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Learning objectives - The Immune System

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1

Describe surface membrane barriers and their protective functions.

Describe surface membrane barriers and their protective functions.

•Skin and Mucous membranes

the acidity of skin secretions inhibits bacterial growth
The stomach mucosa secretes a concentrated HCl solution and protein digesting enzymse to kill microorganisms
Saliva and lacrimal fluid contain lysozyme, an enzyme that destroys bacteria
sticky mucus traps many microorganisms that enter the digestive and respiratory passageways

2

Explain the importance of phagocytosis and natural killer cells in innate body defense.

Explain the importance of phagocytosis and natural killer cells in innate body defense.

•Phagocytosis is important because it is a process where pathogens that made it thru the first line of defense are stopped and engulfed by phagocytes

•Natural killer cells are a unique group of defensive cells that can lyse and kill cancer cells and virus infected body cells before the adaptive is activated. NK cells can eliminate a variety of infected or cancerous cells by detecting the lack of "self" cell-surface receptors and by recognizing certian surface sugars on the target cell.

3

Describe the inflammatory process. Identify several inflammatory chemicals and indicate their specific roles.

Describe the inflammatory process. Identify several inflammatory chemicals and indicate their specific roles.

Prevents the spread of damaging agents to nearby tissues
Disposes of cell debris and pathogens
Sets the stage for repair

Histamine - Granules of mast cells and basophils. Released in response to mechanical injury, presence of certain microorganisms, and chemicals released by

neutrophils. Promotes vasodilation of local arterioles. Increases permeability of local capillaries, promoting exudate formation.

Kinins - A plasma protein, kininogen, is cleaved by the enzyme kallikrein found in plasma, urine, saliva, and in lysosomes of neutrophils and other types of cells. Cleavage releases active kinin peptides. Promotes vasodilation of local arterioles. Increases permeability of local capillaries, promoting exudate formation. Also induce chemotaxis of leukocytes and prompt neutrophils to release
lysosomal enzymes, thereby enhancing generation of more kinins. Induce pain.

Prostaglandins - Fatty acid molecules produced from arachidonic acid found in all cell membranes; generated by enzymes of neutrophils, basophils, mast cells, and others. Promotes vasodilation of local arterioles. Increases permeability of local capillaries, promoting exudate formation. Also induce neutrophil chemotaxis. Induce pain.

Platelet-derived growth factor (PDGF) - Secreted by platelets and endothelial cells. Stimulates fibroblast activity and repair of damaged tissues.

4

Name the body’s antimicrobial substances and describe their function.

Name the body’s antimicrobial substances and describe their function.

•Interferons Proteins - released by virus-infected cells and certain lymphocytes that protect uninfected tissue cells from viral takeover; mobilize immune system

•Complement - Lyses microorganisms, enhances phagocytosis by opsonization, and intensifies inflammatory and immune responses

5

Explain how fever helps protect the body.

Explain how fever helps protect the body.

Fever is a systemic response to invading organisms.
•Cause the body to hold onto iron and zinc which microbes need for reproduction
•Increases body’s metabolic rate to speed repair

6

Define antigen and describe how antigens affect the adaptive defenses.

Define antigen and describe how antigens affect the adaptive defenses.

Antigens - substances that can mobilize the adaptive defenses and provoke an immune response. They are the ultimate targets of all adaptive immune responses.

Most antigens are large, complex molecules (both natural and synthetic) that are not normally present in the body. Consequently, as far as our immune system is concerned, they are intruders, or nonself.

7

Define hapten.

Define hapten.

Hapten - incomplete antigen; a specific nonprotein substance which does not itself elicit antibody formation but does elicit the immune response when coupled with a carrier protein

8

Compare and contrast the origin, maturation process, and general function of B and T lymphocytes.

Compare and contrast the origin, maturation process, and general function of B and T lymphocytes.

•B & T lymphocytes originate in red bone marrow from hematopoietic stem cells.

•Maturation Process
T cells undergo a two- to three-day maturation process in the thymus.
B cells become immunocompetent and self-tolerant in the bone marrow.
Naive B cells and T cells are exported to the lymph nodes, spleen, and other secondary lymphoid organs, where encounters with antigens may occur.

•General Function
B lymphocytes - B cells oversee humoral immunity.
T lymphocytes - T cells are non-antibody-producing lymphocytes that constitute the cell-mediated arm of adaptive immunity.

