8 WBC Flashcards
Types of Immune System
- Innate
2. Adaptive
WBC
- Aka
- Normal value
- Leukocytes
2. 5-10 x 10^3 u/L
Classifications of WBC
- Granulocyte
- Neutrophils, Eosinophils, Basophils - Agranulocyte/Mononuclear Leukocytes
—Monocytes
-Lymphocytes: T cells, B cells, NK cells
Most abundant type of WBC?
Neutrophils
Describe:
1. Neutrophils
- Basophils
- Eosinophils
- Monocyte
- Neutrophils - multilobed, polymorphonuclear, phagocytose foreign invaders
- Basophils - release histamine that help body’s allergic response to pathogen; contains proteases, B-glucuronidase, and lysophospholipase
- Eosinophils - attack organisms that are too big to be phagocytosed e.g. parasites; involved in allergic reaction, autoimmune diseases, and some cancers
- Monocytes: Precursor of tissue macrophages (“large eaters”); phagocytic cells; Antigen presenting cell
- 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
Major part of pus
Dead neutrophils
Least abundant WBC
Basophils
Acute Inflammatory Response
1. Principal Steps
2. Multiple Cell Types Involved A. Basophils: B. Neutrophils C. Monocytes D. Lymphocytes
- 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
Migration of leukocytes from blood to the site of injury or infection IN RESPONSE to chemical signals
Chemotaxis
Diapedesis mechanism
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
What mediates chemotaxis?
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
What are chemokines?
Small 6-10 kDa proteins secreted by activated WBC to attract additional neutrophils to the site of infection
Subclasses of Chemokines
Basis?
Basis: Number and spacing of cysteine residues forming the disulfide bond which stabilizes protein
Types:
- Type C
- intrachain disulfide bond formed by a pair of conserved cysteine residues - Type CC
- Type C + additional cysteine residues lying adjacent to first pair - Type CXC
- Pair of cysteine are separated by an intervening amino acid residue - 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
Integrins
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
Principal Integrins of WBC
VLA-1, -5, -6
Function: Cell-ECM Adhesion
LFA-1
Fxn: Adhesion of WBC to vascular endothelium
Type 1 Leukocyte Adhesion deficiency
- Cause
- Effect
- Manifestation
- Cause: Lack Beta 2 subunit of integrin
- Effect: Impairs ability to adhere to vascular endothelial cells impending diapedesis
- Recurrent bacterial and fungal infections
Phagocytosis
1. Mechanism
*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.
Given these enzymes, give the reaction catalyzed/fxn
- Myeloperoxidase (MPO)
- NADPH oxidase
- Lysozymes
- Defensins
- Lactoferrin
- Elastase, Collagenase, Gelatinase, Cathepsin G
- MPO
Rxn/Fxn: H2O2 + X- +H+ -> HOCl + H2O
-for green color of pus; deficiency can cause recurrent infections - NADPH oxidase
Rxn/Fxn: 2O2 + NADPH -> 2O2 + NADP + H+
-key component of respiratory burst; deficient in chronic granulomatous disease - 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 - Defensins
- Basic antibiotic peptide (20-33 aa)
- Kill bacteria by causing membrane damage - Lactoferrin
- Iron-binding protein
- inhibit growth of certain bacteria by binding iron; may be involved in regulation of proliferation of myeloid cells - Elastase, Collagenase, Elastinase, Cathepsin G
- Protease; abundant in macrophages
- breakdown protein components of infectious organisms; generate fragments for antigen presentation
NADPH oxidase system
- 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
ROS generation steps
Superoxide synthesis via NADPH oxidase system -> Spontaneous dismutation of H2O2 from 2 molecules of superoxide -> Formation of hypohalous acids by myeloperoxidase
Catalyzes production of chlorinated oxidants; present in large amounts in neutrophil granules
Myeloperoxidase
What are chloramines?
Microbicidal agents without causing damage to surrounding tissues; less powerful than HOCl
Chronic granulomatous disease of the upper respiratory tract caused by gram (-) Klebsiella rhinoscleromatis.
Rhinosclerosa
What is Chediak-Higashi syndrome?
No phagolysosome (protein involved in organelle membrane fusion)
What dissolves histone-polynucleotide complexes in NETs to form neutral citrulline residues?
Peptidylarginine deiminase
Phagocyte-derived proteases can damage healthy cells. How? What does the body do to prevent it?
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.
What happens if you lack alpha1-antitrypsin?
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
Leukocyte secrete factors
- Cytokines-mostly glycosylated
- Eicosanoid
- Cytokines: IL, IFN, Chemokines
2. Leukotrienes, Prostaglandin
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
Histamine
