my husband is awesome Flashcards
(85 cards)
1
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Immune system physical barriers
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Skin, Epithelial surfaces, Cilia
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Immune system chemical barriers
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Acids, Mucous, Lisozymes
3
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Immunity is the body’s…….
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Protective reactions to foreign invaders. Provides protection against INFECTIOUS DISEASE and supports HEALING. Malfunctions may result in immunity to self substances…“AUTOIMMUNITY”
4
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Immunity is mediated by the collective coordinated response of….
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Immune cells and the molecules they produce.
5
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Innate immunity
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“Native” immunity…nonspecific, quick (minutes to hours). Includes epithelium, secreted products, phagocytes, NK cells, plasma proteins, some cytokines
6
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Adaptive immunity
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Occurs on exposure to certain antigens (days to weeks). Includes lymphocytes, their secreted proteins (antibodies, cytokines), “antigen-presenting cells” (macrophages)
7
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Adaptive immunity is divided into….
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“Humoral” and “Cellular” components. Provides “memory” of prior exposures.
8
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The immune system has the ability to distinguish…
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“self” from “non-self”
9
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Antigen
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FOREIGN “non self” substance that provokes an immune reaction.
10
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Autoantigens
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Self-Molecules that inappropriately provoke an immune reaction
11
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Allergens
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Antigens that provoke HYPERSENSITIVITY RESPONSES (allergic response)
12
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Most antigen are… (hint, molecular weight)
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LARGE PROTEINS with molecular weight of 10,000 or higher. Insulin <6,000 daltons so doesn’t cause response
13
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Epitope
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Small part of an antigen that INTERACTS WITH A SPECIFIC ANTIBODY or immune cell ANTIGEN RECEPTOR
14
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Any antigenic protein may have
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SEVERAL EPITOPES
15
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Each epitope is
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RECOGNIZED BY A DIFFERENT, SPECIFIC ANTIBODY or immune cell ANTIGEN RECEPTOR
16
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Primary lymphoid tissue
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Bone marrow (red) and Thymus
17
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Secondary lymphoid tissue
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Lymph nodes, lymph nodules and lymph vessels; Spleen
18
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Leukocytes
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White blood cells, WBC
19
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Primary lymphoid tissue are organs where
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Immune and other blood cells are made and matured.
20
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Red bone marrow…
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Provides pluripotent stem cells; Give rise to all of the different types of blood cells.
21
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Thymus
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Gland above the heart in the thorax. Site of T lymphocyte maturation, develop “self tolerance” prior to entering into the blood circulation.
22
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Thymus is located…
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in the thorax between the thyroid and the heart. Thymic tissue hypertrophies during childhood but after puberty it atrophies and is replaced by fat, continues to function to some extent throughout life.
23
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Cells contained within the thymus
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T lymphocytes - present at various states of maturity
Epithelial cells - endocrine gland, produce hormones that direct T cell matruation (thymulin, others)
Macrophages - phagocytes
24
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Secondary lymphoid tissue serves to…
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promote efficient interactions between antigens and immune cells and a controlled environment for the development of immune responses.
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Secondary lymphoid tissues include:
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Lymph nodes (along lymphatic vessels)
Lymph nodules (on mucosal surfaces) Includes tonsils and adenoids, Peyers patches (on intestine), others
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Lymphokinetic motion and pressure gradient (high to low pressure)
Blood capilaries ---> Interstitial Fluid --->Lymph capillaries ---> Lymph veins --->Lymph ducts --->Large circ veins
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The lymphatic vasculature...
Drains tissue fluid, cells and antigens from most tissues, through lymph nodes and back into blood via thoracic duct.
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Lymph node locations?
