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323 Cards in this Set

  • Front
  • Back
What are the roles of the immune system?
1. Defense against infections
2. Recognize and Respond to tissue grafts, and newly introduced proteins and altered self proteins
3. Defense against tumors
Who is the "father" of immunology?
Edward Jenner
What was the first successful vaccine against?
smallpox in 1798
When was smallpox eradicated worldwide?
1980: WHO announced that smallpox was the first disease that had been eradicated worldwide by program of vaccination
What type of immunity are humans born with?
Innate Immunity
Does innate memory produce any memory cells?
What type of immunity is the first, initial type of defense our immune system produces?
Innate Immune response
What types of responses does innate immune response produce?
Antiviral state
--> alert that danger is in the body
_________ immune response stimulates ___________ immune response.
1. Innate
2. Adaptive
What is the largest immune organ in the body?
The skin is the largest immune organ in the body. It acts as a barrier
What are the circulating effector cells of innate immunity?
Neutrophils, Mast cells, platelets, endothelial cells, thrombocytes.
Macrophages and NK cells
What cells are responsible for early phagocytosis and killing of microbes?
Neutrophils, mast cells, platelets, endothelial cells, and thrombocytes
What circulating effector cells are efficient phagocytes that kill microbes, and secrete cytokines that stimulate inflammation?
Natural Killer cells are present in __________ infections.
intracellular infections
What do NK cells do when present during intracellular infections?
NK cels will lyse the infected cell and activate macrophages
What is the purpose of circulating effector proteins?
participate in inflammation
Examples of Complement are:
cytokines, IL-1, TNF, Chemokines, IL-8, and MCP-1
What is the job of complement?
Complement induces killing of microbes, opsonization of microbes, and activation of leukocytes
_______ _______ ________ is a circulating effector protein.
Mannose-binding lectin
What occurs in the Lectin pathway?
in the mannose-binding lectin pathway opsonization of microbes and activation of complement occurs
What do coagulation factors do?
Coagulation factors wall off infected tissues
_ _ _ _ _ are structures that are shared by various classes of microbes but are not present on host cells.
PAMPS: pathogen associated molecular patterns
What type of structures are recognized by innate immune cells?
What type of molecular patterns are found on/in stressed, dying, or dead host cells?
DAMPS: damage associated molecular patterns
Where are most DAMPS normally found?
Many DAMPS are nuclear or cytosolic proteins when released outside the cell following tissue injury move from a reducing to an oxidizing agent resulting in their functional denaturation
What is a PRR?
Pattern recognition receptor
Where are PRRs found?
PRRs are present on macrophages, monocytes, epithelial cells, dendrtitic cells, neutrophils, etc. (front line defense)
_____ senses PAMPS & DAMPS.
PRRS: surface or cytosolic PRRs recognize structures that are characteristic of microbial pathogens & altered self and are not present on mammalian cells
True or False. In the innate immune response there is a functional significance of different cellular locations.
There are Toll-LIke Receptors and Nuclear Oligomerization Domain sensors
Surface TLRs are located on ________ cell walls and molecules.
Bacterial cell walls
TLR2 is a surface TLR that binds to _______ of Gram-Positive bacteria
TLR2 is a surface TLR that binds to PEPTIDOGLYCANS of Gram Positie bacteria
TLR4 is a surface TLR that binds to ____ of Gram Negative bacteria
TLR4 binds to LPS of Gram Negative bacteria
TLR5 is a surface TLR that bids to ________ of various bacteria
TLR5 binds to FLAGELLIN of various bacteria
TLR9 is an endosomal TLR that binds to bacteria un-methylated CPG DNA and ______ DNA.
TLR9 binds to bacteria un-methylated cpg DNA and viral DNA
True or False. Endosomal TLRs bind both bacteria and viruses.
True. These TLRs are TLR9, TLR3, TLR7, and TLR8
What does TLR3 bind to in viruses?
TLR3 binds to ds-RNA
What does TLR7 and TLR8 bind to in viruses?
TLR7 and TLR8 binds to ss-viral RNA
What are the cytoplasmic sensors present in the innate immune response?
Bacterial: NOD1 & NOD2
Viral: RIG-1
_____ binds to peptidoglycans from Gram-negative bacteria inside the cytoplasm.
______ binds to peptidoglycans from Gram-positive bacteria inside the cytoplasm.
True of False.
