Inflammation and Immunity Flashcards
Purpose of Inflammation
-Destroy infectious and injurous organisms
…ex bacterial/viral infections
-Wall off the site of infection to limit damage
-Stimulate and enhance immune response
.. 1) inflamm response 2)immune repsonse
-Stimulate tissue healing and provide a framework for tissue repair
Characteristics of inflammatory response (innate immunity)
-Occurs in Vascular tissue
..occurs in areas w good blood supply
-Immediate
…minutes to hours
-Nonspecific
..always the same
- no memory
- Inflammatory chemicals (cytokines and mediators) can affect anything.. host or non-host
- Self limiting
Components of the inflammatory repsonse
-Cells;
…..WBCs, endothelial cells (lines blood cells), and platelets (blood clotting)
-Inflamm chemicals;
….cytokines, vasoactive inflamm mediators(constriction/dialation of bv), anti-inflamm mediators
-plasma protein systems;
complement, clotting and kinin systems
Activation of the inflammatory Response ;
-Trauma to cell membrane
..triggers; infection, injury
-hypoxic injury
…(low oxygen) ex; myocardial infarction
-Chemical injury
…ex; gastric fluid in the lungs
-Thermal injury
..burns
-ionizing radiation
…chemo
-Infection
…viral, bacterial, hungal infections
-Immune injury
…..auto immune or allergies
overview of inflammatory response to cell injury
******* pic
Cells of inflammation
Mast cell Basophil Neutrophils Eosinophils Monocytes/Macrophages
Inflammation mediators
Histamine
Leukotrienes
Prostaglandins
Mast Cell (location and activators)
- Most important activator of local inflammatory response
- in body tissue
Activators; local cell injury bacterial endotoxin (gram -) complement proteins immunological facotrs: IgE hypersensitivity
Mast cell function
*Degranulation; release of preformed chemicals (dumping)
-Histamine (dumped on bacteria)
>vasodilation
…increased blood flow
((smooth muscle response))
>increased capillary permeability
…allows things to flow out to site of infection
((smooth muscle response/BV and digestive))
>non-vascular smooth muscle contraction
…contraction in digestive and respiratory tract bad
ex; bronchi constriction
((nonsmooth muscle response/ respiratory tract))
-Synthesis of mediators: Arachadonic acid (AA) metabolites
…come form mast cell after degranulation
> leukotrienes: same action as histamine
..dilate arteries,increase leak capillaries
ex; benedryl
> Prosotglandins (PgE2); same as histamine + pain
..triggers pain and fever
ex; advil inhibits prostoglandins
Basophils
- Similar to mast cells; release histamine and leukotrienes in blood
- release heparin; inhibiting blood coagulation
Neutrophils
(we have a ton)
- ACUTE and short lived
- immature neutrophils are called bands
-arrive during acute phase of inflammation after degranulation
-phagoctosis of bacteria and debris
..bacteris is eaten and bombarded with lysosomes and free radicals
-Release of other vasoactive mediators
Eosinophils
-Release chemicals that control inflammation
ex; histamine is inactivated by histaminase release by eosins.
-phagocytosis of parasites
-involved in allergic responses
..ex; type 1 hypersensitivities
Monocytes/macrophages
- can last for a long time
- Released into blood by bone marrow as a monocyte
-migrate to inflammatory site and transform into a macrophage
(lives, spleen lungs and lymph nodes have residential macrophages)
CHRONIC
-Phagocytosis of bacterial & cellular debris
-Release of other vasoactive mediators
-promote wound healing
.activates fibroblasts, stimulates angiogenesis and releases tissue growth factors
inflammation is mediated by three plasma protein systems
- The complement system
- Clotting system
- Kinin system
..each system has inactive plasma proteins called proenzymes which starts a cascade resulting in systems of inflammatory mediators
Complement system
-liver produces plasma proteins
..float in the body and become activated w/ inflammatory response
( if liver cant produce plasma proteins, inflamm resposne cant occur)
Functions
-vasodilation,increased capillary permeability, bronchoconstriction ( like histamine, lukeo/prostogl)
-opsinization .. coats bateria making it ‘tasty’ for phagocytes
-chemotaxis
..release of chemicals that attract WBC to the area
-membrane attack complex.. cell lysing..direct kiling
Clotting System
-Sequental activation of clotting factors resulting in the production of fibrin (involved in hematology)
Funtions of fibrin;
-forms meshwork to stop bleeding
- limits infection
- forms framework for scar tissue formation (wall of fibrin)
Local manifestations of Inflammation
-heat and redness
..increased blood flow to area by vasodilation
-pain
..prostoglandins released by mast cell after degranulation induce/cause pain
-edema/swelling-inflammatory exudate
..accumulation of fluid in interstitial space (outside cell and capillaries)
…increased diffusion distance between cells and capillaries inhibiting oxygen delivery to cells (may cause hypoxic injury)
..can contribute to loss of function
Systematic manifestations of acute inflammation
Fever
..caused by bacterial endotoxins & prostoglandins that rest the body’s thermostat in the hypothalamus
Mechanisms
- increased cell metabolism, shivering and vasoconstriction of arterioles in skin trying to raise body temp.