Axillary, Brachial, Deep cervical, superficial cervical, inguinal, lumbar, mediastinal, mesenteric, popliteal, pancreatic, renal, sacral, sciatic, facial
Axillary - Armpit
Brachial - Biceps beneath pectorals
Deep cervical - behind salivary gland
Superficial cervical - in front of salivary gland
Inguinal - adherent to skin of groin
Lumbar - behind split of abdominal aorta
Mediastinal - thymic region
Mesenteric - Mesentery of small intestine and pancreas
Popliteal - bhind the knee
Pancreatic - between pancreas and stomach
Renal - between aorta and kidneys
Sacral - In front of the split of the abdominal aorta
Sciatic - Below sciatic nerve
Facial - Draining the face
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What do lymph nodes do?
Lymph nodes "filter" the lymph. Provide a space for active immune cells to interact with antigen carried from interstitial fluid. Lymph nodes enlarge during an immune response (due to lyphocyte proliferation).
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Lymph nodules are associated with...
Mucosal surfaces. Gastrointestinal tract, respiratory tract, breast, urogenital tract
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Examples of GI lymph nodules:
Tonsils, adenoids, Peyer's patches on intestinal tract, Lymphoid aggregates in the appendix, small diffuse lymphoid aggregates in the esophagus, on other mucosal surfaces
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Lymph nodules are characterized by...
Overlying epithelial covering with specialized phagocytic epithelial cells that TRANSFER ANTIGEN INTO THE LYMPHOID TISSUE. Immune cells interact with antigen and STIMULATE IMMUNE RESPONSE. Nodules ENLARGE just like nodes during immune response. Results in SECRETORY IgA PRODUCTION, prevents microbial binding to mucosal surfaces.
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Spleen
Located in the LEFT UPPER QUADRANT of the abdomen. Functions as a FILTER FOR ANTIGENS IN THE BLOOD, a site for IMMUNE REACTIONS, and as a STORAGE ORGAN FOR ERYTHROCYTES.
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What surrounds the spleen
TOUGH CONNECTIVE TISSUE CAPSULE surrounds the spleen and short septa extend inwards. Rupture of capsule results in "ruptured spleen", significant abdominal bleeding.
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What surrounds the spleen
TOUGH CONNECTIVE TISSUE CAPSULE surrounds the spleen and short septa extend inwards. Rupture of capsule results in "ruptured spleen", significant abdominal bleeding.
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Three types of immune cells
Lymphocytes (T and B lymphocytes, Natural Killer NK)
Antigen-presenting cells
Granulocytes - Basophils/mast cells, Neutrophils, Eosinophils
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Three types of immune cells
Lymphocytes (T and B lymphocytes, Natural Killer NK)
Antigen-presenting cells
Granulocytes - Basophils/mast cells, Neutrophils, Eosinophils
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Two types of look-alike lymphocytes
B - give rise to PLASMA CELLS which SECRETE IMMUNOGLOBULINS (antibodies)
T - SECRETE CYTOKINES which act on other immune cells (CD4+, HELPER). Some are able to cause LYSIS OF INFECTED CELLS (CD8+, CYTOTOXIC)
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B and T cell lymphoid lineage
B LEAVE THE BONE MARROW fully mature. T released from bone marrow and must undergo further MATURATION IN THE THYMUS GLAND.
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Antigen-Presenting Cells
MONOCYTE/MACROPHAGES, DENDRITIC CELLS. Specialized names: Langerhans cells (skin), Microglia (CNS), Kupffer cells (liver)
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Antigen-Presenting Cells serve a variety of functions in the immune response:
PHAGOCYTOSIS to eliminate microbes and other particles. Secretion of CYTOKINES (IL-1, IL-6, TNF). "ANTIGEN PRESENTATION" necessary for lymphocyte reaction to specific antigens (adaptive immunity)
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Neutrophils
(polymorphonuclear leucocytes or PMN) are "professional" phagocytes. NON-SPECIFIC PHAGOCYTES, primary role to ingest and kill invading organisms, destroy or remove inert materials.
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Eosinophils
Primary role in immune responses against PARASITES. Common INFLAMMATORY CONDITIONS (asthma, allergy). Certain uncommon inflammatory conditions (eosinophillic esophagitis, eosinophillic neuritis)
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Basophils
Found in BLOOD, rarely seen. Called MAST CELLS when found in TISSUES. Non-phagocytic cells which, when activated, RELEASE COMPOUNDS FROM CYTOPLASMIC GRANULES (including HISTAMINE). They play a major role in ALLERGIC RESPONSES, particularly type 1 hypersensitivity reactions (classic allergy).