RIG-1 is a viral cytoplasmic sensor that binds to HCV RNA
Natural killer cell activation is part of the innate immune response to extracellular bacteria.
Natural killer cell activation occurs when there is an intracellular infection
What is the clinical relevance of Toll-Like Receptors?
1. initial response to microbes prevents, controls, and eliminates infection of the host before it become intracellular
2. innate immunity to microbes stimulates adaptive immune responses that may be optimally effective against different types of microbes
3. Excessive/systemic TLR signaling underlies paathophysiology of sepsis
4. TKR signaling in B-cells promotes auto-antibody production.
What are Nod-like receptors (NLRs)?
Nod-like receptors are cytoplasmic sensors that detect microbial or non-microbial endogenous danger signals
How are NLRs activated?
1. form multi-protein inflammasome complexes
2. induce cleavage and activation of Caspase-1
Secretion of IL-1beta and IL-18
What does the overproduction of IL-1beta and IL-18 lead to?
Autoinflammatory and autoimmune disorders
True or Fasle.
TLR and NLRs function in concert.
If a patient suffers from an unregulated inflammasome what is overproduce?
IL-1beta and IL-18 are overproduced
What is the difference in specificity between innate immunity and adaptive immunity?
Innate immunity: No memory (different microbes can have identical receptors that recognize molecular patterns)
Adaptive immunity: Memory (each microbe has a distinct antibody molecule)
What is the difference in receptors between innate immunity and adaptive immunity?
Innate immunity: encoded in the germline & limited diversity
Adaptive immunity: somatic recombination of gene segments & greater diversity/clonal
Describe the distribution of receptors and discrimination of self and non-self in innate immunity.
-Nonclonal identical receptors on all cells of the same lineage
-Host cells are not recognized or they may express molecules that prevent innate immune reaction
Describe the distribution of receptors and discrimination of self and non-self in adaptive immunity.
-Clonal: clones of lymphocytes with distinct specificities express different receptors
-Base on selection against self-reactive lymphocytes; may rise to be imperfect giving rise to autoimmunity
What are the two-types of adaptive immunity?
1. Extracellular/Humoral Immunity
2. Cellular/Intracellular Immunity
Characteristics of Humoral Immunity.
1. Principle defense mechanism against extracellular microbes and their toxins
2. Secreted antibodies produces by B-cells in blood and mucosal secretions bind to these microbes and toxins
What are the antibody effector functions in Humoral Immunity?
1. Complement activation
2. Neutralization of toxins
3. Opsonization
4. Phagocytosis
5. Antibody-dependent cellular cytotoxicity (ADCC)
Characteristics of Cellular Immunity.
1. Principle defense mechanism against intracellular microbes
2. Mediated by T-lymphocytes
3. CD4+ T-cell mediated activation of macrophages that have phagocytosed microbes
4. CD8+ Cytotoxic T-cell killing of infected cells to eliminate reservoirs of infection
What are the phases of the adaptive immune response?
1. Recognition phase (antigen recognition by lymphocytes)
2. Activation phase (duration may vary in different immune responses)
3. Contraction (homeostasis/immune responses are self-limited and decline as infection is eliminated)
4. Memory
What are the key differences between the primary and secondary adaptive immune response?
Secondary responses to antigens are more rapid and larger than primary response to antigens
Name the key features of adaptive immune responses.
1. Specificity: ensures distinct antigens elicit specific responses
2. Diversity: enables immune system to respond to a large variety of antigens
3. Memory: leads to enhanced response to repeated exposures to the same antigen
4. Clonal expansion: increases number of antigen specific lymphocytes to keep pace with microbes
5. Specialization: generates responses that are optimal for defense against different types of microbes
6. Contraction and homeostasis: allows immune system to respond to newly encountered antigens
7. Non-reactivity to self: T-cells are educated in the Thymus to prevent injury to the host during responses to foreign antigens
What is an example of active immunity?
The host plays an active response resulting in memory. An example of this is a vaccine
How is passive immunity gained?
Passive immunity is conferred by adoptive transfer to the recipient with no protection. An example is transfer of maternal IgG antibodies to fetus through the placenta or IgA through milk
Describe signal 1 and signal 2 of the innate immune response
Signal 1: Microbial antigen recognition provide signal 1 for the activation of the lymphocytes
Signal 2: Ensures immune responses are induced only when there is a dangerous infection
What is the Clonal Selection Hypothesis?
