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Immunology Unit 1
N/A
152
Medical
Graduate
03/24/2013

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Term
Immunity
Definition

Reistance to infectious diseases.

 

Occurs after the immune system recognizes and eliminates the pathogen. 

Term
Immune System
Definition

Collection cells, tissues and molecules that mediate this resistance.

 

Term
Immune Response
Definition
Coordinated reaction of cells and molecules to infectious agents.
Term

Vaccination (Immunization)

 

Definition
Preventing severe diseases by teaching the immune system with an infectious agent that cannot cause disease.
Term
Pathigens can be divided into _____, _____, _____, and ______.
Definition
Bacteria, Viruses, Fungi, and Parasites.
Term
Innate Immune Response
Definition

Always present - mediates initial protection.

 

Rapidly eliminates organisms that make it past barriers. 

 

Contains infection within site.

 

Causes inflammation at site of infection (calor, dolor, rubor, tumor).

 

Cells (effectors) and proteins (complement, cytokines)

Term
Adaptive Immune Response
Definition

Provides long-lasting highly specialized defense.

 

Mediated by lymphocytes that are selected by antigen recognition (clonal selection) and undergo clonal expansion. 

 

Immunologic memory (acquired and protective immunity)

Term
Recognition mechanisms of innate immunity
Definition

Rapid Response (Hours)

 

Fixed

 

Limited number of specificities

 

Constant during response

 

Term
Recognition mechanisms of adaptive immunity
Definition

Slow response (days to weeks)

 

Variable

 

Numerous highly selective specificities

 

Improve during response

Term

Cells of the Immune System

 

Definition

Mainly Leukocytes (white blood cells)

 

Derived from pluripotent hematopoetic stem cells via hematopoiesis (1.Yolk sac of embryo, 2.Liver/Spleen of fetus, and 3. Bone marrow just before birth).

 

 

 

Term
Cells of the Innate Immune System
Definition

Granulocytes (Polymorphonuclear leukocytes aka neutrophils, Eosinophils, and Basophils)

 

Monocytes/Macrophages

 

Dendritic Cells

 

Mast Cells


Natrual Killer Cells

 

 

 

 

Term
Functions of Polymorphonuclear leukocytes aka Neutrophils
Definition

Most abundant WBC

 

Capture, Phagocytosis, Killing

 

Short lived effectors of innate immunity

 

PUS


Phagocytosis and killing of microorganisms

Term

Functions of Eosinophils

 

Definition

Defens against intestinal parasites and helminth worms

 

Killing of antibody-coated parasites through release of granule contents. 

Term

Functions of Basophils

 

Definition

Regulating immune response to parasites

 

 

Term

Neutrophils are stored in ____ _____.

 

 

Definition
Bone Marrow
Term

Functions of Monocytes/Macrophages

 

Definition

General Scavengers

 

Phagocytosis/killing

 

Antigen presentation


LONG-lived cells


Monocyte - Circulating precursor cell to macrophage


Macrophage - Phagocytosis and killing of microorganisms. Activtion of T cells and inititation of immune response.

Term
Funcitons of Dendritic Cells
Definition

Phagocytosis of antigens

 

Antigen presentation

 

Activation of T cells and inititation of adaptive immune response

Term
Functions of Mast cells
Definition

Not derived form granulocyte precursor

 

Contribute to inflamation

 

Reside in connective tissue

 

Expulsion of parasites from body through release of granules containing histamine and other active agents

Term
Functions of Natural Killer cells
Definition

Lymphocytes of innate immunity

 

Kill virus-infected cells

 

Secrete cytokines

Term

Cells of the Adaptive Immune system and their functions

 

Definition

B Lymphocytes and T Lymphocytes

 

Lymphocytes (smaller than NK cells, agranular when unstimulated by antigen)

 

The ONLY cells that produce specific receptors for antigens, KEY mediators of adaptive immunity

Term
Functions of T Cells
Definition

Mediators of cell-mediated immunity

 

TCR recognizes antigen

 

CD4+ helper T cell

 

