Chapter 43 ~ The Body’s Defenses

Lines of Defense

Phagocytic and Natural Killer Cells

Neutrophils 60-70% WBCs; engulf and destroy microbes at infected tissue

Monocytes 5% WBCs; develop into….

Macrophages enzymatically destroy microbes

Eosinophils 1.5% WBCs; destroy large parasitic invaders (blood flukes)

Natural killer (NK) cells destroy virus-infected body cells & abnormal cells

The Inflammatory Response

1- Tissue injury; release of chemical signals~ • histamine (basophils/mast cells): causes Step 2... • prostaglandins: increases blood flow & vessel permeability

2/3- Dilation and increased permeability of capillary~ • chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs

4- Phagocytosis of pathogens~ • fever & pyrogens: leukocyte-released molecules increase body temperature

Specific Immunity

Lymphocyctes •pluripotent stem cells... • B Cells (bone marrow) • T Cells (thymus)

Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms)

Antibodies: antigen-binding immunoglobulin, produced by B cells

Antigen receptors: plasma membrane receptors on b and T cells

Clonal selection

Effector cells: short-lived cells that combat the antigen

Memory cells: long-lived cells that bear receptors for the antigen

Clonal selection: antigen-driven cloning of lymphocytes

“Each antigen, by binding to specific receptors, selectively activates a tiny fraction of cells from the body’s diverse pool of lymphocytes; this relatively small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating the antigen.”

 

Induction of Immune Responses

Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen

Plasma cells: antibody-producing effector B-cells

Secondary immune response: immune response if the individual is exposed to the same antigen at some later time ~ Immunological memory

Self/Nonself Recognition

Self-tolerance: capacity to distinguish self from non-self

Autoimmune diseases: failure of self-tolerance; multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus

Major Histocompatability Complex (MHC): body cell surface antigens coded by a family of genes

Class I MHC molecules: found on all nucleated cells

Class II MHC molecules: found on macrophages, B cells, and activated T cells

Antigen presentation: process by which an MHC molecule “presents’ an intracellular protein to an antigen receptor on a nearby T cell

Cytotoxic T cells (T C ): bind to protein fragments displayed on class I MHC molecules

Helper T cells (T H ): bind to proteins displayed by class II MHC molecules

Types of immune responses

Humoral immunity

B cell activation

Production of antibodies

Defend against bacteria, toxins, and viruses free in the lymph and blood plasma

Cell-mediated immunity

T cell activation

Binds to and/or lyses cells

Defend against cells infected with bacteria, viruses, fungi, protozoa, and parasites; nonself interaction

Helper T lymphocytes

Function in both humoral & cell-mediated immunity

Stimulated by antigen presenting cells (APCs)

T cell surface protein CD4 enhances activation

Cytokines secreted (stimulate other lymphocytes): a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells b) interleukin-1 (IL-1): activates helper T cell to produce IL-2

Helper T Cell Activity

Cell-mediated: cytotoxic T cells

Destroy cells infected by intracellular pathogens and cancer cells

Class I MHC molecules (nucleated body cells) expose foreign proteins

Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC)

T C cell releases perforin, a protein that forms pores in the target cell membrane; cell lysis and pathogen exposure to circulating antibodies

Cytotoxic T Cell Activity

Humoral response: B cells

Stimulated by T-dependent antigens (help from TH cells)

Macrophage (APCs) with class II MHC proteins

Helper T cell (CD4 protein)

Activated T cell secretes IL-2 (cytokines) that activate B cell

B cell differentiates into memory and plasma cells (antibodies)

Humoral Response

Antibody Structure & Function

Epitope: region on antigen surface recognized by antibodies

2 heavy chains and 2 light chains joined by disulfide bridges

Antigen-binding site (variable region)

5 classes of Immunoglobins

IgM : 1st to circulate; indicates infection; too large to cross placenta

IgG : most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement

IgA : produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration

IgD : do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells

IgE : very large; small quantity; releases histamines-allergic reaction

Antibody-mediated Antigen Disposal

Neutralization (opsonization): antibody binds to and blocks antigen activity

Agglutination: antigen clumping

Precipitation: cross-linking of soluble antigens

Complement fixation: activation of 20 serum proteins, through cascading action, lyse viruses and pathogenic cells

 

Antibody Action

Immunity in Health & Disease

Active immunity/natural: conferred immunity by recovering from disease

Active immunity/artificial: immunization and vaccination; produces a primary response

Passive immunity: transfer of immunity from one individual to another • natural: mother to fetus; breast milk • artificial: rabies antibodies

ABO blood groups (antigen presence)

Rh factor (blood cell antigen); Rh- mother vs. an Rh+ fetus (inherited from father)

Abnormal immune function

Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine

Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus

Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.