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Dental Histology - Lymphoid 1
Exam 2
63
Medical
Professional
10/14/2008

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Term
Necessary for proper Immunity
Definition
ability of the body to differentiate between 'self' and 'non-self'
Term

Categories of immune reactions

 

(4 total) 

Definition
1. innate immunity
2. acquired immunity
3. cellular immunity
4. humoral immunity 
Term
Innate immunity
Definition
Quick and non-specific
 
    consists of: 
-mucosal and cutaneous barriers
-the complement system 
-phagocytes (macrophages and neutrophils)
-natural killer cells
  
Term
Aquired Immunity
Definition
-More finely tuned and specific
-formation of antigenic memory
-enables faster and specific immune response folloing a future introduction of the pathogen
 
consits of
-B lymphocytes
-T lymphocytes
-antigen presenting cells 
Term
Cellular Immunity
Definition

neutralization of pathogens is accomplished by cells

 

(maily t cells) 

Term
Humoral Immunity
Definition
utilized antibodies to neutralize pathogens
Term
Non-Cellular components of Immune System
Definition

Antigen

Epitopes

Cytokines

Clusters of differentiation molecules

Antibodies 

Term
Antigen (Ag)
Definition
-has ability to react with antibody
-when bound to IgG or IgM = activate complement                                                 system
    -results in destruction of certain microorganisms 
Term
Epitopes (antigenic determinants)
Definition
-small molecular regions of antigen
-contribute to specificity of humoral immunity
             (B cell response) 
-specificity from proteins asscoiated with MHC present              on surface of antigen-presentign cells
 
 
Term
Cytokines
Definition
-low molecular weigh proteins and glycoproteins
-produced mainly by macrophages and lymphocytes
           aslo by endothelial cells and fibroblasts
-wide range of activity
-can affect cells outside the immune system
-inflammatory response, wound healing, hemapoiesis,            and immunity 
Term
3 types of Cytokines
Definition

Interleukins: affect leukocytes

Chemokines: draw leukocytes to site of inflammation

Interferons: produced by virus-infected cells to decrease viral replication 

Term
Clusters of Differentiation (CD) Molecules
Definition
-surface markers
-distinguish seperate lineages/functions of lymphocytes:
 
CD3 - on T cells
CD4 - T helper cells (T-h)
CD8 - cytotoxic T cells
CD20 - found on B cells
CD40 - B cells; allows cell to be activated byT-h cells
CD45 - leukocyte common antigen
 
Term
Antibodies (immunoglobulins)
Definition
-circulation glycoproteins
-produced in response to epitope
-interact with antigen
-produced by plasma cells
-secreted into blood and/or lymphatic circulation
-lable substances as foreign - target for destruction
-form a coat that percipitates groups of bacteria
        = enhanced phagocytosis
 
Term
Antibody Structure
Definition
-2 light chains+ 2 heavy chains held by disulfide bond
-stem = Fc region
        =binds receptors on surfaces of certain cells
-arm = Fab region = amino acid variability
        = specificity of immune reaction 
Term

Classes of antibodies

(5 total) 

Definition
1. IgG (75-80%)
2. IgA (10-15%)
3. IgM (10%)
4. IgE (<1%)
5. IgD (<1%) 
Term

IgG

75-80% 

Definition
-can cross placental barrier
-responsible for protecting fetus and newborn
-activates phagocytosis through opsonization
-stimulates NK cell activity 
Term

IgA

10-15%

 

Definition
-predominant antibody in secretions
-present as dimer
-connected by protein known as J chain and secretory          component
-monomer within blood
-neonatal passive immunity
-mucosal immunity
-helps epsinophils id and kill parasites 
Term

IgM

10% 

Definition
-present as pentamer
-held together by J chains
-commonly found on surface of B cells
        -acts as antigen receptor
   =B cell proliferation and differentiation into plasma        cells
-first Ig ti be produced in an initial response
-can activate te complement system 
Term

IgE

<1% 

Definition
-binds to receptors on basophils and mast cells
-cross-linking by antigen = degranulation = release of          things such as histamine = allergic reaction 
-assists in targeting parasitic worms for destruction 
Term

