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What are the differences between the inflammatory response (innate immunity) and the immune response (adaptive immunity)?
- inflammation is relatively rapid, nonspecific, and short-lived.
- adaptive immunity is slower acting, specific, and very long-lived - it has memory.
Products of the adaptive immune response are...
immunoglobulins (antibodies) and lymphocytes (T and B cell)
The process of production of T and B cells with all possible receptors for antigen is called what?
Generation of clonal diversity
The phase of the adaptive immunity that involves selection, proliferation, and differentiation of individual T and B cells with receptors for a specific antigen is called what?
What is humoral immunity?
The part of the immune response where B-cells produce antibodies in response to the antigens by way of activation of complement and phagocytes.
What is cellular immunity?
The process by which T cells undergo differentiation to develop effector cells that react directly with antigen on the surface of infectious agents. These effector cells include T-reg cells, Tc cells (cytotoxic), and memory cells.
Describe active immunity and give an example.
- Produced by an individual after either natural exposure to an antigen or after immunization.
- Long lived
- Example is tetanus vaccine, or influenza vaccine.
Describe passive immunity and give an example.
- does NOT involve the host's immune response at all. rather it occurs when preformed antibodies or T lymphocytes are tranferred from a donor tothe recipient.
- short-lived or temporary because donors antibodies are eventually destroyed.
- Example: fetal-maternal placental transmission of antibodies.
What is a molecule that can react with antibodies or antigen receptors?
An antigen that induces an immune response resulting in the production of antibodies or functional T cells.
What is the portion of the antigen that is configured for recognition and binding?
What are the criteria that influence the degree of immunogenicity of an antigen?
- 1) foriegnness to the host (type of antigen)
- 2) size
- 3) adequate chemical complexity
- 4) present i nsufficient quantity
In regards to molecular size, which are more immunogenic; proteins, polysaccharides and nucleic acids or amino acids, monosaccharides, fatty acids, purine and pyrimidine bases?
The large molecules of proteins, polysaccharides and nucleic acids or amino acids are more immunogenic.
What is a called when a small molecule becomes immunogenic in combination with larger molecules that function as carriers?
What 3 molecules are able to recognize an antigen?
- 1) Circulating antibodies
- 2) BCR or B-cell receptor: antigen receptors on the surface of B lymphocytes.
- 2) TCR or T-cell recoptor: antigen receptors on the surface of T lymphocytes.
The class of immunoglobulin that is the most abundant and accounts for most of the protective activity agains infections.
The 1st and largest of the immunoglobulins produced during initial, or primary, response to antigens. It is synthesized early in neonatal life.
The immunoglobulin found mostly in blood and body fluids and is held together thru a J chain.
IgA: IgA1 is in blood, IgA2 is in body secretions
The immunoglobulin found in primarily on the surface of developing B lymphocytes.
The most rare/least concentrated immunoglobulin. It is the mediator of common allergic responses and in the defense of parasitic infection.
The specificity required for antibody binding with an antigen is determined by the shape and chemistry of what?
Complementary-determining regions (CDRs)
What are major histocompatibility complexes and what are their functions?
MHCs molecules are glycoproteins found the on the surface of all human cells except RBCs. They serve as the primary antigen presentation units of a cells.
MHC class 1 genes/proteins present which antigens by reacting with what?
Endogenous antigens derived from itracellular proteins by reacting with CD8 receptors on Tc cells.
MHC class II genes/molecules present which antigens by reacting with what?
Exogenous antigens derived from intracellular proteins by reacting with CD4 receptors on Th cells.
What 3 sets of molecules are primarily responsible for antigen presentation?
MHC class I, MHC class II, & CD1.
CD1 molecules present which antigens?
Exogenous lipid antigens derived from extracellular organisms.
Where does the generation of clonal diversity take place?
Primary (central) lymphoid organs like the thymus and bone marrow.
What is central tolerance?
The deletion of autoreactive T cells in the thymus.
What are the 3 types of cells that are considered the "professional" or most effective APCs and what is their function?
- 1) B cells: present antigen to Th cells that facilitate development of the humoral immune response.
- 2) Macrophages: present antigen to memory Th cells in order to initiate a rapid response to antigens.
