IMMUNOLOGIC FUNCTION

The immune system functions as the body’s defense mechanism against invasion and allows a rapid response to foreign substances in a specific manner.

Immunity – refers to the body’s specific protective response to an invading foreign agent or organism.

Immunopathology – refers to the study of dses that result from dysfunctions w/ the immune system

Immune System Disorders:

Autoimmunity – normal protective immune response paradoxically turns against or attacks the body, leading to tissue damage

Hypersensitivity – body produces inappropriate or exaggerated responses to specific antigens

Gammopathies – immunoglobulins are overproduced

Immune deficiencies

a. primary – deficiency results from improper development of immune cells or tissues; usually congenital or inherited

b. secondary – deficiency results from some interference w/ an already developed immune system; usually acquired later in life

epitopes – any component of an antigen molecule that functions as an antigenetic determinant by permitting attachment of certain antibodies

inflammatory response lysis of microbial agents disposal of foreign toxins

The major component of the immune system include:

bone marrow WBC Lymphoid tissues

o Thymus glando Spleeno Lymph nodeso Tonsilso Adenoidso Tissues in the GI, Respi and Repro systems

Bone Marrow

Produces WBC Lymphocytes are generated from stem cells, w/c are undifferentiated cells Lymphocyte – a variety of WBC formed in the lymphoid tissues of the body;

round, colorless, somewhat motile, with a single nucleus and no cytoplasmic granules. They make up 20 to 30% of all WBC and serve as a defense mechanism for the body. Their function is to produce antibodies.

B-lymphocytes (B-cells) – cells that are important for producing a humoral immune response; are those that migrate directly into the tissues w/o passing through the thymus. It

matures in the bone marrow and then enter circulation

T-lymphocytes (T-cells) – cells that are important for producing a cellular immune response; move from the bone marrow to the thymus, where they mature into several kinds of cells with different functions.

Stem cells – precursors of all blood cells; reside primarily in bone marrow

Lymphoid Tissues

The spleen, composed of red and white pulp, acts as a filter. The red pulp is the site where old and injured RBCs are destroyed. The white pulp contains concentrations of lymphocytes.

The lymph nodes are distributed throughout the body. They are connected by lymph channels and capillaries, w/c remove foreign material from the lymph system before it enters the bloodstream. They also serve as centers for immune cell proliferation.

o Axillaryo inguinal

Immune Function

2 general types of immunity:

a. natural (innate) – is a nonspecific immunity that is present at birthb. acquired (adaptive) – develops after birth

Natural (Innate) Immune System

provides rapid specific immunity and is present at birth it has a broad spectrum of defense against and resistance to an infection provides a non-specific response to any foreign invader regardless of

composition the basis of this defense mechanism is the ability to distinguish between

self or non-self coordinates the initial response to pathogens through the production of

cytokines and other effector molecules, w/c either activate cells for control of the pathogen (elimination) or promote the development of acquired immune response.

o Macrophageso Dendritic cellso Natural killer cells

Can be divided into 2 stages:o Immediate (occurring w/in 4h)o Delayed (occurring b/ 4 to 96h after exposure)

WBC Action

Granular leukocytes or granulocytes – fight invasion by foreign bodies or toxins by releasing cell mediators (e.g. histamine, bradykinin, prostaglandins) and engulfing foreign bodies or toxins.

o Neutrophils (also called polymorphonuclear leukocytes, PMNs) – are the first cells to arrive at the site where inflammation occurs.

o Eosinophils and Basophils – increase in number during allergic reactions and stress responses

Non-granular leukocytes (monocytes or macrophages and lymphocytes)

o Monocytes function as phagocytic cells, engulfing, ingesting and destroying greater numbers and quantities of foreign bodies or toxins

o Lymphocytes (B-cells and T-cells) play major roles in humoral and cell-mediated immune responses

Inflammatory Response

Elicited in response to tissue injury or invading organisms. Chemical mediators assist this response by:

o Minimizing blood losso Walling off invading organismso Activating phagocyteso Promoting formation of fibrous scar tissueo Promoting regeneration of injured tissue

Physical and Chemical Barriers

Physical surface barriers:o Intact skino Mucous membrane o Cilia

Chemical barriers:o Mucuso Acidic gastric secretionso Enzymes in tearso Salivao Substances in sebaceous and sweat secretions

Viruses are countered by interferon Interferon – one type of biologic response modifier; is a

non-specific viricidal CHON that is naturally produced by the body and is capable of activating other components of the immune system.

