Patho - Term Test III (Immunity) Flashcards
Define innate (natural or native) immunity.
defense mechanisms that are present at birth and provide the initial response to invasion and injruy
What are the first, second, and third lines of defence? What are their respective functions
1) physical, mechanical, and biochemical barriers (prevent damage from environment or infection by pathogenic microorganism)
2) inflammatory response (activated to protect body from further injury, fight infection, and promote healing - there is already tissue injury/infection at this point)
3) adaptive (acquired/specific) immunity (long term protection against specific invaders)
Define adaptive (acquired or specific) immunity.
refers to immuntiy that develops over someone’s lifetime and provides long-term protection against specific invaders
Adaptive immunity involves “memory” which serves what purpose?
allows for rapid response for future exposures to the same invader because the body already has a memory of this invader
What is the timing of defense of the following:
1) Barriers
2) Inflammatory Reponse
3) Adaptive immunity
1) constant
2) immediate response
3) there is delay between 1st exposure to antigen and max response; immediate response against 2’s exposure to the same antigen
What is the specificity of defense of the following:
1) barriers
2) inflammatory response
3) adaptive immunity
1) broadly specific
2) broadly specific
3) very specific towards target
What cells are involved with barriers?
1) epithelial cells
What cells are involved with inflammatory response?
1) mast cells
2) granulocytes (neutrophils, basophils, eosinophils)
3) monocytes/macrophages
4) NK cells
5) platelets
6) Endothelial cells
What cells are involved with adaptive immunity?
1) T lymphocytes
2) B lymphocytes
3) Macrophages
4) Dendritic cells
Memory is involved with which of the following lines of defense?
1) Barriers
2) Inflammatory response
3) adaptive immunity
4) all of the above
adaptive immunity (specific immunologic memory by T and B lymphocytes)
What molecules are active in innate barriers?
- Defensins
- Collectins
- Lactoferrin
- Bacterial toxins
What molecules are active in inflammatory response?
- Complement activation
- Clotting factors
- Kinins
- Cytokines
What molecules are active in adaptive immunity?
- antibodies
- complement
- cytokines
Innate barriers have what kind of protective functions? (3)
1) anatomical barriers (skin, mucous membranes)
2) cells and secretory molecules (lysozymes, low pH of stomach and urine)
3) ciliary activity
Inflammatory responses have what kind of protective functions? (4)
1) vascular responses
2) cellular components (mast cells, neutrophils, macrophages)
3) secretory molecules of cytokines
4) activation of plasma protein systems
Adaptive immunity has what kind of protective functions?
1) activated T and B lymphocytes
2) cytokines
3) antibodies
How does the following remove infectious microorganisms:
1) skin
2) respiratory tract
3) GI tract
4) urinary tract
1) skin: microorganisms being sloughed off with dead skin cells
2) resp tract: epithelial cells producing mucus to trap microorganisms + cilia (coughing, sneezing it out)
3) GI tract: vomiting, defecation
4) urinary tract: urination
Low temperature on skin and low pH in stomach (activate/inhibit) growth of pathogenic microorganisms.
inhibit
How do epithelial cells trap & destroy invaders?
secrete mucus, saliva, sweat, tears, and earwax & have lethal substances (ex. lyosozymes that attack cell walls of gram+ve bacteria)
How do sebaceous glands kill bacteria/fungi?
- secrete fatty acids and lactic acid
- create acidic environment (pH 3 -5 on skin)
What are antimicrobial peptides? Provide an example.
Host defense peptides that are secreted by epithelial cells and kills/inhibits growth of disease-causing microorganisms
ex. (any one of the following):
- Cathelicidins
- Defensins
- collectins
- mannose-binding lectin
What are defensins?
antimicrobial peptides produced by neutrophils and epithelial cells (disrupts bacterial membranes)
What are collectins?
soluble glycoproteins that facilitate ability of macrophages to recognize and kill pathogenic microorganism, can also activate lectin pathway of complement system
Surfactant is a type of ____________.
collectin
I am cool with manna and mustafa using my flashcards. True or false.
False (just kidding :))
How many racoons can you shove up your butthole?
almost 2
Normal microbiome has a _______ and ________ relationship with the body (parasitic/commensal/opportunistic/etc).
commensal (benefitting microorganism without affecting the body)
mutualistic (benefitting both microorganism and body)
What are 6 functions of normal microbiome?
1) produces enzymes that facilitate digestion of fatty acids and large polysaccharides
2) synthesizes essential metabolites
3) releases antibacterial substances that are toxic to invaders
4) competes with pathogens for nutrients and blocks attachment of pathogens to the epithelium
5) fosters adaptive immunity by inducing growth of gut-associated lymphoid tissue (needed for local and adaptive immunity)
6) contributes to bidirectional communication between brain and GI tract
True or False. Prolonged treatment of broad-spectrum antibiotics can decrease normal microbiome protective activity and lead to overgrowth of pathogenic microorganisms.
True (because broad-spectrum antibiotics target wide range of bacteria so it kills good and bad bacteria)
What are opportunistic pathogens?
pathogens that are part of normal microbiome that are harmless under normal conditions but then can cause disease in immunocompromised individuals who lack usual defense mechanisms
Define inflammation.
Dynamic process programmed to respond to cellular or tissue damage irrespective of location or condition of tissue; it is non-specific
What is the process of acute inflammatory response?
1) cell/tissue damage
2) release of inflammatory mediators (from mast cell degranulation, activation of plasma protein systems)
3) changes in microcirculation
4) migration of leukocytes, plasma proteins, biochemical mediators from circulation into damaged tissue
5) destroy invaders in tissue, limit tissue injury, promote healing
Which of the following is false in regards to inflammatory response?
1) process can occur in vascularized and avascularized tissues
2) activation is rapid
3) response includes cellular and chemical components
4) response is non-specific
1) process can occur in vascularized and avascularized tissues
process can only occur in vacularized tissues because a blood supply is needed for cells and chemical components to go to injury site
What are the cardinal signs of acute inflammation?
Rubor (redness, erythema)
Calor (heat)
Tumor (swelling)
Dolor (pain)
Loss of function
In inflammatory response, what sort of changes occur in the microcirculation (capillaries, venules, arterioles)?
1) hemostasis (coagulation) - clotting cascade and activates platelets (clotting slows blood flow, walls off injury, and provides a meshwork for healing)
2) vasodilation - increases blood volume delivered to injured site and slows velocity of blood flow which allows more time for fluid, cells, chemical movement into surrounding tissues which results in erythema/warmth in injury site
3) increased vascular permeability - endothelial cells contract which cause blood vessels to become porous ==> leads to exudation and edema surrounding injury site
4) WBC adhesion - adhere to inner walls of vessels where they migrate through the enlarged spaces between endothelial cells and into surrounding tissue (influx in phagocytes - neutrophils, macrophages)
Exudation vs edema
exudation - fluid leaking from vessels
edema - tissue swelling from fluid leaking
Lymphangitis vs lymphadenitis
Lymphangitis: inflammation of lymph vessels
Lymphadenitis: inflammation of lymph nodes
What are the 3 key systems for an effective inflammatory response?
1) complement system
2) clotting system
3) kinin system
True or False: Plasma protein systems have multiple proteins/enzymes that are usually inactive (proeznymes) in the blood and get activated when there is tissue damage
True
Purpose of complement system
intensifies/complements capacity of antibiotics/phagocytes to clear pathogens and damaged cells and activate inflammation (so they either destroy pathogens directly or can eradicate pathogens through enhancing activity of other components of the immune response)
Activation of C3 and C4 within the complement system lead to what molecules being produced that are critical to immune response? What are their functions?
1) C3b - serve as opsonins (coats surface of bacteria to increase their susceptibility tto phagocytosis by inflammatory cells) - getting it ready for ingestion
2) C5a - functions as chemotactic factor (stimulates movement of leukocytes and attracts them to injury site)
3) C3a, C5a - anaphylatoxins; induces rapid degranulation of mast cells to release histamine (which induces vasodilation and increased capillary permeability)
What is the membrane attack complex (MAC)?
Component of complement system that is composed of C6-C9 that lead to bacterial destruction and tissue injury by creating pores in outer membranes of cells/bacteria (water infusion occurs, leads to cell death)
What are the 3 major pathways/cascades that control complement activation?
1) classical
2) alternative
3) lectin
How is the classical pathway activated which controls complement activation?
classical pathway is activated by antibodies when they bind to antigens, which then activates complement cascade and triggers infection
How does alternative pathway get activated control complement activation?
activated directly by substances found on surfaces of infectious microorganisms –> forms a complex that then causes activation of complement cascades and triggers infection
How does lectin pathway control complement activation?
does not require antibodies for activation, activated by several plasma proteins (particularly mannose-binding lectin MBL) that bind to the bacteria and activate complement cascade
What is the purpose of the clotting/coagulation system?
A group of plasma proteins that form a blood clot when cascade is activated
What is a blood clot composed of?
meshwork of fibrin strands and platelets
How is the clotting system activated?
By a variety of substanes (collagen, enzymes, bacterial toxins) released during tissue injury/infection
Functions of Clotting/coagulation system include what?
1) plug damaged vessels to stop bleeding (hemostasis)
2) trap microorganisms (localizing them)
3) prevent spread of microorganisms to adjacent tissues
4) provide framework for future repairing and healing
What are the two converging pathways that lead to clot formation? How are these two pathways activated?
extrinsic and intrinsic pathways
Extrinsic (tissue factor) pathway activated by tissue factor/tissue thromboplastin which is released by damaged endothelial cells of blood vessels + reacts with activated factor VII
Intrinsic (contact activation) pathway activated by exposed endothelium and negatively charged substances (resulting from vessel wall damage) coming in contact with factor XII/Hageman factor
Where do the intrinsic and extrinsic pathways of the clotting system converge, and after they converge what is the end product?
They coverge at factor X and form a common pathway that leads to activation of fibrin to eventually form a fibrin clot
Fibrinogen also makes fibrinopeptides that are chemotactic and attract neutrophils and increased vascular permeability
What is the kinin system’s function?
