Orchestration of the Immune Response; Cells of the Immune System Flashcards
Where are important cells of the immune response generated?
Immune Response cells are generated from stem cells in primary lymphoid tissues (spread throughout body).
Bone marrow: Macrophages, Dendritic Cells (DC), B cells, blood cells, granulocytes
Thymus: T cells
These cells then leave these areas and move to secondary sites (spleen, lymph nodes, blood, other tissues) where they fulfill their role of trapping Antigens (effector functions).
How are Macrophages important during the immune response?
They are important in Ag presentation & engulfment of pathogens.
They process Antigen and present it on the cell surface in a form that can be recognized by effector cells (B, T cells).
They also elaborate certain protein factors (cytokines) which activate/stimulate differentiation and reproduction of lymphoid cells (B cells - Plasma cells and Memory cells).
Part of the innate immune system, but activates acquired immunity.
- Trap Ag
- Process Ag (Ag = peptides)
- Present Ag on cell surface (Ag = peptides)
- T cell reacts w/ this complex via TCR, stimulates T cells
How are B cells important during the immune response?
B cells produce Antibodies in response to Antigen. Antibodies can:
- Bind and remove/neutralize Ag.
- Help phagocytes (like macrophages) engulf the Antigen (opsonization). (Both innate/natural (engulf/digest) & acquired/specific (activatation of T cells) immunity involved).
- N_eutralize virus and prevent it from entering cells._
- Antibody binding Antigen can activate the complement cascade, facilitating lysis of bacteria.
How are T cells important during the immune response?
T cells learn self from non-self in the thymus.
Requirement of TCR: can only react with Antigen in the context of a certain cell surface molecule (MHC protein). Partially explains the need for Antigen presentation.
CD4 T cells- respond to Ag by secreting cytokines, help other cells (secrete factors that recruit other cells)
CD8 T cells- kill cells expressing Ag on their surface (with MHC). Stops spread of viruses. Can kill tumor cells.
What are the 2 major classes of T cells?
CD4+: Helper T cells. They elaborate cytokines to improve immune responses (secrete cytokines in response to Antigen). Help turn on CD8 cells and B cells.
CD8+: Cytotoxic activity (CTLs). They kill infected cells expressing foreign proteins (viruses & tumors/cancer).
How does Immunity work?
After Ag presentation, clonal expansion of Ag-specific cells occurs. Cells most be able to respond efficiently to the Ag (i.e., high affinity due to a particular receptor expressed) and preferentially expand over time. This results in a stronger and more rapid (anamnestic) response following the second exposure to Antigen.
NOTE: One is not “immune” to an Antigen prior to the first exposure. One may be resistant due to genetic reasons or innate responses, but “immunity” requires a primary stimulus.
How are innate and anamnestic (acquired immunity) responses linked?
The combination of innate and anamnestic responses has evolved to confer not only resistance but also protection against microbial invasion (and potentially malignant cells) to facilitate survival of higher organisms.
Innate and anamnestic immune responses are linked: Activation of cells in the Innate response (via TLRs) cause i_ncreased ability to present Antigen_ to specific cells, such as T lymphocytes.
How do cells activate the Immune Response?
The same cell in an immature state, is a potent activator of Innate Immune responses.
After encounter with a virus, and subsequent differentiation to a mature form, the cell becomes a potent Antigen Presenting Cell (APC), capable of inducing B & T lymphocyte activation.
What is the difference between the Humoral Response and the Cell-Mediated Response?
Humoral Response: Antibody response. Results in interaction between a B cell and an Antigen. This interaction, combined with CD4+ T cells (Helper T cells), cytokines, and soluble proteins, results in Ab-secreting plasma cells (proliferation/clonal expansion of a single Ab), which results in Antigen elimination by precipitation.
Cell-mediated Response: Involves T cells –> Expansion into CD4 (Helper T cells) and CD8 (Cytotoxic/Killer T cells).
- CD4 + Antigen-Class II MHC molecule: leads to an activated Helper T cell/CD4 T cell, which leads to cytokine secretion. These cytokines help activate both Cytotoxic/CD8 T cells and Antibody-secreting plasma cells (of humoral response), resulting in Antigen elimination.
- CD8 + Antigen-Class I MHC molecule: leads to activated Cytotoxic/CD8 T cell, which kills altered self-cells (viruses and tumors/cancer).
How does a Stem Cell become a Memory or Plasma cell?
In bone marrow: Maturation into mature antigenetically committed B cells. Stem cell –> gene rearrangement –> becomes a mature B cell. Moves out of bone marrow.
In peripheral lymphoid tissue: Antigen-dependent proliferation and differentiation into Memory and Plasma cells. Encounters Antigen –> clonal expansion (theory, explains specificity, memory, and tolerance) –> becomes memory cell or Ab-producing plasma cell.
What are the Cellular Interactions involved in induction of immune responses?
The Antigen is presented on an APC such as a dendritic cell by engulfment, digestion/processing, and display.
When the processed Antigen is presented to a Helper T cell, the APC (with its appropriate class II MHC and a co-stimulatory signal) will interact with the TCR of the Helper T cell. This leads to Helper T cell activation.
The effector (activated Helper T cell) will have cytokine receptors such as IL-2, and will proliferate to become Memory Helper T cells, all w/ cytokine receptors IL-2. ??
Summary: These CD4 Helper T cells require activation and proliferation for generation of a Humoral Response (expansion of B cells to make Ab-producing Plasma cells and Memory cells) & a Cell-Mediated Response (Cytotoxic CD8 T cells kill altered self cells).
Note: AIDS virus kills CD4 Helper T cells!
How is communication between various organs of the Immune System achieved?
Communication is achieved by surface interactions or chemical communication, via Cytokines. These function among elements of the immune system, and between the immune system and other systems (such as the endocrine system or central nervous system).
In the immune system, these are called lymphokines/interleukins (IL-1,2,3…)
What are Lymphokines/Interleukins?
Achieve communication within the Lymphatic System.
Lymphokines: general term for soluble protein mediators postulated to be released by sensitized lymphocytes on contact with antigen, and believed to play a role in _macrophage activation, lymphocyte transformation, and cell-mediated immunity (T cells, as opposed to Humoral immunity/B cells). _
Interleukins: generic term for a group of multifunctional cytokines that are produced by a variety of lymphoid and nonlymphoid cells and whose effects occur at least partly within the lymphopoietic system.
What are the 2 basic aspects of response in the immune system?
- Antigen elimination: Aimed simply at getting rid of Ag. Involves T cells, B cells, Macrophages, and Antibodies. The Antigen is recognized, bound, and eliminated.
- Inflammation: Chemicals released during Antigen elimination cause a variety of responses in other tissues. Many are lymphokines, but also include other chemicals. They cause fever, altered vascular permeability, edema (fluid in tissues, swelling), and even damage to tissue. All involved with protection from infection.
What are the cells of the immune system?
- Granulocytes: Neutrophils, Basophils, Eosinphils
- Monocytes/Macrophages
- Mast Cells
- Dendritic Cells
- Lymphocytes
- B cells
- T cells
