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Immunity's First line of defense
- Innate Resistance
- (Natural or Native Immunity)
- Examples-
- Physical and mechanical barriers-
sloughing off of cells, coughing/sneezing, flushing, vomiting, mucus/cilia - Skin
- Linings of GI, GU, and respiratory tracts
- Biochemical barriers-
saliva, tears, earwax, sweat, mucus
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Immunity's Second line of defense
Inflammation
Inflammatory response activated to protect body from further injury, prevent infection of injured tissue, and promote healing
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Inflammation is caused by:
- Trauma
- Infection
- Surgery
- Caustic chemicals
- Heat and cold extremes
- Ischemic damage
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Vascular response to inflammation
- 1. Vasodilation- slower blood velocity increases blood flod flow to injured site
- 2. Increased vascular permeability-fluid escapes outside of vessel causing edema,
- Edema
- Increased concentration of red blood cells (warmth and redness)
- 3. White blood cell adherence to the inner walls-migrate thru enlarged juctions in vessel
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Goals of Inflammation
- Limit and control tissue damage
- Prevent and limit infection and further damage
- Initiates adaptive immune response
- Initiates healing thru removal of bacterial products, dead cells, and other products of inflammation
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Cellular bags of granules located in loose connective tissues close to blood vessels.
Mast cell
Pg. 125:Figure 5-3
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Where are mast cells located?
- Skin
- Digestive lining
- Respiratory tract
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Activation of mast cell
- physical injury
- chemical agents
- immunologic processes
- toll-like receptors
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Chemicals released from mast cell in two ways.
- 1. Degranulation-release granules
- 2. Synthesis-new production and release of mediators in response to stimulus
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Mast cell degranulation occurs 2 ways:
Histamine-vasoactive amine that causes temporary, rapid constriction of large blood vessels and dilation of postcapillary venules. Retraction of endothelial cells lining capillaries
- Chemotactic Factors-attration "recruit"
- Neutrophil chemotactic factor:Predominant cells need to kill bacteria in early stages of inflammation
- Eosinophil chemotactic factor of anaphylaxis-help regulate inflammatory response
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Mast cell synthesis of mediators:
- Leukotrienes
- Prostaglandins=pain
- Platelet-activating factor
(Review pg 126 in text for functions)
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Plasma Protein Systems Include:
- Complement
- Coagulation
- Kinin
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Complement system:
- Can destroy pathogens directly
- Activates or collaborates with every other componenet of inflammatory response
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Coagulation (clotting) system
Forms fibrinous meshwork at injured or inflamed site
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Kinin system
Functions to activate and assist inflammatory cells
Primary kinin is bradykinin
Causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis
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Review Cellular components and products of inflammation
pgs. 129-134
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Cardinal signs for Local manifestations of inflammation
- Rubor=redness
- tumor=swelling (histamine releases)
- calor=heat
- Dolor=Pain (bradykinin, prostaglandins)
Results from vascular changes and corresponding leakage of circulating components into tissue
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4 types of exudative fluids:
- Serous-watery exudate from plasma indicating early inflammation
- Fibrinous-thick, clotted exudate indicating more advanced inflammation
- Purulent-contains pus, WBC, protein, tissue debris indicating bacterial infection (yellow, green)
- Hemorrhagic-leakage of RBC from capillaries indicating bleeding
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Systemic manifestations of Inflammation
- Fever-caused by exogenous and endogenous pyrogens. Pyrogens act directly on hypothalamus, portion of brain that controls body's thermostat
- Leukocytosis-increased number of circulating leukocytes or white blood cells. Shift to the left refers to ratio of immature to mature neutrophils. Bacteria causes shift to the left and called bands.
- Increased plasm portein synthesis-increased during inflammation, increased fibrinogen increases Erythrocyte Sedimentation Rate (ESR)
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Granuloma
Consist of central area of amorphous caseous (cheeselike) necrosis that is surrounded by zone of activated macrophages, in which multinucleate macrophages (langerhans giant cells) are present. A wall of fibrin is laid down around granuloma, and the contents eventually breakdown and liquefy.
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Inflammation lasting 2 weeks or longer
Chronic inflammation
Often related to an unsuccessful acute inflammatory response.