To activate and assist inflammatory cells
How is the Kinin System activated and what is the end product?
Activated by Hageman factor (Factor XII)
End product: bradykinin
What does bradykinin do, as part of the inflammatory response?
Causes dilation of blood vessels and acts with prostaglandins to induce pain, trigger smooth muscle cell contraction (bronchoconstriction) and increase vascular permeability
All the plasma protein systems are tightly regulated and highly interactive. What are two reasons as to why this would be beneficial for the human body?
1) inflammatory process is critical for survival so interaction of these systems allows for efficient activation regardless of cause of tissue injury
2) biochemical mediators released during inflammatory response are potent and can be harmful to the person so they have to be controlled and confined to injured tissues
Which of the following do not down-regulate or inactive plasma protein systems?
1) protease inhibitors
2) Hageman factor
3) Carboxypeptidase
4) Kininase
5) Histaminase
2) Hageman factor
Formation of clots activates fibrinolytic system. What is the function of this system and how does it work?
The fibrinolytic system functions to limit clot size (works oppositely to clotting system) and degrade clot after bleeding has ceased
How it works: Thrombin (which is made in the clotting system) activates plasminogen which is converted to plasmin which then degrades fibrin polymers in clots
What types of cells/components are involved with inflammation?
1) mast cells
2) endothelial cells
3) platelets
4) phagocytes (neutrophils. macrophages)
5) lymphocytes
Which cells are the most important mediators of inflammation?
Mast cells
Precursors of macrophages are also known as:
monocytes
What lymphocytes are involved with the following?
1) innate immunity
2) adaptive immunity
1) innate: NK cells
2) adaptive: B and T lymphocytes
What are pattern recognition receptors (PRRs)?
set of receptors on cells that are involved in initiating innate immune response and recognize antigens
Where are pattern recognition receptors generally expressed on?
cells in tissues near body’s surface (skin, resp tract, GI tract, genitourinary tract) so they can monitor environment for cell damage/infectious microorganisms
What are the two types of molecular patterns that PRRs recognize?
1) pathogen-associated molecular patterns (PAMPs)
2) damage-associated molecular patterns (DAMPs)
PAMPs vs DAMPs
PAMPs: molecules expressed by infectious agents found either on surface or released as soluble molecules
DAMPs: products of cellular damage
Toll-like receptors: what do they recognize and where are they found?
Recognize PAMPs located on cell wall/surface of microorganisms
Found on outer membrane of phagocytic cells with early contact with infectious microorganisms (i.e. dendritic cells, macrophages)
C-type lectin receptors: what do they recognize and where are they found?
Recognize PAMPs (especially fungal antigens) and DAMPs
Found on outer membrane of phagocytic cells
Nucleotide-binding-like receptors (NLRs) and NOD-like receptors: what do they recognize, what is their function, and where are they found?
Recognize PAMPs and DAMPs
Function: initiate production of proinflammatory mediators and help control inflammatory response
Found in cytoplasm of innate immune cells (lymphocytes, macrophages, and dendritic cells)
Complement receptors: what do they recognize and where are they found? what is their function?
Recognize components of complement system
Found on many cells involved with immune response, platelets, epithelial cells, vascular smooth muscle
Function: result in chemotaxis and activation of innate immune cells
Scavenger receptors: what do they recognize and where are they found? What is their function?
Recognize bacterial pathogens, damaged cells, and soluble lipoproteins (HDL, LDLs, etc.)
They are found on surfaces of macrophages
Functoin: remove old RBcs and cells undergoing apoptosis
What are cytokines?
Small signaling proteins that bind to specific cell membrane receptors to regulate innate/adaptive immunity and are responsible for activating other cells; mediators of inflammation
True or false. Cytokines can be proinflammatory or anti-inflammatory
True - depends on whether they tend to induce or inhibit inflammatory response
Which of the following are not cytokines?
1) interleukins
2) lymphokines & monokines
3) chemokines
4) TNF-a
5) bradykines
6) interferon
bradykines
What are lymphokines, monokines?
cytokines that are secreted from lymphocytes and monocytes (respectively)
What are chemokines?
cytokines that are chemotactic and are typically synthesized in response to proinflammatory cytokines
What are interleukins?
cytokines that are produced primarily by WBCs (macrophages, neutrophils) in response to stimulation of PRRs/other cytokines and serve to alter behaviour of cells; can be proinflammatory or anti-inflammatory
Four functions of interleukins include what?
1) chemotaxis (attracting leukocytes)
2) regulating cell adhesion molecules (CAMs) which are proteins that facilitate binding of cells or with ECM
3) induction, proliferation, and maturation of leukocytes in bone marrow
4) general enhancement/suppression of inflammation and adaptive immune response
Which of the following is not an proinflammatory cytokine?
1) IL-1
2) TNF-a
3) IL-6
4) IL-10
IL-10
What is tumor necrosis factor-alpha (TNF-a)?
What is its role in inflammation?
A proinflammatory cytokine that is primarily secreted by macrophages in response to PAMP and toll-like receptor recognition
Function: contributes to damaging effects of chronic inflammation and causes fever, synthesis of other inflammation-related proteins (acute phase proteins), muscle wasting (cachexia), and intravascular thrombosis
What is interleukin-1 (IL-1)?
A proinflammatory cytokine mainly produced by macrophages and is an endogenous pyrogen (causing fever); also acts as a growth factor for many cells
What is interleukin-6 (IL-6)?
A proinflammatory cytokine produced by macrophages, lymphocytes, fibroblasts and other cells
Function: directly induces hepatocytes in the liver to produce acute phase proteins (proteins needed for inflammation), stimulates growth and differentiation of red blood cells in bone marrow, and growth of fibroblasts for wound healing
Proinflammatory vs anti-inflammatory
Proinflammatory: up-regulate infection with goal of eradicating pathogens (causes fever, further inflammation, tissue death)
Anti-inflammatory: diminish and control inflammatory response
Two important anti-inflammatory cytokines include:
IL-10
TGF-b (transforming growth factor-beta)
What is interleukin-10 (IL) and its function?
Anti-inflammatory cytokine primarily produced by lymphocytes
function:
- suppress activation and proliferation of other lymphoctes
- limit production of proinflammatory cytokines
- results in downregulation of inflammatory and adaptive immune responses
What is transforming growth factor-beta (TGF-b) and its function?
anti-inflammatory cytokine that is produced in response to inflammation
Function: suppress activity of lymphocytes and downregulate production of proinflammatory cytokines by macrophages
What are interferons (IFNs) and its subclasses?
cytokines that protect against viral infections
Type I interferons (IFN-a, IFN-b): produced and released by virally infected cells in response to viral dsDNA; do not kill viruses directly but induces antiviral proteins
Type II inferferons (IGN-y): produced primarily by lymphocytes and increase bactericidal activity of macrophages
List the immunoreactive cells.
1) mast cells
2) endothelial cells
3) platelets
4) neutrophils
5) eosinophils
6) basophils
7) monocytes/macrophages
8) lymphocytes and NK cells
What are mast cells?
Significant, potent activators of inflammatory response with granules containing mediators that are released in tissue injury
What are the two mechanisms in which mast cells release their mediators?
1) degranulation: release of contents of mast cell granules (histamine, chemotactic factors, cytokines)
2) synthesis: production and release of mediators in response to a stimulus
What sort of vascular changes does histamine cause?
- constriction of large blood vessels/smooth muscle and dilation of postcapillary venules (net result: increased blood flow within microcirculation)
- also causes increased vascular permeability secondary to retraction of endothelial cells
Histamine H1 vs H2 receptors?
H1 receptors: causes bronchoconstriction (smooth muscle contraction) when activated - is proinflammatory when histamine binds to it
H2 receptors: when activated, supresses leukocyte function (so function is anti-inflammatory) and induces secretion of gastric acid
Antihistamines and H2 blockers are used against histamine function. What do each of these classes of drugs do?
Antihistamines: drugs block binding of histamine to H1/H2 receptors resulting in decreased vascular effects
H2 blockers: medications that reduce gastric acidity in individuals prone to peptic ulcers/GERD
Mast cells initiate synthesis of other mediators of inflammation. These mediators include what?
1) leukotrienes
2) prostaglandins
3) platelet-activating factor
What are leukotrienes and its functions?
Leukotrienes are lipids that induce smooth muscle contraction (especially bronchoconstriction) and increase vascular permeability ; made from arachidonic acid from mast cell membranes
function: stimulate slower and more prolonged inflammatory response (similar effects to histamine in later stages of inflammatory response)
What are prostaglandins and its functions?
long-chained unsaturated fatty acids that cause increased vascular permeabiity, neutrophil chemotaxis, and pain
they are produced by the action of cyclooxygenase (COX)
What are the two forms of cyclooxygenase (COX)? If inhibited via inhibitor drugs, what will happen?
COX-1: activates platelets and protects stomach lining
- if inhibited, GI tract bleeding and ulcers (think aspirin and NSAIDs suppressing inflammation but causing GI bleeds)
COX-2: associated with inflammation
- if inhibited, increased risk of CV disease due to effects on blood vessels and clotting
What are platelet-activating factors?
- mediators that are produced by neutrophils, monocytes, endothelial cells, mast cells, and platelets
- has similar activity as leukotrienes
- causes endothelial retraction, platelet activation, mast cell activation
Where are endothelial cells found and what do they do?
They are found lining blood vessels and regulate circulation (controlling water and solute movement between blood and tissues)
What happens to endothelial cells when there is tissue injury?
endothelial cells contraction leading to increased capillary membrane permeability (allows for plasma and nutrients to move out of capillaries and into injured tissue)
Platelets have no nucleus and are formed from _______.
megakaryocytes
What do platelets do during inflammation/vascular injury?
- blood clotting
- degranulate and release mediators like serotonin that have similar effects to histamine to accelerate inflammation
- synthesizes thromboxane that vasoconstricts and induce platelet aggregation
- recognizes and kills pathogens
- release growth factors that promote wound healing
What are the three granulocytes?
neutrophils, basophils, eosinophils
The earliest phagocytes at site of inflammation are what?
neutrophils
What is the primary function of neutrophils? How are they removed?
