Flashcards in Chapter 10 (Body Defences) Deck (56):
Functions of the Immune System
- Immunity is the body's ability to resist/eliminate harmful foreign material or abnormal cells
Body defences involve the body's ability to eliminate
1. Potentially harmful foreign substances (microbes)
2. Abnormal and cancerous cells or mutant cells originated in the body.
3. The substances that are foreign or "nonself" to the body.
4. Reject the tissue cells of foreign origin
5. Worn out RBCs, tissue debris, and invading pathogens.
Malfunction of the Immune System
Inappropriate Immune responses can lead to
1. Allergies to environmental chemicals such as pllution, certain food and chemicals
2. Autoimmune disease
eg. Rheumatoid arthritis, multiple sclerosis and diabetes mellitus etc.
Innate/non-specific Immune System
- Non-specific /first line for defense against infectious agents, chemical irritants, and tissue injury.
- Responses are rapid but limited, and work immediately when body is exposed to threatening agents
- Non-selectively defend against foreign invaders
- Uses toll-like-receptors (TLRs) as "eyes" of the innate immune system
- Doesn't involved antibody production
- Cells include: neutrophils, macrophages, basophils, and natural killer cells.
Divided into physical and chemical.
Adaptive/acquire/specific Immune System
- Specifically targets foreign material to which the body has already been exposed
- Body takes time to prepare for attack
- The ultimate weapon against most pathogens
- Responses are mediated by B and T lymphocytes
- Formation of memory cells allows system to react more swiftly against specific invaders in the future
- Involves specific secretion (antibodies)
- Cells include T, B and plasma cells.
Interactions b/w the systems
- Activated leukocytes that destroy the microbes. Then presents part of the microbe (antigen) to the B-cells
- B-cell recognizes microbe (antigen). Then produces antibodies and specific antigens.
- Given to memory cells for next encounter.
Innate Immune Defences
- Prevents microbial invasion upon body's exposure to the external environment
Physical Innate Defence (Skin)
1. Mechanical barrier between the external environment and the body
2. Keratinized layer prevents entry of bacteria and toxic materials.
3. Epidermal enzymes convert potential carcinogens into harmless compounds.
4. Sweat and chemicals (sebaceous gland) are toxic to bacteria
5. Langerhans cells (skin) serves as antigen presenting cells (APC)
Physical Innate Defence (Digestive)
1. Enzymes in saliva lyses certain certain digested bacteria
2. Bacteria in the oral cavity converts nitrate into nitrite; acidification of nitrite into nitrogen oxide in acidic stomach is toxic to a variety of microorganisms.
3. Skin-associate lymphoid tissues (SALT) that lines the intestinal wall provides 100% protection against microorganisms.
Physical Innate Defence (Genitourinary System)
1. Acidic urine and acidic vaginal secretions lyse certain bacteria
2. Mucus from epithelial linings entrap small invading particles and are cleared out by phagocytes
Physical Innate Defence (Respiratory System)
1. Nasal hairs: filtered out the large airborne particles
2. Lymphoid tissue (tonsils and adenoids) provide immunological protection against inhaled pathogens
3. Alveolar macrophages serve as scavengers within the alveoli of the lungs
4. Coughs and sneezes remove irritants from the trachea by forceful expulsion
Chemical Barriers - Complement System
- Exposure to CHO chain on surface of microorganisms invaders and exposure to antibodies against specific organisms activate the system.
- The system directly lyses the invaders.
- This system complements the action of antibodies to kill foreign cells by forming a membrane attack complexes (MAC)
"Destroys the foreign cells by attacking their plasma membrane by forming MAC"
Formation of MAC
Membrane Attack Complex
1. Liver activates complements C1
2. Blood activates C2
3. C2 activates C5
4. C5 activates C9
5. Components C5-C9 assemble to form the MAC
6. MAC punctures the surface membrane of target cell. This causes the membrane to leak, allowing water to enter by osmosis.
7. Target cell swells with water and eventually bursts
"Non-specifically defends against viral infection"
1. It enhances macrophage and phagocytic activity and production
2. Exerts anticancer (NK cells) and antiviral effects (T-cells)
3. Slows cell division and suppresses tumor growth
4. Enhances the actions of NK cells, T lymphocytes, cytotoxic cells to attack and destroy both virally-infected and cancerous cells.
A. "Virally infected cell releases interferon (IFN) into ECF. It acts as a whistle blower that warns healthy neighboring cells of potential viral attacks."