IgD

<1% 

Definition
-poorly understood
-found on surface B cells
-similar function to IgM
Term

Cells of the Immune System

(4 Total) 

Definition
1. Lympoid Cells
2. Mononuclear Phagocytes
3. Antigen-Presenting Cells
4. Granulocytes 
Term

Lymphoid Cells

 

B cells

T cells

Natural Killer cells 

Definition
-20-40% of leukocytes
-continuosly circulate in blood and lymph
-able to migrate into tissue and lymphoid organs
-round cells, larger than erythrocytes
-round nucleus with small indentation
    H&E = dark blue
-thin rim of basophilic cytoplasm
-few organells
-abundent ribosomes 
Term
Initial response of lymphoid cells
Definition
-slow to evolve
-lymphocytes undergo clonal expansion =proliferation     to form effector memory cells 
-second exposure is faster and more powerful
    b/c of immunological memory 
 
B effector cells = plasma cells
T effector cells = cytotoxic and helper
    cytotoxic - destroy foreign/abnormal
    helper - secrete cytokines that activate stuff 
Term

B Lymphocytes

 

formation of memory and plasma cells 

Definition
-mature in bone marrow
-have membrane-bound immunoglobulins
    (antigen receptor)-each Ig has same binding site
-activated by antigen binding to antibody
    -undergoes clonal proliferation
        =many memory and plasma cells
 
 
Term
Plasma Cells
Definition
-produce and secrete a specific antibody
-ovoid in shape
-round, eccentrically place nucleus 'clock-face' distribution of heterochromatin
-cytoplasm deeply basophilic except perinuclear area
 
Perinuclear Area = centriols and Golgi have pale staining quality
Term
Memory Cells
Definition
-express either B cell receptors or TCRs
-do NOT participate in initial immune reaction
-live for years
-stronger attraction to antigens than naive B cells
-formed in large numbers after exposure of original clone to antigen
-rapid/effective response when antigen re-introduced
Term

B Lymphocytes

After exposure and acivation 

Definition
-produce IgM which attaches to surface of pathogen
    =activated complement system
 
or
 
IgM coats viruses and prevent them from attaching to hosts
 
-later, B cells can produce different antibody class if exposed to certain cytokines released by T cells 
Term
T-Lymphocytes
Definition
-formed in bone marrow
-mature in thymus
-cell membrane carries antigen-binding T-recepto cell
        (TCR) - similar to Ig molecules
-TCR does NOT recognize free antigen
-recognized MHC (aka human leukocyte antigen)
    -Ag-MHC present on antigen - presenting cells, cancer cells, virus-infected cells, and graft tissue
Term
MHC - I
Definition
-found on all nucleated cells
--short peptides derived from post-cell proteins
-allows T-h to see if cell is producing self or nonself protiens 
Term
MHC
Definition
-two types I and II
-each genetically distinct person has own type of MHC molecule
-to be stimulated: T cell must recognize epitope and MHC complex 
Term
MHC II
Definition
-found on antigen-presenting cells
-long peptides form sources outside the cell
-allow T-h to see if antigen presenting cell (APC) is encountering self or nonself proteins 
Term
CD Molecules of Lymphocytes
Definition
-subclasses of lymphocytes
-present on surface
CD4+ T cells : only recognize MHC II molecules
                    T HELPER CELLS
CD8+ T cells: only recognize MHC I molecules
                     T CYTOTOXIC CELLS
 
Normal = 2 CD4: 1 CD8
           Aids = ratio drops - less t helper cells
 
Term
T cytotoxic cells
Definition
-interact with MHC I on cell membrane of host
-in conjunction with cytokines
-cells multiple and differentiate into cytotoxix T lymphocyte (CTL)
 
CTL can detect and destroy altered host cells 
Term
T Helper cells
Definition
-MHC II on antien presenting cell
-undergo clonal proliforation to make cells specific for Ag-MHC complex
-after can produce cytokines - interact tith other cells in immune response
 
