Classes 3-4 Flashcards
What are the possible outcomes of chronic inflammation?
Tissue destruction, fibrosis
When does acute inflammation usually stop?
When injurious stimulus is removed, walled off, or broken down.
Outcomes: resolution, abscess formation, chronic inflammation.
What are the 7 morphotypes of inflammation?
Serous Fibrinous Purulent Ulcerative Pseudo membranous Chronic Granulomatous
Serous inflammation
Mildest form of inflammation
Characterized by clear fluid
Occurs in early stage; typical in viral infections, burns, arthritis
Exudate mostly albumin and immunoglobulin
Self limiting
Generally resolves easily.
Fibrinous inflammation
Exudate rich in fibrin
Bacterial infections (strep throat, bacterial pneumonia, bacterial pericarditis).
Does not resolve easily. Often requires antibiotics.
Leads to growth of fibrous tissue (scarring) in parenchyma –> loss of function.
Purulent inflammation
Typically formed by pus-forming bacteria. (Staph and strep)can accumulate on mucosa or in internal organs. May form abscess.
Abscess
Localized collection of pus within an organ or tissue
Does not heal spontaneously; must be surgically excised.
May lead to fistula or sinus.
Sinus
Cavity, usually occupied previously by an abscess that has ruptured, that drains through a tract to the surface of the body.
Fistula
A channel between preexisting cavities and/or hollow organs and/or surface of the body.
Empyema
Accumulation of pus in a preformed cavity (ex. gallbladder)
Ulcerative Inflammation
Inflammation do body surfaces or mucosa.
Leads to ulceration or necrosis of epithelial lining.
Ulcer
Defect involving the epithelium, which can also extend into connective tissue.
Pseudomembranous inflammation
Combination of ulcerative, fibrinous and purulent inflammation.
Ulcerative with fibronopurulent exudate (with mucus and cellular debris) which forms a pseudomembrane on surface of ulcer.
Diphtheria (pseudomembranes form on throat); C. Difficile in large intestines (secondary to antibiotic use)
Chronic inflammation
Because of length of inflammation, produces more tissue destruction, heals less readily and associated with more serious functional deficiencies.
Exudate contains monocytes, lymphocytes, macrophages, plasma cells.
Secretory products stimulate proliferation of fibroblasts (–> scarring –> loss of function) and recruit new inflammatory cells (perpetuating inflammation)
Sm
Granulomatous inflammation
Not preceded by acute inflammation.
Not neutrophil driven.
T-lymphocytes and macrophages accumulate at site of injury.
Lymphocytes release cytokines, which transform macrophages into epithelioid cells.
Epithelial cells fuse with each other and form multinucleated giant cells.
Multinucleated giant cells, epithelium cells and lymphocytes form granulomas, which destroy cells and last long time.
Caseous and non caseous
TB, fungal infections, syphillis.
Clinical correlations of inflammation
Fever 37 degrees +
Leukocytosis
Constitutional symptoms (fatigue, weakness, depression)
What causes fever?
Pyrogenes cytokines (Tumour Necrosis Factor -- TNF -- and IL-1) -- stimulate production of prostaglandins in hypothalamus
Cell categories based on ability to proliferate
- Continuously dividing/labile/mitotic
- Quiescent/facultative mitotic/stable
- Non-dividing/post-mitotic/permanent
Continuously Dividing Cell
Labile, mitotic, stem cells
Typically found in basal layer of skin or mucosa of internal organs.
Outcome: minimal tissue damage, short recovery time
Quiescent Cells
Facultative mitotic, stable
Do not divide regularly but can be stimulated to divide if necessary.
Form the parenchymal organs. (Eg liver, kidneys).
Outcome: regeneration, although may be limited.
Non-dividing Cells
Post-mitotic, permanent.
No capacity to divide period. Ex: neurons.
Outcome: replacement of parenchymal tissue with connective tissue leads to loss of function.
Healing by First Intention.
When wound is clean, free of foreign material and necrotic tissue, and edge are close together.
Scab
PMNs scavenge debris
2-4 days later granulation tissue develops.
3-6 weeks scar develops
Healing by Second Intention
Large break in tissue, inflammation, longer healing and more scarring.
Granulation tissue
Vascularized connective tissue rich in macrophages, myofibroblasts and angioblasts.
Part of wound healing. Develops in 2-4 days.