B. "Virally infected cells (viral nucleic acid) release IFN which triggers the production of viral blocking enzymes in healthy cells. This then:
- Breakdown the viral m-RNA
- Inhibits protein synthesis in host and healthy cells."
1. They are mobile phagocytic cells
2. They act as scavengers to clean debris and broken blood cells.
1. Numbers increase with allergic reactions (asthmas, hay fever, and internal parasite infections).
2. They attach to parasites and secrete substances that kill the parasties.
1. They never circulate in the blood; instead, they mostly reside in the body tissue
2. Synthesize and store histamine and heparin
3. Histamine release in allergic reactions.
1. Monocytes circulate in blood circulation.
2. Once they enter the tissue, they become macrophages.
3. Involved in phagocytosis of foreign materials.
1. They release histamines that play a key role in inflammation and allergic reactions.
1. Nitric Oxide - Macrophages
2. Lactoferrin - Neutrophils
3. Histamine - Mast cells
4. Kallikrein - Neutrophils
5. Endogenous pyrogen - Macrophages
6. Leukocyte endogenous mediator (LEM) - Macrophages
7. Acute phase proteins - Liver upon stimulation by LEM
8. C-reactive proteins - Liver
9. Interleukin 1 (IL-1) - Macrophages
1. A non-specific immune response to foreign materials or tissue damage
2. Consists of highly interrelated events that are set in motion in response to foreign material, and/or tissue damage.
3. It attracts phagocytes and plasma proteins to an invaded or injured area.
a. They then isolate, destroy or inactivate the inavders
b. Remove debris
c. Prepare for subsequent healing and repair
Sequences of Inflammation
1. Defence by resident tissue macrophages
2. Localized vasodilation
3. Increased capillary permeability
4. Localized oedema
5. Walling of the inflammed area
6. Emigration of leukoytes
7. Leukocyte proliferation
8. Marking of bacteria for destruction by opsonin
9. Leukocyte destruction of bacteria
10. Mediation of the inflammatory response by phagocyte-secreting chemicals
11. Tissue healing and repair
Defence by Tissue Macrophages
1. They are stationary but become mobile and migrate to the invaded tissue
2. Macrophages begin to phagocytose foreign microbes when they enter through the skin.
1. Bacterial invasion at the injured tissue site attract mast cells.
2. These cells release histamine which enhances arteriolar dilation, increasing the blood flow to the injured tissue.
3. This results in more phagocytic leukocytes and plasma proteins.
Increased Capillary Permeability
1. Mast cells at the injury site release histamine which increases the capillary permeability by enlarging the capillary pores.
2. This allows for the leakage of proteins from the blood to enter the inflamed area.
1. Accumulation of pl. proteins in interstitial fluid.
2. This elevates the local interstitial fluid colloid osmotic pressure
3. Fluid moves out of the capillary and accumulates at the injured area
4. Causes oedema (swelling)
5. Also causes symptoms of inflammation (redness, heat, swelling and pain)
6. The pain at the injury site is caused by the distension of swollen tissue and substances released by injured tissues (prostaglandins)
Walling off the Inflamed Area
1. Leaked plasma proteins bring thromboplastin - thrombin.
2. This converts the fibrinogen into fibrin
3. Fibrin forms a clot around the bacterial invader and damaged tissue
4. This ultimately prevents the spread of invaders and their toxic products to near by tissue
Emigration of Leukocytes
Emigrated by: Margination, diapedesis and chemotaxis.
1. Inflamed tissues attract neutrophils (within 1 hours) and monocytes (8-12 hours of injury) from the blood
2. They attach to the inner endothelial lining of the capillaries in the affected area - this is called margination
3. CAM cells protrude from endothelial lining and slow down the leukocytes and roll them along the vessel lining.
4. This gives the leukocytes enough time to check for local activating factors (SOS signals)
5. The SOS signals cause the leukocytes to adhere firmly to the endothelial lining.
6. Through Diapedesis, the leukocytes leave the capillary wall and move towards the injured sites (neutrophils come first)
7. The inflamed tissue releases chemokines that attract phagocytic cells through a process called chemotaxis.
8. Chemokines bind with receptors on the pleural membrane of the phagocytic cells, increasing Ca2+ entry into the cell.
9. Ca2+ leads the phagocytic cells towards the inflamed tissue
Inflamed tissue releases chemical mediators that cause bone marrow to proliferate a large number of neutrophils, monocytes, and macrophages to eliminate invaders and to heal the tissue.
