Five cardinal localized signs of inflammation:
- 1.Redness (rubor)
- 2.Swelling (tumor)
- 3.Heat (calor)
- 4.Pain (dolor)
- 5.Loss of function (function laesa)
Sequence of events in the inflammatory process:
i.Increased vascular permeability—mast cells release chemicals such as histamine, prostaglandins, & leukotrienes, which cause vasodilatation, and increased vascular permeability.
- ii.Emigration (diapedesis) of leukocytes from the bloodstream into tissues—neutrophils (and other WBCs) roll and stick to the sides of blood vessels, a process called margination or pavementing.
- a.selectins—are receptors that aid neutrophil pavementing
- b.integrins—aid neutrophil movement through the capillary walls (diapedesis).
- c.chemotaxis—is the process by which leukocytes are attracted to inflamed tissue.
iii.Phagocytosis—if a microbe is small enough to be internalized, the phagosome is fused by a lysosome and digested. Larger particles are attacked by extracellular secretion of digestive enzymes.
Exudate—fluid that leaks out of blood vessels, combined with neutrophils & debris from phagocytosis. Their function is to:
- i.Transport leukocytes & antibodies
- ii.Dilute toxins & other irritants
- iii.Transport nutrients necessary for tissue repair.
Specific adaptive immunity—two “arms” exist:
- i.B cells provide “humoral immunity” because they secrete antibody into body fluids or “humors.”
- ii.T cells provide “cell-mediated immunity” because they recognize antigens presented on the surface of cells.
Mechanisms of cell-mediated immunity (3):
i. T-cells recognize foreign antigens through specialized TCT's (which can recognize only a single epitope)
ii. T-cells that might react to self-antigens are eliminated in the thymus.
- iii.Once T cells’ own TCRs are stimulated, they react in 2 different ways:
- a.T helper (CD4) cells—the CD4 protein binds to a MHC protein, while the TCR binds to its corresponding antigen. Does remembering that we have 4 fingers on a “helping hand” help you remember the “CD4” term?
- b. Cytotoxic (CD8) cells—Cytotoxic T cells require T helper cells before they can be fully effective—cytokines alone are not adequate. How about this for a mnemonic?—8-year-olds can be toxic…
Cytotoxic T cells proliferate into 2 cells types called:
memory cells, and effector cells.
An antigenic determinant, is the part of a macromolecule that is recognized by the immune system, specifically by antibodies
Mechanisms of humoral immunity
- B-cell function, which have B-cell receptors (BCRs), which are specific for a single epitope.
- Some B-cells can respond to nonprotein antigen (like bacterial sugars and lipids). This is important, because T-cells can only respond to protein antigens!
B cells have 2 major subpopulations:
1.memory B cells (which function a lot like memory T cells), and
- 2.plasma cells—which are antibody production factories.
- a. They are basically grown-up B cells that have left home and found a full-time job.
5 classes of antibody:
- i. IgG—most common (75-80% of circulating antibody),
- predominates in the secondary (anamnestic) immune response.
- *Monomer (1 y)
- ii. IgM—10% of circulating antibody
- a.works best to activate complement (only one molecule of IgM is needed to activate complement, while 2 of IgG is needed)
- b.predominant antibody in the primary immune response
- c. (this is the predominant antibody made when our immune system is exposed to a particular antigen for the first time.)
- d.pentamer. (5 “Y”s)
- iii.IgA—found in secretions onto mucus membranes.
- a.Dimer. (There are 2 legs on an “A”)
- iv.IgD—found on B-cell membranes. Functions not well understood.
- v.IgE—found on basophils & mast cells; important in allergies;
Antibody functions (5) (most of what they do is to aid other immune functions)
- 1.precipitation—pulling antigens out of solution (blood stream)
- 2.agglutination—sticking groups of antigens together.
- 3.neutralization—just by binding, can make some bacterial toxins ineffective.
- 4.opsonization—enhance the function of phagocytic cells.
- 5.complement activation—particularly IgM & IgG are good at this
transfer of pre-formed antibody against a particular antigen from an immune person to a non-immune person.
(passive immunity) injection of specific “immune globulins. Examples: rabies immune globulin, hepatitis B immune globulin, West Nile Virus immune globulin, etc.
- i.occurs by antigen exposure and immune response of the person’s own immune system. Can be either:
- a.immunization—deliberate administration of vaccines or
- b.active infection—actually get infected by an organism.
A measure taken for the prevention of a disease or condition.
Excessive immune responses (2):
- a.Autoimmunity—the immune system recognizing ones own antigens as foreign and mounting an immune response against them: the loss of self-tolerance.
