Intro to Pathophysiology Flashcards
1st Line of Defense
physical, mechanical and biochemical barriers
- skin and low temperature
- linings of the GI, genitourinary and respiratory tracts
Two Biochemical Barriers
- Epithelial-Derived Chemicals
- antimicrobial peptides (AMPs): cathelicidins, defensins and collectins - Bacteria-Derived Chemicals
- normal bacterial flora
- inhibit colonization by pathogens
2nd Line of Defense
inflammatory response
- non-specific
- intensity depends on the extent/severity of the injury and reactive capacity of the patient
- vascular and cellular response
What causes 2nd Line of Defense?
Infection Mechanical damage Ischemia Nutrient deprivation Temperature extremes Radiation
What is the goal of the inflammatory response?
a. neutralizes/dilutes the inflammatory agent
b. remove necrotic material
c. establish an environment for healing
Manifestations of Inflammation
a. erythema - hyperemia from vasodilation
b. heat - increased metabolism
c. pain - changes in pH, nerve stimulation by chemical mediators, fluid change
d. swelling - fluid shift, accumulation of exudate
e. loss of function - due to swelling and pain
Vascular Response
Transient Vasoconstriction
- lasts only a few seconds
»
Fibrin clot, release of chemical mediators
- seal off injured area, control inflammatory process
»
Local vasodilation and hyperemia
- increase permeability, facilitate movement of WBC, fluids and nutrients
Cellular Response
Chemotaxis, margination and diapedesis of blood leukocytes >> Migration of leukocytes to the site of injury >> Neutrophils - 6-12 hours, forming pus when it dies Monocytes >> Macrophages - 3-7 days >> Phagocytosis
Chemotaxis
movement of a cell or organism in response to chemical stimulus, along gradient of concentration
Margination
leukocytes get close to the vessel
Diapedesis
leukocytes enter into the vessel
Types of Leukocytes
Neutrophils: phagocytosis of foreign material
Monocytes: mature into macrophages
Eosinophils: kill parasites
Basophils: secrete chemical mediators
(Nice Monkeys Eat Bananas)
What is the order of leukocytes from greatest to least in quantity?
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
(Nobody Likes My Emotional Breakdown)
What is a chemical mediator?
Any messenger that acts on blood vessels, inflammatory cells or other cells to contribute to any inflammatory response
Histamine
chemical mediator stored in granules of basophils, mast cells, platelets
What is the mechanism of action of histamine?
causes vasodilation and increased vascular permeability
Kinins
i.e. bradykinin
chemical mediators that arise from polypeptides that circulate in the blood in inactive form (Kininogens)
What is the mechanism of action of Kinins?
cause contraction of smooth muscle and dilation of blood vessels»_space; pain
Complement component
C3a, C4a, C5a
anaphylatoxic agents generated from complement pathway activation
What is the mechanism of action for complement components?
stimulate histamine release and chemotaxis
Prostaglandins and leukotrienes
chemical mediators produced from arachidonic acid
What is the mechanism of action of prostaglandins?
contribute to vasodilation, capillary permeability, pain and fever
leukotriene B4 stimulates chemotaxis
Cytokines
i.e. interferon, interleukin and growth factors
chemical mediator secreted by various cells of the immune system
3rd Line of Defense
Adaptive Immune System
- works together with inflammation
- recognizes foreign substances
- has memory to provide long-term protection
- specific response, occurs slowly
- can be induced by vaccination
Antigen
a molecule that can react with antibodies or receptors on B and T cells
i.e. common flu virus
Immunogenic antigen
an antigen that can trigger an immune response
Immunogenicity
the ability of a particular substance to provoke an immune response
Antibody
protein made specifically against an antigen, aka immunoglobulin
3 Phases of the Adaptive Immune System
- Recognition phase: antigen recognition by B and T cells
- Activation phase: lymphocyte activation»_space; proliferation and differentiation
- Effector phase: elimination of specific antigen
Humoral (antibody-mediated) Immunity
= causes direct inactivation of a microorganism or the activation of inflammatory mediators
= protects against extracellular microbes and microbial toxins
- Bone marrow produces lymphoid stem cell
- Lymphoid stem cell matures in bone marrow and become immunocompetent B-lymphocyte
- Travels and circulates lymph nodes
- During phagocytosis (phagocytes from innate immune system), B-lymphocytes keep a bit of antigen as marker
- Helper T activates B cells, memory B cells and plasma cells are produced
Memory B cells
- formed following a primary infection
- can generate an accelerated and robust antibody-mediated immune response in case of re-infection (secondary immune response)
Plasma cells
factories that produce antibodies that bind to specific antigen
What do antibodies do?
Direct:
a. neutralization: bind to antigen so that they can’t hook up to tissue
b. agglutination: clumping antigens together to slow them down
Indirect:
a. opsonization: marking antigen as foreign for killer cells to come and destroy them
IgG
- most prevalent
- most of protective activity against infection
- crosses the placenta and blood-brain barrier
IgA
- mostly in secretions
- most of protective activity in body secretions
IgE
- most rare
- mediator of many common allergic responses
- defends against parasitic infections
- release histamine molecules when receptor side binds to antigen
IgD
- not well known
- functions as one type of B-cell antigen receptor
IgM
- largest
- first antibody produced during the initial or primary response to an antigen
Primary and Secondary Immune Response
Primary
- occurs during initial exposure
- IgM antibody for a specific antigen is detected and IgG are produced
Secondary
- more rapid than the primary response due to memory cells
- large amount of IgG are produced, similar quantities of IgM
Cell-mediated immunity
= T-cell differentiation, kills target directly or stimulates activity of other leukocytes
= protects against intracellular pathogens
- Bone marrow produces lymphoid stem cell
- Lymphoid stem cell matures in thymus and becomes immunocompetent T cell
- Travels to spleen
- Naive T cells find infected macrophages that are displaying the antigen-MHC complex
- Helper T activates cytotoxic T lymphocytes, T-regulatory cells and memory T cells
Cytotoxic T lymphocytes
killer T cells
- attack and kill targets directly, trigger apoptosis
- carry cell-surface marker molecules
Helper T cells
- essential role in antibody production, activates B cells telling them which antibodies to produce
- participate in activation of cytotoxic T cells
- activated helper T cells secrete cytokines that influence the functions of nearly all other immune cells
Memory T cells
- subset of antigen specific T cells that persist long after an infection has resolves
- reproduce to large numbers of effector T cells upon re-exposure
Clonal Diversity
production of T and B cells, in the bone marrow, with all possible receptors for antigen
Clonal Selection
selection, proliferation and differentiation of individual T and B cells with receptors for a specific antigen
Primary lymphoid organs
Thymus (T cells) Bone marrow (B cells)
Secondary lymphoid organs
Spleen (T) Lymph nodes (B)
Active Acquired Immunity
antibodies or T cells are produced after either a natural exposure to an antigen or after immunization, long lived
Passive Acquired Immunity
performed antibodies or T lymphocytes are transferred from a donor to a recipient, occurs naturally or artificially, temporary or short-lived