Marking of Bacteria for Destruction by Opsonins
1. Opsonin-C3b is produces by the liver. It attaches to TLR's on the phagocytes.
2. Opsonins increase phagocytosis by linking the foreign cells to phagocytic cells.
Leukocyte Destruction of Bacteria
Macrophages and neutrophils release hydrolytic enzymes (lysosomes). They breakdown and phagocytose the bacteria and trapped material.
- This forms pus (a collection of dead and live neutrophils, macrophages, lysosomal enzymes from phagocytes and bacteria.
Mediation of the Inflammatory Response by Phagocyte-secreting Chemicals
- Microbe-stimulated phagocytes release many chemical mediators
- Chemicals that are highly destructive to microbes
- Other phagocytes (neutrophils) secrete lactoferrin and NO 1 and 2.
- Lack of iron in lactoferrin decreases multiplication of the bacteria.
- Phagocytic secretion stimulates histamine (3) from mast cells which induce the local vasodilation and vascular permeability.
- Some phagocytic chemical mediators trigger both clotting and anticoagulating systems to enhance walling off processes and the dissolution of clots.
Kininogens are activated by kallikrein and become kinins.
1. Stimulate complement system
2. Promotes localized vasodilation and increased capillary permeability
3. Activate pain receptors
4. Act as chemotaxins (this attracts neutrophils, which releases kallikrein)
Positive feedback loop.
Mediation of Inflammatory Responses
Microbe-stimulated phagocytes release chemicals/cytokines that mediate inflammatory responses.
1. Immune activity
2. Local responses to the systemic manifestation
3. Microbe invasion.
4. LEM - Leukocyte endogenous mediator.
a. A decrease in pleural concentration of iron alters metabolism within the liver, spleen and other tissues. This prevents bacterial multiplication.
b. LEM increases granulopoiesis (macrophage and neutrophils) by the bone marrow
c. It stimulates acute phase proteins from the liver, associated with inflammatory processes.
5. Interleukin-1 (IL-1) is secreted by activated macrophages and performs these functions:
a. Increased proliferation and differentiation of B and T lymphocytes for antibody production and cell mediated immunity.
b. IL-1 may be a part of generalized non-specific protective response.
Endogenous Pyrogens (EP): Fever Development
Activated macrophages - endogenous pyrogens are released to the blood. They travel to the hypothalamus where prostaglandins are released. They stimulate the hypothalamic "thermostat" that regulates the body temperature.
- Regenerative tissues undergo cell division to replace injured tissues
- Non-regenerative tissues are replaced by scar tissue
- Fibroblasts rapidly divide and secrete a large amount of collagen to fill the vacated region of the injured tissue to form scar tissue.
Adaptive/Specific Immune Defence
1. Antibody-mediated or humoral immunity
- Involves production of antibodies by beta lymphocyte derivatives known as plasma cells
2. Cell-mediated immunity
- Involves production of activated T lymphocytes that directly attack unwanted cells.
Components of Specific Immune Defences
1. Antigen: A surface protein molecule present on microbes, tags it as a "foreigner". Antigen stimulates B cells to proliferate and differentiate into plasma cells to produce antibodies.
2. Antibody: A protein molecule synthesized by plasma cells in response to a specific antigen. Antibodies neutralize and agglutinate antigen-antibody complexes.
Adaptive Immunity Origins of T and B cells
During fetal life and early childhood:
B cells: Originate from the bone marrow lymphocyte
T cells: Originate from the Thymus
After early childhood:
Both originate from the peripheral lymphoid tissues.
B cells: result in Antibody-mediated immune responses
T cells: result in Cell-mediated immune responses.
- Composed of 4 interlinked polypeptide chains (2 heavy, 2 light/short)
- Antigen-binding site (determines specificity) - Fab
- Tail portion determines functional properties of the antibody - Fc
Classes of Antibodies
IgA: Found in the secretions of the digestive, respiratory and genitourinary systems. (milk and tears)
IgD: Is present on the surface of many B cells - function uncertain
IgE: Helps protect against parasitic worms and is the immune mediator for common allergic responses.
IgG: Most abundant in the blood and is produced when the body is re-exposed to the antigen. Enhances phagocytosis.
IgM: Serves as B-cell surface receptor for antigen attachments and is secreted in the early stages of plasma cell response.
IgG and IgM are responsible for the most specific immune responses against bacteria.
- Each lymphocyte has surface receptors for binding with one particular type of possible antigens
- Antigens stimulate B cells to convert into plasma cells that produce antibodies
- Most B cells differentiate into active plasma cells
- Produce and secrete IgG antibodies
- Antibodies combine with antigens, marking them for destruction
- Initial contact - response is delayed and plasma cells are formed
- Peak is reached in a couple of weeks by the primary response
- After the peak, antibody concentration decreases.