CD8+ cytotoxic T cell

Term
Functions of B cells
Definition

Mediators of humoral immunity

 

Surface antibody

 

Antibody production

Term
Primary (generative) lymphoid tissues
Definition
Express antigen receptors and attain maturity

Bone marrow and thymus
Term
Secondary (peripheral) lymphoid tissue
Definition
Concentrate antigen

Naive lymphocytes meet antigen

Development of adaptive response

Lymph nodes, spleen, mucosal immune system
Term
Lymphocyte recirculation and homing
Definition
Allows lymphocytes to survey entire body for infection or foreign antigen

Maintains balanced distribution of lymphocytes in tissues

Nota a random event
Term
Adaptive immunity to tissue infections- the lymph node
Definition
Pathogen form site of infection reach lymph nodes via lymphatics

Lymphocytes and lymph return to the blood via lymphatics

Venous blood returns to the heart

Naive lymphocytes arrive at lymph nodes in arterial blood

Blood-borne lymphocytes meet lymph-borne pathogens and their products
Term
Architecture of the lymph node
Definition
Drain all epithelia, connective tissues, and parenchymal organs.

APC's in lymph nodes sample antigens that may be present in fluids

Dendritic cells and macrophages capture antigen in periphery and enter lymph nodes via afferent vessel

5 x 10^6 lymphocytes enter and leave every minute

Zones within the lymph node are critical for activation of B and T cells and development of their effector functions
Term
Effector T lymphocyte recirculation
Definition
Effector T lymphocytes home to inflamed or infected tissues anywhere
Term
Activation of adaptive immunity in the draining lymph node
Definition
Lymph draining from infected tissue via afferent lymphatic vessel

Macrophage engulf bacterium

T cells activated by dendritic cells in lymph node
Term
Adaptive immunity to blood stream infections - the spleen
Definition
Organisms that enter the blood are filtered by the spleen

Splenic macrophages, dendritic cells take up organisms and their products

Stimulate B and T cells in the white pulp

Children with asplenia are highly susceptible to encapsulated bacteria ( streptococcus pneumoniae, Haemophilus influenzae). Vaccination required to protect them

Adults who have encountered these pathogens (or who were vaccinated in childhood) have less risk (may require vaccination against S. pneumonia)
Term
Adaptive immunity against mucosal infections
Definition
MALT, BALT, and GALT
Term
Gut-associated lymphoid tissues (GALT)
Definition
Tonsils, adenoids

Appendix, Peyer's patches
Term
Bronchial-associated lymphoid tissue (BALT)
Definition
Less organized aggregates of secondary lymphoid tissue

Respiratory tract
Term
Mucosal-associated lymphoid tissue (MALT)
Definition
Less organized aggregates of secondary lymphoid tissue

Other parts of the body (GI tract, genitourinary tract)
Term
Cutaneous Immune System - UN organized immune cells
Definition
Epidermis - Keratinocytes, Epidermal Langerhan's cells,
Intraepidermal lymphocyte/ gamma delta TCR

Dermis - T cell, macrophage
Term
Adaptive immunity provides memory and protective immunity
Definition
First encounter
-More likely to be symptomatic than later encounters, severe
-Time required to produce adaptive responses
-Leads to production of long -lived memory cells (T and B cells)
-Production of long-lived plasma cells (antibody)

Second encounter
-Far less likely to be symptomatic or even result in tissue damage
-Specific for the pathogen

New pathogen requires building a new bank of cells specific for it
Term
Memory T lymphocyte recirculation
Definition
Memory cells home to submucosal lymphoid tissues, tending to return to site of activation
Term
Innate immunity pathogen recognition
Definition
FIXED répertoire
-Cell surface receptors
-Soluble effector molecules
-Natural selection, over 100 million years

Recognize structures shared by many different pathogens

OR, recognize alterations to human cells induced by presence of pathogens.
Term
Adaptive immunity pathogen response
Definition
ONE molecular type of receptor per cell
-B-Cell receptor
-T-Cell receptor

BUT, almost infinite number of different versions to recognize single ligand (precise targeting)