Chronic inflammation is characterized by dense infiltration of lymphocytes and macrophages. If macrophages are unable to protect the host from tissue damage, the body attempts to wall off and isolate the infected area, thus forming a granuloma
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Examples of chronic inflammation
- splinters
- sutures
- viral
- bacterial
- TB lesion
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Wound healing involves:
- Filling in the wound
- Sealing the wound
- Shrinking the wound
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Wounds that heal under conditions of minimal tissue loss
- Primary intention
- Paper cut
- Sutured surgical wound
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An open wound involves a great deal more tissue and is known as
- Secondary intention
- Abdominal infection
- Pressure ulcers
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Reconstructive phase of wound healing involves
Begins 3 to 4 days after injury and continues for as long as 2 weeks
- Fibroblast proliferation-lay foundation
- Collagen synthesis by fibroblasts
- Epithelialization
- Contraction of wound
- Cellular differentiation
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Most important cells during healing because they secrete collagen and other connective tissue proteins, which are deposited in debrided areas about 5 days after entering lesion
Fibroblasts
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Most abundant protein in body
Collagen
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Continued cellular differentiation in wound healing, can persist for years
Maturation phase
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Scar tissue formation and scar remodeling occur during which phase of wound healing
Maturation phase
During remodeling, cappillaries disappear, leaving scar avascular
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Dysfunctional wound healing during inflammatory response include:
- Hemorrhage
- Fibrous adhesions
- Infection
- Steriods
- Hypovolemia
- Wound Sepsis
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Dysfunctional wound healing during reconstructive phase:
Impaired collagen matrix assembly- keloid scar, hypertrophic scar, scurvy
Impaired epithelialization-steroids, hypoxemia, nutritional deficiency
Impaired contraction-burns, can occur in liver constricting vascular flow
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Wound disruption
dehiscence-pulls apart
- Strain
- Obesity
- Increased risk of sepsis
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Third line of defense
Adaptive (acquired) Immunity
Often called immune response. Develops more slowly than the inflammatory response and is specific and has memory.
- Involves:
- Antigen/Antibody
Humoral and cell-mediated immunity
Active and passive Immunity
Cell Mediated T and B lymphocytes
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Two types of lymphocytes involved in antigen process
B lymphocytes- B cells- produce antibodies that enter blood and react with antigen
T lymphocytes- T cells- attack antigen directly
Both are extremely speciif and recognize only one specific antigen
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Produced by individual after either natural exposure to antigen or after immunization
Active immunity
Long lived
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Does not involve host's immune response. Occurs when preformed antibodies or T cells are transferred from donor to recipient
Passive Immunity
Only temporary because donor's antibodies or T cells are eventually destroyed
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Antigens that induce allergic response
Allergens
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Altered immunologic response to antigen that results in disease or damage to host
hypersensitivity
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Four types of hypersensitivity reactions
Type I: IgE mediated
Type II: Tissue-specific reactions
Type III: Immmune complex mediated
Type IV: Cell Mediated
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Seasonal allergic rhinitis and asthma are examples of:
IgE mediated reaction
Rate of development-Immediate
Antibody involved-IgE
Effector cells involved-Mast cells
Participation of complement-NO
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Autoimmune thrombocytopenic purpura, Graves disease, autoimmune hemolytic anemia are examples of:
Tissue specific reaction
Rate of development-Immediate
Antibody involved- IgG and IgM
Effector cells involved-Macrophages in tissues
Participation of complement-Frequently
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Systemic lupu erythematosus is an example of:
Immune complex mediated reaction
Rate of development-Immediate
Antibody involved-IgG and IgM
Effector cells involved- Neutrophils
Participation of complement-Yes
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Contact sensitivity to poison ivy and metals (jewelry) are examples of:
Cell-mediated reaction
Rate of development-Delayed
Antibody involved-None
Effector cells involved-lymphocytes and macrophages
Participation of complement-No
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Type I hypersensitivity reaction
IgE mediated-result of excessive or inappropriate production of IgE antibodies after exposure to some type of environmental antigen.
With initial exposure to antigen, IgE (immunoglobulin) binds to Fc receptor on surface of mast cell. Individual now sensitized to antigen. Antigens cause allergic responses called allergens. With subsequent exposure to antigen, tiny sacs in mast cells called granules break open and release histamine, which then triggers inflammatory response
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Most potent mediator of Type I reaction
Histamine
- Contracts Bronchial smooth muscles
- Increases Vascular permeability
- Increases blood flow to affected area
- Increased gastric acid secreation (N/V)
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Examples of Type I
- Hay fever
- Food and drug allergies
- Bee stings
- Asthma
- Anaphylaxis
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Clinical manifestations of Type I:
- Sudden onset
- GI symptoms
- Urticaria-hives
- ENT and respiratory symptoms
- Anaphylaxis-rapid onset, urticaria, cramps, difficulty breathing. Caused by bronchospasm, angioedema, hypotension, shock. Can be Lethal
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Who are atopic individuals?