9

Define immunocompetence and self-tolerance, and describe their development in B and T lymphocytes.

Define immunocompetence and self-tolerance, and describe their development in B and T lymphocytes.

Immunocompetence - The ability of a lymphocyte to recognize its one specific antigen by binding to it.

Self-tolerance - lymphocyte is relatively unresponsive to self-antigens so that it does not attack the body’s own cells.

T cells education consists of positive and negative selection. Positive selection, which occurs in the thymic cortex, is essentially an MHC restriction process. It identifies T cells whose receptors are capable of recognizing (binding) self-MHC molecules
and eliminates all others. In this way positive selection produces an army of self-MHC-restricted T cells. T cells that make it through positive selection are then tested to make sure that they do not recognize (bind tightly) self-antigens displayed on self-MHC. If they do, they are eliminated by apoptosis (programmed cell death). This is negative selection, and it occurs in the inner edge of the thymic cortex.
In the bone marrow, self-reactive B cells are either eliminated by apoptosis (clonal deletion), or are given a chance to change their self-reactive antigen receptor by receptor editing, in which there is another rearrangement of the antigenbinding part of the receptor.

10

Name several antigen-presenting cells and describe their roles in adaptive defenses.

Name several antigen-presenting cells and describe their roles in adaptive defenses.

Dendritic cells – present in connective tissues and in the epidermis Dendritic cells are at the body’s frontiers, best situated to act as mobile sentinels. When they present antigens they activate T cells.

Macrophages - widely distributed throughout the lymphoid organs and connective tissues. When they present antigens they activate T cells.

B cells – produces antibodes

11

Define humoral immunity.

Define humoral immunity.

The component of the immune system involving antibodies that are secreted by B cells and circulate as soluble proteins in blood plasma and lymph.

12

Describe the process of clonal selection of a B cell.

Describe the process of clonal selection of a B cell.

1. An antigen presenting cell presents antigen on Class II MHC to a Helper T cell activating it

2. At the same time a B cell that has taken up and degraded the same pathogen displays antigen on its class II

3. The activated helper T cell binds to the B cell releasing cytokines and activating it

4. The activated B cell proliferates and differentiates into:
•memory B cells
•antibody-secreting plasma cells that produce antibodies specific for the pathogen

13

Recount the roles of plasma cells and memory cells in humoral immunity.

Recount the roles of plasma cells and memory cells in humoral immunity.

Plasma cells develop the elaborate internal machinery (largely rough endoplasmic reticulum) needed to secrete antibodies at the unbelievable rate of about 2000 molecules per second. Each plasma cell functions at this breakneck pace for 4 to 5 days and then dies.

Memory Cells - Clone cells that do not become plasma cells They are longlived and can mount an almost immediate humoral response if they encounter the same antigen again at some future time

14

Compare and contrast active and passive humoral immunity.

Compare and contrast active and passive humoral immunity.

•Passive differs from active immunity, both in the antibody source and in the degree of protection it provides. Instead of being made by your plasma cells

•Active Humoral Immunity - When your B cells encounter antigens and produce antibodies against them

•Passive humoral immunity - The antibodies are harvested from the serum of an immune human or animal donor. As a result, your B cells are not challenged by antigens, immunological memory does not occur, and the protection provided by the “borrowed” antibodies ends when they naturally degrade in the body.

15

Name the five classes of antibodies and where found.

Name the five classes of antibodies and where found.

The five major immunoglobulin classes are designated

IgM - first antibody class released to the blood by plasma cells. It readily fixes complement.

IgA - is found primarily in mucus and other secretions that bathe body surfaces. It plays a major role in preventing pathogens from gaining entry into the body.

IgD - always bound to a B cell surface, where it acts as a B cell receptor.

IgG - most abundant antibody in plasma and the only

Ig class that crosses the placental barrier.

IgE - antibodies, found in minute quantities in blood, are the “troublemaker” antibodies involved in some allergies.

16

Explain the function(s) of antibodies.

Explain the function(s) of antibodies.

•Precipitation - soluble molecules (instead of cells) are cross-linked into large complexes that settle out of solution.

•Complement fixation and activation - is the chief antibody defense used against cellular antigens, such as bacteria or mismatched red blood cells. When several antibodies bind close together on the same cell, the complement-binding sites on their stem regions align.