Function: phagocytize pathogenic microbes and remove cellualr debris and dead cells from lesions
Short-lived so removed with purulent exudate (pus) through epithelium or drained through lymphatic system
What are the functions of eosinophils?
primary defence against parasites and regulate vascular mediators released from mast cells (have lysosome enzymes that degrade vasoactive substances to limit vascular effects of inflammation)
What are the functions of basophils?
- release histamine
- also has heparin (anticoagulant)
- important source of cytokines involved in adaptive immune response especially with allergies and asthma
What are monocytes?
The largest WBCs that are produced in bone marrow and migrate to site of inflammation where they transform into macrophages
What is the primary function of macrophages?
prolonged phagocytosis (can survive acidic environment of inflammatory site) so removes debris and promote healing and repair
M1 macrophages: greater bactericidal activity
M2 macrophages: primarily involved in tissue healing and repair
What do dendritic cells do?
Antigen-presenting cells: they recognize invaders via PRRs and internalize invaders, then migrate through lymphatic vessels to lymph nodes where they present the invaders to T lymphocytes
Difference between:
B lymphocytes
T lymphocyes
NK cells
B lymphocytes - produces antibodies
T lymphocytes - directly kills virus/cancer cells
NK cells: part of innate immunity; recognizes and eliminates cells infected with virus/cancerous cells
The two most important phagocytes for ingesting pathogens/damaged cells are:
neutrophils, macrophages
Margination/pavementing is defined as what?
increased adhesion of neutrophils to endothelial cell wall of capillaries and venules (adhesion molecules increase stickiness of the cells)
The emigration of cells through interendothelial junctions is known as:
diapedesis
What are the 5 stages of phagocytosis?
1) Adherence - of phagocyte to its target through PRRs and opsonization
2) engulfment - bind to surface of phagocyte and engulfed into a phagosome
3) Phagosome formation
4) Fusion with lyososomal granules = phagolysosome
5) target destruction - lysosomal enzymes kill and digest microorganisms
What are opsonins?
proteins that coat the target bacteria and act like glue tightening the affinity between phagocyte and target (makes phagocytosis more effective)
ex. the most efficienct opsonins: C3b (from complement) and antibodies
Within the phagolysosome, there are oxygen-dependent and -independent mechanisms that kill the pathogens. Describe how these mechanisms kill the pathogens.
Oxygen-dependent mechanisms: result from production of toxic oxygen species
Oxygen-independent mechanisms: acidic pH, proteins binding to and damaging target cell membrane, enzyme attack on pathogen cell wall, inhibition of bacterial growth
Phagocytes may die at inflammation sites. What occurs as a result of this?
Causes inflammation-associated tissue destruction due to releasing its enzyme contents (but this is minimized with natural inhibitors found in blood)
Define acute inflammation.
Inflammation that is rapid onset and continues only until threat to body is eliminated (self-limiting, usually lasts 8-10 days from injury onset)
Local manifestations of acute inflammation include what?
heat
swelling
redness
pain
potential loss of function
exudate
How do exudative fluids occur?
from increased vascular permeability and leakage of fluid into tissues
Exudate that is water with few plasma proteins and leukocytes (Ex. fluid in blister), and indicates early or mild inflammations is known as what?
Serous exudate
Describe fibrinous exudate and where you would find such?
thick and clotted exudate (indicates more advanced inflammation)
ex. in lungs with pneumonia
Accumulation of large number of leukocytes which occur in persistent bacterial infection (abscesses, pus) is known as what kind of exudate?
Purulent/suppurative exudate
Exudate that is filled with RBCs and indicates bleeding is known as?
hemorrhagic exudate
What are the 3 systemic manifestations of acute inflammation?
fever
leukocytosis
increased plasma protein levels
What causes fever?
endogenous and exogenous pyrogens (specific cytokines release from neutrophils and macrophages) - act directly on hypothalamus which control’s body’s thermostat
Treatment for febrile seizures?
tylenol, removing clothing “(to avoid exacerbation of problem)
What is leukocytosis?
increased in number of circulating WBCs beyond upper limit of normal (11000 ml^3 in adults)
- may also notice “left shift” (i.e. increase in ratio of immature to mature neutrophils)
What is produced by the liver during acute inflammation?
acute phase reactants/proteins
- C-reactive protein
- Fibrinogen
- Haptoglobin
- Amyloid
- Ceruloplasmin
Someone with inflammatory process going on in the body would show _______ (increased/decreased) ESR and _______ (increased/decreased) c-reactive protein.
Increased; increased
True or false. Chronic inflammation lasts at least 2 weeks and is always preceded by an unsuccessful acute inflammatory response
False.
What’s true is that it lasts at least 2 weeks
but this statement is false because chronic inflammation can follow acute inflammation that was inadequate BUT can also be a distinct process on its own
Chronic inflammation is characterized by:
- pus formation
- suppuration (purulent discharge)
- incomplete wound healing
What are granulomas?
A walled-off/isolated infected area full of macrophages (epithelioid cells and giant cells), lymphoctytes, collagen
- may calcify
Epithelioid cell formation vs Giant cell formation
Epithelioid: differentiated macrophages that specialize in taking up debris and small particles
giant cell: multinucleated active phagocytes that take up larger cells
Regeneration is the process of what?
damaged tissue is replaced with healthy tissue of the original type (occurs in wounds that are minor damage with no complications)
Define resolution/maturation in the context of wound healing
returning of injured tissue to its original structure and function (may take up to 2 years)
Resolution may not occur in what wound situations?
1) extensive damage
2) injury site is where original tissue cannot regenerate
3) areas where infection has resulted in abscesses or granuloma formation
4) where fibrin persists in the lesion
Define repair in the context of wound healing
replacement of destroyed tissue with scar tissue
What is scar tissue?
collagen that mostly fills in the lesion to restore tissue integrity and strength but has no physiologic functions of tissue
What are the 4 overlapping stages in wound healing?
1) hemostasis (coagulation)
2) inflammation
3) proliferation with new tissue formation
4) remodeling and maturation
Wounds healing by primary intention are wounds that can be described to have_______.
minimal tissue loss
Surgical incisions and paper cuts are examples of wounds that will heal by _________.
primary intention
Wounds healing by secondary intention are wounds that can be describe as__________.
needing more tissue replacement; more time and care required as well
Open wounds such as pressure ulcers and burns can be described to heal by ____________.
secondary intention
At best, repaired tissue that heals by secondary intention regains ___% of its original tensile strength
80
What are the three regions/areas of the body in which normal tissue can regenerate without scarring ? This type of healing is known as _____________.
- liver
- bones
- epithelium
- known as compensatory hyperplasia
A patient is recovering from an MI. He asks you whether or not his heart and cardiac function can return to normal. What do you say to him?
- MI heals with fibrous scar tissue rather than with cardiac muscle so cardiac function is not restored completely
Phase I of wound healing is known as _______. What happens during this phase?
Hemostasis/coagulation
- vascular injury causes immediate vasoconstriction and then vasodilation, and initiates clotting cascade and platelet activation to form a blood clot
- platelets also degranulate and release factors that cause increased permeability and promote growth factors that initiate proliferation in undamaged cells
Phase II of wound healing is known as _______. What happens during this phase?
Inflammation
- begins within minutes; macrophages and mast cells release cytokines that increase blood flow to wound and bring needed cells and proteins to injury site (neutrophils to clear wound of debris and bacteria; lymphocytes to initiate immune response)
Phase III of wound healing is known as _______. What happens during this phase?
Proliferation and New Tissue Formation
- begins 3-4 days after injury and continues up to 2 weeks
- wound is sealed and fibrin clot is replaced with normal/scar tissue (debridement)
- angiogenesis
- granulation tissue formation
- epithelization occurs: epithelial cells growing into wound (can be sped up with moist wound to prevent it from becoming a scab)
- fibroblast proliferation, collagen formation, wound contraction
What is wound contraction?
a process of wound healing where fibroblasts turn into myofibroblasts and anchor themselves to wound bed to contract their fibers and exert tension on neighbouring cells (needed for closure of all wounds, noticeable 6-12 days after injury)
Phase IV of wound healing is known as _______. What happens during this phase?
Remodeling and Maturation
- begins several weeks after injury and is normally completed within 2 years
- tissue regeneration and wound contraction continue in this phase
- cellular differentiation, scar formation/remodeling (scar tissue becomes avascular)
What factors can contribute to dysfunctional wound healing?
1) ischemia
2) excessive bleeding
3) excessive fibrin deposition
4) predisposing factors/disorders (diabetes, obesity, wound infection, inadequate nutrients, drugs, tobacco smoke)
How does ischemia cause dysfunctional wound healing?
ischemia leads to cell death and infection which prolongs inflammation/delays healing
- also reduces energy production and impairs collagen synthesis & tensile strength of regenerating tissue
How does excessive bleeding cause dysfunctional wound healing?
- delays healing because large clots increase amount of space that granulation tissue must fill
- clots also serve as mechanical barriers to oxygen diffusion
- accumulation of blood is also a great place for bacterial growth leading to infection and inflammation
How does excessive fibrin deposition cause dysfunctional wound healing?
- fibrin can eventually turn into fibrous adhesions which turn into bands that distort/impinge and strangulate organs –> leads to pain and organ dysfunction
How does diabetes cause increased risk of dysfunctional wound healing?
- persistent hyperglycemia leads to wounds being ischemic (small-vessel diseases and impaired blood flow)
- suppresses macrophage function
- hyperglycemia also increases a type of oxygen that does not allow oxygen to be readily realeased into tissues
How does obesity cause increased risk of dysfunctional wound healing?
- impaired leukocyte function predisposes wound to infection
- decrease growth factor production
- increased proinflammatory cytokines
- dysregulation of collagen synthesis
- decrease in angiogenesis
How does wound infection cause increased risk of dysfunctional wound healing?
- continued pathogen invasion into injured area means continuous need for body to fight off infection, uses nutrients, release of inflammatory mediators = delays wound healing
How does inadequate nutrients cause increased risk of dysfunctional wound healing?
