major function of the immune system
to recognize between self and non-self.
guards against a broad range of pathogens and its effectiveness does not depend on prior exposure. Includes 1st (membranes) and 2nd (inflammation, complement, cells etc.) lines of defense
3rd line of defense) immunity directed against specific antigens. 2 types:
Humoral- responsibility of B-lymphocytes: produce antibodies that bind to antigens and tag them for destruction.
Cell-mediated- responsibility of T lymphocytes: directly attach to and destroy diseased or foreign cells
antigens:self, foreign, MHC
(Ag)- a molecule that can trigger an immune response.
• Bacteria, viruses, etc., that can mobilize the immune system and provoke an immune response
o Complete antigens vs. incomplete (haptens) antigens
MCH (major histocompatibility complex) proteins that are found on surface of cells and look like hotdog buns.
• MCH 1 found on all nucleated cells. If it holds self-antigens (self), immune system leaves it alone. If it presents foreign antigens (non-self), it triggers an immune response.
• MCH 2 found only on antigen presenting cells (APCs) to display only foreign antigens. APCs include macrophages and B cells.
certain regions of an antigen molecule that stimulate an immune responses. One antigen molecule can have several different epitopes.
ability to stimulate proliferation (production) of specific lymphocytes and antibodies.
Reactivity-ability to react with products of immunogenicity (lymphocytes and antibodies)
complete antigens vs incomplete antigens
complete: have both immunogenicity and reactivity
incomplete: dont have immunogenicity because they are not antigenic by themselves, but they do have reactivity. I.E. penicillin, poison ivy, detergents, cosmetics
Active/passive immunity and naturally/artificially acquired immunity
Active- body makes own antibodies or T cells against pathogen
Passive- body acquires them from another person or an animal that has developed its own immunity to the pathogen (borrowed)
Naturally acquired- immunity is natural, not induced artificially
Artificially acquired- induced artificially through vaccinations or immune serums
non-specific immunity: first line of defense
external body membranes
Skin-acid mantle and keratin
Mucous membranes- gastric juice, acid mantle of vagina, mucus, saliva, tears/lacrimal secretions, urine
non-specific immunity: second line of defense components
Inflammation- reaction of vascular tissue to injury (burns, chemicals, bacteria, heart attack)
Complement- proteins that circulate in the blood in inactive form and are activated in the presence of pathogens (see classical and alternate pathways of activation)
Interferon- antiviral proteins that alert neighboring cells and protect them from being infected
• Neutrophils-kills bacteria in connective tissue by phagocytosis and respiratory burst Eosinophils- stand guard against parasites, allergens and other pathogens
• Macrophages- any cell of the body, other than a leukocyte, that is specialized for phagocytosis (Kuppfer cells, dendritic cells in epidermis, macrophages in lungs, microglia in brain, etc.)
• NK (natural killer) cells- lymphocytes
• Can kill cancer cells and virus-infected cells
• Do not depend on recognition of specific antigen but detect lack of self cell receptors
• Do not exhibit memory response and are non-phagocytic
• Secrete inflammatory chemicals and perforins
pathways for complement activation and effects of complement (OIL)
Classical pathway- requires an antibody molecule to get started (specific immunity). Forms antigen-antibody complex that produces a reaction cascade called complement fixation. Each step generates an enzyme that catalyzes the production of many more molecules at the next step. Results in the attachment of a chain of complement proteins to the antibody.
Alternative pathway- requires toxins produced by pathogens. Includes a series of reactions in which the complements breaks down into multiple fragments (for ex. C3 slowly breaks down into C3a and C3b, etc.).
Effects of complement: OIL
opsonization = coating of microbial cells= “butters up” or “salts up”the cell. Serves as binding site for phagocyte attachment.
inflammation – contributes to inflammatory response (chemotaxis, cardinal signs, etc)
[cyto]lysis- the rupture and destruction of a pathogen with help of membrane attack complex (forms a hole in the cell and the cell dies)
inflammation- a local defense response to...