Immune Regulation

The immune system’s recognition of one’s own tissues as “foreign” rather than as self is the basis for many autoimmune disorders

Immunoregulation – complex system of checks and balances that regulates or controls immune responses

Acquired (Adaptive Immunity)

Immunologic responses acquired during life but not present at birth – usually develops as a result of prior exposure to an antigen through immunization or by contracting a dse, both of w/c generate a protective immune response.

The acquired immune response is divided into 2 mechanisms:o Cell-mediated response (T-cell)o Effector mechanisms (B-cell)

Two types of acquired immunity:o Active – the immunologic defenses are developed by the person’s

own body o Passive – temporary immunity transmitted from a source outside the

body that has developed immunity through previous dse or immunization

Response to invasion:

The phagocytic immune response The humoral or antibody immune response

The cellular immune response

Phagocytic Immune Response

Involves WBCs (granulocytes and macrophages) which have the ability to ingest foreign particles.

Apoptosis – programmed cell death; is the body’s way of destroying worn-out cells. It involves the digestion of DNA by endonucleases, w/c results in targeting of the cells for phagocytosis.

Phagocytosis – the engulfment and usually the isolation or destruction by phagocytes, or foreign or other particles or cells harmful to the body

Humoral Immune Response

Antibody response The body’s second line of defense Is characterized by the production of antibodies by B-lymphocytes in

response to a specific antigen. Begins with B-lymphocytes, w/c can transform themselves into plasma

cells that manufacture antibodies. These antibodies are highly specific CHON that are transported in the bloodstream and attempt to disable invaders.

Antibodies – are large CHON called immunoglobulins (because they are found in the globulin portion of the plasma). They help defend against foreign invaders in several ways, and the type of defense depends on the structure and composition of bothe the antigen and immunoglobulin.

The antibody molecule has at least 2 combining sites, or Fab fragments. One antibody can act as a crosslink b/w 2 antigens causing them to bind or clump together (agglutination). This helps clear the body of the invading organism by facilitating phagocytosis.

Opsonization – in this process, the antigen-antibody molecule is coated with a sticky substance that also facilitates phagocytosis.

Antibodies also promote the release of vasoactive substances such as histamine and slow-reacting substance, two of the chemical mediators of the inflammatory response.

Antibodies do not function in isolation: they mobilize other components of the immune system to defend against the invader.

The typical role of antibodies is to focus components of the natural immune system on the invader.

Antigenic determinant – the portion of the antigen involved in binding w/ the antibody

All immunoglobulins are glycoproteins and contain a certain amount of CHO

The body can produce 5 different types of immunoglobulins:o IgA (75%)

Appears in serum and tissues (interstitial fluid) Assumes a major role in bloodborne and tissue

infections Activates the complement system Enhances phagocytosis Crosses the placenta

o IgD (15%) Appears in body fluids (blood, saliva, tears,

breastmilk, and pulmonary, GI, prostatic and vaginal secretions)

Protects against respiratory, GI and GU infections Prevents absorption of antigens from food Passes to neonate in breastmilk for protection

o IgE (10%) Appears mostly in intravascular system Appears as the first immunoglobulin produced in response

to bacterial or viral infections Activates the complement system

o IgG (0.2%) Appears in small amounts in serum Possibly influences B-lymphocytes differentiation

o IgM (0.004%) Appears in serum Takes part in allergic and some hypersensitivity reactions Combats parasitic infections

Cellular Immune Response

The body’s third line of defense; involving the attack of pathogen by T-cells Involves T-lymphocytes w/c can turn into special cytotoxic (or killer) T-cells

that can attack the pathogens Stem cells constantly migrate from the bone marrow to the thymus gland,

where they develop into T-cells Antigen – the structural part of the invading or attacking organism that is

responsible for stimulating antibody production Cellular reactions are initiated by the binding of an antigen receptor located on

the surface of a T-cell. The T-cells then carry the antigenic message or blueprint, to the lymph nodes,

where the production of other T-cells is stimulated Role of T-Lymphocytes:

o T-cells include: Effector T-cells – participate in the destruction of foreign

organisms Suppressor T-cells – has the ability to decrease B-cell

production, thereby keeping the immune response at a level that is compatible with health.

