Topic 3, L4 - The Immune System Flashcards
- blood components diagram -
What is the general structure & functional characteristics of leukocytes ?
ONLY formed elements that are complete cells ( have nucleus + organelles )
Comprise <1% total blood volume [ usu 4800 -10,800 WBCs/μl blood ]
- Function in defense against disease*
- Can leave capillaries via diapedesis (move from within blood capillaries thru spaces to migrate to site of infection / inflammation) → Immune and/or inflammatory response
- Move through tissue spaces by amoeboid motion and positive chemotaxis (attracts WBCs to area)
What is leukocytosis ?
Increased WBC count in response to infection / injury, > 11,000 per μl blood
2 categories of Leukocytes
Granulocytes : Contain visible cytoplasmic granules (little sacs within cells)
- Neutrophils, eosinophils, basophils)
- spherical, larger than RBCs, lobed nuclei, cytoplasmic granules, Wright’s stain
- all are phagocytic to some degree
Agranulocytes : Do not contain visible cytoplasmic granules
- Lymphocytes, monocytes)
-No visible granules; nuclei spherical or kidney-shaped
Never Let Monkeys Eat Bananas
(n - neutrophils, l - lymphocytes, m - monocytes, e - eosinophils, b - basophils)
Neutrophils
Most numerous WBCs (50–70% of WBCs)
GRAN
- Granules stain with both acid and basic dyes
- Granules contain either hydrolytic enzymes OR antimicrobial proteins (defensins)
Called polymorphonuclear leukocytes [ PMNs or polys ]: they contain many differently shaped nuclear lobes ( cell has anywhere from 3 - 6 lobes )
- Most phagocytic –> Arrive first at site of injury / infection
- Referred to as “bacteria slayers” (ingest + destroy)
- Kill microbes by process called respiratory burst –> cell synthesizes potent oxidizing substances (bleach or hydrogen peroxide)
- Defensin granules merge with phagosome to form “spears” that pierce holes in membrane of ingested microbe
Eosinophils
Account for 2–4% of all leukocytes
GRAN
- Nucleus has 2 lobes connected by a broad band; resembles ear muffs
- Red-staining granules (acidic) contain digestive enzymes that get released to target large parasitic worms, digesting their surface
- Plays role in allergies and asthma, as well as immune response modulators
Basophils
Rarest WBCs, accounting for only 0.5–1% of leukocytes
GRAN
- Nucleus deep purple with 1-2 constrictions
- Large, purplish black (basophilic) granules contain histamine
- Histamine : Inflammatory chemical that acts as vasodilator and attracts WBCs to inflamed sites
- Are functionally similar to mast cells
Lymphocytes
Second most numerous WBC, accounts for 25%
AGRAN
- Large, dark purple, circular nuclei with thin rim of blue cytoplasm
- Mostly found in lymphoid tissue (eg. lymph nodes, spleen), but a few circulate in blood / Crucial to immunity
2 types of lymphocytes
- T lymphocytes (T cells) act against virus-infected cells & tumor cells
- B lymphocytes (B cells) give rise to plasma cells, which produce antibodies
Monocytes
Largest of all leukocytes; 3–8% of all WBCs
AGRAN
- Abundant pale blue cytoplasm
- Dark purple-staining, U- or kidney-shaped nuclei
- Leave circulation, enter tissues, and differentiate into macrophages
- Actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections
- Activate lymphocytes to mount an immune response
What is leukopoiesis ?