AND provide memory
Term
Immunoglobulins
Definition
B-Cell receptor (BCR) when expressed on surface of B-Cell

Antibodies when secreted
Term
T-Cell receptors
Definition
Expressed ONLY on surface of T Cell
Term
BCR Antigen
Definition
many types of molecules - molecules:proteins, other macromolecules, cell structure, virus particles
Term
TCR antigen
Definition
LINEAR peptide digested from protein
Term
Both BCR and TCR bear
Definition
Variable regions

Constant regions
Term
Principle concept in generation of antibody and TCR diversity

Generated by gene rearrangement
Definition
1. Germline configuration

2. Somatic recombination

3. Rearranged gene
Term
Principle concept in generation of antibody and TCR diversity

Chosen by clonal selection
Definition
During development, progenitor cells give rise to large numbers of circulating lymphocytes, each having a different form of cell surface receptor

The receptor of only a few circulating lymphocytes interact with any given pathogen

Pathogen reactive lymphocytes are triggered to divide and proliferate

Pathogen activated lymphocytes differentiate into effector cells that eliminate the pathogen
Term
T cells recognize antigen peptides in MHC context
Definition
Dendritic Cells (DC) process protein antigens into peptides (8-25 AA) and display in MHC molecules
Term
MHC Class I
Definition
Intracellular pathogens

Endogenous (cytosolic) antigen processing pathway

Recognized by cytotoxic T cell in context of TCR and CD8 receptor

Expressed on almost all nucleated cells in body
Term
MHC Class II
Definition
Extracellular Pathogens

Exogenous (lysosomal) antigen processing pathway

REcognized by helper T cell in context of TCR and CD4 co-receptor

Expressed ONLY on professional antigen-presenting cells (macrophage, DC, B cells)
Term
Functions of T cells in adaptive immunity
Definition
T cell activation in essential first step in most adaptive immune responses
Term
Helper T cell - CD4+ functions in adaptive immunity
Definition
Secrete cytokines

Interact with B cells, stimulating them to produce antibodies

Interact with macrophages, making them more effective at killing phagocytosed pathogens
Term
Cytotoxic T cell - CD8+ functions in adaptive immunity
Definition
Kill infected cells, including other immune cells

Secrete cytokines

Especially effective for cells infected with viruses
Term
B cell functions in adaptive immunity
Definition
Present antigen to helper T cells
-Naive B cells take in antigen by receptor mediated endocytosis

Secrete antibodies
-Become plasma cells
-Can occur with or without T cell help
-Highly specific, neutralizing antibodies to proteins requires helper T cells
Term
Immune responses in defense and disease. Desired effects
Definition
Antibodies, T helper, and cytotoxic T cells combine to eradicate infecting microorganisms or keep them in check

Provides long-lasting protection (immunity) against the provoking pathogen

Eliminate transformed cells to prevent cancer - surveillance
Term
Immune response in defense and in disease. Unwanted effects
Definition
Autoimmune disease lead to chronic inflammation

Transplant rejection may be hyperacute, acute, or chronic

Allergy produce acute and/or chronic symptoms
Term
Innate immunity
Definition
Part preformed, always ready
-Responds in minutes

Part induced when cells detect invader
-hours to days

Critical initial response to foreign antigens: can control, even eradicate, and infection BEFORE the adaptive immune response occurs

No memory, response always the same, time after time after time ..............

Two major types of reactions
-inflammation - recruitment and activation of leukocytes
-antiviral defense - natural killer cells and cytokines, primarily interferons
Term
Mechanisms of tissue damage y pathogens
Definition
Exotoxin release

Endotoxin release

Direct cytopathic effects
Term
Extracellular infection
Definition
Pathogens live and replicate in spaces between cells
Term
Intracellular infection
Definition
Pathogens that live and replicate inside cells

Virtually all pathogens spend some time in extracellular spaces where they can be attacked by the soluble effector molecules of the innate immune system
Term
Antibacterial, Antifungal, Antiparasitic Defenses (primarily)
Definition
Humoral - complement, plasma proteins and peptides, cytokines

