8 WBC Flashcards

1
Q

Types of Immune System

A
  1. Innate

2. Adaptive

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2
Q

WBC

  1. Aka
  2. Normal value
A
  1. Leukocytes

2. 5-10 x 10^3 u/L

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3
Q

Classifications of WBC

A
  1. Granulocyte
    - Neutrophils, Eosinophils, Basophils
  2. Agranulocyte/Mononuclear Leukocytes
    —Monocytes
    -Lymphocytes: T cells, B cells, NK cells
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4
Q

Most abundant type of WBC?

A

Neutrophils

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5
Q

Describe:
1. Neutrophils

  1. Basophils
  2. Eosinophils
  3. Monocyte
A
  1. Neutrophils - multilobed, polymorphonuclear, phagocytose foreign invaders
  2. Basophils - release histamine that help body’s allergic response to pathogen; contains proteases, B-glucuronidase, and lysophospholipase
  3. Eosinophils - attack organisms that are too big to be phagocytosed e.g. parasites; involved in allergic reaction, autoimmune diseases, and some cancers
  4. Monocytes: Precursor of tissue macrophages (“large eaters”); phagocytic cells; Antigen presenting cell
  5. Lymphocytes
    - B Cells: Mature in BM -> develop into plasma cells -> secrete ABs
    - T cells: Mature in thymus -> Secrete chemicals -> recruit other immune cells and help coordinate attach
    - NK cells: target virally infected and malignant cells for destruction
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6
Q

Major part of pus

A

Dead neutrophils

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7
Q

Least abundant WBC

A

Basophils

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8
Q

Acute Inflammatory Response
1. Principal Steps

2. Multiple Cell Types Involved
A. Basophils:
B. Neutrophils
C. Monocytes
D. Lymphocytes
A
  1. Principal steps
    Increased vascular permeability -> Entry of activated leukocytes into tissues -> Platelet activation -> Spontaneous subsidence/resolution if microoorg has been dealt with

2.
A. Basophils: secrete histamine -> fluid accumulation
B. Neutrophils: phagocytosis -> Use of ROS, hydrolytic enzymes
C. Monocytes: Macrophages -> Phagocytose
D. Lymphocytes: Produce ABs and tag microbes for elimination

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9
Q

Migration of leukocytes from blood to the site of injury or infection IN RESPONSE to chemical signals

A

Chemotaxis

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10
Q

Diapedesis mechanism

A

Amoeboid mechanism involving the cytoskeleton-mediated contortion of the cells

Pseudopod extends between cells of the capillary endothelium -> Once anchored on other side, cytoskeletal proteins squeeze contents of cell through the projection -> fill distal end of pseudopod -> form new translocated cell body & leave behind deflated remains

Once within tissues -> amoeboid locomotion occurs

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11
Q

What mediates chemotaxis?

A

GPCRs!!! PPLC -> PIP2 -> DAG + IP3 -> IP3 release Ca2+ activate actin myosin cytoskeleton -> Cell migration and granule secretion in neutrophils

DAG + Ca2+ -> Activate PKC -> P of other proteins

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12
Q

What are chemokines?

A

Small 6-10 kDa proteins secreted by activated WBC to attract additional neutrophils to the site of infection

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13
Q

Subclasses of Chemokines

Basis?

A

Basis: Number and spacing of cysteine residues forming the disulfide bond which stabilizes protein

Types:

  1. Type C
    - intrachain disulfide bond formed by a pair of conserved cysteine residues
  2. Type CC
    - Type C + additional cysteine residues lying adjacent to first pair
  3. Type CXC
    - Pair of cysteine are separated by an intervening amino acid residue
  4. Type CX3C
    - Pair of cysteine is separated by 3 intervening amino acid
    - largest of the 4 types
    - longer C terminus that includes sites of covalent modification by glycosylation
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14
Q

Integrins

A

A. Facilitates diapedesis
B. Mediates adhesion of leukocytes to vascular endothelium
C. Non covalently associated alpha and beta subunits
D. Contains extracell-, TM, and intracellular segments

Extracellular segment:
Bind to ECM proteins possessing R-G-D

Intracellular segment:
Bind to cytoskeletal components e.g. actin and vinculin

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15
Q

Principal Integrins of WBC

A

VLA-1, -5, -6
Function: Cell-ECM Adhesion

LFA-1
Fxn: Adhesion of WBC to vascular endothelium

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16
Q

Type 1 Leukocyte Adhesion deficiency

  • Cause
  • Effect
  • Manifestation
A
  • Cause: Lack Beta 2 subunit of integrin
  • Effect: Impairs ability to adhere to vascular endothelial cells impending diapedesis
  • Recurrent bacterial and fungal infections
17
Q