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Inflammation
The result of an innate immune response. Mediated by immune cells, other tissue cells, secreted products, blood proteins (complement). PROTECTS AGAINST INFECTION and helps INITIATE THE HEALING PROCESS. MAY BE HARMFUL if unregulated or directed against non-threatening agents. Acute - minutes, hours, < 6 weeks Chronic - > 6 weeks to years
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Acute inflammation
Characterized by ERYTHEMA, WARMTH, SWELLING, PAIN. Three major components of acute inflammation: ALTERATIONS IN BLOOD FLOW, INCREASED VASCULAR PERMEABILITY, ACCUMULATION OF LEUKOCYTES.
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Altered blood flow
After inflammatory stimulus/injury there is RAPID ARTERIOLAR DILATION. Results in VASCULAR "CONGESTION" WITH RBC (stasis) which allows WBC to attach blood vessel endothelial cells and MIGRATE INTO TISSUE. INITIATED BY HISTAMINE release from mast cells.
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Mast Cells
MAST CELLS ARE FOUND IN MOST TISSUES. Cytoplasm filled with granules containing mediators of inflammation. They "DEGRANULATE" when binding to surface IgE. Granules contain multiple compounds including HISTAMINE, PLATELET-ACTIVATING FACTOR, CYTOKINES, EICOSANOIDS (prostaglandins and leukotrienes)
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Mast cell mediators
Histamine and eicosanoids result in VASCULAR DILATION, ENDOTHELIAL PERMEABILITY, AND INCREASED VASCULAR LEAKAGE. Other affects of granule compounds: ATTRACT LEUKOCYTES (CHEMOTACTIC) and PROMOTE LEUKOCYTE ENTRY INTO TISSUES by inducing adhesion molecule expression on endothelial cells.
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In addition to activation SURFACE IgE by antigens, mast cells degranulate in response to...
DIRECT TRAUMA, BURNS, CHEMICAL INJURY, AND TOXINS (like bee venom)
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Vascular Permeability
CAPILLARY ENDOTHELIAL CELLS CONSTRICT IN PRESENCE OF HISTAMINE
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Accumulation of Leukocytes
LEUKOCYTES MIGRATE through the endothelium into the affected tissue...margination, rolling, adhesion. Migrate in direction of CHEMOTACTIC STIMULI (granule contents, complement)
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Other cells, other stimuli
EOSINOPHILS - PARASITES, ALLERGY
MONOCYTE/MACROPHAGES - late acute or CHRONIC INFLAMMATION
LYMPHOCYTES - CHRONIC INFLAMMATION
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Accumulation of Leukocytes...margination enhanced by...
BLOOD STASIS. "ACTIVATED" ENDOTHELIAL CELLS express "ADHESION MOLECULES" which FACILITATE ADHESION AND TRANSMIGRATION into tissues (selectins and integrins)
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CHEMOTAXIS is the process of
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LEUKOCYTE MOVEMENT TOWARDS A CHEMICAL MEDIATOR...
BACTERIAL cell wall products
COMPLEMENT components
EICOSANOIDS (leukotrienes)
CYTOKINES
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When exposed to certain stimuli, leukocytes become...
"ACTIVATED". ACTIVATED LEUKOCYTES ACTIVELY EXPRESS FUNCTIONS. Activation induced by: EICOSANOIDS, CYTOKINES, MAST CELL GRANULE COMPONENTS, COMPLEMENT COMPONENTS.
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PHAGOCYTOSIS
The act of a CELL "EATING" IN AN ATTEMPT TO DESTROY another cell or particle. Enhanced by some IMMUNOGLOBULINS, COMPLEMENT. Primary phagocytes are NEUTROPHILS AND MONOCYTE/MACROPHAGES. Killing/digestion occurs by LYSOSOMAL ENZYME DIGESTION in phagolysosome, exposure to toxic OXYGEN RADICALS, and other TOXIC LYSOSOMAL ENZYMES and compounds.
