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Pathway of adaptive (specific) defense
1. Pathogen begins to enter the body
2. First line of defense
3. Pathogen enters body
4. Second line of defense/third line of defense
First line of defense
Mechanical barriers (skin and mucous membranes)
Second line of defense
Chemical barriers (enzymes, pH, salt, interferons, defensins, collectins, complement)
Natural killer cells
Inflammation
Phagocytosis
Fever
Third line of defense
Cellular immune response
Humoral immune response
Antigens
Receptors on the surface of lymphocytes enabling cells to recognize non-self antigens
Examples of antigens
Proteins, polysaccharides, glycoproteins, glycolipids
Large and complex
Most effective antigens are _____ and _____ molecules
Haptens
Small molecules that are not antigenic by themselves, but when they combine with a large molecule in the body, they can evoke an immune response
T lymphocytes (T cells)
Specialize in thymus
After release from thymus, make up 70-80% of circulating lymphocytes
Some settle in lymphatic organs, such as lymph nodes, thoracic duct, white pulp of spleen
B lymphocytes (B cells)
After release from bone marrow, make up 20-30% of lymphocytes in blood
Abundant in lymph nodes, spleen, bone marrow, intestinal lining
T cells
Origin of undifferentiated cell: Red bone marrow
Site of differentiation: Thymus
Primary locations: Lymphatic tissues, 70%-80% of the circulating lymphocytes in blood
Primary functions: Provide cellular immune response in which T cells interact directly with the antigens or antigen-bearing agents, to destroy them
B cells
Origin of undifferentiated cell: Red bone marrow
Site of differentiation: Red bone marrow
Primary locations: Lymphatic tissues, 20%-30% of the circulating lymphocytes in blood
Primary functions: Provide humoral immune response in which B cells interact indirectly, producing antibodies that destroy the antigens or antigen-bearing agents
Antigen-processing cell
T cell activation requires presence of processed fragments of antigen attached to the surface of an _____
Major histocompatibility complex (MHC)
T cell activation begins:
Macrophage phagocytizes bacterium via lysosomes
Bacterial antigens move to macrophage's surface and displayed near protein molecules part of the _____
MHC antigens
Help T cells recognize an antigen is foreign
Class I and class II
Class I MHC antigen
Within cell membrane of all body cells except red blood cells
Class II MHC antigen
On surfaces of antigen-presenting cells, thymus cells, and activated T cells
Helper T cells
Become activated when its antigen receptor combine with displayed foreign antigens
Antibodies
Activated T cell stimulates B cell to produce _____
Cellular immune response
T cells attach to foreign, antigen-bearing cells and interact differently, by cell-to-cell contact→_____ or cell-mediated immunity
Colony-stimulating factors
Stimulate bone marrow to produce lymphocytes
Interleukins (IL-1 & IL-2)
Control lymphocyte differentiation and proliferation
Tumor necrosis factor
Stops tumor growth, releases growth factors, causes fever that accompanies bacterial infection, stimulates lymphocyte differentiation
Interferons
Block viral replication, stimulate macrophages to engulf viruses, stimulate B cells to produce antibodies, attack cancer cells
Helper T cells
CD-4 cell; activate other cells by secreting cytokines; stimulate B cells to produce antibodies and stimulate activity of cutotoxic T cells; any harm to them destroys immunity
Cytotoxic T cells
Attack virally infected or cancerous cells; secrete perforin
Memory T cells
Provide future immune protection
Regulatory T cells
Suppress immune responses after defeat of pathogens, which lowers chance of developing an autoimmune disease
B cells
May become activated upon encountering an antigen
Most antigens require T cell "help" to activate _____
Some differentiate into memory cells and others into plasma cells
Plasma cells
Produce and secrete antibodies→humoral immune response
Millions
Each person has _____ of varieties of T and B cells
Clones
Members of each variety originate from a single cell→_____
Antigen receptor
Each member has specific _____ that respond to specific antigen→antibodies combine with antigen-bearing agent and react against it
Polyclonal response
Singly type of B cell carries info to produce single type of antibody→immune response can have several types of antibodies crated against a single microbe or virus→_____
B cell activities
1. Antigen-bearing agents enter tissues
2. B cell encounters an antigen that fits its antigen receptors
3. Either alone or more often in conjunction with helper T cells, the B cell is activated. The B cell proliferates, enlarging its clone
4. Some of the newly formed B cells differentiate further to become plasma cells
5. Plasma cells synthesize and secrete antibodies whose molecular structure is similar to the activated B cell's antigen receptors
T cell activities
1. Antigen-bearing agents enter tissues
2. An antigen-presenting cell, such as a macrophage, phagocytizes the antigen-bearing agent, and the macrophage's lysosomes digest the agent
3. Antigens from the digested antigen-bearing agents are displayed on the membrane of the antigen-presenting cell
4. Helper T cell becomes activated when it encounters a displayed antigen that fits its antigen receptors
5. Activated helper T cell releases cytokines when it encounters a B cell that has previously combined with an identical antigen-bearing agent
6. Cytokines stimulate the B cell to proliferate, enlarging its clone
7. Some of the newly formed B cells give rise to cells that differentiate into antibody-secreting plasma cells
Antibody molecules
Soluble, globular proteins
4 chains of amino acids linked by disulfide bonds→Y-shaped structures
Two light chains and two heavy chains
End of chains are variable regions→react with shape of specific antigen
Idiotypes
Antibodies can bind with certain antigens due to conformation of variable regions→antigen-binding sites→_____
IgG
80% of antibodies; act on bacteria, viruses, toxins
IgA
