Body Defenses Flashcards
Immunity/body’s defences involve the body’s ability to eliminate…
- potentially harmful foreign substances (microbes)
- abnormal and cancerous cells or mutant cells originated in the body
- the substances are “foreign” or “non-self” to the body
- reject the tissue cells of foreign origin
- worn out RBCs, tissue debris and invading pathogens
- mounting inappropriate immune responses to allergies
If the body’s defences fail to work…
inappropriate immune responses can occur, allergies to environmental chemicals, autoimmune diseases
Innate immune system
- non-specific/first line of defence
- responses are rapid but limited and work immediately when the body is exposed to threatening agents
- non-selectively defend against foreign invaders
- uses toll-like receptors (TLRs) as the “eyes” of the innate immune system
- do not involve antibody production
Cells of the innate immune system
neutrophils, macrophages, basophils, natural killer cells
Adaptive or acquired/specific immune system
- specifically targets foreign material to which the body has already been exposed
- the body takes time to prepare to attack
- it is an ultimate weapon against most pathogens
- responses are mediated by B and T lymphocytes
- the formation of memory cells allows the system to react more swiftly against specific invaders in the future
- involves specific secretion (antibodies)
Cells of the adaptive immune system
T cells, B cells and plasma cells
Non-specific responses are ___ or ___-__- defence mechanisms
Non-specific responses are inherent or built-in- defence mechanisms
Innate immune defenses provide a first line of defense against …
infectious agents, chemical irritants or tissue injury from mechanical trauma and burns
Physical/External defenses prevents …
microbial invasion upon the body’s exposure to the external environment
The physical/external defences consist of the following…
the skin/integument, the digestive system, the genitourinary system and the respiratory system
Physical/external defense: The skin
- mechanical barrier
- keratinized layer (skin)
- epidermal enzymes
- sweat and chemicals (sebaceous gland)
- Langerhans cells (the skin)- antigen-presenting cells (APC)
- skin-associated lymphoid tissue (SALT)
Physical/external defense: digestive system
- salivary enzymes lyse ingested bacteria
- bacteria in the oral cavity convert nitrate into nitrite and nitrite to nitrogen oxide in the stomach (acidification)
Physical/external defense: The genitourinary system
- acidic urine and acidic vaginal secretions lyse certain bacteria
- mucus- entraps small invading particles
Physical/external defense: The respiratory system
- nasal hair
- lymphoid tissue (tonsils and adenoids)
- alveolar macrophages
- coughs and sneeze
Innate immune defences are divided into …
physical/external and chemical/internal
Chemical/internal defenses
first line of defense, non-specific, rapid but limited response
Chemical/internal defenses include the following…
- interferon
- complement system
- inflammation
- natural killer cells (NK)
Interferon and viruses
1) Virally infected cell
2) Release interferon (IFN)
3a) act as “whistle blower” to..
3a’) triggers the production of viral blocking enzymes in healthy cells to ..
4a) warn healthy neighbouring cells of
potential viral attack
4a’) breakdown the viral mRNA and inhibit protein synthesis in host/healthy cells
Interferon also performs the following functions..
- enhances macrophage phagocytic activity and antibody production
- exerts anticancer (NK cells) and antiviral effects (T-cells)
- slows cell division and suppresses tumor growth
- enhances the actions of NK cells, T lymphocytes, cytotoxic T-cells to attack and destroy both virally-infected and cancerous cells
The complement system
- exposure to CHO chains on the surface of microorganisms or the exposure to antibodies against a specific invader
- activates the complement system
- directly lyse the invaders
The complement system “compliments” the action of ..