- your tissues at the wound already have increased metabolic demands so lacking nutrients is no good
- vitamin A and C are requrred for collagen synthesis so lack of this leads to poorly formed connective tissue and significantly impaired healing
- others include iron, zinc, manganese, and copper
How does tobacco smoke cause increased risk of dysfunctional wound healing?
- toxic agents (CO, hydrogen cyanide) delay wound healing
- nicotine also vasoconstricts which predisposes the tissue to ischemia and infection, thus compromising wound healing
How do various drugs (antineoplastic/anticancer agents, NSAIDs, steroids) cause increased risk of dysfunctional wound healing?
- antineoplastic agents: slow cell division and inhibit angiogenesis
- NSAIDs suppress acute inflammation and inhibit prostaglandin production which delays wound healing + associated with excessive scarring
- steroids: disrupt wound healing by preventing macrophages from migrating to injruy site
Which scars are likely to recur despite surgical removal?
keloids
Which demographics have been shown to have a higher incidence of keloids with wound healing?
darker skin pigmentation
familial tendency
Define dehiscence. How does this happen and what is the treatment for it?
Complication where wound pulls apart at suture line (generally occuring 5-12 days after suturing)
Happens due to excessive strain; increase risk in obese people because adipose tissue is difficult to suture
Tx: prompt surgical attention
What is a contracture?
excessive wound contraction that leads to anatomic deformity
Where can contractures occurs and what is the management/treatment for this?
- Can occur with burns, particularly at joints
- internal contractures can occur in duodenum (from improper healing of peptic ulcers); esophagus (from chemical burns like lye ingestion); abdomen from surgery/infection/radiation
Treatment/prevention:
- proper positioning
- ROM exercises
- compression
- surgery for internal contractures
Newborn innate immunity is limited. Where do they get their immunity from?
At the beginning as their own immunity is building, their immuntiy is acquired from their mother through placenta and breast milk
Describe how the following affect/present in an infant’s innate immunity/healing ability (relative to an adult’s):
1) inflammatory response/inflammatory cytokine production
2) complement levels
3) monocyte/macrophage levels
4) Susceptibility to chemotactic defects
5) severity of sepsis and meningitis if infected
6) newborns via C-section
7) ability to fight off infection in utero
1) depressed inflammatory response, limited production of cytokine production
2) diminished complement levels
3) normal monocyte/macrophage numbers but delayed chemotaxis of monocytes
4) Predisposition to infections associated with chemotactic defects (especially cutaneous abscesses caused by Staph or Candidiasis)
5) predisposition to overwhelming sepsis and meningitis when infected by bacteria with no circulating maternal antibodies
6) reduced gut microbial diversity in newborns delivered via C-section
7) weak ability to fight off in utero infectio becaused infants have compromised oxidative and bactericidal response
Describe how the following factors affect/present in an elderly’s innate immunity/healing ability (relative to an adult’s):
1) number of cells associated with innate immunity & cell function
2) risk of chronic inflammation
3) Ability to heal and repair
4) subcutaneous fat
5) epidermal changes
6) efficacy of vaccines
1) normal number of cells associated with innate immunity, diminished cell function (decreased phagocytic activity, antibody protection, and altered cytokine synthesis)
2) increased risk
3) risk of decreased/impaired healing and increased infection associated with chronic diseases
4) less subQ fat which diminishes layers of protection against injury
5) atrophied epidermis & underlying capillaries so decreased perfusion and increased risk of hypoxia in wound beds
6) diminished effectiveness due to normal aging process
How may ASA interfere with wound healing?
ASA is an antiplatelet which prevents blood clotting so if there is excessive bleeding froma cut, it may lead to hemorrhagic stroke
What are the two effectors for adaptive immunity?
lymphocytes and antibodies
When does adaptive immunity kick in?
When external barriers have been compromised and innate immuntiy activated
What are the main purposes of adaptive immunity?
- slowly ehance the first responder’s job (inflammation) & promote processes against reinfection
- destroy infectious invaders that are resistant to inflammation
- long term protection against future exposure to same invaders
What are the 4 characterists of adaptive immunity? Describe each briefly.
1) inducible - effectors (lymphocytes and antibodies) do not pre-exist in large numbers but are produced in response to infection
2) specific - to the infecting microbe
3) long-lived: here for a good time and a long time (different than inflammatory mediators that need to be cleared out quickly before they cause more harm than good)
4) memory: if re-infected by the same microbe, lymphocytes and antibodies are produced immediately
What are antigens?
molecular targets of antibodies and lymphocytes (recognized by antibodies)
How do lymphocytes become T and B cells?
lymphocytes go through extensive differentiation in the fetus before any exposures and then further differentiate when they go to primary lymphoid organs (thymus - turn into T cells; bone marrow - B cells) and they develop origin specific cell surface proteins and antigen receptors that allow you to differentiate between the two
True or False: one individual lymphocyte is programmed to recognize only one specific antigen
True
Before birth, each individual has produced enough B and T lymphocyes to recognize at least _____ different antigens. This is know as ______.
10^8
Generation of clonal diversity
Define clonal diversity
the process by which extensive diversity of antigen receptors on B and T cells is established/produced
True or false. Only a small selection of B and T cells undergo clonal selection at a given time.
True - because not every B and T cells have the same receptors for the antigen so some are chosen while others are just chilling (think like they are the chosen ones because they have certain characteristics)
B and T lymphocytes leaving the primary lymphoid organs are immunocompetent. What does this mean?
Immunocompetent means they are able to respond to antigens but have not had any exposure to antigens yet and are thus naive
Where do immunocompetent B and T cells go once leaving primary lymphoid organs?
enter blood and lymphatic vessels and migrate to secondary lymphoid organs (lymph nodes, spleen, tonsils, adenoid, peyer patches)
How is clonal selection activated and what happens during this process?
- Initiated when there is an actual exposure to an antigen
- antigens are processed and presented on the surface of phagocytes to lymphocytes (Th cells)
- B and T cells that recognize that antigen are then chosen and differentiated into even more specialized cells (B cells into plasma cells that produces antibodies; T cells into Tc cells that identify and kill target cell)
- also differentiate into memory cells
Cellular immunity is mediated by what cells?
effector T cells that kill target cells (Tc cells) OR regulate immune response (Treg cells) + memory T cells that respond more quickly to re-exposure to antigen
Humoral immunity is mediated by what cells/molecules?
soluble proteins produced by plasma cells + memory B cells that can produce more antibody rapidly to re-exposure
Antibodies are also known as:
immunoglobulins
What are antibodies
proteins used by the immune system to identify and neutralize foreign objects like bacteria and viruses
Antibodies binding to antigens on bacteria and viruses are known as what sort of immune response?
humoral immune response
Cell-mediated immune response involves what?
Effector T cells that circulate in the blood and tissues and defend against invaders/abnormal cells by killing targets directly and stimulating other leukocytes
Active immunity vs passive immunity
Active: develops in response to exposure to an antigen (so now you are actively immune to this antigen by developing antibodies) –> long lived
Passive: receiving preformed antibodies/lymphocytes; they eventually get killed off by your own body so these are short-lived and not as strong
A child acquiring immunity through her mother’s breast milk/placenta at birth is known as:
passive immuity (or passive acquired immunity)
A patient receiving an injection of antibodies to a disease is known as what type of immunity?
passive immunity
If the antigen source is infectious agents, how are you protected through:
a) your body
b) vaccines
Also indicate dx and tx of infectious agents.
a) body has antibody response against pathogenic microorganisms
b) vaccines induce a safe and protective immune response (like childhood vaccines)
Dx: measure circulating antigen or antibody
Treatment: passive tx with antibody to treat/prevent infection (i.e. administering antibodies into patient)
Your patient asks you how your body and vaccines works to protect you from cancerous antigens. They also ask you how cancers are diagnosed and treated against cancerous antigens. What do you say?
- body has immune surveillance to prevent early cancers and tumor growth/spread
- vaccines with cancer antigens induce immunity to prevent tumor/growth and spread
Dx: measuring circulating antigens
Tx: immunotherapy (treatment with antibodies that are against cancer antigens)
If the antigen source was from environmental substances, how are you protected through your body?
Also indicate dx and tx against environmental substances.
a) your body tries to prevent them from coming in (secretory IgA are in bodily secretions and limits systemic exposure to potential allergens)
Dx: measure circulating antigen or antibody (Ex. dx of allergy measured by circulating IgE)
Tx: immunotherapy (administration of antigen for desensitization of individuals with severe allergies)
If the antigen source is self-antigens, how are you protected through:
a) your body
b) vaccines
Also indicate potential diagnosis and treatment related to self-antigens?
a) your body’s immune system is tolerant to self-antigens (but can be altered by an infectious agent leading to autoimmune disease)
b) typically don’t need vaccines to protect against self-antigens; but some vaccines may alter tolerance to self-antigens (autoimmune disease)
Dx: measuring circulating levels of antibody against self-antigen for dx of autoimmune disease
Tx: no clear example
Antigens vs. immunogens
Antigens: molecules that can bind with antibodies or antigen receptors on B/T cells
Immunogens: molecules that bind to receptors and will induce an immune response
(therefore all immunogens are antigens but not all antigens are immunogens)
Most immunogenic antigens are (large/small) molecules
large (ability of an antigen to induce immune response is frequently relate to the size of antigen)
What are haptens?
super small molecules that are too small to induce an immune response by themselves but become immunogenic after combining with large molecules that function as carriers
Poison ivy contains a hapten known as _______ that chemically changes upon skin contact and binds to larger proteins in the skin to become immunogenic. This leads to T-cell response and the onset of ______ symptoms.
urushiol
poison ivy rash
When does the following occur?
1) generation of clonal diversity
2) clonal selection
1) primarily in fetus
2) primarily after birth and throughout life
B cells in bone marrow develop a variety of necessary surface markers as it matures in order to allow for further differentiation and proliferation of B cells. These receptors are known as what?
