chronic inflammation Flashcards

Question

describe MHC 2

Answer 1

- -Major histocompatibility complex class II (MHC class II) 1) Located on the surface of antigen‑presenting cells (APCs; dendritic cells, monocytes/macrophages, B lymphocytes): encoded in HLA‑DR, HLA‑DP, and HLA‑DQ 2) Comprised of two polypeptide chains of equal length (alpha and beta) that each contains two domains (α1, α2, and β1, β2) 3) Antigen-presenting cells can ingest exogenous material (extracellular pathogens) into fragments via phagocytosis and present them on the cell surface via MHC class II receptors. 4) MHC II-antigen complexes are assembled in acidified endosomes after the release of the invariant chain. 5) Antigen presentation leads to the activation of CD4+ T lymphocytes, which then activate B lymphocytes and, thus, provides a connection between innate and adaptive immunity.

Answer 2

1) Located on the surface of all nucleated body cells and platelets 2) Encoded in HLA‑A, HLA‑B, and HLA‑C 3) Comprised of two polypeptide chains of different length: The long-chain contains the alpha domains (α1, α2, α3), the short-chain is the peptide β2-microglobulin and carries the β2 domain. 4) Continuously presents endogenous fragments of proteins located in the cell, which allows for rapid detection and destruction of cells in infections with intracellular pathogens (e.g., viruses) and cells that produce atypical proteins (neoplastic or malignant cells) → cytotoxic T‑cell reaction 5) The exception is the cross-presentation of extracellular antigens by dendritic cells → primes CD8+ T cells, which can only interact with MHC I 6) Antigens are peptides, lipids, or polysaccharides which are transported to the RER via transporter associated with antigen processing (TAP). 7) MHC I-antigen complexes are assembled in the RER. 8) The polymorphic zone presents antigens derived from within the cell. The nonpolymorphic zone binds to CD8 T lymphocytes. 9) Several viruses prevent the expression of MHC class I on the cell surface. The absence of MHC class I receptors on infected or malignant cells is recognized by natural killer cells (NK cells).

Answer 3

A group of proteins that mediate the immune response (e.g., chemotaxis of inflammatory mediators, antibody production, sensitization to antigens). Also implicated in the development of type IV hypersensitivity reactions. Produced by T cells.

Answer 4

- -B cells are produced in the bone marrow - -Activation à plasma cells ( secretes monoclonal immunoglobulins, predominately IgM, but also IgA, IgE, IgG, that target a specific antigen)

Answer 5

1) Common in many allergic inflammatory reactions (mediated by IgE and parasitic infections) 2) Effective killers of parasites 3) Recruitment depends on eotaxin. 4) Phagocytic (limited) 5) Have granules containing major Basic Protein (MBP is toxic to parasites and contributes to tissue damage as it lyses mammalian epithelium) 6) Mediate tissue damage

Answer 6

The immune response against parasites

Answer 7

1) Proinflammatory cytokines (Th1 cytokines): stimulate the immune system - Interleukins 1, 6, 8, 12, 18, IFN-γ, and tumor necrosis factor - Induce fever, inflammation, and tissue destruction in response to infection, injury, or ischemia - Uncontrolled action is deleterious and can lead to multiorgan dysfunction 2) Anti-inflammatory cytokines (Th2 cytokines): suppress the immune system - Interleukins 4,10, 11,13, TGFβ, and receptor antagonists of IL-1 and TNFα - Suppress proinflammatory cytokine secretion and inhibit binding of proinflammatory cytokines to their receptors - An imbalance between the pro-inflammatory and anti-inflammatory cytokine response is responsible for several immune-mediated diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis).

Answer 8

- Major basic protein: produced by eosinophils in response to antibody-dependent processes (IgE, antibody-dependent cell-mediated cytotoxicity) and important in the defense against helminthic infections. - IgE coat pathogens → recognized by Fc receptor-bearing granulocytes (eosinophils) → release of major basic protein → destruction of the pathogen

Answer 9

1)A specific form of chronic inflammation 2)Characterized by focal accumulations of activated macrophages (granulomas) If the immune system is unable to completely eliminate a foreign substance (e.g., persistent pathogen, foreign body), the resulting granulomatous inflammation attempts to wall off the foreign substance within granulomas without completely degrading or eradicating it.