Memory T-cells – are responsible for recognizing antigens from previous exposure and mounting and immune response

o Effector T-cells Helper T-cells – are activated on recognition of antigens

and stimulate the rest of the immune system. When activated, they secrete cytokines, which attract and activate B-cells, cytotoxic T-cells, NK cells, macrophages and other cells of the immune system. They also produce lymphokines, w/c activate other T-cells, natural and cytotoxic T-cells and other inflammatory cells)

Cytotoxic T-cells – killer T-cells; attack the antigen directly by altering the cell membrane and causing cell lysis (disintegration) and by releasing cytolytic enzymes and cytokines.

o Cytokines – non-antibody proteins that act as intercellular mediators, as in the generation of immune response.

o Lymphokines – substances released by sensitized lymphocytes when they come in contact with specific antigens.

o Lysis – dissolution or disintegration of bacteria and cells by the action of a lysin.

o Lysin – an antibody that has the capability of causing dissolution of cells.

o Null Lymphocytes – destroy antigens directly coated with antibody

o Natural killer cells – defend against microorganisms and some types of malignant cells

Lymphocytes Involved in Immune ResponsesType of Immune Response Cell Type FunctionHumoral

Cellular

Nonspecific

B-lymphocyte

T-lymphocyteHelper T

Helper T1Helper T2

Suppressor TMemory T

Cytotoxic T(killer T)

Non-T or Non-BLymphocyte

Null cell

Natural killer (NK)cell (granular lymphocyte)

Produces antibodies or immunoglobulins

Attacks foreign invaders (antigens) directly

Initiates and augments inflammatory response

Increases activated cytotoxic T-cellsIncreases B-cell antibody productionSuppresses the immune responseRemembers contact with an antigen and on subsequent exposures mounts an immune response

Lyses cells infected with virus; plays a role in graft rejection

Destroys antigen already coated with antibody

Defends against microorganisms and some types of malignant cells; produces cytokines

Stages of Immune Response:

Recognition stage o Recognition of antigens as foreign or non-self by the immune

system.o The body accomplishes recognition using lymph nodes and

lymphocytes o Lymphocytes patrol the tissues and vessels that drain the

areas served by the lymph nodes. They recirculate from the blood to the lymph nodes and from the lymph nodes back into the bloodstream, in a never-ending series of patrols.

o Macrophages and neutrophils have receptors for antibodies and complement; as a result, they coat microorganisms with antibodies, complement, or both, enhancing phagocytosis.

Proliferation stage o Enlargement of the lymph nodeso T and B-lymphocytes enlarge, divide and proliferateo T-lymphocytes differentiate into cytotoxic T-cellso B-lymphocytes produce and relese antibodies

Response stage o The differentiated lymphocytes function in either a humoral or

cellular capacityo The production of antibodies by the B-lymphocytes begins the

humoral response.

o Humora l refers to the fact that the antibodies are released into the bloodstream and therefore reside in the plasma

o With the initial cellular response, the returning sensitized lymphocytes migrate to areas of the lymph node

o Transformation of lymphocytes to cytotoxic T-cells Effector stage

o Either the antibody of the humoral response or the cytotoxic T-cell of the cellular response reaches and connects with the antigen on the surface of the invader.

o The connection initiates the total destruction of the invading microbes or the complete neutralization of the toxin. It involves the interplay of antibodies (humoral immunity), complement and action by the cytotoxic T-cells (cellular immunity)

Differences in Cellular and Humoral Immune Responses:

HUMORAL IMMUNE RESPONSE (B-CELLS)

Bacterial phagocytosis and lysis Anaphylaxis Allergic hay fever and asthma Immune complex dse Bacterial and some viral infection

CELLULAR RESPONSES (T-CELLS)

Transplant rejection Delayed hypersensitivity (tuberculin reaction) Graft vs. host dse Tumor surveillance or destruction Intracellular infections Viral, fungal, and parasitic infections

Complement System

Complement – series of enzymatic proteins in the serum that, when activated, destroy bacteria and other cells.

3 major fxns:o Defending the body against bacterial infectiono Bridging natural and acquired immunityo Disposing of immune complexes and byproducts associated with

inflammation Activating the complement system:

o Classic pathway – activated by antigen-antibody complexes; it begins with when antibody binds to a cell surface and ends with lysis of the cell

o Alternative and Lectin pathway – initiated with the release of bacterial products (endotoxins)

Complement components, prostaglandins, leukotrienes and other inflammatory mediators all contribute to the recruitment of inflammatory cells

Complement-Mediated Immune Responses

ResponseComplement

Products Effects

Cytolysis

Opsonization

Chemotaxis

Anaphylaxis

C5b – C9

C3b, C5b

C3a, C5a

C3a, C5a

Lysis and destruction of cell membranes of body’s cells or of pathogens

Targeting of the antigen so that it can be easily engulfed and digested by macrophages and other phagocytic cells

Chemical attraction of neutrophils and phagocytic cells to the antigen

Activation of mast cells and basophils with release of inflammatory mediators that produce smooth muscle contraction and increased vascular permeability