B cell receptors (antibody complex; it’s basically an antigen receptor)
B cell receptors (BCRs) in incompetent B cells are made up of what?
membrane-associated IgM with or without IgD antibodies that have identical specificities for antigens
Somatic recombination can occur in B and T cells. What does this mean and what is the significance of this?
Somatic recombination is the rearrangement of existing DNA in B/T cell development while in their primary lymphoid organs which allow for specificities of BCR/TCR
HOWEVER: for this can cause the BCR/TCR to recognize and attack self-antigens which leads to autoimmune diseases (this is controlled by clonal deletion/central tolerance which is apoptosis)
Clonal deletion/central deletion occurs in ____% of B cells, and ___% of T cells
>90%; >95%
T cell receptors (TCRs) in incompetent T cells are made up of what?
two protein chains: alpha and beta chains
During T cell differentiation, surface molecules CD4 and CD8 also develop during development. What happens to these happens as T cells mature?
as T cells mature, either CD4 or CD8 is retained (one or the other)
- CD4-retaining cells become Th cells (60% of immunocompetent T cells)
- CD8-retaining cells become Tc cells (40% of immunocompetent cells)
What are antigen-presenting cells (APCs)?
cells that process and present the antigens to the immune cells
- dendritic cells, macrophages, B cells
Major Histocompabitility complex (MHC): What are they and where are they found?
glycoproteins that present antigens on APC surfaces for recognition by appropriate T cells; found on all cell surfaces of humans cells except RBC
MHC are also called?
HLA - human leukocyte antigens
What are the two classes of MHC molecules
MHC Class I - found on all nucleated cells and present endogenous antigens that are recognized by Tc cells
MHC Class II - found only on APCs and present exogenous antigens which are recognized by Th cells
What cells have both MHC class I and II molecules on their cell surface?
APCs - meaning they can present both endogenous and exogenous antigens to Tc and Th cells respectively
What are the two steps in clonal selection?
1) antigen processing and presentation
2) cellular interactions in immune response
Any cell that actively response to a stimulus and effects from change is known as:
an effector cell
In clonal selection, three signaling events are required to produce a protective immune response (producting effector and memory cells for adaptive immunity). What are the three signaling events?
1) antigen-specific recognition through TCR/BCR complex
2) activation of intercellular communication
3) response to specific groups of cytokines
What are Th (T-helper) cells?
cells that help the antigen-driven maturation of B and T cells (they are the ones that APCs present antigens to)
What are the 6 steps of activating Th cells?
- APC presents antigen which is recognized and binds on Th cell
- antigen binding is strengthened by binding CD4 on Th cells with MHC class II molecule (on APC)
- intracellular signaling pathways activated (by CD3 and CD4)
- intercellular communication occurs and further activates Th cell
- IL-1 secreted by APC and provides an additional signal through IL-1 receptor on Th cell
- IL-2 secreted by Th cell and acts as an autocrine (self-stimulating) to induce further maturaiton and proliferation of Th cell
Activated Th cells undergo differentiation into what 4 cells?
Th1
Th2
Th17
Treg
Describe the function of the following cells:
1) Th1 cells
2) Th2 cells
3) Th17 cells
4) Treg cells
Th1: provides help in developing Tc cells (so is part of cell-mediated immunity) & defends against pathogens
Th2: provides help in developing B cells (so involved wih humoral immunity)
Th17: secrete lymphokines that activate macrophages to site of inflammation
Treg: limit immune response by suppressing response and maintaining tolerance against self-antigens
What are superantigens (SAGs)?
A group of molecules produced by bacteria viruses that bind to portion of the TCR/MHC that is outside of the normal binding site causing the APC to not be able to process and present it to an immune cell
What effect does superantigens have on the body?
leads to excessive systemic inflammatory response (fever, low BP, potentially fatal toxic shock)
Two examples of superantigens include:
Staphylococcus aureus
Streptococcus pyogenes
Tcytotoxic cells (Tc cells) do what?
starts off as immunocompetent Tc cell that can react with antigen but cannot kill target cells
their TCR recognizes antigens presented by MHC Class I molecules and on virus/cancerous cells and then signals happen which then allow Tc to turn into effector Tc cells that are able to kill the bad cells (via apoptosis)
How do B cells turn into plasma cells?
- B cell binds with antigen
- B cell gets activated to process and present antigen on MHC class II molecules to TCR on Th cell
- Th cells activated
- intercellular communication induces Th2 cell differentiation and secretion of cytokines
- B cell proliferation initiated and maturation into plasma cells
What do plasma cells do?
make antibodies (that recognize the identical antigen as the BCR)
What are T-cell independent antigens?
large bacterial products that bypass cellular interactions of B cells and Th cells leading to direct stimulation of B cell maturation and proliferation
Class switch is a major component of B cell maturation. What is class switch?
the process that results in change in antibody production from one class to anotehr
What are memory cells?
B and T cells that have differentiated and now remain inactive until there is another exposure to the same antigen
- these cells will rapidly become plasma cells/effector T cells without cell interactions and go do their things
The most abundant Ig and accounts for most of the protective activity against infections is:
IgG (80-85%)
True or false: during pregnancy, maternal IgG is transported across placenta and protects newborn child during first 6 months of life
true
How many subclasses does IgG have?
4 (IgG-1 to IgG-4)
The Ig that is found predominantly in blood is
IgA
The Ig that is found predominantly in bodily secretions is:
secretory IgA (or IgA-2)
What is the benefit/important role of secretory IgA?
the secretory component of it protects the Ig from being degraded by proteolytic enzymes (meaning it can survive harsh GI environments and protect against microbes that multiple in body secretions)
The largest antibody and the first one to be produced during primary response to an antigen is:
IgM
IgE presence and function in the body:
The antibody that is normally low in circulation and has specialized functions as a mediator of many common allergic responses and defense against parasitic infections
What is IgD’s function?
part of BCR antigen receptor on surface of early B cells
Before exposure to antigens and Th2 cells, B cells produce what two Ig that are used as cell membrane receptors?
IgM, IgD
TRUE OR FALSE - During clonal selection, B cell proliferates and developes into plasma cells. at this point, B cells have the option of becoming secretor of IgM or changing class to secreted form of IgG, IgA, IgE
True
What are the 3 structural parts of an antibody?
think of a Y
two identical fragments bind antigen (antigen-binding fragments or Fab)
third fragment: Fc or crystalline fragment that is responsible for functions of antibodies
Antibody has how many polypeptide chains in its structure?
4 (2 light chains, 2 heavy chains)
Epitope vs paratope
epitope: antigenic determinant (the precise area of the antigen that is recognized by antibody)
paratope: antigen-binding site (the matching portion on the antibody)
Antibodies can function to protect against infection through direct or indirect mechanisms. What are the direct mechanisms (through action of antibody alone)?
1) neutralization: inactivating or blocking antigens from binding to receptors (ex. using antitoxins to bind to toxin and prevent interaction with host cell)
2) agglutination: clumping insoluble particules that are in suspension
3) precipitation: making a soluble antigen into an insoluble precipitate
Antibodies can function to protect against infection through direct or indirect mechanisms. What are the indirect mechanisms (i.e. done through activating other components of innate immune response)?
can be done through Fc portion of antibody, activating complement and phagocytes
1) inflammation (inducing this)
2) phagocytosis: antibodies acting as opsonin to facilitate phagocytosis of bacteria (usually IgG)
3: complement activation: to produce factors that destroy pathogens or increase activity of other components of inflammatory/adaptive immune response (IgM is the best for this one)
What are monoclonal antibodies?
antibodies that are produced in the lab from B cells that has been cloned so entire antibody is of the same class, specificity, and function (can be used for immunotherapies that is resistant to standard chemotherapy tx)
How does IgE protect from parasitic infections?
IgE is designed to specifically initiate an inflammatory response to attract eosinophils, this is done by:
1) parasitic antigens causing B cells to produce IgE
2) IgE binds to mast cell which degranulates and releases factors that attract eosinophil
3) eosinophil attaches to surface of parasite and releases potent lysosomal enzymes
What happens when IgE is produced against innocuous environmental antigens?
causes common allergies (this is the primary cause)
Systemic vs. secretory immune system
Systemic: made up of immunocompetent lymphocytes that migrate among secondary lymphoid organs and tissue
Secretory: immune system that protects external surfaces of the body through lacrimal and salivary glands and various lymphoid tissues (plasma cells in these sites secrete antibodies into bodily secretions to prevent them from infecting body’s surface and eventually causing systemic disease)
Immune responses to antigen has two phases. These are known as what?
primary and secondary immune response
How does primary immune response differ from secondary immune response?
primary:
- single initial exposure that leads to latent period/lag phase (this is where clonal selection is happening)
- IgM antibody is detected first followed by IgG, both against same antigen
- if no further exposure to antigen, antibodies catabolized but immune system is primed
Secondary:
- more rapid production of lots of antibodies because memory cells are all ready to go
- IgM transiently produced but IgG production is increased by lots making it dominant class of Ig during this phase
Endogenous antigens are recognized by:
Tc cells (adheres to antigen, induces target cell to undergo apoptosis)
What are NK cells?
group of lymphocytes that lack antigen-specific receptors but has other cell surface activation receptors to identify protein changes on cell surface when infected with virus/cancer
Antibody-dependent cellular cytotoxicity (ADCC) is known as what?
an immune mechanisms where Fc receptors on the antibodies allow for antigen to attach, followed by NK cells to attach and activate normal killing mechanisms
Newborns cannot produce all classes of antibodies. What antibodies are produced before and after birth?
- In utero: IgM (if utero infections are present) & lots of IgG but from mother
- After birth: newborn’s own IgG production begins and rises steadily through 1st year of life while maternal IgG is destroyed
What happens to our immune function and thymus as we age?
decreased immune function, T cell function, and reduced antibody responses to antigens
thymus also reaches max size at sexual maturity and then starts to shrink so less T cell function
(there is also decrease in thymic hormone production and organ’s ability to mediate T-cell differentiation)
Inappropriate responses or hypersensitivity reactions may include which of the following?
1) allergies
2) alloimmunity
3) autoimmunity
4) immune deficiency
5) all of the above
all of the above
What are hypersensitivity reactions?
altered immunologic responses to an antigen that results in disease or damage to the individual
How are hypersensitivity reactions classified?