Cellular - neutrophils(PMN), macrophages(MP), natural killer cells
Term
The complement system
Definition
A set of plasma protein made constitutively in the liver and present in the blood, lymph, and extracellular fluids

-Proteolytic enzymes (proteases) found in functionally INACTIVE forms (pro-enzymes or zymogens)

-Infections triggers complement ACTIVATION, a cascade of enzymatic activations in which each enzyme cleaves and activates the next in the pathway

-More than 30 proteins in the system - C3 most important

-Infection activation of complement always leads to C3 cleavage into C3a and C3b
Term
Activation of C3
Definition
1. Cleavage of C3 to C3a and C3b

2. Cleavage of C3 exposes thioester bond

3. Nucleophilic attack on thioester bond

4. If attacked by water then C3b is soluble/If attacked by R-OH or R-NH2 C3b binds to pathogen surface.

5. Fixation of complement
Term
Pathways of complement activation
Definition
1. Alternate pathway (pathogen surface alone)

2. Lectin pathway (Mannose binding lecitin on pathogen surface)

3. Classical pathway (CRP or antibody on pathogen surface)

Complement activation

Cleavage of C3; C3b fixation

Recruitment of inflammatory cells, Opsonization and phagocytosis, and Perforation of pathogen membrane

Death of pathogen
Term
Alternate pathway - response to bacterial infection
Definition
C3 spontaneously hydrolyzes (thioester bond), activating C3

C3b binds factor B; Factor B is activated by Factor D

C3 is split into C3a and C3b

Properdin stabilizes C3bBb binding forming C3 Convertase of alternative pathway. C3 Convertase converts more C3.

More C3 is activated, some binds to microbe, some forms C3bBbC3b, the C5 convertase of the alternative pathway.

No C5 convertase = No pores
Term
Regulation of complement deposition
Definition
To prevent uncontrolled numbers of C3 converses from forming on microbial surfaces
- Factors H and I
- Lack of Factor I -> too many C3 converses form, entire store of C3 in body used up
-Too little C3b in pathogen surfaces
-Less phagocytic clearance
-Increased numbers of ear infections, abscesses caused by encapsulated bacteria
-iC3b does not convert C5 convertase
Term
Regulation of complement activation
Definition
To prevent activation of complement on membranes of human cells
-Decay accelerating factor (DAF)
-Membrane co-factor protein (MCP)
Term
Function of C3b and IC3b
Definition
Enhances function of phagocytes, especially macrophages - opsonization

C3b bound to bacteria recognized by CR1 (complement) receptor 1) on macrophages

IC3b bound to bacteria recognized by CR3 and CR4
Term
Formation of the membrane attack complex
Definition
C5b, C6, C7, C8 form a sort of primer, C9 then forms pore
Term
Regulation of MAC formation
Definition
Membrane proteins prevent assembly of C9 molecules
-CD59 or protectin
-Homologous restriction factor (HRF)

Impairment in glycosylphosphatidylinositol lipid tail formation leads to lack of membrane DAF, CD59, HRF
-complement-mediated lysis if red blood cells
-Paroxysmal nocturnal hemoglobinuria
-most visible in the morning, after sleep
Term
Functions of MAC
Definition
Forms membrane-spanning channel that disrupts cell integrity and can lead to cell death
-Laboratory evidence dramatic -> development of test for humoral immunity
-Clinical evidence of importance sparse
-EXCEPT for susceptibility to infection by Neisseria gonorrhoeae and Neisseria meningitis
Term
Functions of C3a and C5a
Definition
Increase inflammation at site of complement activation - ANAPHYLATOXINS

-Fluid leakage brings more complement factors and other plasma proteins from bloodstream into site of infection

