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Immunology > 1 - Natural defences and innate immune system > Flashcards

1 - Natural defences and innate immune system Flashcards

1
Q

what are the defenses against the infection?

A
  • Non-specific defenses
  • Innate immune response
  • Adaptive immune response
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2
Q

what are the natural defenses against the infection?

A
  • Aspects of normal body structure and function which protect against infection
  • Highly effective at reducing the risk of infection
  • Frequently breached in sick patients
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3
Q

how skin protects against infection?

A

• Physiological: dry & high salt content
• Mechanical barrier
• Resident flora
Eg. Staphylococcus epidermidis and other commensals
• Transient flora (removed by handwashing) includes Staphylococcus aureus and Gram negative bacilli such as E. coli

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4
Q

what composes skin barrier?

A

Tight junctions between epithelial cells

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5
Q

what is the role of respiratory tract in innate immunity?

A
  • Nasal hairs and mucus (with lysozyme)
  • Normal flora of mouth, upper tract
  • Ciliated epithelium- damaged by smoking & inflammation
  • Cough and sneezing reflex
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6
Q

what is the role of ciliated columnar epithelium?

A

A type of epithelium that consists of simple columnar cells with hair-like projections. Predominantly found in the respiratory tract (e.g., bronchioles) and oviducts (e.g., Fallopian tubes) of the female reproductive tract. In the respiratory tract, these cells propel mucus from the airway; in the female reproductive tract, they move the ovum towards the uterine cavity.

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7
Q

Mucus (chemical barrier) contains nonspecific and specific protective substances against infection. What are they?

A
  • -Lysozyme: enzyme formed from neutrophils, granulocytes, and macrophages that can lyse linkages in peptidoglycans (e.g., the cell wall of gram‑positive bacteria).
  • -Lactoferrin: exhibits enzyme‑like properties and bind iron (iron is essential for the metabolism of numerous bacteria. By binding to lactoferrin, iron is made unavailable for bacterial metabolism. As a result, lactoferrin has an antibacterial effect.)
  • -Immunoglobulins (particularly IgA) bridge the innate and adaptive immune responses.
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8
Q

how eyes protect against the infection?

A
  • Eyebrows and eyelashes prevent foreign bodies such as dirt entering the eye
  • Lacrymal fluid & Blink reflex Windscreen action Lysozyme can lyse bacteria
  • Infections difficult to treat due to poor penetration by antibiotics
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9
Q

what is the lysozyme?

A

An enzyme produced by neutrophils, granulocytes, and macrophages that can lyse linkages in peptidoglycans (e.g., the cell wall of gram-positive bacteria). Plays important antibacterial functions in mucosal barriers (e.g., digestive tract).

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10
Q

how the genitourinary tract protects from infection?

A
  • Free flow of urine with dilution
  • Lysozyme in bladder
  • Acid pH of vagina due to glycogen metabolism by lactobacilli
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11
Q

how the GI tract defends themselves from infection?

A 
•	Acid
•	Peristalsis
Small and large bowel
•	Peristalsis (diarrhoea)
•	Normal flora, especially anaerobes
•	Colicins& short chain fatty acids
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12
Q

what are the defensins?

A

Defensins are single-chain strongly cationic peptides that have a broad spectrum of antimicrobial activity against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. They work synergistically with other host defense molecules such as lysozyme and lactoferrin. The antimicrobial activities of defensins include the ability to form pores in target membranes, to interfere with protein synthesis, and to directly damage DNA.
Alpha-defensins (α-defensins) are found in neutrophils, macrophages, and Paneth cells in the intestine. Paneth cell defensins are called crypticidins and serve to reduce the number of bacteria in the intestinal lumen. Beta-defensins (β-defensins) are secreted by most leukocytes and epithelial cells.