PMN’s role in wound healing
Scavenge briefly at injury site
The role of connective tissue cells in wound healing
Produce scar tissue.
Include myofibroblasts, angioblasts, fibroblasts
Epithelial cells and wound healing
Undergo mitosis and extend across wound.
Macrophages and wound healing
Stay at site and produce cytokines and growth factors.
Myofibroblasts and wound healing
Hybrids – have properties of smooth muscle and fibroblasts.
In first few days, contract reduces defect and holds margins together.
Secrete matrix substances like fibroblasts.
Angioblasts and wound healing
Precursors of blood vessels
Appear 2-3 days after incision and new blood vessels permeate site by 5-6th day.
New vessels provide route for scavenger cells to remove scab and debris and allow influx of nutrients and O2
Fibroblasts and wound healing
Produce most of ECM
Fibronectin- forms scaffold
Collagens – form fibrils in interstitial spaces
Healing Process
- Blood clot formation
- Inflammation develops
- Cellular debris removed by phagocytes, monocytes and macrophages
- Granulation tissue develops in gap
- Epithelial cells insert mitosis and extend across wound
- Fibroblasts produce collagen
- Fibroblasts and macrophages produce cytokines which attract more fibroblasts.
- Fibroblasts stimulate epithelial cell proliferation and migration and angiogenesis.
- Cross linking and shortening of collagen fibres
- Capillaries decease.
Contracture
Fixation and deformity of the joint
Adhesion
Bands of scar tissue that join two normally separated surfaces b
Immunity
Protection from disease, especially infectious disease.
Natural and acquired.
Natural immunity
Primitive, nonspecific, inherited.
Include mechanical factors like skin and cilia, and phagocytic and NK cells.
Also includes protective proteins.
Natural immunity includes what protective proteins?
- Complement
- Properdin (plasma protein that activates alternative complement pathway)
- Lysozome (bactericidal protein found in tears, and in nasal and intestinal secretions)
Acquired immunity
Based on body’s ability to:
- Distinguish self from non-self
- Generate an immunologic memory
- Mount an integrated reaction of various cells
Immune competence
The body’s ability to mint and appropriate immune response
Cells of the immune system
- Lymphocytes
- - T lymphocytes (T helper and T suppressor/cytotoxic cells)
- - B lymphocytes - Plasma cells
Primary lymphoid organs
Thymus
Bone marrow
Secondary lymphoid organs
Most notably lymph nodes and spleens.
Also GI tract and bronchial mucosa
MALT
Mucosa associated lymphoid tissue.
Formed by lymphocytes. Unencapsulated, integrated in mucosa.
T lymphocytes
Lymphocytes that have matured in thymus.
Account for 2/3 lymphocytes in blood. Also found in lymph nodes and spleen.
Include T helper (CD4) and T suppressor/cytotoxic cells (CD8)
All T cells have a membrane T cell receptor (TCR) linked to CD3 protein. Used for recognition of antigens.
Natural Killer (NK) cells
T cells that do not express TCR-CD3 complex
Mediate innate immune reactions; not involved in T & B cell mediated reactions.
React against virus infected cells, and foreign and cancer cells
T Helper Cells
Help B cells produce antibodies
Express CD4 on their surface.
Secrete cytokines. Classified as Th1 or 2 depending on which cytokines produced
TH1 Cells
T helper cells that produce interleukin 2 (IL-2) and interferon gamma (IFN-gamma).
Stimulate macrophages to become phagocytic
Mediate formation of granulomas
TH-2 cells
T helper cells that make IL-4, IL-5 and IL-13
Important for secretion if IgE and other immunoglobulins and activation of eisinophils
T Suppressor/Cytotoxic cells
Express CD8 on their surface
Suppress unwanted antibody production
Mediate killing of virus-infected and tumour cells.
Normal ratio of CD4:CD8 cells
2:1
B lymphocytes
Cells that mature in the bone marrow.
When stimulated by antigens, differentiate into plasma cells
Plasma cells
Fully differentiated descendants of B cells
Produce antibodies.
Cytoplasm contains an abundance of ribosomes and RER.
Antibodies
Protiens of the immunoglobulin class secreted by plasma cells
Made up of about 110 amino acids
IgM
Mega immunoglobulin (biggest) Composed of five basic units
Functions to neutralize microorganisms.
First to appear after immunization.