-Migration of monocytes and neutrophils increased

-Microbicidal activity of phagocytes enhanced
Term
Lack of factor D or properdin
Definition
Associated with susceptibility to Neisseris meningitis and other Neisserial infections
Term
Deficiency in C3
Definition
Associated with susceptibility to pyogenic infections
Term
Deficiency in MBL
Definition
(5% of population) associated with recurrent infections
Term
Deficiencies in C1q, C1r, C1s, C4, or C2
Definition
associated with susceptibility to immune complex diseases
Term
Deficiencies in C5, C6, C7, C8, C9
Definition
Associated with susceptibility to Neisseris meningitides and other neisserial infections
Term
Lack of DAF and MCP
Definition
Paroxysomal nocturnal hemoglobinuria

Unregulated complement activation occurs on RBC

Hemoglobinuria most pronounced in the morning
Term
Lack of C1 INH
Definition
Heredity angioneurotic edema

Uncontrolled, pathological activation of C1

Production of vasoactive protein fragments

Leakage of fluid (edema) in larynx and other tissues (gut)
Term
Plasma proteins that limit spread of infection
Definition
Coagulation system
-cascade of enzymes that leads to formation of blood clots
-immobilizes microbes in fibrin net

Kinin system
-cascade of enzymes that leads to activation of vasoactive peptide bradykinin
-causes vasodilation

Protease inhibitors
-Alpha2 Macroglobulins and their receptors found on hepatocytes, fibroblasts and macrophages
Term
Protease inhibitor function
Definition
Bait and trap

alpha2 macroglobulin enshrouds the protease and is covalently bonded to it
Term
Alpha defensins - antimicrobial peptides
Definition
Neutrophils, Paneth cells
-Intestinal epithelium, placenta, cervical mucus plug
-Salivary glands, GI tract, female genital tract, breast milk
-Eyes

Constitutive and two types induced by sexually transmitted diseases
Term
Beta defensiins - antimicrobial peptides
Definition
Epithelial cells
-GI tract, respiratory tract, urogenital tract skin, eyes, salivary glands, kidneys, blood plasma
-stomach, testes

Constitutive and induced by infection
Term
Cellular Receptors fot Microbial Products
Definition
Have specificity for molecules shared by classes of microbes-molecules not found in the host cells
-Pathogen-associated molecular patterns (PAMPs)

Are encoded in germline, limited diversity, but gene polymorphisms expand the repertoire

Are non clonal, found on all cells of same lineage

Do not react against host
Term
Macrophages express many different cell surface receptors
Definition
Lectins-carbohydrates
-Mannose, glycans

Negatively charged ligands - gram pos.
-Nucleic acids, lipoteichoic acid, sulfated polysaccharides

Lipopolysaccharide (LPS) - gram neg.

Lipophosphoglycan - fungi

N-formyl peptides
Term
Toll-like receptors
Definition
10 different TLR's expressed on different type of cells
-TLR4, macrophages (LPS)
-TLR3, natural killer cells

Pathogen recognition domain

Cytoplasmic signaling domain
-Cell surface: TLR1:TLR2, TLR2:TLR^, TLR4, TLR5
-Endosome: TLR3, TLR7, TLR8, TLR9
Term
Results of TLR4 recognition of LPS
Definition
1. TLR4-MD2-CD14-LPS complex

2. Recruitment of adapter proteins. Activation of kinase cascade.

3. Activation of transcription factors NFkB

4. Gene transcription and synthesis and secretion of cytokines.
Term
TLR4 signaling leads responses
Definition
TLR4 in ONLY TLR that uses two pathways
-MyD88-IRAK4 more frequent
-Requires IKK (inhibitor of kB kinase)

TRIF-TRAM pathway most often used by TLR3 (antiviral state in response to dsRNA)
Term
NFkB-induced _______ ________ leads to __________
Definition
cytokine synthesis; inflamation
Term
IL-6
Definition
Systemic effects

Fever induces acute-phase protein production by hepatocytes
Term
TNF alpha
Definition
Local effects
-Activates vascular endothelium and increases vascular permeability, which leads to increased entry of complement and cells to tissues and increased fluid drainage to lymph nodes

Systemic effects
-Fever mobilization of metabolites, shock
Term
IL-1beta
Definition
Local effects
-Activates vascular endothelium, activates lymphocytes, Local tissue destruction increases access of effector cells