1. Every individual posses numerous clonally derived lymphocytes
2. Each clone is capable to recognizing and responding to a distinct antigenic determinant
3. When an antigen enters, it selects a specific pre-existing clone and activates it --> few lymphocytes with same receptor
Where do lymphocyte clones mature?
Lymphocyte clones mature in generative lymphoid organs in the absence of antigens
What activates antigen-specific clones?
Antigen-specific clones are activated by antigens
What are immune system cells derived from?
Immune systems cells are derived from pluripotent hematopoitic stem cells in the bone marrow
__________, ____________, & __________ are the 3 cell lines derived from pluripotent hematopoitic stem cells
Lymphoid, Myeloid, and Erythroid cells are the 3 cell lines
B-cells differentiate into ________ cells
Plasma cells
T-cells differentiate into ________
activated T-cells
NK cells differentiate into _________ cells
activated NK cells
What are the 4 common lymphoid cells?
B-cells, T-cells, NK cells, and Dendritic cells
When a B-cell comes into contact with a microbe what are the effector functions?
Neutralization of microbes, phagocytosis, complement activation
When microbial antigens are presented by antigen presenting cells what are the effector functions?
Activation (proliferation & differentiation) of T and B lymphocytes.
-- T-helper, Th1, Th2, Th17
-- These are Class II MHC restricted
Cytotoxic T-lymphocytes are _______ restricted.
MHC-I restricted
When a cytotoxic T-lymphocyte comes into contact with an infected cell expressing microbial antigen what are the effector functions?
Killing of the infected cells
-- This is class I MHC restricted
Regulatory T-lymphocytes _________ the immune response
Natural killer cells are part of the innate immune response. What is there job? Are they antigen dependent?
Natural killer cells kill the infected cells and do not require antigen recognition
Principle functions of B-lymphocytes:
mediators of humoral immunity
Principle functions of T-lymphocytes:
mediators of cell-mediated immunity
Principle functions of Natural Killer cells:
NK cells function in innate immunity
What are the three main types of antigen-presenting cells?
dendritic cells, macrophages, and follicular dendritic cells
Principle functions of macrophages:
initiation and effector phase of cell-mediated immunity
Principle function of dendritic cells:
initiation of T-cell responses
Principle function of follicular dendritic cells:
display of antigens to B-lymphocytes in humoral immune responses
As an effector cell what is the job of T-lymphocytes?
T-lymphocytes are helper cells and cytotoxic lymphocytes, as well as regulatory lymphocytes
As effector cells what is the job of macrophages?
Macrophages and monocytes are cells of the mononuclear phagocyte system
As effector cells what is the job of granuloytes?
The granulocytes job is to eliminate antigens. The Granulocytes are neutrophils and eosinophils
What are the CD markers for Natural Killer Cells?
The role of _________ _______ cells is in the innate/non-specific host defense against viral infected or tumor target cells
Natural killer cells
Do Natural killer cells have T-cell markers but lack antigen specific receptors?
NK cells have receptors to detect MHCI or MHC II molecules?
If a Natural killer cell has receptors for class I MHC molecules what is it detecting?
1. Detects lack of self
2. Activating and killing inhibitory receptors
True or False.
NK cells pass through the thymus to reach maturity.
False. NK cells do not pass through the thymus to mature.
Where do NK T-cells reside at in the body.
NK T-cells and NK cells are two different types of cells.
NK T-cells reside in epithelia of lymphoid organs and in the liver
NK cells have two different mechanisms for killing pathogens
1. Direct killing by releasing perforin by apoptosis
2. Non-specific killing
NK cells can detect stress in a cell. What will the cell decrease its expression of to signal NK cells.
If a cell is stressed the cell will decrease its expression of MHC-I molecules.
Viruses can infect cells and up or down regulate MHC-I molecules. What type of immune cell detects this?
NK cells
CD3+, CD4+, and CD8- are phenotype markers for what class of lymphocytes?
CD4+ is the most abundant lymphocyte
*Helper T-cells
What is the most abundant lymphocyte in the body?
CD4+ T-helper cell
CD3+. CD4-. and CD8+ are the phenotype markers of what lymphocytes?
Cytotoxic lymphocytes
*CD8+ is the main phenotype
Fc receptors, MHC-II molecules, CD19, and CD21 are the phenotypes of what immune cells?
