Inflammation Flashcards
What is a vital reaction
Only happens in living tissue
Ex: Inflammation
5 cardinal signs of inflammation
- Calor (heat)
- Rubor (redness)
- Tumor (swelling)
- Dolor (pain)
- Functio laesa (disturbed function)
4 major categories of changes in inflammation
Circulatory
Vascular
Humoral
Cellular
Circulatory changes
First response to injury is change in blood flow
Increased blood flow to capillaries = redness, swelling, warmth
Inflammatory edema leaks from capillaries and venules due to increased pressure
Hyperemia definition
Increased blood flow
Rouleax
More than 4 red blood cells stacked together
Go to the middle of the flow and slow it
Due to proteins covering the negative charges so they can stick together
3 steps in pathogenesis of inflammation
- Margination of neutrophils
- Adhesion of platelets
- Pavementing of neutrophils
Vascular changes
Increased permeability (caused by 4 things)
4 things that cause increased permeability
Increased hydrostatic pressure
Slowed circulation
Leukocyte and platelet adhesion to endothelial cells
Soluble mediators
2 classes of inflammatory mediators and what defines them
- Plasma derived (need to be activated)
2. Cell-derived (pre-fromed, formed de novo, or may need to be activated)
Histamine
Releases from platelets and mast cells
Stimulates contraction of endothelial cells
Inactivated by histaminase, so is an immediate transient reaction
Enzyme that inactivates histamine
Histaminase
Bradykinin
Works like histamine but slower
Also causes pain
2 complement proteins that are anaphylatoxins
C3a
C5a
Arachadonic acid
Part of cell membranes
Has to be acted on by enzymes to do anything
2 paths that arachadonic acid can enter
- Lipoxygenase pathway
2. Cyclooxygenase pathway
Lipoxygenase pathway
Makes leukotrienes and lipoxins
Leukotrienes
Promote chemotaxis and increase vascular permeability
Cause contraction of smooth muscle (bronchospasm)
Allergy and anaphylaxis
Lipoxins
Negative regulators
Counteract the effects of leukotrienes
Cyclooxygenase pathway
Makes thromboxanes, prostaglandins, and prostacyclins
Thromboxanes
Promote platelet aggregation and vasoconstriction
Prostaglandins
Cause vasodilation and increased permeability
Pain and fever
Prostacyclin
Negative regulator
Counteracts effects of thromboxanes and prostaglandins
Transudation
Leakage of fluid into interstitial space
Transudate
Fluid that leaks out of leaky vessels at site of inflammation
Has lots of proteins and few blood cells
Exdate
Formed by emigration of cells across vascular walls
More protein that transudate
Contains inflammatory cells
Neutrophils
Also called polymorphonuclear cells Most abundant WBC Involved in acute inflammation Mobile, phagocytic, acute mediator, involved in pain Short life spane
Monocyte
Big phagocytic cell
Turns into macrophage in tissue
Eosinophils
Involved in chronic inflammation (last longer in blood)
Allergies and parasitic infections
Basophils
Contain similar molecules to eosinophils
Store and release histamine
IgE mediated allergies
Works similarly to mast cells but in blood
Lymphocytes
B, T, NK cells
Involved in cellular immunityy
Platelets
Fragments of megakaryocytes
No nucleus
Granules with mediators
Form primary plug in clotting
4 ways to classify inflammation
Duration
Etiology
Location
Morphology/pathological characteristics
Acute versus chronic inflammation
Acute: sudden onset, duration of hours to days
Chronic: duration of weeks to years
Primary versus secondary chronic inflammation
Primary: no acute phase
Secondary: follows an acute phase (usually this way)
Serous inflammation
Mild inflammation
Exudation of serum (liquid part of blood, lots of proteins)
Typical of many viral infections
Can also be found in autoimmune diseases affecting the serosa
Joint swelling can be due to physical trauma
Blisters can be due to thermal injury
Serous fluid is usually reabsorbed and lesions heal without permanent consequences
Fibrinous inflammation
Exudate is rich in fibrin (large protein)
Causes larger defects - severe inflammation!