Systemic effects
-Fever, production of IL6
Term
CXCL8
Definition
Chemotactic factor recruits neutrophils and basophils to site of infection
Term
IL-12
Definition
Activates NK cells
Term
TLR4 is crucial for defense against Gram - _______ bacteria
Definition
negative
Term
Consequences for lack of TLR4
Definition
Persons heterozygous for defective allele of TLR4 gene over-represented in patients who suffer septic shock

Only person with known homozygosity for defective allele died in adolescence from an E. Coli infection of the kidney
Term
Mutation in NFkB essential modifier gene (NEMO) lack IKK
Definition
Blockade transcription of genes activated by NFkB

Suffer severe bacterial infections despite vaccination

Have chronic viral infections and intractable Mycobacterium avium infections
Term
Neutrophils
Definition
Dedicated phagocytes
-Summoned by macrophages when wounding or infection occurs in tissue
-Short-lived but abundant
-60% hematopoetic activity devoted to their production (50 billion in circulation daily)
-Cannot enter healthy tissue
-Main functions - phagocytosis and killing of bacteria
--Pyogenic (pus forming) bacteria
--Staphylococcus aureus, Streptococcus pyogenes
Term
Neutrophils enter tissues by process of ________
Definition
extravasation
Term
Neutrophils entering tissue process
Definition
Vascular endothelial P-selectin and/or E-selectin binds slalyl-Lewis slowing PMN to roll along vessel wall
-Leukotriene B4, C5a, histamine
-LPS, TNF-alpha

LFA-1 and CR3 bind ICAM-1 tightly at site of infection
-TNF-alpha, CXCL8

PMN's diapedese between endothelial cells, secreting proteases to break through basement membrane

Migrate to site of infection via chemotaxis
Term
Phagocyte recruitment
Definition
1. Injury site

2. Macrophage signaling, Vascular endothelial activation
-Tissue injury, Complement activation

3. Tumor necrosis factor, Interleukin-1
-Anaphylatoxins (C3a, C5a), CXCL8

4. Changes in adhesion molecules of endothelial cells of vessel lumen

5. Plasma proteins - transferrin, CRP

6. E-selectin, P-selectin
Term
Phagocyte migration
Definition
7. Sialyl-Lexis surface carbohydrates

8. Integrins

9. Diapedesis
Term
NADPH + O2 ----_________---> NADPH + 2O2 + H
Definition
NADPH oxidase
Term
2H + 2O2 -----________----> H2O2 + O2
Definition
superoxide dismutase
Term
H2O2 ---________---> 2H2O + O2
Definition
catalase
Term
Without NADPH oxidase
Definition
no phagocyte oxidases
Term
Acute inflammation response
Definition
Bacteria enter central nervous system (meninges)

Fibroblasts and macrophages sense presence of invader
-IL-6, TNF, CXCL8, chemokines

Changes in endothelial cells, expression of adhesion molecules

Influx of neutrophils
Term
Bloodstream evidence of acute inflammation
Definition
Leukocytes
-Left shift, starting to deplete neutrophils
-Younger and younger neutrophils mobilixzed from bone marrow into blood

Can lead to exhaustion of bone marrow supply of neutrophil precursors
-crash in WBC count
-may prove fatal
Term
Chronic granulomatous disease
Definition
Specific failure of phagocytes to produce peroxide and superoxide due to non function of NADPH

Inability to eradicate bacteria and fungus Aspergillus

Formation of granulomas
Term
Leukocytes adhesion deficiency
Definition
Most commonly because of genetic defect in CD18, the common beta chain of 3 integrins

Failure to express LFA-1 (CD11:CD18), Mac-1 (CD11b:CD18; aka complement receptor 3) and gp150,95 (CD11c:CD18; aka CR4)

Recurrent pyogenic infections, problems with wound healing, early death

Massive leukocytes with neutrophilia

Lymphocyte homing NOT affected; T cell function seems to be normal despite lack of LFA-1
Term
Chediak-Higashi syndrome
Definition
Defect in cytoplasmic vesicle formation and trafficking
-Neutrophil and macrophage defect in phagocytosis and killing
-Defect in endocytosis and antigen processing
-Defect in cytotoxic killing by CD8 T cells and NK cells