- Only a small percentage
- Remain dormant
- Upon re-exposure to an antigen, they are ready for immediate action compared to the original lymphocytes.
- The secondary response is quicker, more potent, and longer-lasting.
- Can be induced by disease or vaccination.
Antibody Mediated Immunity Against Bacteria
- Receptors are referred as the "eye of the adaptive immune system"
- A given lymphocyte can see only one unique antigen
- As lymphocytes can't respond directly to antigens, they must be presented by a macrophage (APC)
- Antibodies can physically hinder some antigens from exerting their detrimental effects.
- Antibodies bind to some viruses, preventing them from entering into neighboring cells.
- Binding of many antibodies to many antigens form a chain or lattice, called antigen-antibody complexes.
- A process by which foreign cells (bacteria) or mis-matches transfused RBC bind together into clumps.
- When a antigen-antibody complexes involving soluble antigens (toxins), lattices or chains, become large and seperate from the solution.
Clonal Selection Theory
1. B-cells randomly create new cells with very randomized and specific receptors.
2. If one of them is stimulated by an antigen, then they begin to rapidly clone in order to fight the infection.
3. Most become plasma/effector cells, which secrete antibodies, but some become memory cells that will be used for later encounters.
Results from exposure to an antigen
- Results from transfer of preformed antibodies
- Can provide immediate protection or bolster resistance.
- Eg, the transfer of IgG antibodies from mother to fetus.
Acquiring Long-term Immunity
Long-term immunity can be acquired through having the disease or being vaccinated against it. Having exposure to the antigens causes the creation of long-term memory cells, amongst other B-cells.
Cell Mediated Immunity - T Lymphocytes
- They carry out cell-mediated immunity
- Do no secrete antibodies - directly bind to targets
- Killer T cells release chemicals that destroy targeted cells
- T cells are activated for foreign attack only when it is on the surface of a cell that carries foreign and self antigens
- Learn to recognize foreign antigens only in combination with a person's own tissue antigens
- A few days are required before T cells are activated to launch a cell-mediated attack.
2 Main Types
1. CD8 Cells (Cytotoxic or killer T-cells). They destroy host cells harboring anything foreign.
2. CD4 cells (mostly helper T-cells). They modulate activity of other immune cells. They also secrete chemicals that amplify the activity of other immune cells.
- B-cell growth factor
- T-cell growth factor (Interleukin 2)
- Macrophage-migration inhibition factor.
1. Macrophages secrete interleukin 1 (IL-1), which enhances B-cell proliferation and antibody secretion
2. Macrophages process and present bacterial antigen to B- and T- lymphocyte clones specific to the antigen.
3. Helper T cells secrete B-cell growth factors that enhance B-cell proliferation and antibody secretion
4. Plasma cells secrete antibodies that bind with the antigenic bacteria.
5. Antibodies enhance phagocytosis by coating the bacteria and serving as opsonins.
Mechanism of Killing
1. The killer cell binds to it's target
2. As a result of this binding, the killer cell perforin-containing granules fuse with the plasma membrane
3. The granules disgorge their perforin by exocytosis into a small pocket of intercellular space between the killer cell and it's target.
4. On exposure to Ca2+ in the ECF space, the individual perforin molecules change from a spherical to a cylindrical shape.
5. The remodeled perforin molecules bind to the target cell membrane and insert into it
6. Individual perforin molecules group together like staves of a barrel to form pores.
7. The pores admit salt and H2O causing the target cell to swell and burst.
- Plasma membrane-bound glycoproteins called MHC molecules
- Synthesis is directed by a group of genes called major histocompatibility complex (MHC)
- Exact pattern of MHC molecules vary from one individual to another.
Class 1 vs. Class 2 MHC
Class I MHC Glycoproteins:
- Recognized only by cytotoxic T-cell
- Cytotoxic T cells can destroy body cells if invaded by foreign (viral) antigens
- Found on the surface of all cells.
- Recognized only by helper T cells
- Helper T cells enhance activity of these immune cells when they are combating antigenic invaders.
- Found on the surface of special immune cells (B cells, cytotoxic T cells and macrophages)
- They arise from a loss of tolerance to self-antigens
- Exposure of normally inaccessible self-antigens sometimes induces an immune attack against these antigens.
- Normal self-antigens may be modified.
- Exposure of the immune system to a foreign antigen structurally identical to a self-antigen
- May be related to pregnancy, arising from lingering fetal cells in the mother's body postpartum.