Ex: strep throat, bacterial pneumonia, bacterial pericarditis
Resolution, not reabsorption. Requires reorganization (new blood vessels, ingrowth of fibroblasts, obliteration of tissue space)
Purulent inflammation
Involves formation of pus
Also rich in fibrin (fibropurulent)
Pus can accumulate on or within tissue/organ
Pus
A viscous yellow fluid
Made of dead/dying neutrophils and necrotic tissue
2 genera of pus forming bacteria
Streptococci
Staphylococci
Sinus definition
When an abscess in a solid tissue comes into contact (communicates) with open air
Fistula defintion
A hollow space comes into contact with another hollow organ or the outside air
Ex: bladder to colon, or colon to air
Empyema definition
Accumulation of pus in a preformed cavity
Ex: pleural cavity, gallbladder, etc
Ulcerative inflammation
Ulceration is the loss of epithelial lining of a body surface or mucosa
Ulcers may extend into deeper connective tissue
Pseudomembranous inflammation
Ulcerative inflammation combined with fibropurulent exudation
Exudate forms a pseudomembrane on the surface of ulcers
If pseudomembrane is scraped away, ulcer can bleed badly
C dificile can cause this, or diptheria
Chronic inflammation
Defined by duration
Exudate contains lymphocytes, macrophages, plasma cells
Stimulate fibroblast proliferation, recruit new inflammatory cells
Loss of parenchymal cells and scarring occurs
Scarring may affect tissue/organ function
Granulomatous inflammation
Granulomas are destructive accumulations of cells that form nodules (of lymphocutes, epithelioid cells, and multinucleated giant cells)
T cells accumulate and secrete cytokines, which attract macrophages
Infectious granulomas - caseous necrosis
Caseous necrosis
In the center of the granuloma the tissue dies
Looks kind of cottage cheese
4 branches of the innate immune system
Mechanical (barriers like the skin, pH differences in our body, mucus in linings) Phagocytosis (monocytes, macrophages, neutrophils – can recognize complement opsonized pathogens) NK cells (don’t need to see antigen – always ready to kill a cell – if a cell is expressing enough self proteins then they won’t kill) Protective proteins (have a lot of functions)
3 main mechanisms the innate immune system protects us through
Inflammation
Combating viral infections
Mounting a general response to damaged cell products
Antigen versus immunogen
Antigen: any substance that binds specifically to antigen receptors
Immunogen: any substance that elicits an immune response
Antigen-antibody complexes bind and activate complement which does… (3 things)
Lysis of cells
Agglutination
Recruitment of inflammatory cells
Functions of:
IgM
(2)
Complement fixation
Neutralization
Functions of:
IgG
(3)
Opsonization
Can fix complement
Transported across placenta
Functions of:
IgA
(2)
Found in body secretions and at mucosal sites
Neutralization
Functions of:
IgE
IgD
(1 each)
E: Allergy
D: Activation of B cells
What are the 4 hypersensitivity reactions?
Type I: Anaphylactic or atopic reaction
Type II: Cytotoxic antibody-mediated reaction
Type III: Immune complex-mediated reaction
Type IV: Cell-mediated or delayed type reaction
Type 1 hypersensitivity
Anaphylactic or atopic reaction
Mediated by IgE and mast cells or basophils
Examples: hay fever, atopic dermatitis, bronchial asthma, anaphylactic shock
Type 2 hypersensitivity
Cytotoxic antibody-mediated reaction
Ex: erythroblastosis fetalis, transfusion reactions, Graves disease, Goodpasture syndrome, Myasthenia gravis
Graves’ disease
Type 2 hypersensitivity
Hyperthyroidism caused by autoantibodies to the TSH receptor on follicular cells of the thyroid
Antibodies cause overproduction of thyroid hormones
Myasthenia Gravis
Type 2 hypersensitivity
Antibodies to receptors for acetylcholine on surface of striated muscle cells
Muscle contraction is blocked
Progressive muscle weakness and paralysis
Goodpasture’s syndrome
Type 2 hypersensitivity
Antibodies to collagen type IV activate complement and attract neutrophils that contribute to the damage and rupture the glomerular basement membrane
In the kidney
Type 3 hypersensitivity
Immune complex-mediated
Systemic: immune complexes are in circulation
Local: immune complexes are formed in tissue
Examples: serum sickness, systemic lupus erythematosus, post-strep GN, polyarteritis nodosa
Serum sickness
Type 3 hypersensitivity
Immune complexes form during antigen excess, and are deposited in tissue
Tissue legions caused by activated complement and leukocytes attracted to immune complexes
Systemic lupus erythematosus
Type 3 hypersensitivity
Immune complexes formed of antibodies and autoantigens
Deposited in tissues, causing kidney disease, arthritis, skin disease, etc
Post-streptococcal glomerulonephritis
Type 3 hypersensitivity
Acute kidney disease after strep throat
Antibodies react with soluble streptococcal antibodies “planted” onto glomerular basement membranes during filtration
Or, form immune complexes in circulation and deposit in in glomerular basement membrane
Complement-mediated inflammatory response
Polyarteritis nodosa
Type 3 hypersensitivity
Antigen-antibody complexes precipitate, usually in vessel wall
Complement is activated, which attracts white blood cells
Localized acute inflammatory response occurs, characterized by fibrinoid necrosis of the vessel wall
Damaged vessels tend to thrombose and become occluded, causing tissue ischemia and infarcts
Type 4 hypersensitivity
Cell-mediated or Delayed type
Involves T cells and macrophages, which typically form granulomas at the site of injury
Antigen is taken up by macrophages and presented to T cells, which become activated and produce IFN-γ
Infections (M. tuberculosis, M. leprae, fungi), tumors, idiopathic (e.g., sarcoidosis)
IFN-gamma
Recruits more macrophages, turns them into epithelioid macrophages, activates them, makes them fuse into giant multinucleated cells
Definitions:
Autograft
Allograft
Xenograft
Grafted tissue comes from the recipient
Grafted tissue comes from someone else
Grafted tissue comes from another species