Neutralize and destroy the offending agent
Restrict tissue damage
Alert the individual to the impeding threat of tissue injury
Prepare injured area for healing
• 5 cardinal signs of inflammation are seen at the site of injury:
loss of function (caused by first 4 signs)
Vascular and cellular components of inflammatory response
vascular- changes in blood flow (vessel calibre) and increased permeability of blood vessels with formation of the fluid exudate ( passage of water, salts and some proteins from the plasma into the damaged area)
cellular- escape of cells (emigration of the neutrophils) from the blood into the tissues with local responses like phagocytosis
Vascular response: mediated vs. non-mediated
Reasons for increase in permeability and blood flow
Mediated – happens when chemical mediators (serotonin, histamine) dilate blood vessels and lead to the retraction of endothelial cells with increase in intercellular gaps and increase in permeability
Non-mediated –happens with necrosis of vascular endothelium by toxins and physical agents
cellular response main calls involved
Neutrophils-phagocytosis and respiratory burst (first cells at site of injury)
Monocytes-turn into macrophages and get rid of debris (later)
Also cells that release chemical mediators of inflammation :
o Mast cell- histamine, serotonin, which are
o Platelets-histamine, serotonin
Steps of cellular response
Margination-flow of neutrophils close to the vessel wall
Pavementing-the adhesion of neutrophils to endothelium and aggregation along the vessel walls into cobblestone appearance. Only seen in venules.
Emigration-migration/passage of leukocytes by active amoeboid movement through the walls of venules and small veins (by inserting pseudopodia between endothelial cells and migrate through gap. Does not damage cells)
Chemotaxis-attraction of neutrophils from the vessel lumen into a damaged area. Mediated by chemotactic factors (for ex. Complement)
Phagocytosis and respiratory burst – ability of neutrophils to destroy pathogens by engulfing them (phagocytosis, cell eating) or by producing oxidizing agents and creating killing fields around the neutrophils. Has a drawback, as it can damage healthy tissues as well. Contributes to pus=a combination of white blood cells, dead WBC, pathogens and tissues, exudate.
Systemic signs of inflammation:
Pyrexia (fever)- caused by endogenous pyrogens (fever producing agents) that reset the hypothalamus (our thermostat). Fever is not always damaging. Can be a protective response to reduce multiplication of pathogens.
Constitutional symptoms- malaise, anorexia, weight loss
Reactive hyperplasia of the reticulo-endothelial system: lymph node enlargement, spleen enlargement
Hematological changes- leukocytosis (in response to CSF and IL from T-cells and macrophages), anemia, C-reactive protein
humoral vs. cell mediated immunity
humoral- mediated by antibodies, which do not directly destroy a pathogen, but tag them for destruction later. effective against extracellular viruses, bacteria, yeasts, protozoans, and noncellular pathogens
cell-mediated- uses lymphocytes that directly attack and destroy diseased cells
T cell, B cell, or both?
1. originates in bone marrow from hemocytoblast
2. forms plasma cells
3. includes a type crucial for all types of immunity
4. includes suppressors, helpers, killers (cytotoxic)
5. attacks extracellular pathogens
6. recognizes the antigen directly
7. is involved in a recall response
8. is responsible for directly attacking foreign cells or virus-infected cells
9. works through PLAN
10. is attacked by HIV
11. produce antibodies that are released to body fluids
12. bears a self-surface receptor capable of recognizing a specific antigen
13. attacks intracellular pathogens
14. has to be presented with an antigen to recognize it. needs APC's.
15. is involved in anamnestic response
16. forms clones upon stimulation
17. has memory cells
18. exerts a lethal hit
19. is responsible for cell mediated immunity
20. is responsible for humoral immunity
21. accounts for most lymphocytes in the circulation
22. becomes immunocompetent in thymus
1. originates in bone marrow from hemocytoblast- T
2. forms plasma cells- B
3. includes a type crucial for all types of immunity-T
4. includes suppressors, helpers, killers (cytotoxic)-T
5. attacks extracellular pathogens-B
6. recognizes the antigen directly-B
7. is involved in a recall response-T
8. is responsible for directly attacking foreign cells or virus-infected cells-T
9. works through PLAN-B
10. is attacked by HIV-T
11. produce antibodies that are released to body fluids-B
12. bears a self-surface receptor capable of recognizing a specific antigen-BOTH
13. attacks intracellular pathogens-T
14. has to be presented with an antigen to recognize it. needs APC's.-T
15. is involved in anamnestic response-B
16. forms clones upon stimulation- BOTH
17. has memory cells- BOTH
18. exerts a lethal hit-T
19. is responsible for cell mediated immunity-T
20. is responsible for humoral immunity- B
21. accounts for most lymphocytes in the circulation- T
22. becomes immunocompetent in thymus- T
the lymphocyte developed a self-surface receptor capable of recognizing a specific antigen
where are T cells and B cells produced, released, and matured?
