Immunity Flashcards
WHAT IS IMMUNITY?
Both the innate and adaptive immune responses protect the host from infections by pathogens, and both innate and adaptive immunity are essential for survival. Immunity may be naturally occurring ( when we generate an immune response through exposure to antigen), artificially induced by exposure to antigens (vaccination), or passively when we receive antibodies or immune cells from an immune individual.
The immune system
The main function of the immune system is to prevent or limit infection by microorganisms. The first line of defense is the intact skin and mucous membranes. If microorganisms breach this line and enter the body, then the innate arm of the immune system (second line of defense) is available to destroy the invaders. Because the components of the innate arm are preformed and fully active, they can function immediately upon entry of the microorganisms. The ability of the innate arm to kill microorganisms is not specific. Eg. A neutrophil, assisted by complement, can ingest and destroy many different kinds of bacteria.
Highly specific protection is provided by the adaptive (acquired) arm of the immune system (third line of defense), but it takes several days for this arm to become fully functional. The two components of the adaptive arm are cell-mediated immunity and antibody mediated (humoral) immunity. The cell mediated arm consists primarily of T cells whereas the antibody mediated arm consists of antibodies and B cells. The main function of antibodies are 1) to neutralise toxins and viruses and 2) to opsonize bacteria (pokes holes in them). Both the cell-mediated and antibody mediated responses are characterised by three important features: 1) they exhibit remarkable diversity, 2) they have long memory and can respond many years after the initial exposure and 3) they exhibit exquisite specificity – which is essential or the immune system attacks the host.
NATURAL KILLER CELLS are large granular lymphocytes that do not pass through the thymus, do not have an antigen receptor and do not bear CD4 or CD8 proteins. They recognise and kill target cells, such as virus-infected cells and tumor cells, without the requirement that the antigens be presented in associated with MHC proteins. Rather, NK cells target those cells to be killed by detecting that they do not display class I MHC proteins on the cell surface. This detection process is effective because many cells lose their ability to synthesise class I MHC proteins after they have been infected by a virus.
Primary and secondary immune response
Primary and secondary adaptive immune responses. The primary response induces both immune cells and antibodies. The antigens given at day 0 and day 100 must be identical to induce a secondary response. The secondary response may generate more than 10-fold increases in immune cells and antibody concentrations.
Cells of the immune system
Immune cells develop from mutipotent stem cells in the bone marrow into either myeloid precursors or lymphoid precursors. These precursors in turn differentiate into end cells that have various immune functions
The primary function of dendritic cells is to capture and present protein antigens to naive T-lymphocytes. (Naive lymphocytes are those that have not yet encountered an antigen.) Dendritic cells engulf microorganisms and other materials and degrade them with their lysosomes.
Mast cells, found throughout theconnective tissueof the skin and mucous membranes, carry out the same functions as basophils. They releasehistamine, leukotriens, and prostaglandins, chemicals thatpromotes inflammationby causing vasodilation, increasing capillary permeability, and increasing mucous production. Mast cells are the cells that usually first initiate the inflammatory response
Innate immune cells
What is the difference between Neutrophil and Macrophage?
Both are part of the Innate Immune system which is non inducible and pre-existing
• Macrophages can live longer than neutrophils.
• Since macrophages are larger than neutrophils, they can phagocyte greater number of invader pathogens than neutrophils.
• After infection, neutrophils dominate the infected site early while macrophages dominate infected sites at later stages (1 to 2 days after infection).
• Unlike the neutrophil, macrophage can present the antigenic fragments to the T lymphocytes in the context of MHC (Major Histocompatibility Complex) class II molecules after engulfing the bacterial cells.
• Unlike the macrophage, neutrophil has multilobed nucleus. The nucleus of macrophage is big and round shaped.
Haptens
A hapten is essentially an incomplete antigen. These small molecules can elicit an immune response only when attached to a large carrier such as a protein; the carrier typically does not illicit an immune response by itself. Many hapten carriers are normal molecules that circulate through the body. When haptens and carriers combine, the resulting molecule is called an adduct, the combination of two or more molecules. Haptens cannot independently bind to MHC complexes, so they cannot be presented to T cells.The first haptens used were aniline and its carboxyl derivatives (o-, m-, and p-aminobenzoic acid). One well-known hapten is urushiol, the toxin found in poison ivy and a common cause of cell-mediated contact dermatitis. When absorbed through the skin from a poison ivy plant, urushiol undergoes oxidation in the skin cells to generate the actual hapten, a reactive molecule called a quinone, which then reacts with skin proteins to form hapten adducts. Usually, the first exposure causes only sensitization, in which there is a proliferation of helper and cytotoxic T cells. After a second exposure, the proliferated T cells can become activated, generating an immune reaction and producing the characteristic blisters of poison ivy exposure. Some haptens induce autoimmune disease. An example is hydralazine, a blood pressure-lowering drug that occasionally causes lupus erythematosus (an autoimmune inflammatory disorder) in certain individuals with genetic predispositions to the disease. This also appears to be the mechanism by which the anesthetic gas halothane can cause life-threatening hepatitis and penicillin-class drugs cause autoimmune hemolytic anemia. Other haptens, such as flourescein, detect proteins with which they form adducts. This makes them a common part of molecular biology lab techniques.