Recurrent bacterial infections

Other defects
-Partial absence of pigmentation of skin, hair, eyes (albinism)
-Tendency to bleed (platelet dysfunction)
-If survive into adolescence, develop neurological defects
Term
Cytokines and pyrogens produce ____ ______
Definition
systemic effect
Term
Response to IL-1, IL-6, TNF-alpha
Definition
Liver - Acute phase proteins (C-reactive protein, mannose-binding lectin) -> Activation of complement opsonization

Bone marrow and endothelium - Neutrophil mobilization -> Phagocytosis

Hypothalamus - Increased body temperature -> decrease viral replication and increased neutrophil function

Fat, muscle - Protein and energy mobilization to generate increased body temp -> decrease viral replication and increased neutrophil function
Term
Results of acute phase response
Definition
Fever

Somnolence

Lessening of appetite
Term
Acute phase proteins that opsonize and activate complement
Definition
CRP - Pentraxin that binds phosphocholine of LPS and S. pneumonie C-polysaccharise

MBL - Calcium-dependent lectin binds mannose of pathogens but not humans
Term
MBL activation
Definition
1. Activated MASP-2 cleaves C4 to C4a and C4b. Some C4b binds covalently to microbial surface

2. Activated MASP-2 also cleaves C2 to C2a and C2b

3. C2a binds to surface C4b forming the classical C3 convertase, C4b2a

4. C4b2a binds C3 and cleaves it to C3a and C3b. C3b binds covalently to the microbial surface
Term
CRP triggers the _______ pathway of complement activation
Definition
classical
Term
Antiviral defenses (Primarily)
Definition
Humoral - type 1 interferons

Cellular - NK cells, macrophages
Term
Functions of Type I IFN's (IFN- alpha, IFN-beta)
Definition
Virus infected cells

IFN-alpha, IFN-beta

Interferon response

Induce resistance to viral replication in all cells, Increase expression of ligands for receptors on NK cells, Activate NK cells to kill virus infected cells

Antiviral state:
-Activates 2',5' oligoadenylate synthetase->endoribonucleases->degrades vRNA
-Activates protein kinase R->phosphorylates eIF-2->prevents protein synthesis

Systemic effects: Fatigue, Fever, Flu-like symptoms, Myalgia, Anorexia, headache, Somnolence
Term
Special interferon-producing cells
Definition
Lymphocyte-like cells

Secrete 1000X more IFN than other cells

Express TLRs 6, 7, 9, 10 and respond to a variety of viral infections

After 24 hrs, differentiate into plasmacytoid dendritic cells
-produce interferon
-move to T cell areas of draining lymph nodes
-Function in lymph node, not fully known - do not activate T cells
Term
NK cells
Definition
Constitute 5-25% of lymphocytes in peripheral blood
-Larger than B and T cells
-Contain cytotoxic granules
Recognize infected (viruses and some intracellular pathogens) and/or stressed cells
-Kill the cells via induction of apoptosis
Term
NK cell receptors
Definition
Killer activating receptors carry ITAM's
-NKGD2 - receptor for stress-induced proteins
-FcgammaRIII receptors (CD16) for IgG

Killer inhibitory receptors carry ITIM's
-killer cell immunoglobulin-like receptor (KIR) recognizes class I MHC molecules
-CD94/NKG2 recognizes HLA-E (important in pregnancy)
Term
Immunoassays
Definition
Diagnosis of disease
-Assess presence of pathogens
-Assess response to pathogens
-Assess presence of antibodies to tissues
--Autoimmunity, transplant reactions, tumor immunity

Function and status if immune system
-Assess presence (or absence) of specific cell types, cell markers of maturation, and molecules
-Assess ability of immune cells to perform their functions
Term
Antigens and Anitbodies
Definition
Many antigens contain multiple epitopes (polyvalent); some exhibit multiple repeats of the same epitopes (multivalent)