*B-cells populate mostly the spleen and the lymph nodes
CD19 is the main phenotype for B-lymphocytes
Fc receptors for IgG and CD16 are phenotypes for which type of immune cells?
Natural killer cells
CD16 is the main phenotype marker
Where are APC's primarily found?
APC's are found primarily in the skin, lymph nodes, spleen, and thymus
The main role of antigen presenting cells is to present _______ to ________, phagocytosis, and cytokine production.
antigens to lymphocytes
True of False.
Neutrophils do not present antigens, they phagocytose and kill invaders.
How are APC's classified?
Based on the ability to phagocytose antigens, location in the body and expression of MHC-I and MHC-II molecules.
What are the three types of phagocytic Antigen Presenting Cells?
1. Dendritic cell
2. Macrophage
3. B-cell
What type of immune response are dendritic cells part of?
Adaptive Immune response
______ is the co-stimulator of the dendritic cells in the adaptive immune response.
Macrophages are part of _________ & ______ immune responses.
innate & adaptive immune responses
Follicular dendritic cells reside in _______ centers of lymphoid follicles.
Germinal centers
Follicular dendritic cells express complement receptors, Fc receptors, and _______ ligand.
True or False.
Follicular dendritic cells are derived from precursors of bone marrow.
Follicular dendritic cells are not derived from precursors of bone marrow.
Do follicular dendritic cells present antigens to helper T-cells?
Do not present antigen to helper T-cell
Do not produce MHC-II
Display antigens on surface so B-cells to recognize antigens trapped by complement products and antibodies
What is the normal levels of leukocytes in the the human body?
4500-1100 per micro-liter
The roles of a neutrophil in the immune cell response are:
1. inflammation
2. first cells to arrive at site of inflammation
3. doesn't act as APC
What is the most abundant circulating white blood cell?
Phagocytic, bactericidal, and enzymatically digest microbes descrives what type of granulocyte?
If a patient has a deficiency in neutrophils this is called _________. What could this cause?
-causes severe bacterial infections
Deficiency in neutrophils function is called:
Chronic Granulomatous Disease
Eosinophils kill _________ coated in antibodies by exocytosis.
When are eosinophil numbers increased?
Heightened number of inflammatory infiltrates such as bronchial infections and asthma
Are Basophils phagocytic?
Basophils release active substances during _________ and ___________ reactions.
Allergic & Hypersensitivity reactions
Basophils are similar to _______ cells in structure and function.
Mast cells
Mast cells secrete:
histamine, prostaglandins, and leukotrienes
Stimulation of mast cells occurs by ________ or by _________ of surface IgE.
anaphylotoxins or by cross-linking
What is the major effector cell of allergic and hypersensitivity reactions?
Mast cells
What are the two most numerous leukocytes in circulation?
60% Neutrophils
30% Lymphocytes
5% monocytes
4% eosinophils
<1% basophils
Where do lymphocytes first express antigen receptors and attain maturity and clones develop?
In generative lymphoid organs
In the fetal mammal where do B-lymphocytes development occur?
1. yolk sac
2. Liver
3. Spleen
4. Bone marrow (adult life)
______ ________ is the site of B-cell maturation
Bone marrow
Where does hematopoiesis occur if the bone marrow is damaged?
When the bone marrow is damaged hematopoiesis may occur at sites such as the liver and spleen
The Thymus is the site of ________.
T-cell maturation/education
What occurs in the cortex of the thymus in respects to T-cells?
T-cell maturation of unique T-cell receptors begins here
True or False.
Mature lymphocytes migrate toward the medulla in the thymus.
True or False.
Bone marrow derived macrophages and dendrtitic cells are present in the thymus.
Bone marrow derived macrophages and dendritic cells are NOT present in the Thymus.
What is the most important function of the thymus?
T-cell education:
1. positive selection: Thymocytes whose receptors bind with low avidity to self-peptide-self-MHC complexes are stimulated to survive
--Thymocytes that do not recognize self MHC are permitted to die
2. Negative selection: the process in which thymocytes whose receptors bind strongly to self-peptide-self MHC complexes are deleted.
A syndrome in which there is a congenital absence of the thymus.
DiGeorge Syndrome
Where are naive lymphocytes located that are activated by antigen to become effector cells to initiate induction of adaptive immunity?
1. Lymph node
2. Spleen
3. Mucosal & cutaneous lymphoid tissue
What are the layers of the lymph node?
Outer cortex
Germinal center
paracortical cords
What is the site of antigenic stimulation by FDC antigen activated B-cells?