Two ways:
1) by immunologic mechanism that causes disease (Types I-IV)
2) by source of antigen that immune system is attacking (allergy, autoimmunity, alloimmunity)
True or False. The mechanism that initiates onset of hypersensitivity reactions is unknown however likely a combination of genetic, infectious, and environmental agents
True
Type I hypersensitivity reaction is also known as ______. Describe the following for this reaction:
1) rate of development
2) class of antibody involved
3) principal effector cells involved
4) is complement involved?
5) example of this type of reaction
IgE-mediated reaction
1) immediate development
2) IgE
3) Mast cells
4) No
5) seasonal allergies, asthma
Type II hypersensitivity reaction is also known as ______. Describe the following for this reaction:
1) rate of development
2) class of antibody involved
3) principal effector cells involved
4) is complement involved?
5) example of this type of reaction
Tissue-specific reaction
1) immediate development
2) IgG, IgM
3) NK cells, macrophages, neutrophils
4) Frequently
5) Graves disease
Type III hypersensitivity reaction is also known as ______. Describe the following for this reaction:
1) rate of development
2) class of antibody involved
3) principal effector cells involved
4) is complement involved?
5) example of this type of reaction
Immune complex-mediated reaction
1) immediate development
2) IgG, IgM
3) neutrophils
4) Yes
5) SLE
Type IV hypersensitivity reaction is also known as ______. Describe the following for this reaction:
1) rate of development
2) class of antibody involved
3) principal effector cells involved
4) is complement involved?
5) example of this type of reaction
Cell-mediated reaction
1) delayed
2) none
3) lymphocytes, macrophages
4) no
5) contact sensitivity to poison ivy, metals (jewelry), latex
Immediate vs delayed hypersensitivity reactions
Immediate: occurs within minutes to few hours after exposure to antigen, generally caused by antibody
delayed: hours to appear (and max severity days after exposure), caused by cells (T cells, NK cells, macrophages
The most severe and immediate hypersensitivity reaction is:
anaphylaxis
Most common allergic reactions are which type of hypersensitivity reaction?
Type I (against environmental antigens)
What does sensitization mean? And what is the mechanism behind it?
Sensitization means your body recognizes what you’re allergic to
During first exposure:
1) APCs present antigen to B cells under direction of Th2
2) causes B cells to turn into plasma cells and secrete IgE
3) IgE binds to mast cell and when enough is bound, mast cell is sensitized
After sensitization occurs, what happens during re-exposure to an allergen (in type I hypersensitivity reactions)?
allergen connects with IgE and causes mast cell degranulation –> histamine is released causing local edema, smooth muscle contraction, mucous secretion, and other sx of acute inflammatory reaction
what happens when histamine binds to H1 receptors in the body?
bronchioconstriction
edema (increased vascular permeability)
vasodilation (increased blood flow)
what happens when histamine binds to H2 receptors in the body?
increased gastric acid secretion
Allergic reactions caused by food allergies (due to type I hypersensitivity) present with what symptoms?
nausea/vomiting
diarrehea
abdo pain
Most common food allergy in adults
shellfish
What happens to the skin during allergic reactions by type I hypersensitivity?
- urticaria (localized release of histamine and increased vascular permeability resulting in edema)
- wheal and flare reaction: wheals (white fluid blisters) and flares (redness) + pruritus
What happens to the mucous membranes in response to allergic reactions?
- conjunctivitis (inflammation of membrane lining eyelids)
- rhinitis (inflammation of mucous membranes of nose)
- asthma (bronchoconstriction)
What happens in the lungs in response to allergic reactions?
- bronchospasm (airways constrict)
- edema
- thick secretions
- leads to breathing insufficiencies/difficulties, wheezing
An individual is described as atopic, what does this mean?
those who are genetically predisposed to develop allergies (tend to have higher quantities of IgE and more Fc receptors for IgE on mast cells)
What tests/evaluations can be done to determine IgE hypersensitivity? How about treatment?
Dx:
- food challenges
- skin tests
- lab tests for total IgE and allergen-specific IgE
Tx:
- antihistamines to block histamine receptors
- block mediators to stop them from functioning (corticosteroids, leukotriene receptor inhibitor, PAF inhibitor)
What are type II hypersensitivity reactions?
aka tissue-specific hypersensitvity reactions and are generally immune reactions against a specific cell or tissue
what are tissue specific antigens?
antigens that are expressed on plasma membranes of only certain cells
There are 5 general mechanisms by which type II hypersensitivity reactions can affect cells. What are they?
1) antibodies activate complement which destroys cells
2) antibodies cause cell destruction via phagocytosis by macrophages (complement is activated by antibodies, an opsonin from complement is deposited on target cell -> increased phagocytosis)
3) neutrophil-mediated damage (molecules are released and bind to antibody, activates complement which makes chemotactic factors for neutrophils = tissue destroyed)
4) antibody-dependent cell-mediated cytotoxicity (ADCC) - antibodies on target cells are recognized by Fc receptors on NK cells, macrophages, or neutrophils and toxic substances are released that kill cell
5) target cell malfunction (Does not destory target cell but causes it to malfunction; antibodies change the function of the receptor on cell surface by blocking, stimulating, or destroying receptor)
What are type III hypersensitivity reactions?
aka immune complex-mediated hypersensitivity reactions
disease reactions caused by antigen-antibody (immune) complexes that are formed in circulation and deposited in vessel walls/other tissues
How do type III hypersensitivity reactions lead to tissue damage?
complement is activated, and neutrophils are trying to destroy the immune complexes but this means lots of lysosomal enzymes are released into inflammatory site instead of into phagolysosomes leading to tissue damage
What is the primary difference between Type II and III mechanisms for hypersensitivity reactions?
Type II: antibody binds to antigen on cell’s surface
Type III: antibody binds to soluble antigen that was released into blood or body fluids
Immune complex-mediated hypersensitivity reactions most commonly result in what disorders/symptoms?
vasculitis in skin, kidneys, and lungs
There are two model types/mechanisms that can describe various type III hypersensitivities. What are they?
Serum sickness
Arthus reaction
What happens in serum sickness?
reaction that happens due to immune complexes are formed in the blood and then depositied in target tissues
An example of serum sickness is Raynaud phenomenon. What is this?
condition caused by temperature-dependent deposition of immune complexes (cryoglobulins) in capillary beds of peripheral circulation
- precipitates at temps below normal body temp particularly in tips of fingers, toes, and nose
- ends up blocking circulation and cause localized pallor and numbness followed by cyanosis (can become gangrenous if circulation is not restored)
What happens in arthus reaction?
- reactions are cutaneous/localized
- deposition of immune complexes mainly in the vascular walls leading to vasculitis
- lesions are similar to typical inflammatory reaction (increased vascular permeability, accumulation of neutrophils, edema, hemorrhage, clotting, tissue damage)
What are type IV hypersensitivity reactions?
cell-mediated hypersensitivity reactions
reactions that are mediated by T lymphocytes and do not involve antibodies
- antigens stimulate T cells to attack cell target directly or recruit phagocytes to do it
Graft rejections, TB skin reactions, and allergic reactions from poison ivy and metals are what type of hypersensitivity reactions?
Type IV
What is the delayed hypersensitivity skin test?
testing for TB exposure
- slow onset
- TB antigen is injected into the dermis of someone who has latent/active TB
- if there is a reaction (induration - clear hard center that is indicated of macrophages and lymphocytes) and erythema, it is a +ve skin test result for TB infection
For type IV hypersensitivity reactions, what happens during first exposure vs re-exposure?
first contact: sensitization (produces reactive T-cells) but symptoms-wise, no rash/dermatitis
re-exposure: type IV cell-mediated reaction activated - dermatitis is present
Allergy (atopy) is defined as:
hypersensitivity to environmental antigens (medicines, natural products, infectious agents, and others that are not naturally found in the individual)
Define allergens
antigens that cause allergic responses
Bee stings cause type ___ hypersensitivity reaction.
I
A patient comes in with GI issues and throat tightness. On further evaluation, you obtain a low BP. What could this patient be suffering from and what is the treatment for such?
anaphylaxis
tx:
1) epinephrine - reverses bronchodilation effects (antihistamines are NOT effective here because they’re already bound)
2) potential clinical desensitization to allergens (small incremental doses over prolonged period)
Define autoimmunity
disturbance in the immunologic tolerance of self-antigens
True or false. everyone has autoantibodies (antibodies that are against our own antigens).
true. in small quantities that do not develop into autoimmune diseases
Autoimmune disease are more common in (men/women).
women
Define tolerance (in the context of immune control) and its relevance to autoimmune diseases.
Tolerance is the state of immunologic control so that individual does not make a detrimental immune response against his/her own cells and tissues
- in autoimmune diseases, there is a breakdown of tolerance
Symptoms of SLE result from a type III hypersensitivity reaction. What does this mean?
means that autoantibodies react with antigens and form immune complexes that are then deposited in the kidneys causing severe kidney inflammation
SLE tends to occur more in which individuals?
- women, especially 20-40 age group
- black individuals more than white individuals
- genetic predisposition (increased incidence in twins, familial hx with SLE)
What are the 11 most common clinical findings of individuals with SLE (i.e. symptoms)?
1) rash (on face/cheeks)
2) discoid rash (raised patches, scaling)
3) photosensitivity (skin rash from light)
4) oral/naso ulcers
5) non-erosive arthritis
6) serositis
7) renal dysfunction
8) neuro disorders
9) hematologic manifestations (anemia, leukopenia)
10) immunologic disorders
11) present of antinuclear antibodies (ANA)
Dx and Tx of lupus includes?
Dx: lab testing to show positive ANA screening on test and medical history
Tx: no cure but prevention/management of sx include:
- NSAIDs (for pain and inflammation)
- corticosteroids for active disease
- immunosuppressants
- antimalarial meds
- protection from sun exposure
What is alloimmunity?
immune response to non-self antigens from members of the same species (alloantigens/isoantigens)
occurs when immune system of one individual produces an immunologic reaction against tissues of another individual
Provide 3 examples of when alloimmune responses can occur.