Phagocytosis

1. Mechanism

A

*Opsonization - tagging of invader w/ protective proteins to facilitate recognition by phagocytic leukocytes

Mech:
A. Neutrophil binds Ag molecule on opsonized microbe via a receptor -> Neutrophil envelops microbe -> Secretory granules fuse with newly internalized phagosome, delivering their contents -> Granule-derived enzymes and cytotoxins destroy microorganisms -> Phagosome exocytoses remaining debris => Debris endocytosed by Th cells and route to MHC -> Antigen presentation to stimulate production of new Abs.

18
Q

Given these enzymes, give the reaction catalyzed/fxn

  1. Myeloperoxidase (MPO)
  2. NADPH oxidase
  3. Lysozymes
  4. Defensins
  5. Lactoferrin
  6. Elastase, Collagenase, Gelatinase, Cathepsin G
A
  1. MPO
    Rxn/Fxn: H2O2 + X- +H+ -> HOCl + H2O
    -for green color of pus; deficiency can cause recurrent infections
  2. NADPH oxidase
    Rxn/Fxn: 2O2 + NADPH -> 2O2 + NADP + H+
    -key component of respiratory burst; deficient in chronic granulomatous disease
  3. Lysozyme
    Rxn/Fxn: Hydrolyzes link between N-acetylmuramic acid and N-acetyle-o-glucosamine found in certain bacterial cell walls
    -Hydrolyzes bacterial peptidoglycans; abundant in m
  4. Defensins
    - Basic antibiotic peptide (20-33 aa)
    - Kill bacteria by causing membrane damage
  5. Lactoferrin
    - Iron-binding protein
    - inhibit growth of certain bacteria by binding iron; may be involved in regulation of proliferation of myeloid cells
  6. Elastase, Collagenase, Elastinase, Cathepsin G
    - Protease; abundant in macrophages
    - breakdown protein components of infectious organisms; generate fragments for antigen presentation
19
Q

NADPH oxidase system

A
  • Comprised of: Cyt b558
  • Upon activation, cytoplasmic peptides assoc with Cyt b558 -> initiate respiratory burst

Respiratory burst:

  • Accompanying surge in O2 consumption during ROS production
  • After internalization of microbe
  • large qts of NADPH is required via PPP
  • Cell is protected from any superoxide that may escape from the phagosomes by superoxide dismutase
  • H2O2 can be used as substrate for MPO or disposed by gluta
20
Q

ROS generation steps

A

Superoxide synthesis via NADPH oxidase system -> Spontaneous dismutation of H2O2 from 2 molecules of superoxide -> Formation of hypohalous acids by myeloperoxidase

21
Q

Catalyzes production of chlorinated oxidants; present in large amounts in neutrophil granules

A

Myeloperoxidase

22
Q

What are chloramines?

A

Microbicidal agents without causing damage to surrounding tissues; less powerful than HOCl

23
Q

Chronic granulomatous disease of the upper respiratory tract caused by gram (-) Klebsiella rhinoscleromatis.

A

Rhinosclerosa

24
Q

What is Chediak-Higashi syndrome?

A

No phagolysosome (protein involved in organelle membrane fusion)

25
Q

What dissolves histone-polynucleotide complexes in NETs to form neutral citrulline residues?

A

Peptidylarginine deiminase

26
Q

Phagocyte-derived proteases can damage healthy cells. How? What does the body do to prevent it?

A

Can damage healthy cells when small amounts of proteinases leak out into normal tissues

What the body does:
Alpha2 macroglobulin
-antiproteinase forming a noncovalent complex with certain proteinases. Thus, inhibiting their activity.

27
Q

What happens if you lack alpha1-antitrypsin?

A

Elastase activity in pulmonary tissue is uninhibited

=Disintegration of alveolar septum 2’ to elastase proteolytic activity

=Septal rupture & loss of alveolar elasticity

=Pulmonary emphysema

*Smoking oxidizes a met residue involved in binding alpha1-antitrypsin to elastase

28
Q

Leukocyte secrete factors

  1. Cytokines-mostly glycosylated
  2. Eicosanoid
A
  1. Cytokines: IL, IFN, Chemokines

2. Leukotrienes, Prostaglandin

29
Q

Secreted by activated basophils and mast cells

Maintains blood flow to site of injury or infection

Stimulate accumulation of fluid/edema which facilitates leukocyte migration

A

Histamine