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13
Q
  • Has been on broad-spectrum antibiotics
  • Profuse bloody diarrhea
  • What is happening?
A

C. difficile associated diarrhea

  • -An infection of the lower gastrointestinal tract with C. difficile that produces toxins that cause colonic inflammation and profuse, characteristically malodorous diarrhea. Severe cases are characterized by the formation of pseudomembranous colitis due to necrosis of the colonic mucosa and exudation of fibrin.
  • -C. difficile colonizes the intestinal tract following damage to the bacterial flora (caused by antibiotic treatment). The bacteria has a selective advantage due to its resistance against the most frequently used antibiotics, which destroy other bacterial flora.
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14
Q

what are the non-specific defenses?

A
  • Skin
  • Mucous membranes
  • Mucociliary elevator
  • Gastric acid
  • Peristalsis
  • Flow of fluid eg urine
  • Normal flora
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15
Q

what is the role of inflammation in innate immunity?

A
  • Localises infection
  • Facilitates delivery of cells and proteins of the immune system to the site of injury
  • Promotes local coagulation
  • Increases production of protective proteins
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16
Q

in inflammation, macrophages are activated to secrete…

A

TNF-alfa and IL-6

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17
Q

which interleukine produced by macrophage promotes the liver to synthesize the acute phase proteins…

A

IL-6

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18
Q

what is the acute phase reaction?

A 
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.
--fever
--increase sleep
--decreased appetite
--acute-phase proteins
--hemodynamic effects
--neutrophilia
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19
Q

what are the endothelial effects of IL-1 and TNF?

A
  • -leukocyte adherence
  • -prostaglandin syntheisis
  • -procoagulant activity
  • -syntheiss of IL-1, 6, 8, PDGF
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20
Q

what are the fibroblast effects of IL-1 and TNF?

A
  • -proliferation
  • -collagen synthesis
  • -increase activity of collagenases and proteases
  • -Prostaglandin synthesis
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21
Q

what is the role of IL-1?

A

An interleukin released after immune system contact with lipopolysaccharides (e.g., the wall of gram-negative bacteria). Causes fever and acute inflammation, including chemokine secretion to recruit white blood cells. Induces vasodilation and promotes the adhesion and diapadesis of inflammatory cells by activating endothelium. Dysregulation of IL‑1 in cartilage leads to damage and osteoarthritis, as IL-1 activates osteoclasts.

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22
Q

what is the role of TNF-alfa?

A

A cytokine produced predominantly by macrophages that play a key role in systemic inflammation, apoptosis, and immunity. TNF-α primarily acts as an upregulator of the immune response. It induces fever and increases the production of acute-phase reactants and other pro-inflammatory cytokines. It also enhances the cytotoxic effects of leukocytes and the expression of endothelial adhesion molecules.

  • -Pyrogenic
  • -Cytotoxic and inhibits carcinogenesis of certain tumors
  • -Mediates septic shock
  • -Cause of malignant cachexia
  • -Maintenance of granulomas (critical defense against mycobacterial infections)
23
Q

does innate immunity generate memory?

A
  • Developmentally primitive
  • Provides rapid response
  • Not organism specific – uses pattern recognition molecules
  • Memory not generated
24
Q

does innate immunity act rapid or slow?

A

Response to pathogens is rapid, occurring within minutes to hours of exposure. Preformed mediators (vs adaptive immunity)

25
Q

what are the toll-like receptors?

A
  • -Pattern recognition receptors that bind to pathogen-associated molecular patterns (PAMPs)
  • -Activate the NF-κB pathway
26
Q

what are the pathogen-associated molecular patterns (PAMPs)

A

A group of molecules that are recognized by receptors of the innate immune system as foreign to the host. PAMPs are typically essential for microorganism survival and thus relatively conserved among a class of microorganisms.

27
Q

what is the NF-kB?

A

A transcription factor involved in the regulation of multiple inflammatory and immunologic processes. Activates COX-2. Glucocorticoid therapy inhibits NF-κB and results in immunosuppression.

28
Q

innate vs adaptive immunity?

A 
1)Innate Immunity
•	Pattern recognition receptors
•	Recognise class of pathogen
•	Eg. Toll-like receptors
2)Adaptive Immunity
•	Highly specific receptors formed following recombination of DNA
•	Pathogen-specific
29
Q

pattern recognition molecules?