Answer 10

Antigen-presenting cells present antigens to CD4+ Th cells and secrete IL-12 → stimulate differentiation into Th1 cells → Th1 cells activate macrophages by secreting IFN-γ → macrophages release cytokines (e.g., TNF), which stimulates the formation of epithelioid macrophages and giant cells Epithelioid cells secrete TNF-α, which serves to maintain the granuloma. Macrophages within the granuloma ↑ calcitriol (1,25-[OH]2 vitamin D3) activation → hypercalcemia

Answer 11

-A type of macrophage that resembles epithelial cells ----Can fuse together to form Langhans giant cells (multinucleated giant cells), which are components of granulomas (e.g., in tuberculosis).

Answer 12

- - a nodular collection of central macrophages, epithelioid cells, and giant cells, surrounded by fibroblasts and lymphocytes - -Giant cells contain: 1) Asteroid bodies: a star-shaped, eosinophilic inclusion body consisting of various lipids (e.g., from sarcoidosis, foreign body reactions) 2) Schaumann bodies: a type of cellular inclusion body consisting of intracytoplasmic calcium and protein with laminar stratification (e.g., sarcoidosis, tuberculosis, Crohn disease, berylliosis)

Answer 13

1) Caseating granulomas: granulomas with central necrosis - -Occurrence: infections (e.g., tuberculosis, fungal infections) 2) Non-caseating granulomatous inflammation: granulomas without central necrosis - -Occurrence: immune-mediated diseases (e.g., sarcoidosis, Crohn disease), vasculitis, foreign body exposure

Answer 14

- Tuberculosis - Fungal infections (e.g., histoplasmosis) - Bartonella henselae (cat scratch disease) - Listeria monocytogenes (granulomatosis infantiseptica) - Treponema pallidum (tertiary syphilis) - Schistosoma parasites (schistosomiasis)

Answer 15

- Sarcoidosis - Crohn disease - Subacute thyroiditis (de Quervain) - Primary biliary cholangitis

Answer 16

True. - Granulomatosis with polyangiitis - Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) - Giant cell arteritis (temporal arteritis) - Takayasu arteritis

Answer 17

True. - Berylliosis - Talcosis - Hypersensitivity pneumonitis - Breast implants - Penetrating trauma with glass, wood, etc.

Answer 18

--It occurs in response to poorly digestible foreign material 1)Exogenous • Splinter • Suture • Graft material 2)Endogenous • Keratin • Hair shafts in pilonidal sinus --Incited by particles that can’t be readily phagocytosed by a single macrophage but do not elicit a specific immune response (suture or talc).

Answer 19

-Interactions between CD4 T helper cells and macrophages -Macrophages present Ags via MHC II to CD4 helper cells causing their activation -T cells produce cytokines (IL-2 and IFN-γ) • TB • Fungal infection • Sarcoidosis

Answer 20

IL-2 and IFN-γ

Answer 21

- Macrophages cluster around the foreign material | - Multinucleated giant cells with haphazardly arranged nuclei throughout the cytoplasm

Answer 22

type 4 (delayed) hypersensitivity reaction

Answer 23

 Lungs and lymph nodes are the main sites of infection

Answer 24

* Central necrosis * Epithelioid macrophages and Langhans ’giant cells * T-helper cells (within the granuloma) * Occasional plasma cells * A peripheral rim of suppressor T cells and fibroblasts

Answer 25

Ziehl-Nielsen for MTB

Answer 26

An idiopathic, chronic inflammatory disease characterized by the formation of noncaseating granulomas, typically in the lung and, less commonly, in the liver, eyes, and skin. Predominantly occurs in young, African-American women. A chest x-ray often reveals bilateral hilar adenopathy. A biopsy is the gold standard for diagnosis. First-line treatment is corticosteroids.