antibodies to kill foreign cells by forming membrane attack complexes (MAC)
Formation of MAC
- Liver complements C1
- activates C2, C5 and C9
- components C5-C9 assemble to form membrane attack complex (MAC)
- this punches holes in the surface membrane of the victim’s cell
- makes membrane extremely leaky and causes entry of water by osmosis
- victim cell swell and burst
Summary of the innate immune defenses:
Interferon=
The complement system=
Inflammation=
Natural killer cells=
Interferon= non-specifically defend against viral infection
Complement system= destroy the foreign cells by forming MAC
Inflammation= a non-specific response to tissue injury with the help of macrophages and neutrophils
Natural killer cells= non-specifically lyse and destroy virally-infected host cells and cancerous cells
Inflammation
- non-specific immune response to foreign material or tissue damage
- an essential innate response to microbial invasion
- consists of highly interrelated events set in motion in response to foreign material, tissue damage or both
- attracts phagocytes and plasma proteins to an invaded or injured area that isolate, destroy, or inactivate the invaders, remove debris and prepare for subsequent healing and repair
Nitric Oxide (NO): secreted by and function
Secreted by: macrophages
Function: toxic to nearby microorganisms
Lactoferrin: secreted by and function
Secreted by: neutrophils
Function: protein that binds with iron, making it unavailable for use by invading bacteria
Histamine: secreted by and function
Secreted by: mast cells
Function: induces local vasodilation and increases capillary permeability
Kallikrein: secreted by and function
Secreted by: neutrophils
Function: converts specific plasma proteins precursors produced by liver into activated kinins
Endogenous pyrogen (EP): secreted by and function
Secreted by: macrophages
Function: induces development of fever
Leukocyte endogenous mediator (LEM): secreted by and function
Secreted by: macrophages
Function: decreases the plasma concentration of iron by altering iron metabolism within the liver, spleen and other tissues, also stimulates synthesis and release of neutrophils by the bone marrow
Acute phase proteins: secreted by and function
Secreted by: Liver upon stimulation by LEM
Function: play role in inflammatory process, tissue repair, and immune cell activities
C-reactive protein: secreted by and function
Secreted by: Liver
Function: specific acute phase protein that is clinically used as a blood-borne marker of inflammation
Interleukin 1 (IL-1): secreted by and function
Secreted by: macrophages
Function: enhances proliferation and differentiation of B and T lymphocytes
Sequences of the inflammation
- defense by resident tissue macrophages
- localized vasodilation
- increased capillary permeability
- localized oedema
- walling off the inflamed area
- emigration of leukocytes
- leukocyte destruction of bacteria
- mediation of the inflammatory response by phagocyte-secreting chemicals
- tissue healing and repair
Defense by resident tissue macrophages
- they are stationary but become mobile and migrate to the invaded tissue
- begin to phagocytose foreign microbes when entering through the skin
Localized vasodilation
- bacterial invasion at injured tissue
- attracts mast cells
- release histamine
- enhances arteriolar dilation, increasing the blood flow and velocity to the injured tissue
- this brings more phagocytic leukocytes and plasma proteins
Increased capillary permeability
- mast cells at injured site
- release histamine
- increases capillary’s permeability by enlarging the capillary pores
- this allow the leakage of proteins from the blood to enter the inflamed area
Localized edema
- accumulation of plasma proteins in the interstitial fluid
- elevate the local interstitial fluid colloid osmotic pressure
- tend to move fluid out of capillary and accumulate in the injured area
- this causes edema (swelling)
- also causes symptoms of inflammation
- pain is caused by the distension of swollen tissue and substances released by injured tissues (prostaglandins)
Cardinal signs of inflammation
heat, redness, swelling, pain and loss of function
Walling off the inflamed area
- leaked plasma proteins also bring thromboplastin- thrombin
- converts fibrinogen into fibrin
- forms a clot around the bacterial invader and damaged tissue
- this walling off inflamed area prevent the spread of invaders and their toxic products to a nearby tissue
Leukocytes are emigrated to the injured and invaded tissue by
margination, diapedesis, chemotaxis
Emigration of leukocytes
- inflamed tissue attracts neutrophils (within 1 hr) and monocytes (8-12 hrs of injury) from blood
- these leukocytes attach to the inner endothelial lining of the capillaries in the affected area (margination)
- CAM (cell adhesion molecule-selectin) protrude from endothelial lining slows down the leukocytes and rolls them along the vessel lining
- gives enough time for leukocytes to check for local activating factors (SOS signals) from nearby injured tissues
- these factors cause leukocytes to adhere firmly to the endothelial lining
- adhered leukocytes leave the capillaries by diapedesis and move toward the injured sites (neutrophils come first)
- inflamed tissue release chemical mediators- chemokines which will attract phagocytic cells by a process called chemotaxis
- phagocytic cell increases Ca2+ entry into the cell
- Ca2+ then switches cellular contractile apparatus to lead the crawling of phagocytic cells toward the inflamed tissue
Damaged tissue –> ___ –> __
Damaged tissue –> chemokines –> Ca2+
Leukocyte proliferation
- inflamed tissue releases “chemical mediator”
- this causes the bone marrow to proliferate a larger number of neutrophils, monocytes and macrophages to eliminate invaders and heal the tissue
Marking of bacteria for destruction by opsonin
- opsonins- C3b (produced by the liver) attach to the TLRs on the phagocytes
- opsonin increases phagocytosis by linking the foreign cell to a phagocytic cell
Mechanism of opsonin action
one of the activated complement molecules, C3b, links a foreign cell, such as a bacterium, and a phagocytic cell by nonspecifically binding with the foreign cell and specifically binding with a receptor on the phagocyte. This link ensures that the foreign victim does not escape before it can be engulfed by the phagocyte