A
  • -NK cells – NK receptors (KIRs) recognise absence of self- MHC
  • -Macrophages – carbohydrate receptors
  • -Toll - like Receptors
30
Q

what are the important Toll-like receptors?

A
  • -TLR 1: bacterial lipoprotein
  • -TLR 2: bacterial peptidoglycans
  • -TLR 3: viruses
  • -TLR 4: LPS
31
Q

where are PAMPs located?

A
  • on microbes – not mammalian cells
  • essential for microbe survival
  • invariant within class of microorganism
32
Q

what are the examples of PAMPs?

A

Bacterial lipopolysaccharides (LPSs), endotoxins found on the cell membranes of gram-negative bacteria, are considered to be the prototypical class of PAMPs. LPSs are specifically recognised by TLR4, a recognition receptor of the innate immune system. Other PAMPs include bacterial flagellin (recognized by TLR5), lipoteichoic acid from gram-positive bacteria (recognized by TLR2), peptidoglycan (recognized by TLR2), and nucleic acid variants normally associated with viruses, such as double-stranded RNA (dsRNA), recognized by TLR3 or unmethylated CpG motifs, recognized by TLR9.

33
Q

how innate immunity recognize bacteria and viruses?

A

recognizes PAMPs

34
Q

what are the cells involved in innate immunity?

A

1) Granulocytes
- -Neutrophils
- -Eosinophils
- -Basophils
2) Mast cells
3) Antigen-presenting cells
- -Mononuclear phagocyte system
- -Monocytes
- -Macrophages
- -Dendritic cells
- -B cells (link to adaptive immunity)

35
Q

what are the mast cells?

A

A type of granulocyte cell found in interstitial connective tissue (e.g., around submucosa and surrounding blood vessels). Expresses receptors for the Fc portion of IgE antibodies. In response to allergen contact, IgE antibodies can trigger degranulation of mast cells, which causes histamine secretion, inflammation, and allergic symptoms.

36
Q

what are the natural killer cells?

A

A type of lymphocyte that can detect downregulation of MHC class I molecules (e.g., by tumor cells or virally-infected cells). In response, they activate and release cytotoxic granules (perforin and granzyme) that induce lysis of target cells.

1) Kill via
- -Induction of apoptosis (granzymes, perforin)
- -Antibody-dependent cell-mediated cytotoxicity (activated by binding of CD16)
2) Cytokine production: INF-γ and TNF-α
3) Function enhanced by IFN-α and IFN‑β, IL-2, IL-12

37
Q

what is the association of NK cella and MHC I?

A

NK cells are inhibited by MHC-I receptors. If a cell is lacking these receptors, NK cells secrete perforin and granzyme, resulting in the death of the MCH-I-negative cell.

38
Q

how neutrophils migrate to tissues?

A
  • -margination
  • -rolling
  • -adhesion
  • -diapeesis
  • -migration
39
Q

what re the molecules required for neutrophil rolling?

A

1_On endothelial cells

  • -P-selectin: stored and released from Weibel-Palade bodies within the endothelium in response to inflammation
  • -Release is mediated by histamine.
  • -E-selectin: released in response to inflammatory mediators, such as TNF and IL-1
  • -Other: GlyCAM-1, CD34
    2) On leukocytes
  • -Neutrophils and other leukocytes express Sialyl-LewisX and L-selectin, respectively.
  • -These molecules transiently bind to and dissociate from endothelial selectins, allowing leukocytes to roll along the vascular wall
40
Q

how neutrophils adhere to endothelium?

A

1) On endothelial cells
- -Intercellular adhesion molecule (ICAM, also called CD54)
- -Vascular adhesion molecule (VCAM, also called CD106)
- -Both upregulated by TNF and IL-1
2) On neutrophils and lymphocytes
- -Neutrophils: β2-integrin (lymphocyte function-associated antigen-1, LFA-1, composed of CD18 and CD11a) → binds to ICAM
- -Lymphocytes and monocytes: β1-integrin → binds to VCAM
- -Expression of integrins is activated by leukotriene B4 (LTB4) and C5a

41
Q

how do neutrophils move through the blood vessel wall?