Hypersensitivity: Anaphylaxis (I)
IgE binds to mast cells or basophils, causes degranulation of mast cell or basophil and release of reactive substances such as histamine. Leukotrienes and prostaglandins. = swelling, redeness, increased mucus secretion, smooth muscle contraction (breating difficulty)
Hypersensitivity: Cytotoxic (II)
Generally involve activation of complement by the combination of IgG or IgM antibodies with an antigenic cell. This activation stimulates complement to lyse the affected cell which might be either a foregin cell or a host cell that carries a foreign antigenic determinant such as a drug on its surface. Additional cellular damage may be caused within 5-8 hours by the action of macrophages and other cells that attach antibody-caoted celss. The most familiar cytotoxic hypersensitivity reaction are transfusion reactions, in which RBC are destroyed as a result of reacting with circulating antibodies.
Hypersensitivity: Immune Complex (III)
Type III reactions involve antibodies against soluble antigens circulating in the serum. The antigen-antibody complexes are deposited in organs and cause inflammatory damage. These complexes circulate in the blood, pass between endothelial cells of the blood vessels, and become trapped in the basement membrane beneath the cells. In this location, they may activate complement and cause a transient inflammatory reaction: attracting neutrohphils that release enzymes. Repeated introduction of the same antigen can lead to more serious inflammatory reactions causing damage to the basement membranes endothelial cells within 2-8 hours.
Glomerulonephritis is an immune complex condition, usually resulting from ainfections that causes inflammatory damage to the kidney glomeruli, which are sites of blood filtration. SLE, rheumatoid arthritis
Hypersensitivity: Delayed (IV)
These may take a day or more to manifest because of the time required for the T cells and macrophages to migrate to and accumulate near the foreign antigens. Sensitisation occurs when foreign antigens, particularly those that bind to tissue cells (like poison Ivy) are phagocytised by macrophages and presented to receptiors o n the T-cell surface.. Contact causes the T cells to proliferate and mature creating memory. On subsequent re-exposure inflammation occurs leading to dermatitist etc. Is the basis of latex allergies
Autoimmunity
Molecular mimicry as a result of foreign antigens resembling a comonent of the body
Sequestered Antigens come from immunological priveleged sites such as the CNS, eye, sperm and if they enter the circulation accidentally they elicit damaging immune responses
Epitope Spreading is new exposure of sequestered autoantigens as a result o famage ot cells caused by viral infection. Eg. MS
Regulatory T cells suppress the proinflammatory effects of other T cells. Patients with a mutation in one of the surface proteins found on Tr cells can develop auotimmune diseases such as SLE
Acquired Immunodeficiency
Decline of T-helper (Th) lymphocytes and progress of HIV/AIDS: An untreated HIV infection progresses to AIDS. The number and functional ability of the T helper cells gradually declines, while the viral load, measured as HIV-specific RNA copies per mililiter of blood, increases after an initial decline. The lack of an effective immune response leads to an increase in life-threatening infections and death.
HIV treatment
Immunosuppression by HIV is complex and not fully understood. It is thought to damage the immune system by direct killing of infected T4 cells, destruction of virus-infected immune cells by CD8 cytotoxic T cells. The loss of T4 cells diminishes the ability of the patient to produce sufficient numbers of antibodies or lymphokines, since functional T4 cells are required for the initiation of immune responses. Thus the infected host become slowly more susceptible to infections and cancers that a healthy immune system would normally prevent. HIV also attacks the nervous system directly, carried into the brain by infected monocytes, altering cytokine levels and causing release of toxic substances. The natural (untreated) course of HIV infection has three clinical phases: Acute infection, 2-4 weeks after infection and includes acute flu-like illness with fever, headache, pharyngitis, nausea, lymphadenopathy, ulcers and rash. Asymptomatic HIV, a variable period of a few years to longer than a decade of few or no signs and symptoms. Low viral replication, T4 count >500/uL and apparent good health.