Germinal center of lymph node
Where do Naive B & T-cells enter the lymph node & why?
Naive B & T-cells enter the node through the High Endothelial Venules in the cortex of the lymph node.
-Naive T-cells express CCR7 receptors for chemokine in T-cell zone
-Naive B-cells express CDCR5 receptors for chemokines in follicles
Where are B-cells found in the spleen?
B-cells are found in the germinal center of the white pulp (lymphoid follicle)
T-cells are found in the ___________ area of the spleen.
T-cells are found in the periarteriolar lymphatic sheath (PALS)
-close proximity to the arteriole
What types of cells are found in the red pulp of the spleen?
Arterioles end in vascular sinusoids scattered with large numbers of erythrocytes, macrophages, and dendritic cells
Macrophages remove ________ and ________ in from the blood in the spleen.
Macrophages remove the microbes and dying rbc's from blood
_______ is the major site of ________ of antibody coated microbes.
the spleen is the major site of phagocytosis of antibody coated microbes
True or False.
Pneumococci and Meningococci bacteria are encapsulated and are normally cleared by opsonization and phagocytosis. Individuals lacking the spleen are extremely susceptible to infections of this type of bacteria.
What cells are present in the epidermis that contribute to the cutaneous immune system?
Keratinocytes, Melanocytes, Langerhan cells, and intraepidermal T-cells
_____ and ________ T-cells comprise the dermis T-cells and dermal Dendritic cells.
CD4+ and CD8+ T-cells
Define GALT.
Peyer's patches are in lamina propria of small intestine
-B-cells make up 70% and T-cells make up 1-=30% and are predominately CD8+
Define BALT
Bronchus associated lymphoid tissue comprises of the pharyngeal tonsils
Cluster of Differentiation markers are ______.
A cell type expresses characteristic surface molecules which identify them
What are the CD markers of Helper T-cells?
What are the CD markers of Cytotoxic T-cells?
MHC-I, IgM, B7, CD19, CD20, CD21, and CD40 are the CD markers of ________.
CD40 binds to ______ on T-cells.
True or False.
All nucleated cells have MHC-I molecules.
The immune cell surface CD antigens for ________ are MHC-I, CD16, and CD56.
NK cells
CD14 binds to ______ on macrophages/dendritic cells.
LPS receptors
MHC class II are cell surface markers for this type of immune cell.
Macrophages and dendritic cells
what is the complement systems primary function?
the complement system primarily serves to fight bacterial infections. this is an important link between innate and adaptive immune responses.
Recognize, alert, recruit phagocytes
what are the 3 main effects of complement?
1. opsonization
2. inflammation
3. lysis
define opsonization in terms of complement
by complement product C3b-enhancement of phagocytosis
define inflammation in terms of complement
generation of mediators that participate in inflammation and attract neutrophils
define lysis is terms of complement
lysis of cells (bacteria, allograft, tumor cells)
what are the three activation pathways of complement?
1. classical pathway
2. lectin pathway
3. alternative pathway
what cells mainly produce complement proteins?
complement proteins are primarily produced by hepatocytes, although monocytes, macrophages, and epithelial cells can also produce important amounts
describe the alternative pathway
1. spontaneous cleavage of C3
2. Hydrolysis and activation of C3b in fluid phase
3. C3b binds covalently to microbial surfaces, binds Factor B
4. Cleavage of Factor B by Factor D: stabilization by properdin
5. Cleavage of additional C3 molecules by cell-associated C3 convertase
6. C3b covalently binds to cell surface binds to C3bBb to form C5 convertase
7. Cleavage of C5: initiation of late steps of complement activation
What are important components of complement activation in the alternative pathway?
Binding and cleavage of Factor B to form C3 convertase
describe the classical pathway of complement activation
1. binding of antibodies to multivalent antigen: binding of C1 to antibodies
--- bound IgM or 2 IgGs on a cell activates C1q
2. Binding of C4 to Ig-associated C1q
3. Cleavage of C4 by C1r2S2 enzyme covalent attachment to C4b to antigenic surface and to antibodies
4. binding of C2 to C4: cleavage of C2 to form complex C4b2b complex (C3 convertase)
5. Cleavage of C3 by C3 convertase
6. *** Binding of C3b to antigenic surface and to C4b2b complex
7.*** Cleavage of C5 initiation of late steps of complement activation
---- Steps 7 & 8 release of anaphylotoxins C3a (mast cell) and C5a (chemotactic) occurs
in the classical pathway at what stage does the release of anaphylotoxins C3a and C5a occur?
