Non-specific defense mechanisms

• 1st line- skin and mucous– Cilia lined trachea, hairs in pathways

• 2nd line- – phagocytic WBC– antimicrobial proteins (compliment & interferon)– inflammatory response

Phagocytic WBC

• Neutrophils (60-70% of all WBC)• attracted by chemical signals from damaged cells and enter

tissues

• Monocytes (5% of all WBC)– develop into macrophages which use psudopodia to

capture invading bacteria

• Eosinophils (1.5% of all WBC)– used to attack bigger invaders “worms”

• natural killer cells – attack virus-infected cells to prevent spreading

Antimicrobial proteins

• Compliment – various proteins in the plasma that work with antibodies, phagocytes, and on their own non-specifically to enhance immune response.

• interferon-proteins secreted by virus-infected cells. Inhibits virus reproduction in neighboring cells. Can be mass produced now and may be used to treat cancer patients.

Inflammatory response• 1. Damaged tissues release chemical signals such as

histamine (contained in basophils WBC and mast cells of connective tissue) and prostaglandins to increase blood flow.

• 2. Prostaglandins induce vasodilation and increased permeability to clotting factors.

• 3. Chemokines release chemicals that mediate the arrival of phagocytic cells to the area

• Phagocytes consume debris and pathogens forming pus• Sometimes allergies cause massive release of histamine to

“safe” invaders, so antihistamines block this response

Specific defense (3rd line)• Four major features

– Specificity (recognize particular antigens)– diversity (responds to millions of different invaders)– self/nonself recognition- – memory - acquired immunity so the second time

body is infected the response will be quick enough to avoid serious infection. This is the basis for vaccination.

Cell surface markers

• Blood cells A, B, and Rh Factor proteins• Major histocompatibility complex (MHC) are

glycoproteins marking cell as self• MHC class I are on all nucleated cells• MHC class II are only on specific immune cells• These allow cytotoxic T-cells (MHC I) and helper

T-cells (MHC II with antigen fragments attached) to bond to cells

• Huge amount of variety, so each individual is unique in their MHC proteins.

Humoral immunity

• Results in production of antibodies– Free antigens activate B- cells– B- cells make the antibodies and then develop

into Plasma cells and memory B-cells for next time

– Plasma cells secrete antibodies– antibodies attach to antigens making them easy

“prey” for phagocytes and complement

Formation of lymphocytes

• Lymphocytes are WBC formed in the bone marrow. (B and T cells)

• B- cells fully develop in the bone marrow before being released

• T - cells then travel to the the thymus for further development before leaving.

• In the thymus they pick up recognition of MHC complex as self.

Cell-mediated immune response• Antigens displayed by MHC class I glycoproteins in

infected cells activate Cytotoxic T cells

• Cytotoxic T cell give rise to memory T cells and Active cytotoxic T cells

• Activated cytotoxic T cells attack cells by binding to and lysing them

2nd exposure

• 2nd time the antigen stimulates Memory B cells and memory T cells to activate both humoral and cell-mediated responses.

• 2nd defense (about 3 days) where as 1st response is usually 7-10 days.

• Supressor T cells are thought to help turn off the immune response when antigens are gone.

Antibodies

• A class of proteins referred to as the immunoglobulins (Ig) with 4 polypeptides (2 heavy chains and 2 light chains) held together by disulfide bridges to give them their quaternary structure

• Most of the antibody structure is identical for all antibodies with the “tips” variable that bind to the epitope (exposed) region on the antigen surface.

• Five types of immunoglobulins are divided by their constant regions IgM, IgG, IgA, IgD, and IgE.

Immunoglobulin classes• IgM: large molecule that initiates response by

agglutinating (clumping up) the antigens• IgG: Most plentiful, triggers complement

proteins• IgA: Prevents attachment of antigens to

epithelial linings. Plentiful in mucus.• IgD: found on B-cells and probably initiate the

development of B-cells into plasma cells• IgE: small number, trigger the histamine release

of basophils and mast cells via receptor binding.

Helper T-cells

• Helper T cells are stimulated by interleukin 1 of macrophages after engulfing antigens and presenting them.

• Helper T cells in turn stimulate the B cells of the humoral defense and the Cytotoxic T cells of the Cell mediated defense by releasing interleukin 2.