1) transfusions
2) transplanted tissue
3) fetus during pregnancy
What are the two types of alloantigens?
1) blood group antigens
2) histocompatibility antigens (HLAs)
A and B blood group antigens are co-dominant. True or False.
True - both can be expressed at the same time
Universal donor is blood type ____.
Universal recipient is blood type ___.
donor: O
recipient: AB
The natural occuring blood group antibodies (i.e. anti-A antibodies, anti-B antibodies) are also known as:
isohemagglutinins
If blood types were inappropriate mixed, what would happen?
severe transfusion reaction - agglutination or complement-mediated lysis
The most important antigen of the Rh blood group is?
D antigen
Most people in North America are Rh (positive/negative).
positive (85%)
People who have D antigen are Rh_____.
positive
What is hemolytic disease of the newborn? What is the treatment?
disease caused by IgG anti-D alloantibody produced by Rh-negative mothers against RBCs of Rh positive fetuses (mom’s antibody crosses the placenta and destroys baby’s RBCs)
tx: RhoGAM shot
Why does transplant rejection occur?
because HLA antigens are different between donor and recipient, and the recipient is having an immune response against foreign HLA antigens on donor tissue leading to rejection
What occurs prior to any transplantation procedures to minimize tissue rejection?
tissue typing to identify differences in HLA antigens
Transplantation rejection can be classified as:
Hyperacute
Acute
Chronic
What is a hyperacute transplantation rejection? How do you avoid this?
Hyperacute: immediate and rare, rejection occurs due to presence of pre-existing antibodies (type II reaction) to HLA antigens on vascular endothelial cells in graft tissue
- usually found in those with previous hx of multiple blood transfusions/transplants
- white graft appears
- HOW TO AVOID: testing the recipient for pre-existing antibodies prior to transplant
What is an acute transplantation rejection? What is the tx for this?
cell-mediated immune response that occurs days to months after transplant & occurs when recipient develops an immune response against unmatched HLA antigens after transplantation (type IV reaction)
treatment: combo of corticosteroids and antirejection drugs that block adaptive immune function
What is a chronic transplantation rejection? What is the treatment for this?
occurs after months/years of normal function and characterized by slow, progressive organ failure
- usually from chronic inflammation and weak cell-mediated reaction (type IV) against minor histocompatability antigens on grafted tissue
- occurs in those who were poorly matched, have comorbidities, who received a damaged graft, or have required multiple acute rejection episodes
- treatment: few; possible graft replacement with new transplant
Define immune deficiency:
failure of immune or inflammatory response to function normally resulting in increased susceptibility to infections
primary/congenital vs secondary/acquired immune deficiency?
primary: caused by genetic defect
secondary: caused by another condition (cancer, infection, aging)
True or false. Primary/congenital immune deficiencies are far more common than acquired forms.
False. Acquired forms are far more common
What is the clinical hallmark sign of immune deficiency?
tendency to develop unusual/recurrent severe infections
In children, how do severe primary immune deficiencies present?
failure to thrive
If a patient indicates that they are experiencing reccurent infections with microorganisms that require opsonization, what deficiencies may be contributing to his immune deficiency?
B-cell/phagocyte deficiencies
Primary immune deficiencies are mostly a result of:
single gene defects (sporadic mutations, not inherited)
The three most commonly diagnosed primary immune deficiencies are:
1) common variable immune deficiency
2) selective IgA deficiency
3) IgG subclass deficiency
Combined deficiencies are resulting from defects of what part of the immune system?
development of both B and T lymphocytes
Severe combined immunodeficiencies (SCIDs) are the most severe kind of the combined deficiencies. It is characterized by what?
1) few detectable lymphocytes in circulation and 2’ lymphoid organs
2) underdeveloped thymus (due to absence of T cells)
3) absent or reduced IgM and IgA levels
Adenosine deaminase (ADA) deficiency is due to:
accumulation of toxic purines (classified under SCIDs)
What happens in Bare Lymphocyte Syndome?
- adequate B and T cells but defective cooperation
- lymphocytes and macrophages unable to produce MHC therefore antigen presenting and intercellular cooperation are not effectively occuring
- can result in life-threatening infections in children, usually die before 5 yo
What is Wiskott-Aldrich syndrome (WAS)?
X-linked recessive disorder (gene mutation) where IgM antibody production is ++depressed + major defect in platelet function
Clinically: bleeding secondary to thrombocytopenia (low blood platelet count), eczema, recurrent infections
What is DiGeorge syndrome? Include S/S and Tx.
- disorder due to gene deletion leading to lack/parial lack of thymus (thymic aplasia/hypoplasia) and thus greatly decreased T cell numbers and function
- parathyroid gland also absent so inability to regulate calcium concentration
- S/Sx: abnormal development of facial features (low set ears, fish shaped mouth, wide set eyes, shortened upper lip, underdeveloped chin)
- Tx: transplant of fetal thymus tissue or thymic epithelial cells but this is only temporary improvement.
Which category of primary immune deficiencies is the most common?
Predominantly antibody deficiencies
Predominantly antibody deficiencies result from what? It can lead to what conditions?
defects in B-cell maturaiton or function
- can lead to hypogammaglobulinemia (low levels of circulating Ig) or agammaglobulinemia (totally or near absent Ig)
Treatment for B-cell immune deficiencies that lead to hypo/agammaglobulinemia includes:
IV Ig administration (antibody-rich) which replaces individual’s antibodies temporarily so continuous treatment is needed
What is selective IgA deficiency? Include S/S.
when class switch to IgA does not occur
- mostly asymptomatic but with recurring sinus, pulmonary, and GI infections; + chronic intestinal candidiasis
- may lead to allergens/diseases worsening due to secretory IgAs not doing what they normally do in bodily secretions
What is Bruton agammaglobulinemia? Include S/S
X-linked agammaglobulinemia caused by blocked development of mature B cells in bone marrow (so there are few/none circulating)
- S/Sx: repeated bacterial infections (strep throat, septicemia, conjunctivitis, middle ear infection)
What is chronic granulomatous disease (CGD)? Include S/S.
Severe defect in oxidant manufacturing system that is needed for bacterial destruction in phagocytic killing
- S/S: recurrent pneumonias
- tumour-like granulomata in lungs, skin, bones
- infections with opportunistic microorganisms
What is Chronic mucocutaneous candidiasis? What are S/S and Tx?
disease caused by ineffective interaction between Th17 lymphocytes and macrophages so macrophages cannot be activated
S/S: recurrent candida infections in mucous membranes and skin
Tx: transplant of fetal thymus tissue/thymic epithelial cells (only temp improvement)
What is C3 deficiency?
A complement immune deficiency leading to complement cascade not being activated
Results in life-threatening infections with encapsulated bacteria (influenza, pneumonia)
What is mannose-binding lectin (MBL) deficiency?
A complement immune deficiency with primary defect in lectin pathway of complement activation
- results in increased risk of infection with microorganisms that have mannose-rich capsules
Evaluation of Primary Immune Deficiencies include:
- complete blood count (CBC) with differential
- quantitative determination of Ig (IgG, IgM, IgA)
- assay of total complement
Treatment for primary immune deficiencies include:
- replacement therapy (i.e. replacing the missing component of the immune system)
- gene therapy (long term replacement of specific immune factors)
- bone marrow transplant (for SCID)
Treatment for SCID presents a risk of graft-versus-host disease (GVHD). What does this mean?
complication to transplant. occurs when T cells in transplanted graft are mature and therefore capable of cell-mediated immunity against recipient’s HLA
- this can be diminished by removing mature T cells from tissue used to treat individuals with immune deficiences
Three of the more severe secondary/acquired immune deficiencies include:
1) malignancies
2) immunosupressive treatment
3) AIDS
How are malignancies related to immune deficiency?
- disease itself or tx of malignancies can cause immunosuppression
- cancer cells are also able to protect themselves by suppressing T lymphocytes
What is acquired immunodeficiency syndrome (AIDS)?
acquired immunodeficiency that develops in response to viral infection (HIV)
- it is the most advanced stage of HIV infection
How does HIV affect immune system?
HIV infects and destroys CD4+ Th cells which are needed for development of B cells and T cells which means it destroys the cells that regulate normal immune response
How can HIV be transmitted?
blood borne so via blood products, IV drug use, sex, maternal-child transmission
The most common route to be affected by HIV is _______ and (women/men) make up majority of those with HIV/AIDS.
heterosexual activity; women
The primary target cell of HIV is:
helper T cells
What are the viral enzymes involved in HIV infecting host cell?
1) reverse transcriptase - converts RNA into DNA
2) integrase - helps new DNA insert into infected cells’ genetic material
3) protease: processes the genetic material to make a new virion core
When a new virion is released from host cell, how does it make itself less vulnerable to adaptive immune attack?
takes some of the host cell membrane with it
Treatment for HIV/AIDS?
Antiretroviral therapy
At time of dx of AIDS/HIV infection, how may the patient present?
1) serologically negative (no detectable antibody)
2) serologically positive (positive for antibody against HIV proteins)
3) early stages of HIV disease
4) AIDS
What is the window period?
The period between infection and appearance of antibody against HIV proteins
Acute HIV syndrome occurs when?
weeks after infection (virus at this time is progressively infecting T cells and other cells and spreads to lymphoid organs) - sharp decrease in number of circulating CD4+ T cells
When does clinical latency of HIV infection/AIDS occur? What is happening during this time period
between ~9 weeks to 7/8 years
- person is asymptomatic but virus replicates and T cell destruction continues
Average time between HIV infection and development of AIDS is:
just over 10 years
Who is recommended to be screened for HIV infection?
- ages 13-64 who have been informed to do so
- men x men
- pregnant women
- those with STDs or TB
Early stages of HIV disease mimic those of:
influenza (headaches, fever, fatigue)
How does HIV infection differ in children compared to adults?