Answer 27

Round calcium and protein inclusions in the cytoplasm with laminar stratification, seen in granulomas of sarcoidosis

Answer 28

a star-shaped, eosinophilic inclusion body consisting of various lipids (e.g., from sarcoidosis, foreign body reactions)

Answer 29

- Serous inflammation - Fibrinous inflammation - Suppurative inflammation - Ulcers - Sinus - Fistula

Answer 30

inflammation with a thin and watery fluid that lacks fibrinogen and fibrin. It can be seen in viral serositis as well as in skin inflammation (e.g., blisters). It is derived from the blood serum or secretion of the mesothelial lining (this is called an effusion)

Answer 31

``` 1)Effusion •Peritoneal •Pleural •Pericardial 2)Skin blisters (the skin blister resulting from a burn or viral infection represents a large accumulation of serous fluid, either immediately beneath or within the epidermis.) 3)Viral infection 4)Burn ```

Answer 32

Due to an increase in vascular permeability, large molecules such as fibrinogen pass the barrier and fibrin are formed and deposited at in extracellular pace. -Accumulation of fluid and fibrin -Body cavities -May be removed by fibrinolysis (resolution) -Organisation Fibrous exudate is characteristic of inflammation in linings of body cavities (meninges, pericardium).

Answer 33

Fibrous exudate is characteristic of inflammation in linings of body cavities (meninges, pericardium)

Answer 34

by fibrinolysis --Since the fibrinolytic system continuously cleaves and degrades fibrin, hemostasis, and fibrinolysis are processes that occur simultaneously in the circulatory system. --Physiological fibrinolysis Tissue injury → release of factor XII, urokinase and tissue plasminogen activator (tPA) → Breakdown of plasminogen, leading to the formation of active plasmin → breakdown of fibrin by activated plasmin → Release of degradation products, including D-dimers Regulation of fibrinolysis: tPA activity is reduced if tPA binds to plasminogen activator inhibitor (PAI).

Answer 35

-A descriptor for conditions that cause inflammation and the production of purulent exudate (e.g., cutaneous infections).

Answer 36

- Characterised by large amounts of pus - Can be seen in association with certain organisms (staphylococcus) - May lead to abscess formation

Answer 37

- -inflammation → pus formation and tissue necrosis - -The focus of necrosis is separated from healthy tissues by a fibrous capsule. - -have a central region that appears as amass of necrotic leukocytes and dead cells

Answer 38

1) An ulcer is formed when the surface covering an organ or tissue is lost due to necrosis and is replaced by inflammatory tissue (sloughing off of inflamed tissue). 2) Local defect in an epithelial surface(can only occur tissue necrosis and resulting inflammation near the surface such as mucosa of the mouth) 3) Produced by shedding of dead epithelial cells 4) Skin and mucosal surfaces e.g. peptic ulcer 5) They are distinguished from erosions by the extent of tissue loss

Answer 39

A morphologic descriptor used to describe several types of lesions. In dermatology, refers to a loss of a portion of or all of the epidermis. In gastroenterology, refers to a superficial mucosal lesion with intact muscularis mucosae. In dentistry, refers to a loss of tooth enamel.

Answer 40

1) Acute - Loss of the full thickness of the epithelium - May or may not be associated with scarring at the base of the ulcer - Base consisting of fibrin and debris 2) Chronic ulcers - Usually deep penetrating - Always associated with scarring at the base of the ulcer

Answer 41

fibrin and tissue debris

Answer 42

Always associated with scarring at the base of the ulcer

Answer 43

- Tract lined by granulation tissue leading from a chronically inflamed cavity to a surface 1) “Sinuses associated with osteomyelitis” (inflammation of the bone) 2) “Pilonidal sinus”(nest of hairs)

Answer 44

granulation tissue

Answer 45

A pilonidal cyst (intergluteal pilonidal disease) is a skin condition caused by local inflammation of the superior midline gluteal cleft, which may progress to a local abscess or fistula. It is currently hypothesized to be an acquired condition with local penetration of hair follicles and debris in stretched intergluteal pores. Affected individuals – typically obese, sedentary men with excessive body hair and a deep gluteal cleft – may be asymptomatic or present with mild local symptoms such as local oozing or erythema; however, abscesses can also cause severe pain. Pilonidal cysts are diagnosed based on patient history and clinical examination. To treat the condition, radical resection with secondary wound healing is usually necessary. Asymptomatic patients can be treated conservatively.