T cells- produced in red bone marrow and released in the blood. Mature in the thymus
B cells- produced and mature in the red bone marrow or other lymphatic organs
recognition process for T and B cells
T cells- need APC's to present them with the antigen to be able to recognize them
B cells- can directly recognize the antigen. B cells are an example of APC
antigen presenting cell (APC)
a cell that phagocytizes an antigen and displays fragments of it on its surface (MHC 2) to present to T cells, so that T cells can recognize it I.E. macrophages and B lymphocytes
engulf the antigen, but Th cells must complete activation
undergo clonal selection (form B cells with the same receptor on the surface): most cells become plasma cells and secrete antibodies(work through PLAN), some cells become B-memory cells (involved in anamnestic response)
cell mediated immunity
need antigen to be present to them on MHC protein (MHC 2 for Th and MHC 1 for Tk)
Th cells must complete activation of Tk
Undergo clonal selection (forms T cells with same receptor on surface): most cells become activated Tk cells and attack antigen (lethal hit), some cells become memory cells (for T cell recall response)
Th cells are pivotal for the immune response, since they influence humoral immunity (by activating B cells), cellular immunity (by activating Tk cells) and by activating non-specific defenses (macrophages). when HIV attacks Th cells, the body loses the ability to fight infections
attack phase for B cells
P- Precipitation= multiple soluable molecules are linked together with antibodies. Soluable molecules fall out of solution
L- Lysis= destruction of cell
A- Agglutination= antibodies can bind to more than one antigen and cause clumping/agglutination
N- Neutralization= simpliest method, antibodies block and neutralize functional sites/receptors on the antigen (virus/bacteria)
attack phase for T cells
Perforin- proteins that create holes in the plasma membrane and lyse cells
Lymphtoxins- cause DNA destruction
Tumor necrosis factor TNF)- aids in macrophage activation and kills cancer cells
Interferons- inhibit viral replication and recruit and activate macrophages
structure of the antibody
antibodies belong to a class of plasma proteins known as gamma globulins (only plasma proteins produced by plasma cells, not liver). Basic structural unit of an antibody is an antibody monomer, composed of four polypeptides linked by disulfide bonds. The monomer has two heavy chains which have a hinge reaction, giving it a T or Y shape. Also has 2 light chains.
All four chains have a variable (V) region- gives antibody uniqueness; has an antigen binding site on each arm
Rest of each chain is a constant (C) region- determines mechanism of an antibody's action like if it can bind complement proteins
response to the first exposure to antigen
Lag time about 3-6 days
Time required for B cells to clone and produce antibodies and for T calls to activate
Leaves one with an immune memory
During clonal selection, some members of the clone become memory cells that are involved in secondary responses
response to repeted exposure to the same antigen. Called anamnestic in humoral immunity and T cell recall response in cellular immunity
Shorter lag time- hours
Greater number of antibodies of Tk cells produced
Antibodies remain in the blood longer
Homeostatic Imbalances- role of Th cells in immune response
Th cells are pivotal for the immune response, since they influence humoral immunity (by activating B cells), cellular immunity (by activating Tc cells) and by activating non specific defences (macrophages)
HIV/AIDS- HIV destroys Th cells and therefore strikes at all defenses making the patient more susceptible to infections
excessive, harmful immune reaction to antigens that most people can tolerate. What we mostly know as allergies (to pet dander, pollen, antibiotics). Anaphylactic shock is the most dangerous.
immune system is deficient and fails to respond to intruders.
Autoimmune diseases- failure of self tolerance. Immune system fails to distinguish self antigens from foreign ones and produces auto antibodies that attack body's own tissue. Rheumatic arthritis and diabetes mellitus I.
cytolytic protein secreted by NK cells
cells that produce the stroma of lymphatic organs in the thymus