- b.Hypersensitivity—an excessive or inappropriately triggered immune response. Four varieties exist: I-III involve antibody; IV only T cells.
Type I—IgE mediated hypersensitivity (4 points):
2.immediate hypersensitivity reaction because signs/symptoms of allergic reaction occurs immediately after contact with an allergen.
- 3.Mast cells are the principal effector cells, with cross-linking of IgE receptors on mast cell membranes the stimulus for degranulation and release of chemical mediators, including histamine which causes reactions like:
- a.Increased vascular permeability
- b.Vasodilatation (with flushing)
- d.Smooth muscle constriction
- f.Increased gut permeability
4.Treatment ranges from: nothing (mild cases), antihistamines, epinephrine, steroids, allergic desensitization, allergen avoidance, mast cell stabilization, etc.
Type II—tissue-specific, cytotoxic, or cytolytic hypersensitivity (2 points):
1.antibody binding to tissue-specific antigens, which then causes complement activation
- 2.Examples of Type II reaction mechanisms include:
- a.Transfusion reactions—you should understand ABO blood typing system and the basics of this reaction, which is complement mediated.
- b.Hemolytic disease of the newborn—direct phagocytosis by effector cell (like macrophages) of antibody-coated fetal erythrocytes.
- c.Myasthenia gravis—antibodies against acetylcholine receptors at the motor end-plate causes complement to attack the receptor.
III—immune complex or Arthus reaction (3 points):
1.Not tissue specific: the damage is done when complexes of antigen/antibody are deposited in tissues, then complement is activated & neutrophils & mast cells go into action.
2.The different between II & III is that in type III reactions, the antigen/antibody complexes precipitate out of the bloodstream into whatever tissue is nearby, or oppositely electrically charged
- a.Immune complex glomerulonephritis—usually occurs after streptococcal bacterial infections, with immune complexes deposited in the glomerular basement membrane.
- b.Systemic lupus erythematosus (SLE)—characterized by autoantibodies against nuclear antigens. ANY organ system can be involved.
Type IV—delayed hypersensitivity:
1.Tissue damage caused by delayed reaction to an antigen.
2. Antibody not involved;
3.principal mediators are lymphokines—produced by lymphocytes;
4.principal effector cells are mast cells (only early in the reaction), lymphocytes & macrophages (not neutrophils).
- a.Contact hypersensitivity—an epidermal reaction to a hapten, which is processed by Langerhans cells. Antigens include such things as nickel, clothing, plant oils (poison ivy/oak), ointments, etc.
- b.Tuberculin-type reaction—a dermal reaction to injected tuberculosis antigen. Used to diagnose previous TB exposure.
- c.Granulomatous hypersensitivity—indigestible antigen engulfed by macrophages, which then form epitheliod cells +/or multinucleated giant cells.
A small molecule that can elicit an immune response only when attached to a large carrier such as a protein
Deficient immune responses—come in two types:
- i.Primary immune deficiencies—not attributable to another cause;
- ii.Secondary immune deficiencies—consequence of other disease processes or treatments.
Primary immunodeficiency disorders:
- 1.B-cell & T-cell combined disorders:
- a.severe combined immunodeficiency disorders—the most severe form is reticular dysgenesis: failure of ALL leukocytes to form.
- b.Wiskott-Aldrich Syndrome—X-linked; IgM low; IgA/IgE high, IgG variable.
- 2.T-cell disorders:
- a.DiGeorge syndrome or thymic hypoplasia—total or partial loss of thymus function. Total loss fatal.
- b.Chronic mucocutaneous candidiasis—autosomal recessive; selective deficiency of cell-mediated immunity against Candida albicans (“yeast”). The correct cytokine necessary to combat this organism is missing.
- 3.B-cell disorders:
- a.IgA deficiency—affects 1 in 400 people; can be either autosomal recessive or dominant. They tend to have lots of respiratory, GI, and genitourinary tract infections, a higher incidence of vascular & collagen autoimmune diseases. Usually doesn’t shorten life, and many cases not diagnosed.
- b.Bruton X-linked agammaglobulinemia (congenital hypogammaglobulinemia—lack of normal bursal-equivalent tissue (where B cells mature).
- c.It was the first immunodeficiency disorder identified—1952.
Secondary immunodeficiency disorders—include reactions to:
- i.Stress—burns, trauma, pregnancy, infancy,
- iii.nutritional deficiencies (both malnutrition and overnutrition!),
- iv.cancer chemotherapy drugs,
- vi.post-splenectomy patients reduces serum IgM and the antibody response to encapsulated bacteria.
- vii.Advanced age
- viii.And lots of others…