It occurs as parts of the last step of the classical pathway sequence.
Mast cells release C3a
Chemotatic factors release C5a
does C1 binding occur with antibodies that have not complexed with antigens?
C1 binding does not occur to antibodies that have not complexed with antigen
describe the structure of C1 in the classical pathway
C1 is a multi-unit subunit consisting of 6 identical subunits with central core with arms-H
binds to Fc region of IgG and IgM antibody once they have interacted with antigen
C1 is made of up C1q, C1r, and C1s. What occurs as the C1 binds to an antibody
C1q binds antibody
activates C1r/C1s as proteases
C1s cleaves C4 and C2
C4b & C2b form C3 convertase
How many Fc portions must the C1q bind to in order to activate the complement cascade of the classical pathway?
C1q must bind to two or more Fc portions to activate complement cascade
What are the complement proteins involved in the alternative pathway?
Factor B
Factor D
What is the function of C3 in the alternative complement pathway?
C3b binds to the surface of a microbe where it functions as an opsonin and as a component of C3 and C5 convertase
C3a stimulates inflammation
what is the function of Factor B in the alternative complement pathway?
Bb is a serine protease and the active enzyme of C3 and C5 convertase
What is the function of Factor D in the alternative complement pathway?
plasma serine protease which cleaves Factor B when it is bound to C3b
The function of Properdin in the alternative complement pathway is:
Stabilizes the C3 convertase (C3bBb) on microbial surfaces
compare the serum concentration of the proteins involved in the alternative complement pathway
C3 >>> Factor B >> Properdin > Factor D
__________ is the function of C1 in the classical pathway.
remember that C1 is a complex (C1qr2s2)
initiates the classical pathway
C1q binds to Fc portions of antibody
C1r and C1s are proteases that lead to C4 and C2 activation
C4 functions to __________ in the classical complement pathway
C4b covalently binds to surface of microbe or cell where antibody is bound and complement is activated
C4b binds to C2 for cleavage by C1s
C4a stimulates inflammation
C2a is a serine protease. What are its functions in the classical complement pathway?
C2a is a serine protease functioning as an active enzyme of C3 and C5 convertase
Mannose binding lectin has what function in the lectin pathway?
initiates the lectin binding pathway.
MBL binds to terminal mannose residues of microbial carbohydrates
A MBL associated protease activates C4 and C2 as in the classical pathway
when is the lectin pathway activated?
the lectin pathway is activated in the absence of antibody
Why is the lectin binding pathway present in humans?
many bacterial surfaces contain mannose sugar molecules. Initiated by the binding of plasma Mannan binding lectin to bacterial surfaces with mannose containing polysaccharides
-MBL functions similar to C1q of classical pathway
how does MBL act similar to C1r and C1s?
MBL after binding mannose rich glycans, associated with MASP-1, MASP-2 (MBL serine protease similar to C1r and C1s) in normal serum to cleave C4 and C2 forming C3 convertase (C4b2b)
If there is a deficiency in the lectin pathway, what will the result be?
in early childhood the patient will suffer from increased bacterial infections
what are the proteins of recognition/initiation in the classical, alternative, and lectin pathways?
Classical: IgM or 2 IgG molecules react with C1qrs
Alternative: Bacterial is the recognition and Cell surface antigen initiates
Lectin: Mannose binding lectin binds microbial polysaccharides
what proteins are involved in the activation of the classical, alternative and lectin pathways?
Classical: C1qrs, C2, C3, C4, C4b2b
Alternative: Ticking over of C3, C3, Factor B & D, Properdin, C3bBb
Lectin: MASP1/MASP2, serine protease, C4b2b
What proteins make the complex of the C3/C5 convertase in the classical, alternative, and lectin pathways?
classical: C42b3b
alternative: C3bBb3b
Lectin: C4b2b3b
What proteins are responsible for the lytic pathway of the classical, alternative, and lectin pathway?
classical: C5, C6, C7, C8, C9
alternative: C5, C6, C7, C8, C9
lectin: C5, C6, C7, C8, C9
what proteins complex together to produce the MAC in the three different complement activation pathways?
classical: C5b6789
alternative: C5b6789
lectin: C5b6789
What is a 'NEURON' also known as in the 'NERVOUS SYSTEM' terminology?