13% of antibodies; found in exocrine gland secretions
IgM
6% of antibodies; act on antigens in foods and bacteria
IgD
<1% of antibodies; found on B cell surfaces, common in infants
IgE
<1% of antibodies; found in exocrine gland secretions
Antibody direct attack
Types of effect: Agglutination, precipitation, neutralization
Antibody activation of completement
Types of effect: Opsonization, chemotaxis, agglutination, lysis, neutralization
Antibody localized changes
Type of effect: Inflammation
Agglutination
Antigens clump; clumps antigen-bearing cells
Precipitation
Antigens become insoluble
Neutralization
Antigens lose toxic properties; alters the molecular structure of viruses, making them harmless
Opsonization
Alters antigen cell membranes so cells are more susceptible to phagocytosis
Chemotaxis
Attracts macrophages and neutrophils into the region
Lysis
Allows rapid movement of water and ions into the foreign cell causing osmotic rupture of the foreign cell
Inflammation
Helps prevent the spread of antigens
Primary immune response
Detectable levels of antibodies appear 5-10 days following exposure
Production and release of antibodies continues for several weeks
Secondary immune response
Antibodies may be produced within a day or two of exposure
Naturally acquired active immunity
Mechanism: Exposure to living pathogens
Result: Stimulation of an immune response with symptoms of a disease
Artificially acquired active immunity
Mechanism: Exposure to a vaccine containing weakened or dead pathogens or their components
Result: Stimulation of an immune response without symptoms of a disease
Naturally acquired passive immunity
Mechanism: Antibodies passed to fetus from pregnant woman with active immunity or to newborn through colostrum or breast milk from a woman with active immunity
Result: Short-term immunity for newborn without stimulating an immune response
Artificially acquired passive immunity
Mechanism: Injection of antiserum containing specific antibodies or antitoxin
Result: Short-term immunity without stimulating an immune response
Type I hypersensitivity reaction (immediate-reaction)
Response: Overproduction of IgE antibodies
Example: Hay fever
Type II hypersensitivity reaction (antibody-dependent cytotoxic reaction)
Response: Phagocytosis and complement-mediated lysis of antigen
Example: Mismatched blood transfusion
Type III hypersensitivity reaction (immune complex reaction)
Response: Phagocytosis and lysis cannot clear antigen-antibody complexes
Example: Autoimmunity
Type IV hypersensitivity reaction (delayed-reaction)
Response: T cells and macrophages release chemical factors into the skin
Example: Dermatitis
Tissues and organs that can be transplanted
Bone, cornea, kidney, liver, pancreas, heart, bone marrow, skin, lungs
Tissue rejection reaction
Recipient's cells recognize donor's tissues as foreign and try to destroy transplanted tissue
Graft-versus-host disease (GVHD)
Transplanted tissue may produce substances that harm recipient's tissues
Rapid and severe
The greater the antigenic difference between MHC antigens of recipient and donor tissues, more _____ and _____ the rejection reaction
Match
Attempt to _____ donor tissues that are antigenically like those of the person needing transplant
Isograft
Donor: Identical twin
Example: Bone marrow transplant from a healthy twin to a twin who has leukemia
Autograft
Donor: Self
Example: Skin graft from one part of the body to replace burned skin
Allograft
Donor: Same species
Example: Kidney transplant from a relative or closely matched donor
Xenograft
Donor: Different species
Example: Heart halves from a pig
Autoimmunity
An attack by the immune system against its own tissues
Autoantibodies
The immune system fails to distinguish "self" from "non-self" and the body produces antibodies called _____
Cytotoxic
_____ T cells also attack the body's tissues and organs
Autoimmune disorders
Various _____ affect different types of cells
There are several theories concerning the cause(s) of _____, but no single cause has been established
Glomerulonephritis
Symptoms: Lower back pain
Antibodies against: Kidney cell antigens that resemble streptococcal bacteria antigens
Graves' disease
Symptoms: Restlessness, weight loss, irritability, increased heart rate and blood pressure
Antibodies against: Thyroid gland antigens near thyroid-stimulating hormone receptor, causing overactivity
Type 1 diabetes mellitus
Symptoms: Thirst, hunger, weakness, emaciation
Antibodies against: Pancreatic beta cells
Hemolytic anemia
Symptoms: Fatigue and weakness
Antibodies against: Red blood cells
Multiple sclerosis
Symptoms: Weakness, incoordination, speech disturbances, visual complaints
Antibodies against: Myelin in peripheral nerves and in the white matter of the central nervous system
Myasthenia gravis
Symptoms: Muscle weakness
Antibodies against: Receptors for neurotransmitters on skeletal muscle
Pernicious anemia
Symptoms: Fatigue and weakness
Antibodies against: Binding site for vitamin B on cells lining stomach
Rheumatic fever
Symptoms: Weakness, shortness of breath
Antibodies against: Heart valve cell antigens that resemble streptococcal bacteria antigens
Rheumatoid arthritis
Symptoms: Joint pain and deformity
Antibodies against: Cells lining joints
Systemic lupus erythematosus
Symptoms: Red rash on face, prolonged fever, weakness, kidney damage, joint pain
Antibodies against: Connective tissue
Ulcerative colitis
Symptoms: Lower abdominal pain
Antibodies against: Colon cells
HIV (Human Immunodeficiency Virus)
A virus that breaks down immune system function
AIDS (Acquired Immune Deficiency Syndrome)
HIV may stay silent for years, and then progress to _____; then opportunistic infections begin
Macrophages and helper T cells
HIV attacks _____ and then _____
Decline
Helper T cell numbers _____→B cells cannot produce antibodies
Cytotoxic T cells
Later, HIV variants affect _____ too
Dies
Person with HIV/AIDS _____ from loss of immune response against pathogens, cancers
HIV/AIDS modes of transmission
Sexual contact, contaminated needles, birth or milk from infected mother, receiving infected blood or tissues from donor