- 3) Dendritic cells: most effective in presenting antigen to naive immunocompetent Th cells. Immature dendritic cells function as phagocytes and carry processed antigen from the site of inflammation to the T-cell-rich areas of lymph nodes.
The process that dentritic cells go thru to process and present antigens to naive lymphocytes to initiate clonal selection only results in activation of an acquired immune response if 3 things are in place. What are those 3 things?
- 1) the antigen is of the appropriate type
- 2) the lymphocytes are prepared to recognize the presented antigen,
- 3) the antigen is presented appropriately
What is the function of Th cells?
Helps the antigen-driven maturation of both B and T cells by facilitation and magnifying the interaction between APCs and immunocompetent lymphocytes.
List the 3 steps Th cells take to facilitate the interaction between APCs and immunocompetent lymphocytes.
- 1) Th cell directly interacts with the APC thru a variety of antigen-specific and antigen-independent receptors (TCR-CD4 receptors)
- 2) Th cell undergoes a differentiation process during which a variety of cytokine genes (IL-1) are activated
- 3) depending on the pattern of cytokines expressed, the mature Th cell interacts with either immunocompetent B or T cells to enhance their response to antigen. This results in differentiation into eithe rplasma cells or effector T cells, such as Tc cells.
What is the function of Th1 cells?
Activate macrophages and Tc cells that leads to cellular immunity
What is the function of Th2 cells?
Activate B cells that leads to the development of antibodies and humoral immunity.
What is the function of TH17 cells?
Attraction on neutrophillsn and macrophages and induce chemokine protein production that leads to the inflammatory response.
What is the function of the T-reg cells?
Suppress the immune response by producing immunosuppressive cytokines to prevent the immune response from being excessive.
What happens during the lag phase/latent period of primary immune responses?
B-cell differentiation and proliferation. IgM antibody is the first to be detected in the circulation followed by IgG. The phase allows for clonal selection, antigen processing and presentation, induction of Th cells, interaction between immunocompetent B cells and Th cells, and the maturation and proliferation of the B cells into plasma cells and memory cells.
Describe the secondary immune response.
A more rapid production of a larger amount of antibody than the primary response due to the presence of memory cells. IgM is produced just as in the primary response. IgG, however, is produced in larger amounts compared to the primary response. Thus, IgG is the predominant antibody of the secondary immune response.
During clonal selection, B cells differentiate into what types of cells?
antibody-producing plasma ceslls and long-lived memory cells.
What are the 2 main effector functions of activated T cells?
- 1) direct killing of foreign and/or abnormal cells (Tc cells)
- 2) assistance and/or activation of other cells, such as macrophages (T-reg cells and memory T cells)
What are the 3 "direct antibody" protection functions?
- 1) Neutralization: inactivating or blocking the binding of an antigen to a receptor (neutralize bacterial toxins and viral toxins and opsonization of bacteria))
- 2) Agglutination: clumping of insoluble particles that are in suspension
- 3) Precipitation: making a soluble antigen into an insoluble precipitate
What is the indirect protection effect of antibodies?
Enhance and activate several components of innate immunity (complement and phagocytes)
The process by which antibodies that make the pathogen more susceptible to phagocytosis thru binding to various receptors (Fc or C3b) on the phagocytes surface.
These are responsible for cell-mediated destruction of such targets as tumor cells or cells infected with viruses.
Tc cells or CTLs.
What is the difference between Tc cells and Natural Killer (NK) cells?
Tc cells kill malignant cells expressing MHC class I, NK cells kill abnormal cells with suppressed MHC class I expression.
Is the primary response or secondary response stronger in the fetus and why?
Primary response is stronger because the immunoglobulin produced in utero is mostly IgM. The fetus is unable to produce IgG.
At what point does infant total immunoglobulin levels reach a minimum and why?
At age 5-6 months of age because the mothers antibodies from in utero are catabolized quicker than the infant can produce more. This is the age when infants are most at risk for infections.
What happens to the immune function with age?
- 1) Decreased T-cell activity
- 2) decreased mature T cells because the thymus is less able to mediate T cell differentiation (shift in populations of T cell subtypes)
- 3) decrease in B cell antibody production (less memory cells)
- 4) decrease in memory B-cells. (poorer long-term immunity)
What are the 4 inappropriate immune responses?