- Predisposition to develop allergies
- Genetic tendency
- Higher quantities of IgE
- More Fc receptors on mast cells which connect IgE
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Type II:Tissue-specific Reactions
Blood transfusions-red blood cell reaction
Specific cell or tissue (tissue specific antigens) is target of immune response. Direct interaction b/t IgG and IgM class antibodies and tissue or cell surface antigens.
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Five mechanisms of Type II
- 1. Cell is destroyed by antibodies and complement
- 2. Antibody may cause cell destruction through phagocytosis
- 3. Toxic products produced by neutrophils
- 4. Antibody dependent cell mediated cytotoxicity (ADCC)
- 5. Cell malfunctions
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Examples of Type II
Erythroblastosis Fetalis-Rh or Abo incompatibility b/t blood of mother and fetus
Hemolytic anemia-antibodies produced against red blood cells could be drug induced
Transfusion reaction-Antibodies produced against donor cells
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Type III:Immune complex mediated
Abnormal creation that forms. ex-autoimmune disorder
caused by antigen antibody immune complexes formed in circulation and deposited later in vessel walls and other tissue.
Size influences whether remain in plasma or lodge in tissues where they result in tissue damage.
Complement activated and neutrophils degranulate enzymes damage tissue. can damage and destroy healthy tissue
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Examples of Type III
- Serum sickness
- Systemic lupus erythematosus
- arthus reaction-local reaction
- Acute glomerulonephritis that follows strept infection
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Type IV Hypersensitivity Reaction
- Mediated by Sensitized T lymphocytes
- Don't involve antibody
- Reaction delayed-24-72 hours after exposure
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Examples of Type IV reaction
- Graft rejection
- Skin test for TB
- Allergic contact dermatitis- poison ivy and metals
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Autoimmunity
Breakdown of tolerance to own antigens
- Examples-pg 171 other examples
- SLE
- Chronic multisystem inflammatory disease-abnormal antibodies attack RBC's
Autoantibodies against nucleic acids, erythrocytes, Coagulation porteins, platelets
Deposition of circulating immune complexes containing antibody against host DNA
More common in females
Clinical manifestation-Butterfly rash, Lupus
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Common Findings of SLE-serial or simultaneous presence of at least four
Not just localized-can become systemic
- facial rash
- discoid rash
- photosensitivity
- Oral or nasophyaryngeal ulcers
- arthritis
- serositis
- renal disorders
- neurologic dis
- hematologic disorder
- immunologic disorder
- Presence of antinuclear antibody-blood test of ANA-titer. some reaction going on in body if ANA is elevated
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alloimmunity
Immunse sys reacts w/antigens on tissue of genetically dissimilar members of same species
- ex.
- graft rejection
- transplant rejection classified to time:hyper, acute, chronic
- Hyperacute;immediate rejection
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Graft-versus-host disease (GVHD)
cellular immune system of transplant tissue can attach unrelated recipient tissue
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Immune Deficiencies
Failure of immune mechanisms of self defense
Primary (congenital) immunodeficiency (Pg 196:Table 7-13)
Secondary (acquired) immunodeficiency-caused by another illness (cancer, infection) More common
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Syndrome caused by viral disease-Human Immunodeficiency virus (HIV).
Acquired Immunodeficiency Syndrome (AIDS)
Blood borne pathogen. Increasing faster in women than men.
- Depletes CD4 Th cells
- Incidence:Worldwide 5 mill/yr
- US 31K/yr
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Pathogenesis of AIDS
Retrovirus
Genetic information stored in RNA rather than DNA
Contains reverse transcriptase to convert RNA into double stranded DNA
Integrase inserts new DNA into infected cells genetic material
Structure:GP 120 proteins bind to CD$ molecule found on surface of CD4 Th cells
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Normal CD4 count
800-1000 cells/mm3
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Clinical manifestations of AIDS
- Antibody 4-7 wks after blood products
- Antibody 6-14 mo after sexual transmission
- Window period
- Can still be infectious
Early signs-flu symptoms, swollen lymph glands, diarrhea, fatigue
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Opportunistic infections (pg 201, Box 7-2)
Organisms produce infection in persons w/impaired immune function
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Neurologic Complications of AIDS
- Encephalopathy
- Myelopathy
- Neuropathy
- Viral meningitis
- Opportunistic infections
- Neoplasms
- Bleeding
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