All leukocytes originate from hemocytoblast pluripotent stem cell, gives rise to all cells part of hematopoietic systemstem cell that branches into 2 pathways :
- Lymphoid stem cells produces lymphocytes (B & T cells)
- Myeloid stem cells produce all other elements (basophils, neutrophils, monocytes)
Process is hormonally regulated according to body’s need by interleukins (ILs) & colony-stimulating factors (CSFs)
- Bone marrow stores mature granulocytes (not erythrocytes); usu contains 10-20X more granulocytes than in blood
- Reticulocytes released in bloodstream → mature there
- Lifespan of granulocytes = 0.5-9.0 days (most die in line of duty)
Leukemias
Cancerous condition involving overproduction of abnormal WBCs /usually involve clones of single abnormal cell
Named according to abnormal WBC clone involved :
- Myeloid leukemia – Myeloblast descendants
- Lymphocytic leukemia – Involves lymphocytes
- Acute leukemia (quickly advancing – fast developing) derives from stem cells - primarily affects children
- Chronic leukemia (slowly advancing) involves proliferation of later cell stages -more prevalent in older people (cell metastasized further down differentiation pathway, closer to pluripotent stem cell becomes cancerous → more acute disease)
Bone marrow taken over by cancerous cells →
Severe anemia (produce less RBCs), clotting problems (produce less) (also fever, weight loss, bone pain)
WBCs numerous but non-functional - death usu from internal bleeding & overwhelming infections
Infectious Mononucleosis
Highly contagious viral disease (“kissing disease”)
Usually seen in young adults
- Caused by Epstein-Barr virus
- Results in high numbers of typical agranulocytes
- Involve lymphocytes that become enlarged
- Originally thought cells were monocytes, so disease named mononucleosis
Symptoms : Tired, achy, chronic sore throat, low fever
Runs course with rest in 4–6 weeks (trickier for immunocompromised)
Leukopenia
Abnormally low WBC count - usu due to drugs, esp. glucocorticoids & anticancer agents
The Immune System
Provides resistance to disease, 2 intrinsic systems :
Innate (nonspecific) defense system → BORN WITH IT
- Constitutes first & second lines of defense
- First line of defense : External body membranes (skin and mucosae)
- Second line of defense : Antimicrobial proteins, phagocytes, and other cells (inhibit spread of invaders; inflammation most important mechanism)
- Protects against foreign substances/abnormal cells without having to specifically identify them
Adaptive (specific) defense system → ACQUIRED
- Third line of defense attacks particular foreign substances (takes longer to react than innate)
subpopulations of lymphocytes recognize the specific target (usually specific cell surface proteins) and attack the target
- **Does NOT develop until we are exposed to pathogen
Innate Defense - Surface Barriers
Surface barriers are skin & mucous membranes, along with their secretions
- Physical barrier to most microorganisms
- Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins
- Mucosae provide similar mechanical barriers
Skin and mucous membranes produce protective chemicals that inhibit or destroy microorganisms :
- Acid: Acidity of skin and some mucous secretions inhibits growth; called acid mantle
- Enzymes: Lysozyme of saliva, respiratory mucus, and lacrimal fluid kills many microorganisms; enzymes in stomach kill many microorganisms
- Mucin: Sticky mucus that lines digestive and respiratory tract traps microorganisms
- Defensins: Antimicrobial peptides that inhibit microbial growth
- Other chemicals: Lipids in sebum and dermicidin in sweat are toxic to some bacteria
Respiratory system also has modifications to stop pathogens
- Mucus-coated hairs in nose trap inhaled particles
- Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus toward mouth
Surface barriers breached by nicks or cuts trigger the internal second line of defense that protects deeper tissues
Innate Internal Defense - Cells & chemicals
Innate internal system necessary if microorganisms invade deeper tissues; includes:
- Phagocytes
- Natural killer (NK) cells
- Inflammatory response
- Antimicrobial proteins
- Fever
Phagocytes
- WBCs that recognize, ingest and digest (eat) foreign invaders
- Neutrophils: Most abundant phagocytes, but die fighting; become phagocytic on exposure to infectious material
- Macrophages: Develop from monocytes (which leave the blood stream) are chief and most robust phagocytic cells
- Free macrophages
- Fixed macrophages
Phagocytosis
Phagocytes recognizes & binds to pathogen’s carbohydrate “signature”
[ Some pathogens hide their surface carbohydrates, helping them evade phagocytosis ]
Opsonization : Immune sys. uses antibodies or complement proteins as opsonins that coat pathogens
Some pathogens are not killed with acidified lysosomal enzymes (eg. TB bacteria) :
Helper T cells trigger macrophage to produce respiratory burst, which kills pathogens resistant to lysosomal enzymes by:
- Releasing cell-killing free radicals /producing oxidizing chemicals (e.g., H2O2) / increasing pH & osmolarity of phagolysosome
- Defensins (in neutrophils) also help by piercing membrane of pathogen
Natural Killer (NK) Cells
Nonphagocytic, large granular lymphocytes that police blood & lymph
- DONT identify invaders; just recognize abnormalities on surface of body cells such as loss of self-antigens – recognize cells that are “stressed”
- Contact target + inject toxins inducing it to undergo apoptosis
- Secrete potent chemicals that enhance inflammatory response
NK population greatly reduced in people with AIDS
Inflammation
Tissue response triggered by injury
What are the benefits of inflammation ?
