The Immune System

• Chapter 43 ~

Lines of Defense

Nonspecific Defense Mechanisms……

PCA:

• List the organs involved in the immune sytem:

Innate Immunity:

• Specialized phagocytic white blood cells

• Antimicrobial proteins

• Inflammatory response

Innate Immunity: 5 types of Leukocytes• Neutrophils

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

Short lived• Monocytes• 5% WBCs; develop into….

• Macrophages 1)phagocytosis

• 2)lysosomal enzymes destroy microbes

• Dendritic cells:

• Stimulate development of the acquired immune system

Innate Immunity: 5 types of Leukocytes

• Eosinophils

• 1.5% WBCs; destroy large parasitic invaders

• Enzymatic action- no phagocytosis

• Natural killer (NK) cells

• destroy virus-infected body cells & abnormal cells

• apoptosis

Antimicrobial Proteins:

1. Complement system- group of 30 proteins Once activated can cause invading cells to

lyse – burst

2. Interferons (α, β and γ) Immune response to viruses Activates macrophages

The Inflammatory Response• Tissue injury; release of chemical signals~ • histamine (basophils/mast cells):

causes Step 2... • prostaglandins: increases blood flow & vessel permeability• Dilation and increased permeability of capillary~

• chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs• Phagocytosis of pathogens~

• fever: leukocyte-released molecules increase body temperature

Acquired 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

Acquired Immunity:•Epitope- antigenic determinant • Small area on antigen recognize by lymphcyte

T cell receptors and MHC:

• Major Histocompatibility Complex (MHC)• Antigen presentation- bind to fragments and bring

them towards the cell surface

• Two classes: • Class I MHC

• Class II MHC

MHC

• Class I MHC(nucleated body cells): recognizes antigen fragments in the cell, binds to them and displays them at the cell surface– Cytotoxic T cells will bind and destroy fragments

• Class II MHC: recognizes antigen fragments in the cell, binds to them and displays them at the cell surface– Helper T cells will bind and initiate a process to

destroy fragments

Cytotoxic T cell mechanism

• Destroy cells infected by intracellular pathogens and cancer cells

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

• cell lysis and pathogen exposure to circulating antibodies

Cytotoxic T cell mechanism:

• the activated cytotoxic T cells release:– perforins which form pores in the target cell

membrane– and proteolytic enzymes which enter the cell via

endocytosis and initiate apoptosis• Cytotoxic T cell becomes first activated by the secretion of

cytokines from helper T cells

Cytotoxic T cell mechanism

Helper T cell mechanism:

• Function in both humoral & cell-mediated immunity

• Stimulated by antigen presenting cells• T cell surface protein CD4 enhances

activation(similar to CD8 of class II MHC)

• 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 mechanism:

• a helper T cell recognizes the complex becomes activated with the aid of cytokines secreted by the macrophage forming a clone of activated helper T cells

• an activated T cell binds to the B cell

• B cell becomes activated with the help of cytokines

Helper T cell mechanism

Clonal Selection: • 1. antigen binds to antigen receptors of a specific

lymphocyte• 2. the selected lymphocyte proliferates forming a

clone of identical cells bearing the same receptors• 3. some of the proliferated cells develop into short-

lived effector cell(plasma cell if B lymphocyte, helper T cell or cytotoxic T cell if T lymphocyte) that secrete antibodies specific for the antigen or destroy the antigen

• 4. some proliferated cells develop into long lived memory cells that can respond rapidly upon exposure of the same antigen

Clonal Selection

Induction of Immune Responses•primary immune response- the selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to a particular antigen (10-17 days)

•secondary immune response- if individual is exposed again to the same antigen, the response is faster( 2- 7 days)- immunological memory

Induction of Immune Responses

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

intracellular pathogens such as bacteria, viruses, fungi, protozoa, and parasite s; and cancer cells

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)

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• Opsonization: antibody binds to and blocks antigen

activity-coats antigen surface enhancing macrophage activity

• Agglutination: antigen clumping- antibodies contain at least two antigen binding sites

• Precipitation: cross-linking of soluble antigens- forms immobile aggregates that are disposed of by phagocytosis

• Viral Neutralization: antibodies bind to certain proteins on the surface of a virus blocking its ability to infect a host cell

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

• Transfer of antibodies from rabid(immune) animal to non-rabid (non-immune) animal

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

Blood Group and Transfusions: • See PCA: Explain why blood type AB is

considered the universal recipient and blood type O is considered the universal donor?

Abnormal immune function• Allergies (anaphylactic shock): hypersensitive

responses to environmental antigens (allergens); causes dilation and blood vessel permeability

• Allergy symptoms can be diminished with antihistamines– The hormone epinephrine counter acts this allergic reaction

• Autoimmune disease: • Immunodeficiency disease: SCIDS (bubble-boy);

A.I.D.S.

Essay: 10pts.

• 1. Describe the main role of the following cells types: helper T cells, cytotoxic T cells and B cells.

• 2. What is responsible for the activation of these molecules?

• 3. What deficiencies, if any would result from an individual born without a Thymus?