Answer 46

An abnormal connection between two epithelium-lined surfaces. Examples include gastrocolic fistula, pancreaticoduodenal fistula, and arteriovenous fistula. It can be surgically created (e.g., an arteriovenous fistula created for hemodialysis access) or occur as a complication of trauma or a disease process. - Gastrointestinal fistula in Crohn's disease (acquired fistula) - Tracheo-oesophageal fistula (congenital fistula)

Answer 47

tracheoesophageal fistula

Answer 48

- The acute phase reaction is the initial response of the organism to systemic or local disturbances (e.g., operation, trauma, inflammation, infection, malignancy). - It provides rapid protection for the host by destroying pathogens and promoting the healing processes. Part of this response is the release of more than 30 acute phase reactants, which are produced in the liver and leukocytes.

Answer 49

SIRS (systemic inflammatory response syndrome)

Answer 50

pyrexia (fever)

Answer 51

1. Temperature elevation occurs in response to Pyrogens (substances that stimulate PG synthesis in the hypothalamus). 2. The endotoxin stimulates the leukocyte release of IL-1 and TNF-a that increases COX production of prostaglandins. 3. In the hypothalamus, PGE2 stimulates secondary signals that reset the temperature set point.

Answer 52

PGE2 (synthesized in the hypothalamus!!!!!!!)

Answer 53

IL-1 and TNF-a

Answer 54

by overexpressing COX enzymes

Answer 55

Acute-phase proteins

Answer 56

- C-reactive protein (CRP) - serum amyloid A (SAA) - Fibrinogen à binds to RBCà ↑ESR (erythrocyte sedimentation rate) - Iron regulating peptide- hepcidinà reduce the availability of iron àiron-deficiency anemia associated with chronic inflammation (AOCD) - ferritin - α1-Antitrypsin → protection from protease activity - Serum amyloid A - IL-6

Answer 57

-promotes opsonization of pathogens -Increases the capacity of macrophages to phagocytose -High sensitivity for detecting inflammation -In bacterial infections, especially marked increase -Increases about 6–12 hours after the the inflammatory process begins -Half-life of 24 hours -Not specific to any disease or organ

Answer 58

- protein that stores and releases iron - Serum ferritin levels increase in the case of an infection or malignancy to reduce the amount of free iron available to pathogens or tumor cells, respectively. - In contrast, some organisms (e.g., Pseudomonas) cause serum ferritin levels to drop.

Answer 59

- is the same as leukocytosis - due to accelerated release of bone marrow cells., typically with immature neutrophils in the blood (shift to left). Shift to left means a high number of immature cells. - Usually 4-8 (per microliter of blood)  rises to 15-20 - Bacterial infections = neutrophilia - Parasites = eosinophilia - Viruses = lymphocytosis (increased lymphocyte numbers) - Certain infections (some viruses) = induce leucopenia (decreasing number of WBCs)

Answer 60

A persistent leukocytosis > 50,000 cells/mm³ that is caused by reactive proliferation within the bone marrow (typically of myeloid elements) and elevated LAP in response to stress or infection.

Answer 61

An enzyme found in mature leukocytes. The staining of LAP on a peripheral blood smear is used to calculate the LAP score. A high LAP score is associated with an increased number of mature white blood cells (e.g., from leukemoid reaction or myeloproliferative disorders); a low LAP score is associated with an increased number of immature white blood cells (e.g., from CML).

Answer 62

eosinophils

Answer 63

-Increased pulse and blood pressure -Decreased sweating and rigors (due to redirection of blood flow from cutaneous to deep vascular beds, to minimize heat loss through the skin) -Tendency to sleep -Anorexia and malaise (due to action of cytokines on brain cells) -Severe sepsis -- DIC, hypotension, and shock In severe bacterial infections (sepsis), the large number of organisms and LPS in blood stimulate the production of large amounts of cytokines (mostly TNF and IL-1) --these cause clinical manifestations such as disseminated intravascular coagulation, cardiac failure, and shock.

Answer 64

due to redirection of blood flow from cutaneous to deep vascular beds, to minimize heat loss through the skin

Answer 65

lipopolysaccharide of G- bacteria (endotoxin) | although in clinical practice the most common cause of sepsis is G+ bacteria