Polyclonal antibodies
-The response to antigens with multiple different epitopes is the development of different antibodies specific to each epitope of the Ag

Monoclonal antibodies
-Engineered antibody response through hybridoma production
-Antibody is specific to ONE epitope of the Ag

Antibodies from one species are antigens to another species
Term
Antigen may be ______ or _______ to cell or tissue
Definition
Bound, soluble
Term
Antibodies target_____ antigens
Definition
Surface
Term
Antibodies developed against specific known antigens can be used _ ______ ___ _____ within body fluids, on cells surfaces, or within cells (diagnosis of particular disease)
Definition
to detect that antigen
Term
Antigens associated with a particular disease or cell type can be used in assays in vitro __ _______ _______ _______ within a persons serum specific for that antigen (immune response to a particular disease)
Definition
to detect specific antibodies
Term
Detection of soluble antigen by precipitation and agglutination
Definition
Equivalence
Term
Radial Immunodiffusion
Definition
Used to determine con. of immunoglobulins IgG, IgM, IgA; complement proteins; coagulation proteins
Term
Radial Immunodiffusion
Definition
Used to determine con. of immunoglobulins IgG, IgM, IgA; complement proteins; coagulation proteins
Term
Rituximab
Definition
Anti CD 20

Binds to normal and cancerous b cells

Targeting their destruction by Nk cells
Term
Adalimumab
Definition
Anti TNF alpha

Binds TNF alpha and prevents inflammation

Treatment of rheumatoid arthritis
Term
Palivizumab
Definition
Anti respiratory syncytail virus (RSV)

Neutralizes RSV and prevents infection in premature infants
Term
Somatic recombination - RSS
Definition
Carried out by enzymes that cut and rejoin DNA

Directed by recombination signal sequence RSS
Term
Somatic recombination - RAG
Definition
V(D)J recombinase specified by RAG-1 and RAG-2
Term
IgM/ig alpha/ig beta
Definition
BCR
Term
Diversification of antibodies after Bcells encounter antigen
Definition
Sectreted antibodies are produced by an alternative pattern of heavy chain RNA processing

Rearranged V-region sequences are further diversified by somatic hypermutation

Isotype switching produces immunoglobulins with different C regions but identical antigen specificities

Antibodies with different C regions have different effector functions
Term
Rearranged v-region sequences are further diversified by somatic hypermutation
Definition
In Bcell activated by antigen, the activation induced cytidine deaminase becomes functional

Conversts cytidine in ssDNA to uracil and then to any DNA base

only in v region

changes concentrated in CDR's, especially CD3
Term
First antibody made in primary response
Definition
IgM

Pentameric form

greatest avidity

great for activation of complement, but limited in other effector functions to clear antigen
Term
Isotype switching
Definition
enables a different c region (with a different effector function) to be used with the same effective V region already produced

occurs only during active immune response

REgulated by cytokines produced by antigen activated t cells

occurs in proliferating B cells and is AID dependent
Term
NEutralization
Definition
IgG1, IgG2, IgG3, IgG4, and IgA
Term
Opsonization
Definition
IgG1
Term
Sensitization of mast cells
Definition
IgE
Term
Activation of complement system
Definition
IgM
Term
Mucosal immunity transport across epithelium
Definition
IgA
Term
Transport across placenta
Definition
IgG1
Term
Development of B cells in the bone marrow
Definition
Driven by transcription factor PAX5
Term
ccr7
Definition
expressed by immature bcells
Term
cd 19
Definition
bcell co receptor
Term
cr2
Definition
binds c3d
Term
Antibody response to certain antigens does not require T-cell help
Definition
TI-1 (thymus independent) antigen

signals provided by signaling receptors of innate immunity

TLR, for LPS (TLR$ + CD14) of gram -

for bacterial DNA TLR 9

only igM produced
Term
Ti - 2 antigen
Definition
carbs and proteins at high conc on surface

extensive cross linnking overrrides need for BCR/co-receptor linking

s. pneumoniae

often B-1 b cells

mainly igM produced
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