- 1) Allergy: exaggerated against environmental antigens
- 2) Autoimmunity: misdirected agains the host's own cells
- 3) Alloimmunity: directed agains beneficial foreigh tissues, such as transfusions or transplants.
- 4) Immune deficiency: insufficient to protect the host.
Reactions that occure within minutes to a few hours are termed what?
Immediate hypersensitivity reactions
Reactions that may take several hours to appear and are at maximum severity days after reexposure to the antigen are termed what?
Delayed hypersensitivity reactions.
The most rapid and severe immediate hypersensitivity reaction that occurs within minutes of reexposure to the antigen and can be either systemic (generalized) or cutaneous (localized) is what?
Describe the characteristics of a Type 1 (IgE)-mediated hypersensitivity reaction.
- Mediated by IgE
- Products of tissue mast cells
- Allergy reactions - most occur against environmental antigens
- Most potent mediator is histamine
What are the actions of histamine caused from mast cell degranulation from H1 receptors?
- contracts bronchial smooth muscles causing bronchial constriction
- increases vascular permeability causing edema
- causes vasodilation increasing blood flow into the affected area
What are the actions of histamine through H2 receptors?
- increased gastric acid secretion
- decrease of histamine released from mast cells and basophils
What are the 5 general mechanisms by which type II hypersensitivity reactions can affect cells?
- 1) compliment mediated lysis with IgG or IgM antibodies
- 2) Opsonization/phagocytosis of the target cell caused by IgG and C3b opsonins that bind to receptors on the macrophage.
- 3) Neutrophil-mediated tissue damage due to antibody and complement attraction of neutrophils
- 4) Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells that release toxic substances that destroy the target cell.
- 5) Modulation of cellular function causing the target cell to malfunction by reactions to the antibody binding alone.
What are some characteristics of Type III: Immune Complex-Mediated Hypersensitivity?
- **Can be systemic or localized
- **Caused by antigen-antibody (immune) complexes that are formed in the circulation and deposited later in vessel walls or extravascular tissues.
- **Antibody binds to soluble antigen that was released into the blood or body fluids and then the complex is deposited into the tissues.
- **NOT organ specific
- **Attraction of neutrophils and subsequent release of lysosomal enzymes cause most of the resulting tissue damage.
What is serum sickness and give an example?
The systemic prototype of Type III: immune complex-mediated hypersensitivity reaction.
Caused by the formation of immune complexes in the blood and their subsequent generalized deposition in target tissues.
Example is Raynaud phenomenon: caused by the temperature-dependent deposition of immune complexes in the capillary beds of the peripheral circulation.
What is Arthus reaction?
The prototypic example of a localized immune complex-mediated inflammatory response.
Describe characteristics of Type IV: cell-mediated hypersensitivity reactions?
Mediated by T lymphocytes and DO NOT involve antibodies.
Occur thru Tc cells or Th1 (lymphokine-producing) cells. Tc cells attack and destroy cellular targets directly. Th1 cells produce cytokines that recurit and activate phagocytic cells (macrophages).
Example: graft rejection and allergic reactions resulting from contact with poison ivy (contact dermatitis) and metals (atopic dermatitis)
How does the epi-pen work on bee sting allergies?
It binds to specific receptors on smooth muscle and reverse the effects of histamine and result in muscle relaxation.
Give an example of a universal blood donor and explain it.
type O blood lacks both A and B antigens so anyone can accept their red blood cells.
Give an example of a universal recipient and explain it.
Type AB blood lacks both anti-A and anti-B antibodies and can be transfused with any ABO blood type.
Primary cellular targets for HIV include:
- CD4-positive Th cells
- dendritic cells
- CD8-positive Tc cells
- thymic cells
- NK cells
What portion of the HIV virion binds to the CD4 and chemokine receptors on the surface of Th cells?
How does HIV go from being single-stranded RNA to dbl-stranded DNA and where in the cell does this take place?
It makes its way into the cytoplams of the infected cell and uses reverse transpriptase to convert its RNA to DNA.
Where does the newly formed HIV DNA integrate itself into the infected cell's genetic material?
the infected cell's nucleus
What is the function of integrase?
It is a viral enzyme that helps the virus (HIV) to integrate itself into the host cell's genetic material.