-types of cytokines can modify type of immune response elicited 
Term
T-Helper 1 response
Definition
-cytokines involves activate certain T cells and macrophages
-sytokines support an inflammatory reaction
-invloves an underlying bacterial or viral infection 
Term
Virally-Transformed Cells
Definition
-APC presents epitope to T-h1 cell - activation
-T-h1 releases TNF, IL-2 = cell proliferation, INF-gamma (activatesT-c cells)
 
 
        
 
Term

Virally-Transformed Cells

CTL activation 

Definition
Only if:
1. CTL is bound to APC
2. CD8 molecule on CTL recognizes the epitope-MHC 1 complex on the APC 
Term

Virally-Transformed Cells

CTL Activated and Proliferated 

Definition

Daugther cells look for infected cells to kill via:

a. Perforins:

    -released by CTL after binding to target cell 

    -glycoproteins that insert into targent cell memb

    -assemeble into strucures and form pores

    -more assembeled = mem distrupted = lysed

b. Perforins + Granzymes:

    -released by CTL after binding to target cell 

    -granzymes enter target through perforin pores

    -induce apoptosis 

Term
Bacteria
Definition
-engulfed by macrophages
-retain ability to proliferate inside phagosomes
 
To Destroy:
    Machrophages must be activated by T-h1 cells 
Term

To Destroy bacteria:

The process of activating macrophages via T-h1 cells 

Definition
1. TCR and CD4 of T-h1 recognize epitope MHC II         complex of macrophage
2. T-h1 cell produces IL-2 receptors on itself and         secretes IL-2 to activate = rapid proliferation of         Th-1 cells which contact bacteria macrophages
3. After recognizing epitope, T-h1 releases                     IFN-gamma = activate macrophage 
4. Macrophage expresses surface TNF-alpha receptors,     then releases TNF-alpha 
5. IFN-gamma and TNF-alpha bind to their receptors     =macrophage produce O2 radicals = KILL bacteria 
Term
T Helper Cell 2 response
Definition

activates B cells and antibody-dependent immune reactions

 

usually invlolves parasitic infection or infection of the mucosa 

Term

T Helper Cell 2 response

Step 1


 

Definition

Step 1

-antigen bound to B cell receptor go into cytoplasm

-epitope cleaved off

-fuse to MHC II molecule

-new colpex goes to cell surface and presented to T-h

Term

T Helper Cell 2 response

Step 2

Definition
Step 2

-two signals made

    1. T-h must recognize epitope with TCR and MHC II          complex with CD4 molecule

    2. CD40 receptor must bind to the CD40 molecule          on the surface of B cell 

Term

T Helper Cell 2 response

Step 3

Definition

Step 3

-B cell activated and begins dividing

-simultaneously, T-h cell produces

        IL-4, 5, and 6 

    -causes differntiation of new cells into memory and         plasma cells

-produced IL-10 = inhibits T-h proliferation 

Term
Regulatory (suppressor) T cells
Definition
-inhibit activity of T and B cells
-therefore terminate immune response
-mechanism of action debatable 
Term
Natural Killer Cells (NK)
Definition
-large lymphocytes (5-10% of circulating lymph)
-granular cytoplasm
-do NOT have characteristic cell surface markers
-activity NOT restricted by MHC
-eliminate wide range of altered host cells in absence of previous exposure
 
-effective againd tumor cells and some virus-infected cells 
Term

Natural Killer Cells (NK)

2 ways 

Definition
1. detect decrease in MHC I mol or abnormalies in cell    surface markers in altered host cells
2. have a receptor (CD 16) for the Fc protion of IgG;       enable them to bind to antibody and destroy cell;     occurs through release of perforins and granzymes
 