•Neutralization - the simplest defensive mechanism, occurs when antibodies block specific sites on viruses or bacterial exotoxins (toxic chemicals secreted by bacteria). As a result, the virus or exotoxin loses its toxic effect because it cannot bind to receptors on tissue cells to cause injury. The antigen-antibody complexes are eventually destroyed by phagocytes.

•Agglutination - cell-bound antigens are cross-linked, the process causes clumping,
Antibodies PLAN of Action -precipitation, lysis (by complement), agglutination, and neutralization

17

Define cellular immunity and describe the process of activation and clonal selection of T cells.

Define cellular immunity and describe the process of activation and clonal selection of T cells.

the mechanism of acquired immunity characterized by the dominant role of T cell lymphocytes. Cellular immunity is involved in resistance to infectious diseases caused by viruses and some bacteria and in delayed hypersensitivity reactions, some aspects of resistance to cancer, certain autoimmune diseases, graft rejection, and certain allergies. It does not involve the production of humoral antibody but instead involves the activation of Mo and natural killer cells.

18

Describe the roles of different types of T cells.

Describe the roles of different types of T cells.

TH cell help in humoral immunity
1. TH cell binds with the self-nonself complexes of a B cell that has encountered its antigen and is displaying it on MHC II on its surface.
2. TH cell releases interleukins as costimulatory signals to complete B cell activation.

TH cell help in cell-mediated immunity
1. Dendritic cell engulfs an exogenous antigen, processes it, and displays its fragments on class II MHC protein.
2. Immunocompetent CD4 cell recognizes antigen-MHC complex. Both TCR and CD4 protein bind to antigen-MHC complex.
3. CD4 cells are activated, proliferate (clone), and become memory an effector cells

19

Describe T cell functions in the body.

Describe T cell functions in the body.
T cells are non-antibody-producing lymphocytes that constitute the cell-mediated arm of adaptive immunity.

•CD4+ T cells - T helper cell (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. They express the CD4 protein on their surface.

•CD8+ T cells - Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. They express the CD8 glycoprotein at their surface.

•Memory T cells - are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells).

•Regulatory T cells - (Treg cells) are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.

•Natural killer T cells - (NKT cells) bridge the adaptive immune system with the innate immune system.

20

Give examples of immune deficiency diseases and of hypersensitivity states.

Give examples of immune deficiency diseases and of hypersensitivity states.

Immunodeficiency - Any congenital or acquired condition that causes immune cells, phagocytes, or complement to behave abnormally

Hodgkin’s disease - a cancer of the B cells, can lead to immunodeficiency by depressing lymph node cells.

Hypersensitivities:
Allergies, Immune responses to a perceived (otherwise harmless) threat (usually involves haptens), Causes a histamine response: inflammatory reaction, Causes tissue damage. Localized or systemic reactions can occur, Risk of anaphylactic shock for severe allergies (respiratory shut down) which is treated with epinephrine

21

Cite factors involved in autoimmune disease, HIV and AIDs.

Cite factors involved in autoimmune disease, HIV and AIDs.

Acquired Immune Deficiency Syndrome (AIDS) - which cripples the immune system by interfering with the activity of helper T cells.Cripples the immune system by destroying helper T cells
•Characterized by severe weight loss, night sweats, and swollen lymph nodes
•Opportunistic infections occur, including pneumocystis pneumonia and Kaposi’s sarcoma
•Caused by human immunodeficiency virus (HIV) transmitted via body fluids—blood, semen, and vaginal secretions
•Treatment with antiviral drugs
•Incurable, and massive infection or cancer kills the sufferer

HIV (human immunodeficiency virus) - destroys TH cells, depressing cell-mediated immunity. Although B cells and TC cells initially mount a vigorous response to viral exposure, in time a profound deficit of B cell and cytotoxic T cell function develops. The whole immune system is turned topsy-turvy.

22

Describe changes in immunity that occur with aging and stress.

Describe changes in immunity that occur with aging and stress.

The newborn’s immune system depends primarily on antibodies, and hence on TH2 lymphocytes. The TH1 system is educated and gets stronger as a result of encounters with microbes—both harmful and harmless.

Our immune system normally serves us very well until late in life. Then its efficiency begins to wane, and its ability to fight infection declines. Old age is also accompanied by greater susceptibility to both immune deficiency and autoimmune diseases. The greater incidence of cancer in the elderly is assumed to be an example of the progressive failure of the immune system.


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