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Chronic inflammation
Prolonged Inflammatory Response. Examples include persistent infections, prolonged exposure to toxins/particles, autoimmune processes
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Principle features of chronic inflammation
MONONUCLEAR CELL INFILTRATES, TISSUE DESTRUCTION, FIBROSIS
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Chronic Inflammation Cells
MACROPHAGES continue to enter and accumulate at the affected area. ACTIVATED MACROPHAGES continue to attack local tissue and "invaders". Macrophages merge into multinucleate "GIANT CELLS". T AND B LYMPHOCYTES, MAST CELLS, and EOSINOPHILS are also found in areas of chronic inflammation.
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Tissue repair...Scar formation and maturation
Formation takes DAYS TO WEEKS TO FORM. MONTHS TO YEARS TO MATURE. REMODELS TISSUE. SCAR SHRINKS (CONTRACTION) and CHANGES COLOR (HYPERPIGMENTED EARLY ---> HYPOPIGMENTED LATE).
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Tissue repair...Scar remodeling
COLLAGEN FIBERS RE-ALIGN WITH STRESS. Scars always have LESS TENSILE STRENGTH than the tissue they replace.
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Granulomatous Inflammation
Granulomas are focal areas of CHRONIC INFLAMMATION, contain MACROPHAGES AND LYMPHOCYTES. PERSISTENT DISORDERS such as tuberculosis, leprosy, syphilis, sarcoidosis. Other stimuli include MATERIALS WHICH ARE RESISTANT TO DIGESTION or INSOLUBLE IMMUNE COMPLEXES.
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Morphologic Patterns
- SEROUS INFLAMMATION is characterized by CLEAR, THIN SEROUS FLUID (plasma like)
- FIBRINOUS INFLAMMATION characterized by ACTIVATION OF CLOTTING PROTEINS IN SEROUS FLUID, may form fibrous scarring.
- SUPPURATIVE INFLAMMATION characterized by large amounts of PUS/PURULENT EXUDATE (acute appendicitis)
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Complement
NON-SPECIFIC defense system; VERY FAST, ALWAYS AVAILABLE. CAUSE LYSIS of cells, bacteria and viruses. Enhances PARTICLE BINDING to phagocytes. Results in CLEARANCE of microbes, viruses from blood.
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Complement has SIMILIARITIES TO, and "CROSS-TALK" WITH, THE BLOOD CLOTTING CASCADE...
Similarity: CASCADE OF ENZYMES, which activate each other
Similarity: TWO PATHWAYS of activation
Crosstalk: FACTOR XIIa (Hageman Factor) activates both clotting cascade and complement cascade.
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Complement: Activation
Classical pathway activated by IMMUNOGLOBULINS IgM, IgG (antibodies); HAGEMAN FACTOR, and C-REACTIVE PROTEIN.
Alternative pathway activated by MICROBIAL CELL MEMBRANE components and INSECT EXOSKELETON (chitosan).
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Complement: Regulation
Activated complement components rapidly inactivated (SHORT HALF-LIFE) by serum components:
C1 INHIBITOR
PROTEIN S
Other serum inhibitory factors
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Complement: Anaphylatoxins
Activate phagocytic leukocytes and induce chemotaxis.
LEUKOCYTE ACTIVATION by fragments C3a, C4a, C5a
CHEMOTAXIS by fragment C3a and C5a
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Phagocyte Activation
Activation causes:
- Release of REACTIVE OXYGEN SPECIES (microbial killing, killing surrounding tissue cells)
- Release of MEDIATORS (other leukocytes)
- Release of HISTAMINE (mast cells, stimulate inflammation)
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Assessment of Complement Activation
GENERAL/COMMON PATHWAY
- Measurement of TOTAL C3 (depleted with complement activation by any pathway)
- C3a, C5a (only produced with complement activation)
Classical Pathway
- Measurement of C1 qrs (only produced with complement activation through classical pathway)
- Measurement of C2b or B4b2a (only produced with complement activation through classical pathway)
Alternative Pathway - Can't see words on slide...