- Prevents spread of damaging agents to nearby tissues
- Disposes of cell debris & pathogens
- Sets the stage for repair processes
- Alerts the adaptive immune system
Sometimes a 5th sign, impairment of function, is seen if movement or use of area is hampered
What are the stages of inflammation ?
- see table -
1. Inflammatory chemical release
- Chemicals (eg. histamine released by mast cells) are released into ECF by injured tissues or immune cells
- Involves kinins, prostaglandins (PGs), cytokines ( & complement if pathogens involved )
- All make capillaries leaky / many attract phagocytes to area
2. Vasodilation & increased vascular permeability
- Vasodilation causes hyperemia — Which leads to redness & heat
- Increased capillary permeability causes exudate(fluid containing clotting factors + antibodies) to leak into tissue
- Results in local swelling (edema)
- Swelling also pushes on nerve endings, resulting in pain
3. Phagocyte mobilization
- Neutrophils flood area first; macrophages follow
- If inflammation is due to pathogens, complement is activated; adaptive immunity elements arrive
Steps for 3. Phagocyte mobilization
- Leukocytosis : Release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells
- Margination: Endothelial cells of capillaries in inflamed area project cell adhesion molecules (CAMs) into vessel lumen that grab onto passing neutrophils, causing them to slow and roll along, clinging to vessel wall
- Diapedesis: Neutrophils flatten and squeeze between endothelial cells, moving into interstitial spaces
- Chemotaxis: Inflammatory chemicals act as chemotactic agents that promote positive chemotaxis of neutrophils toward injured area
Antimicrobial Proteins
Enhance innate defense by :
- Attacking microorganisms directly, or
- Hindering microorganisms’ ability to reproduce
Most important antimicrobial proteins :
- Interferons
- Complement proteins
Interferon (IFN)
Family (α, β, γ) of immune modulating proteins
secreted by virus-infected cells to warn healthy neighboring cells (only produced after infection)
- Enter nearby non-infected cells stimulating production of proteins that block viral reproduction & degrade viral RNA (α & β)
- NOT virus-specific
Also activate macrophages & mobilize natural killer cells (α & β), allowing for some anti-cancer effects as well
INF-γ secreted by lymphocytes, activates macrophages, widespread immune mobilizing effect
Complement
Consists of ~20 blood proteins that circulate in blood in inactive form
- Includes proteins C1–C9, factors B, D, and P, and regulatory proteins
- Provides major mechanism for destroying foreign substances
- Activation enhances inflammation + directly destroys bacteria (enhances both innate and adaptive defenses )
Complement System Activation
1. Classical Pathway
- Antibodies first bind to invading organisms and then bind to complement components, activating them –> double binding, called complement fixation
- Once initial complement proteins are activated, an activation cascade is triggered
2. Lectin Pathway
- Lectins are produced by innate system to recognize foreign invaders
- When lectin is bound to specific sugars on foreign invaders, it can also bind + activate complement
3. Alternative Pathway
- Complement cascade is activated spontaneously when certain complement factors bind directly to foreign invader
- Lack of inhibitors on microorganism’s surface allows process to proceed
Fever
Abnormally high body temperature that is a systemic response to invading microorganisms
- Body’s thermostat normally set at 37 C +/- 5
- Reset by pyrogens released by leukocytes & macrophages exposed to bacteria & other foreign substances
HI fever dangerous - denatures body’s own proteins, cell injury / death
