The Immune

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Chapter 43 Campbell & Reece

Non Specific Defenses

• Anatomical Barriers- 1st line of defense • skin of mucous membranes and cilia • keratin -avoid rips and tears • epithelium

The Inflammatory Response

• (2nd line of defense) Lymph/ WBC’s attracted by release of Histimines from broken skin.

• WBC’s engulf invaders, blood clots form, temp. rises to kill bacteria.

• SWELLING= inflammatory response

Interferons

• (IFNs) are natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to infection.

• Are active against parasites, tumors, and bacteria, and inhibit viruses.

• Do not act directly, but stimulate body’s defenses

White Blood Cells• Aka “Leukocytes” - made in bone marrow stem cells• Granulocytes- types of circulating WBC’ s, classified by staining properties;

"granules", actually – Neutrophils (50 – 70%): 1st to injury site, go out into tissues to phagocytize

invaders – Eosinophils ( 1-4%) responsible for combating infection by parasites in the body – Monocytes- ( 2.8% of WBC’s ) protects against blood-borne pathogens and

moves quickly (aprox. 8-12 hours) to sites of infection in the tissues. (Wikipedia). These are chemically attracted to site of infection; form Macrophages which trap/engulf in the tissues. (Wikipedia)

– Basophils (0.1%) store histamine, a chemical that is secreted by the cells when stimulated in certain ways (histamine causes some of the symptoms of an allergic reaction). Like all circulating granulocytes, basophils can be recruited out of the blood into a tissue when needed. (Wikipedia)

Types

Lymphocytes• Immune response is highly specific; " tailored" to each specific invader• NK cells are a form of cytotoxic lymphocyte which constitute a major

component of the innate immune system. NK cells play a major role in the host-rejection of both tumors and virally infected cells.

• B Lymphocytes play a large role in the humoral immune response (making antibodies).

• T Lymphocytes play a central role in cell-mediated immunity. Have special receptors on their cell surface that recognize/bind.

• Mammals site of proliferation to differentiation is bone marrow and thymus gland (in chest)

• Lymph Nodes: clean microorganisms out of lymph (tissue fluid)• Spleen and Tonsils are rich in lymphocytes and particle-trapping cells

B-Lymphocytes and the formation of antibodies

• >2 trillion lymphocytes in body (some circulatory, some sessile) in lymph nodes,etc.

• Plasma cells: antibody factories, live a few days• Memory cells: make antibodies, live long time• (ex. smallpox, mumps, measles, polio)• Antibodies = complex, globular proteins aka"

immunoglobulins"• Antigen = a molecule (invader) that triggers

antibody production

B cells and T cells work together

Antibody structure and function:• Action:– "specificity" may coat the antigen and cause clumping

(agglutination) combine with antigen to disrupt their action may lyse and destroy foreign cells

– structure: 3-D structure to fit with specific antigen surface made up of 2 light chains, 2 heavy chains.

Antibody Formation• Antibodies (immunoglobins) are

made by a group of lymphocytes (WBC’s)

• they are large protein molecules that Recognize and combine with foreign macromolecules (antigens)

• Made up of 2 heavy (long) polypeptide (AA) chains, and 2 light (short) chains.

• 2 Regions: Constant and Variable– a) Constant region; characteristics

of the species of organism and class of antibody

– b) Variable region: highly specific; interacts with the antigen

Five distinct classes of immunoglobins:

• IgG: gamma globulin (most common; circulating)

• IgA: mucosal immunity (tears, saliva, milk, mucous)

• IgD: found on surface of B lymphocytes, for initial antigen binding

• IgM: found on surface of B lymphocytes, 1st to be secreted, short term

• IgE: role in expulsion of parasites (worms); also in allergic reactions

The Clonal Selection Theory of Antibody Formation:

• Great number of antigens can be fought (mouse can form antibodies against 10 million different antigens!).

• Each person has a large # of B lymphocytes, each only able to synthesize one type of antibody (on its surface).

• When an antigen is introduced, only a small # of B-cells can bind to it and they will proliferate (make plasma and memory cell).

• The antigen-antibody interaction "selects" particular lymphocytes.

• General lymphocyte population; few "fit" the antigen, then "customize"- make more of the specific one that "fits").

• V regions are "variable" in light and heavy chains composed of 300 DNA sequences= 18 billion combos!!

T Lymphocytes and Cell- Mediated Immunity

• Made from self-regenerating stem cells in bone marrow• Thymus Gland causes differentiation, selection, maturation

of T cells• Not affected by antibodies circulating in fluid, but by cell-

to-cell interaction • Circulating antibodies formed, by B lymphocytes are

primarily active against viruses and bacteria • T-lymphocytes act against other eukaryotic cells (body and

own cells that are infected) • T cells will LYSE the infected cell (kill it), thus exposing the

viruses to antibody action • Also the principle agents in immune response to tissue

transplants

Functions of T Cells:• One kind of T-cell has Cytotoxic function; when exposed to

a certain antigen, it divides and daughter cells become: active cell or memory cell

• Active cells- release chemicals (lymphokines) that attract macrophages and stimulate phagocytosis "killer cells"

• T- "helper" cells: necessary for activation of both B lymphocyte and cytotoxic T cells

• T- "Suppressor"-cells: moderate the activities of B cells and other T cells , inhibit their differentiation/ multiplication

• "MHC genes"- major histocompatability complex group of at least 20 different genes (with multiple alleles) coding for "self" antigens.

Immune Disorders:• Allergies: exposure to environmental antigens (pollen, dust,

food….) triggers production of IgE antibodies and memory cells are formed.

• Re-exposure produces more IgE, etc. which bind to basophils and mast cells, which release histamines and chemicals which induce inflammation.

• Autoimmune Disease: individual makes antibodies against his/her own cells; Prominent examples include:– diabetes mellitus type 1 (IDDM)– systemic lupus erythematosus (SLE)– Sjögren's syndrome– Hashimoto's thyroiditis– Graves' disease– rheumatoid arthritis (RA).

Other Medical Ramifications• Tissue and Organ transplants: MHC genes

must be a close match, or face rejection.• Blood Transfusion: A, B, AB, O• Agglutination caused by mixing types

• "universal recipient"• "universal donor"

Blood Antigens Antibodies

A Type A Anti-B

B Type B Anti-A

AB Type A & Type B none

O none Anti-A & Anti-B

The Rh factor:• Rh+ – Dominant allele codes for rhesus protein (called RhD

antigen) in blood– About 85% of pop.

• Rh- – Recessive allele– Lack this antigen in blood

• Can cause disease during pregnancy. • Rh- mother may form antibodies against Rh+ fetus;• The following pregnancy may results in death of the

next baby.

And…• Inheritance of Blood Type

– Co-Dominant IA, IB

– Recessive io

• Organ Transplants: T-lymphocytes can cause graft rejection (e.g. skin)

• tutorials:• http://highered.mcgraw-hill.com/olc/dl/120110/micro38.swf

• - Cytotoxic T-cell Activity Against Target Cells - Interaction of Antigen Presenting Cells and T-helper Cells - Monoclonal Antibody Production - IgE Mediated Hypersensitivity