-also have receptors for diff cytokins including:
    IFN-alpha-beta, IL-12, bacterial lipopolysaccharide
-in turn secrete IFN-gamma inducing macrophages kill bacteria
Term
Mononuclear Phagocytes
Definition
-arise from granulocyte-monocyte lineage in bone marrow
-monoblast is precursor
    -differentiates into promonocyte
-promonocyte = big baso cell, indended nucleus
-after 2 cell division, promonocyte enters bloodstream     -gives rise to mature monocytes
    -have abundent RER and golgi 
Term
Monocytes
Definition
-do NOT have specific granules - (not granulocytes)
-have cytoplasmic granules in form of primary lysosomes
-circulate for about 8 hours
-enter tissue and differentiate into machrophages 
Term
Machrophages
Definition
-differentiation= sign increase in size
-increase in quantity and complexity of organelles
-enhanced phagocytic ability
-increase levels of hydrolytic enzymes
-able to secrete variety of molecules in immune response
-have wide distrubution 
Term
Distribution of Macrophages
Definition
1. Alveolar Macrophages = lung
2. Histocytes = connective tissue
3. Kupffer Cells = liver
4. Mesangial Cells = kidney 
5. Microglia = brain
6. Osteoclasts = bone 
Term
Activation of Macrophages during immune response
Definition
-antigen phagocytosis is initiating event
    = increased activity following cytokine release by             T-h cells (especially IFN-gamma), inflammatory          mediators, and exposure to compounds on              surface of bacteria 
-once activated=increased phagocytosis, secretion of      inflammatory mediators, and T-H activation 
-proteins that kill bacteria, virsus and tumors made
-also increases expression og MHC II molecules on          cell surface = imporved ability to act as APC 
Term
Phagocytosis
Definition

ability to engulf and digest extracellular substances

 

enhanced when antigen coated with antibodies

-opsonization 

Term
Phagocytosis Process
Definition
-migration of marophage towards antigen to be eaten
    via chemotaxis
-antigen binds to cell mem of macrophage
-pseudopod extensions around substance form             phagasome 
-moves to center + combines with lysosome
    =phagolysosome
-enzymatic digestion
-products expelles via exocytosis 
Term

Antimicrobial Action

4 ways 

Definition
1. oxygen-dependent killing
2. oxygen-independent killing
3. antigen processing and presentation
4. secretion of factors 
Term
Oxygen-Dependent Killing
Definition
-production of reactive O2 and nitrogen intermediates
-ingestion of microorganism = increase in metabolism     called respitory burst
-results in chemical cascade converting O2 into             superoxide radical 
    =very destructive to microorganisms
-NO generated when bacterial lipopolysaccaride is            exposed to the macrophage in the company of          IFN-gamma 
Term
Oxygen-Independent Killing
Definition
-microorganism destroyed by:
    lysozyme, defensins, and hydrolytic enzymes                          (funtion in absense of O2)
 
-tumor necrosis factor-alpha (TNF-alpha) can be affective against certain tumor cells 
Term
Antigen Processing and Presentation
Definition
 
 
can present antigen to T-h cells after first digesting it into smaller peptides and expressing them on the surface in conjunction with MHC II molecules
Term
Secretion of Factors
Definition
-macrophages produce wide variety of proteins with diff functions
 
Significant Ones:
    IL 1, 6, alpha, TNF-alpha, and complement protein
-they are concerned with:
    -initiation+maintenance of inflammatory response 
    -removal of microorganisms
    -induction of hematopoiesis 
Term
Antigen-Presenting Cells
Definition
-derived from bone marrow
-include:
    B lymphocytes, Langerhans cells, dendritic cells
-ingest foreing particle
-break them into endosomes
-express resulting smal peptides on surface by linking     them to MHC II molecules
        (proteins from viruses and certain bacteria and         parasites are linked to MHC I molecules)
-process necessary for activation of T cell 
Term

Granulocytes

(5 types) 

Definition
1. dendritic cells
2. neutrophils
3. eosinophils
4. mast cells
5. basophils 
Term

Dendritic Cells

( 4 major types) 

Definition
1. Langerhans Cells
2. Interstitial Dendritic Cells
3. Myeloid Cells
4. Lymphoid Dendritic Cells 
Term
Dendritic Cells
Definition
-morphologiccally = elongated cytoplasmic processes
-involved in antigen presentation to T-h cells                 following phagocytosis and processing
-cellular precursors have wide distribution
(they engulf and proces antigend in peripheral tissue)
-contain high quantity of MHC II and stimulatoruy         surface molecules (B7) 
    -enable quicj funtion w/out becoming activated
-migrate to regional lymph nodes or spleen
    -make antigen presentation in areas containg large      amounts of T cells 
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