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Acute Phase Response
Inflammation (local/systemic, minor/major) causes a SYSTEMIC RESPONSE called the ACUTE PHASE RESPONSE. May be associated with TRAUMA, other physical or psychological STRESSES, OBESITY, SMOKING, CHRONIC INFLAMMATION (such as cancer, CVD)
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APR is characterized by...
Fever, gluconeogenesis, lethargy and somnolence, anorexia, cachexia, hematologic abnormalities (such as anemia of chronic disease, leukocytosis, thrombocytosis), changes in plasma protein and hormone concentrations.
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Most APR effects caused by ....
3 CYTOKINES: IL-1, IL-6, and TNF-alpha
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The purpose of the APR is to...
ENHANCE IMMUNITY.
- Increase LEUKOCYTE NUMBERS
- RASE BODY TEMPERATURE in order to inhibit microbial proliferation
- ENHANCE IMMUNE PROTEIN concentrations (antibodies)
- ENHANCE SUBSTRATE for host immune response
- REDUCE OTHER SUBSTRATES to inhibit microbial growth.
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ACUTE PHASE PROTEINS
Positive and Negative
- POSITIVE APP: concentrations INCREASE with APR
- MAJOR APP (C-Reactive Protein, Serum Amyloid A and P)
- Complement Proteins (enhances function), Complement components, C1 Inhibitor
- Coagulation Proteins (enhances coagulation), Fibrinogen, Von Willebrand factor, Prothrombin, Factor VIII
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Other Positive APP
PROTEINASE INHIBITORS - enhances COAGULATION, protects against widespread tissue destruction. (Plasminiogen activator inhibitor 1)
METAL-BINDING PROTEINS - makes metals unavailable for bacterial growth. (Ferritin)
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Negative APP
Concentrations DECREASE with APR (shifts metabolism to support immunity)
- Albumin, Transthyretin, Transferrin
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Metabolic Effects of APR
Release of CATECHOLAMINES
- INHIBITS INSULIN SECRETION (causes hyperglycemia)
- REDUCES PERIPHERAL INSULIN ACTION
- STIMULATES GLUCAGON SECRETION
- INCREASES ACTH and ADH SECRETION
ACTH and ADH also INCREASE CORTICOSTEROID PRODUCTION (positive feedback cycle)
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Metabolic Effects
- hyperglycemia
- glycogenolysis and gluconeogenesis
- adipose release of free fatty acids
- muscle breakdown to support gluconeogenesis
- increased metabolic rate resulting in higher rate of muscle and adipose mobilization
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Assessing the APR
- C-REACTIVE PROTEIN; very sensitive to inflammation and APR, concentrations may increase up to 1,000 fold normal.
- HIGH SENSITIVITY CRP; reliably measures much smaller changes in CRP, primarily used as indicator of CARDIOVASCULAR RISK in combination with other factors.
- HIGHLY SENSITIVE, but NON-SPECIFIC
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Erythrocyte Sedimentation Rate
- Measure of the rate at which RBCs SETTLE OUT OF ANTICOAGULATED BLOOD.
- Used to MONITOR INFLAMMATORY DISEASES, much LIKE CRP.
- Sensitive, but non-specific
- Caused by RBC forming ROULEAUX ("coin" stacks); stacks settle quicker under gravity.
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Fibrinogen andgamma globulins (antibodies/immunoglobulins)
PROMOTE ROULEAUX FORMATION.
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Elevated albumin and high hematocrit
Retard formation
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Normal Erythrocyte Sedimentation Rate varies....
By age and gender.
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Adults:
Men under 50 <15mm/hr
Men over 50 <20mm/hr
Women under 50 <20mm/hr
Women over 50 <30mm/hr
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Children:
Newborn 0 to 2 mm/hr
Newborn to puberty 3 to 13 mm/hr
[Age (in years) + 10 if female] divided by 2 = ESR mm/hr