Purpose
..Disrupt metabolism of temp. sensitive bacteria, increased wbc activity ( high temps help WBC resposne)
Harmful effects;
too hot causes cell injury and dysfunction
Leukocytosis (systemic manifestation)
*Increase in total WBC count
ACUTE inflamm
- increase neutrophil count (early on)
- increase in bands (immature neutrophils)
CHRONIC inflamm
-Increase in monocyte count
Increased circulating plasma proteins (systemic manifestation)
- Acute phases reactants
- released by liver in response to inteleukins
- Plasma proteins produced by liver are released into the bloodstream
-***C-reactive proteins (CRP)
normal; < 1 mg/dL
with bacterial infection > 10 mg/dL
..good marker of inflammation
Increased erythrocyte sedimentation rate (ESR) (systemic manifestation)
- When plasma protein levels in the plasma are elevated (ex; acute phase reactants released during inflamm)
- RBC aggregate and precipitate rapidly in the presence of plasma proteins
Vascular response to systemic or severe inflammation
Vasodialation to the whole body drops the blood pressure
Causes;
- blood stream infection (bacteremia)
- severe localized infection (UTI)
- massive trauma ex; crush/burn injuries)
- hypotension
- systemic edema
- hypovolemia- dehydration in blood stream
Role of the Immune System
-Prevent and eradicate infections
..also involved in surveillance and destruction of cancer cells
-Immune response can cause cell injury & stimulate pathologic inflammation (may become over- reactive)
..ex; allergies or auto immune
- responsible for allergic responses and hypersensitive reactions
- recognizes and responds to tissue grafts
- May attack its own tissues causing autoimmune
Cells of immune repsonse
(All come from bone marrow)
-B-lymphocytes
…produce antibodies
-T-lymphocytes
… direct killing and foreign tissue
Characteristics of immune response (adaptive immunity)
- Slower
- specific
- memory
- involves lymphocytes and antibodies
- may be induced by vaccination
Antigen
*a molecule recognized by lymphocytes and reacts with antibodies.. usually on plasma memb of cell
FOREIGN (NON-HUMAN) ANTIGEN
- viruses (flu)
- Bacteria (e. coli)
- pollen / environmental allergens
- food/drugs (immune rxns such as a nut)
SELF ANTIGEN
-Human leukocyte antigen (HLA) in wbc’s
…cell surface proteins distinguishing self from nonself
allowing the immune system to not attack you
….present on all cell membrane except RBC’s and platelets
….major histocompatibility complex (MHC); genomic region that directs synthesis of HLA antigen.. code for HLA in chromosome 6
-RBC antigen (A,B and Rh antigen)
..(+) have Rh
B lymphocyte response (self-antigen)
Called ‘humoral response’
-Mature B lymphocytes (plasma cells) produce immunoglobulins (antibodies)
immunoglobulin; term used to denote all types of Y shaped protein
antobody; immunoglobulins that have specificity for particular antigens
*all antibodies have a Y shaped structure
Antibody Classes
*have antigen, structural and functional differences
IgM- general antibody, highest titers present during primary immune response
IgG- general antibody, highest titers present during secondary immune response
IgA- preformed antibody found in sweat, saliva,tears and breast milk (in secretions of mucus memb., places where microgorgs enter the body)
IgE- antibody produced during allergic responses (type l hypersensitivity rxns)
Function of Antibodies
*begins with antigen binding to form antigen-antibody complexes
-Neutralizes bacteria and viruses
….prevents virus from binding
-Promotes phagocytosis of bacteria and viruses via opsonization
….complimentary proteins and antibodies are coated making them easier to identify
-Activate the complement cascade
…antibody bound to bacteria engages complement
Primary and secondary immune response
-PRIMARY
Antigenic challenge with production of measurable immunoglobins (antibodies), primary IgM, after a latent period of about 5 days
-SECONDARY
A second antigen challenge with more rapid and larger production of immunoglobins, primary IgG
*memory cells trigger antibodies
T-Lymphocyte Response
*also called cellular response
-Cytotoxic T cells (Tc);
..attack antigen directly and kill cells bearing foreign antigen
(release toxin and enzymes to kill surrounding cells)
-Helper T Cells (Th);
..Required to activate the primary B and T lymphocyte response , right at response gets antibody and cytotoxic cells going.(No helper t = No immune response)
-Memory T Cells (Tm);
…induced secondary immune response . Next time you’re exposed, Tm cells recognize and induce cytotoxic T cells to attack
-Regulatory T cell (Treg)
…develop in the thymus or peripheral tissues and suppress B Cell and T cell activation . Release cytokine to keep immune system from attacking us preventing autpimmune
Vaccination
A process of stimulating a protective immune response against microbes through exposure to nonpathogenic forms or components of the microbe.
Types of traditional vaccinations
*most traditional vaccines mainly stimulate the B lymphocyte (antibody) response
-INACTIVATED
…virulent microbes are kiled to abolish their infectivity and pathogenicity, yet still retain their immunogenicity. Large, multiple does often required along w/ boosters.
ex; Hepatitis A
-LIVE ATTENUATED
…Microbes treated to reduce their infectivity and pathogenicity, yet still retain their immunogenicity. May not be safe for immunocompromised individuals. Boosters are not required as often.
ex; mmr, varicella, flu
-TOXOID
…vaccine is made from inactivated bacterial toxin
ex; tetanus toxoid
Development of Immunity
- Immune system cells recognize the antigen associated with the vaccine, destroys the vaccine, then develops memory for the antigen
- When the microorganism is encountered, the immune system mounts the rapid and potent secondary immune response with high levels of antibodies (IgG mainly) and a Tc cell response