the effector cells are specialized to remove and eliminate the pathogen and its noxious substances. The effectors further prevent the spread of pathogens by either neutralizing the substance or the source triggering the “symptoms/disease”.
What are the 4 functional units that the adaptive immune repsone is divided into?
attached is slide 19 of PP
After clearance of a pathogen, how does the adaptive immune response persist? Explain the capacity of these cells to recognize pathogens after initial exposure.
After clearance of the pathogen, the adaptive immune response persists in the form of memory cells. The memory cells allow for a faster and stronger immune response upon re-exposure to the same pathogens. HOWEVER, memory cells that develop to one pathogen as a long-lasting adaptive immune response will not be useful against infection by a different pathogen. Also, memory cells will not recognize mutations of foreign substances made by the responding pathogens.
Both innate and adaptive immune responses are required for protection against pathogens. Common to both adaptive and innate immune responses is their ability to distinguish self from non-self.
What is the purpose of memory cells?
What is the primary response to a pathogen? What is the secondary response?
What happens to effector cells after they have cleared a pathogen? What is the purpose of this?
lymphocytes develop into memory cells to:
- preserve the best responding lymphocyte to an antigen and
- to mount an effective and larger response following a future exposure to the same pathogen.
This ensures that the pathogen expressing the specific antigen is cleared immediately and effectively before they cause damage or disease.
A primary response is when the first encounter to an antigen leads naïve cells to form effector and memory cells.
A secondary response is when a second antigen encounter occurs and the memory cells interacting with the antigen respond rapidly and to a higher degree.
When the response from the effector cells is finished and diminishes, the effector cells are eliminated through a process known as activation-induced cell death or apoptosis. This allows room for expansion of another clone of lymphocytes that encounter another (novel) antigen to expand and eliminate the pathogen carrying the novel antigen.
An appropriate immune response results in the elimination of the infectious organism or noxious agent and allows the host to deal with newly encounter challenges, yet maintains homeostasis with memory.
•Note that few surviving cells after antigenic stimulation become memory cells for the next encounter of the pathogen/tumor cells. 95% undergo apoptosis.
please see slides 25-34 of PP