Natural antibody against ABO antigens
Complement activator.
IgG
Gnomish. (Smallest immunoglobulin)
Most abundant.
Produced in small amounts on initial immunization but production is boosted upon re-exposure.
Can cross placenta.
Acts as opsonin.
IgA
Aw yucky
Found in mucosal secretions (tears, nasal secretions), milk and intestinal secretions.
IgE
Evil (allergies)
Secreted by plasma cells in tissues
Locally attached to mast cells
Mediates allergic reactions (Type 1 hypersensitivity reaction)
Present in trace amounts in serum.
IgD
Doh!
Cell-membrane bound; on B cells
Participates in antigenic activation of B cells; not released into serum or body fluids.
Antibody production
Foreign antigen attaches to B-lymphocyte antigen receptor complex.
B cells internalize antigen and function as Antigen Presenting Cells
Present antigen to T cells. T helper cell produces cytokines, which transform B cell into plasma cell, which produces antibodies.
Major histocompatability complex
Proteins present on surface of cell that identify cell as self/other.
The “identity” of pathogen that allows for specific immunity to be developed.
Ag-Ab reaction
Ab and Ag bind to form complexes.
If large enough, may be phagocytosed in spleen/liver by fixed macrophages.
If small, may bind on RBCs or endothelial cells, or filter through capillary walls.
AbAg complexes on RBCs can cause agglutination –> hemolysis
Hypersensitivity Reaction
An abnormal immune response to exogenous antigen or endogenous auto-antigen
Types of hypersensitivity
I. Anaphylactic type reaction
II. Cytotoxic Ab-mediated type reaction
III. Immune complex mediated reaction
IV. Cell-mediated, delayed type reactions.
Type I Hypersensitivity
Anaphylactic type
IgE mediated.
AgAb complex on mast cells trigger release of histamines
Hay fever (allergic rhinitis)
Eczema (atopic dermatitis)
Bronchial asthma
Anaphylactic shock.
Type II Hypersensitivity
Mediated by IgM or IgG
Cytotoxic Abs react with Ags in cells or tissues.
Activates complement system (MAC) then cell lysis, or attracts cytotoxic T cells
Re exposure may lead to autoimmune disorders: Goodpastures, hemolytic anemia, Graves Disease, or Myasthenia gravies
Goodpasture’s Syndrome
Type II hypersensitivity disorder
Autoimmune reaction against Coolagen Type IV
Leads to renal and pulmonary damage
Hemolytic Anemia
Type II hypersensitivity disorder
Can occur as a result of acute hemolytic reaction (transfusion of mismatched blood) or SLE (systemic lupus erythematosus)
Epitope
Part of antigen that is recognized by immune system.
Graves Disease
Type II hypersensitivity disorder
Form of hyperthyroidism in which antibodies to thyroid stimulating hormone receptors cause overproduction of thyroid hormones.
Myasthenia Gravis
Type II hypersensitivity disorder
Antibodies to ACh receptors in NM junction prevent binding.
Results in severe weakness and paralysis.
Type III Hypersensitivity Disorder
Mediated by AgAb complexes.
Complexes get trapped in semipermeable membranes, and active complement system, triggering inflammation characterized by fibrotic necrosis.
Systemic Lupus Erythrematosus (SLE)
Lupus
Involves Type III hypersensitivity
Circulating AgAb complexes deposit on tissues and cause kidney disease, arthritis, skin disease, Eric.
Post streptococcal Glomerulonephritis
Type III hypersensitivity disorder
Acute renal disease following URT strep infection.
AgAb complex gets stuck in glomerular basement membrane, evoking complement mediated inflammation.
Polyarteritis Nodosa
Type III hypersensitivity disorder
AgAb mediated
Involves small to medium sized arteries.
Acute: fibroid necrosis and acute inflammation
Chronic: destruction of vessel wall; thrombosis and occlusion –> ischemia and infarcts
Type IV Hypersensitivity Reaction
Cell mediated or Delayed Type Immune Reaction
Involves T cells and macrophages, which aggregate and form granulomas.
Accounts for granulomas developing in response to tumours, and idiopathic granulomatous diseases.
Response to M tuberculosis, mycobacterium Leprae, and fungi.
Contact dermatitis most common clinical form.
Types of transplantation
Autograft – self to self
Isograft – identical twin to twin
Homografts: human to human
Xenografts: nonhuman to human