A

Requires expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, also called CD31) on neutrophils, endothelial cells, and platelets

42
Q

what are the mediators of chemotaxis?

A
  • -Leukotrienes: e.g., LTB4
  • -Platelet-activating factor (PAF)
  • -Chemokines: e.g., IL-8
  • -Kallikrein
  • -Complement fragments: e.g., C5a
  • -Bacterial products
43
Q

how phagocytes kill engulfed bacteria?

A

1) Oxygen-dependent:
- -Involves production of reactive oxygen species (see Respiratory burst)
- -Diseases associated with defective oxygen-dependent killing
- -Chronic granulomatous disease of childhood: deficiency of NADPH oxidase → lack of superoxide ion → recurrent or persistent infections with catalase-positive organisms (e.g., S. aureus)
- -Myeloperoxidase deficiency: recurrent fungal infections
2) Oxygen-independent: involves lysosomal enzymes such as acidic hydrolases and lysozyme

44
Q

what are the important phagocyte recognition receptors?

A

Phagocyte receptor b Ligand

  • -Mannose receptor——-Mannose, fucose, N-acetylglucosamine
  • -Scavenger receptor——Low-density lipoprotein
  • -Opsonin receptor———Fc fragment of IgG, C3b
45
Q

what abnormal cells are detected by NK cells?

A
  • -Detection and destruction of cells that do not express MHC-I receptors
  • -Cells infected with viruses (especially herpes viruses)
  • -Tumor cells
46
Q

what are the soluble factors of innate immunity?

A
  • Natural opsonins
  • Complement
  • Interferons
  • Cytokines
47
Q

what is the function of the complement system?

A
  • -Opsonization: the process of altering bacteria to increase their susceptibility to phagocytosis. C3b and IgG are the two main opsonins for bacteria (via C3b).
  • -Lysis of bacteria (particularly gram‑negative bacteria).
  • -C5–C9 form the membrane attack complex (MAC) → perforation of the cell wall → cell lysis
  • -Activation of mast cells and granulocytes (C3/C4/C5) → anaphylaxis
  • -Chemotaxis of neutrophils → C5a
  • -Clearance of immune-complexes → C3b
48
Q

what are the interferons?

A

cell-signaling proteins secreted by cells infected by viruses, bacteria, or parasites, as well as by leukocytes and fibroblasts in response to infection or neoplastic proliferation. Interferons have antiviral, antimicrobial, and antiproliferative properties. Part of the innate immune system.

49
Q

what is the function of IFN-α?

A
  • -First line of defense against all viral infections
  • -Inhibits viral protein synthesis by activating ribonuclease L (leads to the degradation of cellular and viral mRNA)
  • -Promotes the expression of MHC class I molecules → activation of NK cells and cytotoxic T cells
  • -Inhibits megakaryocyte stem cell differentiation and proliferation
50
Q

IFN-α synthesis is stimulated mainly by…

A

viral dsRNA produced during viral replication. DNA viruses provoke a less intense response.

51
Q

what is the function of IFN-β

A
  • -Promotes the expression of MHC class I molecules → activation of NK cells and cytotoxic T cells
  • -Inhibits viral protein synthesis by activating ribonuclease L (leads to the degradation of cellular and viral mRNA)
  • -Suppresses inflammation
52
Q

what is the function of IFN-γ?

A
  • -Activates macrophages to increase phagocytosis (positive reinforcement)
  • -Formation of granulomas (critical against mycobacterial infections)
  • -Suppresses a Th2 response (negative feedback)
  • -Promotes the expression of MHC class II molecules
53
Q

what is the dendritic cell?

A

A phagocytic antigen-presenting cell. Expresses MHC class II and Fc receptors. Inhibited by interleukin-10.

54
Q

what is the role of IL-12?

A

An interleukin that induces the maturation of naive T-cells into helper T (Th)-cells and the production of IFN-gamma and TNF-alpha by Th-cells. Reduction of IL-12 activity (e.g., IL-12 receptor deficiency) can cause immunodeficiency.

Immunology (9 decks)

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