- more aggressive infection
- neuro invovlement (failure to obtain developmental milestones, loss of intellectual ability, motor deficits, impaired brain growth, brain atrophy)
Define endemic disease
A disease that is consistently present in a certain geographical location (high but constant rates of infection in a particular population)
Define: Symbiosis
benefits only human, no harm to microorganism
Define mutualism
benefits both human and microorganism
Define commensalism
benefits only microorganisms, no harm to human
Define pathogenic relationship
benefits microorganisms, harms human
Define opportunism
where benign microorganisms become pathogenic because of decreased human host resistance
Direct transmission of infection can include:
1) vertical transmission (ex. mother to child)
2) horizontal transmission (one person to another through blood/bodily fluids)
3) zoonotic infections: from animals
Indirect transmission of infection can include:
1) coming in contact with infected materials
2) inhalation/droplet infection
3) ingestion/contamination of food/water
4) vaccination
Define colonization
ability of pathogenic microorganism to survive and multiply on/within human environment
- chances increase with making biofilms and increased adherence
Define dissemination
spread of infection by direction extension through surrounding tissue or through blood/lymphatic vessels
Define communicability
ability to spread from one individual to another and cause disease
Define immunogenicity
ability to induce an immune response
Define infectivity:
ability to invade and multiply in host
Define pathogenicity
ability to produce disease (depends on communicability, infectivity, extent of tissue damage, and virulence)
Define toxigenicity
ability to produce soluble toxins/endotoxins (toxic byproducts)
- greatly influences degree of virulence
Define virulence
capacity to cause severe disease
Define epidemic
number of new infections in a particular population greatly exceeds the number usually observed
Define pandemic:
epidemic that spreads over large area (continent/worldwide)
What are the four stages of infection?
1) incubation period: between initial exposure and onset of first symptoms
2) prodromal stage: when first sx occur (often mild, general malaise)
3) invasion/acute illness period: rapid multiplying of pathogens here, patient is symptomatic and immune/inflammatory responses are triggered
4) convalescence: immune system does its job to remove infectious agents; sx decline, may be fatal, or enter latency phase
Describe structure/composition of bacteria
- prokaryotes (no nucleus)
- small
- aerobic or anaerobic
- motile or immotile
Three types of bacteria, categorized by structure
cocci - spherical bacteria
bacilli - rod-like forms
spirochetes - spiral forms
Gram-negative vs. gram-positive bacteria
difference is in structure of their bacterial cell wall (both have inner cell membrane but gram- negative has outer memebrane as well that stops antibiotics from penetrating the cell)
What are the 5 virulence factors that help bacteria cause infection?
1) pili (fimbria) - hair like projections that increase attachment and adhesion to cells and invade tissue
2) flagella: mobility and expresses adhesion molecules
3) capsules: outer covering resists host immunity and prevents phagocytosis
4) enzymes: promote tissue invasion
5) toxins
What effect does botulinum toxin have?
neurotoxic protein produced by bacteria Clostridium botulinum that prevents release of neurotransmitter acetylcholine from axon endings at the NMJ and thus causes flaccid paralysis
Bacteremia vs septicemia
Bacteremia: occurs when bacteria are present in the blood
Sepsis/Septicemia: occurs when bacteria are growing in blood and release large amounts of toxins (growth)
what bacteria is the major cause of nosocomial infection?
Staphylococcus aureus (opportunistic)
What are viruses?
obligatory intracellualr microbes that have nucleic acid protected by capsid
What are the 5 modes of transmission for viruses?
1) aerosal (respiratory tract fluids)
2) infected blood
3) sexual contact
4) vector
5) zoonotic infection
What is the viral life cycle?
1) attachement - to target cell
2) penetration - entrance via endocytosis/membrane fusion
3) uncoating - release of viral nucleid acid
4) replication - synthesis of viral proteins and mRNA (injected material into host)
5) assembly - new virions formed
6) release - existing of new virions by lysis or budding of cell
Define antigenic variation
viruses making small changes to genes that produce viral surface antigens to escape immune defenses
antigenic drift vs antigenic shift
antigenic drift: minor changes where it results in combination of two different strains of a virus making a new virus (but we have partial protection)
antigenic shift: major changes where two or more different viruses combine to form a new strain
Influenza is transmitted by what routes?
aerosols, body fluids (highly infectious)
Symptoms between ____ days after infection and include what?
1-4 days
- chills, fever, sore throat, muscle aches, severe headaches, coughing, weakness, generalized discomfort, nausea, comiting, potential pneumonia
Describe the structure of fungi
- relatively large eurkaryotes (have nucleus) with thick, multilayered walls of polysaccharides
- reproduction by simple division or budding
What are the two basic structures of fungi?
1) single celled yeasts (spheres)
2) multicellualr molds (filaments, hyphae)
dimorphic fungi ar those that can exist in either form^
Infections cause by fungi are known as
mycoses
Fungi that invade skin, hair, and nails to digest keratin are known as
dematophytes
The most common fungal infection in humans is
C albicans
What are parasitic microorganisms?
microorganisms that establish a relationship in which parasites benefit at the expense of other species
What are the modes of transmission for parasitic infections?
human to human via vectors and ingestion
Most common parasite worldwide?
malaria
Some antibiotics are bactericidal while others are bacteriostatic. What do these terms mean?
bactericidal: kill microorganisms
bacteriostatic: inhibit growth until microorganism is destroyed by individual’s own protective mechanism)
What are the 4 main mechanisms of action of most antibiotics?
1) inhibition of function or production of cell wall/membrane
2) prevention of protein synthesis
3) blockage of DNA replication
4) interference with folic acid metabolism
How can microbes resist/inactivate antibiotics?
- make resistance genes and spread them to to other generations of microbes
- degrade or alter antibiotics
- eject antibiotics from the cell
- modify cell wall to prevent antibiotic binding or uptake
- modification of cellular target of antibiotic
What species cause septic shock and multiple organ failure?
- endotoxins (aka lipopolysaccharide or LPS) from gram-ve bacteria
- exotoxins from gram+ve bacteria
(because they activate complement and clotting systems which lead to overproduction of various cytokines that cause fever platelet activation, intravascular coagulation and increased vascular permeability = hypotension, shock, organ failure)
What happens during gram-ve sepsis/septicemia?
when bacteria are growing in the blood and release large amounts of endotoxins leading to endotoxic shock
Staphylococcus aureus are (gram-ve/gram+ve) bacteria that are (cocci/bacilli/spirochetes).
gram+ve cocci
How can Staphylococcus aureus be transmitted?
- direct skin contact
- indirect contact with shared items/contaminated surfaces
*it is a common inhabitant on normal skin and nasal passages, is opportunistic, secretes exotoxins
Staphylococcus aureus is known to be antibiotic resistant (penicillin). How does this occur?
production of beta-lactamase which is an enzyme that destroys peniciilin
Staphylococcus aureus resistance of methicillin leads to what?
MRSA (superbug that leads to resistance)
The ability of pathogens to cross surface barriers is known as:
invasion/penetration
Which microorganism is involved with urinary tract infection?
Neisseria gonorrhoea
How does bacteria survive in extracellular environments?
use virulence mechanisms to proliferate in body fluids (induces formation of humoral antibodies due to extracellular bacterial antigens)
How does bacteria survive in intracellular environments?
can enter and survie in cells where they evade humoral antibodies and can disrupt cell structure and function; can only be eliminated by a cellular immune response
Function of exotoxins
directly injure cells by damaging cell membranes or by entering cells and changing their function - causes production of antitoxins (antibodies)
The most poisonous exotoxin is
botulinum neurotoxin (from Clostridium botulinum) whih is used in botox
H1N1 swine flu is an example of an antigenic ______.
shift
Influenza virus expresses two surface proteins that are essential to virulence. What are they?
HA - hemagglutinin (glycoprotein necessary for entrance into ell receptors on respiratory tract epithelium)
NA - neuraminidase (enyme that releases new virions from infected cells)
Without a major shift occurring, influenza is usually considered (epidemic/endemic/pandemic).
epidemic
Please identify the following conditions:
1) dermatophytes affecting the scalp
2) dermatophytes affecting the feet
3) dermatophytes affecting the grown
1) tinea capitis
2) tinea pedis (athlete’s foot)
3) tinea cruris (jock itch)
A patient has an infection caused by his indewlling catheter and IV lines. The microorganism most responsible for this infection is:
a) Toxoplasma gondil
b) Candida albicans
c) Plasmodium falciparum
d) none of the above
b) Candida albicans - fungal infection (easy access straight ito the bloodstream(
What can disseminated candidiasis look like in a patient
- abscesses in organs (because deep infections of internal organs)
- persistent/recurrent fever
- gram-ve like symptoms (hypotension, tachycardia)
- disseminated intravascular coagulation (DIC) - blood clotting disorder
The most common parasitic infections in the US are:
- Toxoplasma gondil (lifelong infection that may cause blindness, miscarriage, and CNS abscesses)
- Trichomonas vaginalis (common sexually transmitted infection)
What are antibiotics?
natural products of fungi, bacteria, and related microorganisms that affect growth of other microorganisms (used to prevent spread of infection)
How can overuse of antibiotics lead to Superbugs?
Overuse of antibiotics lead to destruction of normal microbiome which lead to selective overgrowth of antibiotic-resistant strains/pathogens can occur (aka Superbugs)
What method results in the strongest resistance against future infections from the same microbe?
Recovery from infection (so actually getting it and then recovering from it)
What are vaccines?
biological preparations of antigens that stimulate production of protective antibodies or cellular immunity against a specific pathogen without causing potentially life-threatening disease
What is the purpose of booster vaccines?
Primary immune response to a vaccine is usually short lived so booster shots help push the immune system through multiple secondary responses that result in large numbers of memory cells and sustained protective levels of antibody/T cells
What are toxoids? What is their clinical significance?
- purified exotoxins that have been chemically detoxified without loss of immunogenicity
- Clinical significance: Vaccination against systemic exotoxins (i.e. diphtheria, tetanus, pertussis) has been achieved using toxoids
Vaccines for rabies, hep A and hep B are examples of (passive/active) immunity
passive
*with rabies, you get one shot of Ig (passive immunity) and then multiple shots of active immunization (killed viral vaccine)