(*There are 2 other names)
which two complement pathways form the same C3 and C5 convertase?
classical and lectin binding pathways
C3 convertase: C4b2b
C5 convertase: C4b2bC3b
what does assembly of the major attack complex (MAC) involve?
assembly of MAC involves polymerization to form membrane pore on microbial surface or infected or tumor cell
what initiates assembly of the MAC?
C5b initiates the assembly of the MAC
C5a stimulates inflammation
what does C5 convertase convert C5 to?
C5 convertase (C4b2bC3b) converts C5 to C5a and C5b which is involved in the late steps of the complement activation
how does the rest of the complement components form the MAC?
1. C5b initiates assembly of the MAC
2. C5b is bound and MAC accepts C7
3. C5b and 6 are bound and the MAC is inserted into the lipid membrane
4. MAC binds C5b, 6, 7 and initiates binding and polymerization of C9
5. Component of the MAC bindnis C5b, 6, 7, 8, and polymerizes to form membrane pores
what forms the membrane pores in microbes/infected cells/tumor cells in the complement activation pathways?
C5b, C6, C7, C8
what complement activation factor causes edema?
what is the control factor of C2a?
what are the products of the C3a anaphylatoxin?
mast cell degranulation
enhanced vascular permeability
What are the control factors of C3b opsonin?
Factor H and Factor I
What is the product of C3b opsonin?
opsonization, phagocyte activation
what is the product of C4a
What is the action of C4b opsonin?
phagocyte activation
what are the control factors of C4b
C4-BP and Factor H
what type of complement factor is C5a?
C5a is a chemotactic factor
it is an anaphylactic and attracts PMN and activates basophil, mast cells
what is the control factor of C5a?
C5b67 causes:
chemotaxis, inflammation, attaches to other membranes
what is the control factor of C5b67?
Protein S
What is the function of C1 inhibitor (C1 INH)?
inhibits C1r and C1s serine protease activity
where is C1-INH found?
in the plasma
what is the regulating protein for complement?
Factor I
proteolytically cleaves C3b and C4b
What does Factor H inactivate?
Factor H inactivates Alternative Pathway
-causes dissociation of alternative pathways C3 convertase subunits
-cofactor for Factor I-mediated cleavage of C3b
What inactivates the classical pathway?
C4 binding protein (C4BP)
causes dissociation of classical pathway C3 convertase subunits
-cofactor for Factor-I mediated cleavage of C4b
What is found on epithelial cells that inhibits C3 convertase action?
DAF on epithelial cells inhibits C3 convertase action
What is Membrane cofactor protein's function?
it is found on leukocytes, epithelial cells and endothelial cells
-cofactor for Factor-I mediated cleavage of C3b and C4b
what is DAF?
Decay Accelerating Factor
-causes dissociation of C3 convertase subunits
If a patient has a Ci inhibitor deficiency what does it cause?
Hereditary angioedma is caused by a C1 inhibitor deficiency
Repeated pyogenic infections is caused by what type of deficiency?
Deficiency of C3 causes repeated pyogenic infections
how does C1 INH function?
dissociates C1r and C1s from active C1 complex
How do factor H and factor I work together?
Factor H and Factor I together cleave C3b.
H displaces B enabling the cleavage of C3b to iC3b by factor I
what cleavage products are anaphylatoxins?
smaller cleavage products
-C3a, C4a, C5a
The function of the smaller cleavage products in the fragmentation of complement activation is:
C3a, C4a, & C5a attract phagocytes, cause mast cell degranulation, enhance vessel permeability, and facilitate access of plasma proteins and leukocytes to the site of infection
what is the biologic function of complement?
1. opsonization & phagocytosis
2. Complement mediated cytolysis
3. Stimulation of inflammatory reactions
describe the process of opsonization and phagocytosis
1. binding of C3b to microbe activation of late components of complement
2. recognition of bound C3b receptor
3. Phagocytosis and killing of microbes
describe the complement mediated cytolysis
1. binding of C3b to microbe activation of late components of complement
2. formation of the membrane attack complex
3. osmotic lysis of microbe
describe the stimulation of inflammatory reactions from complement
1. Proteolysis of C3, C4, C5 to release C3a, C4a, C5a
2. Recruitment and activation of leukocytes by C5a, C3a, C4a
3. Destruction of microbes by leukocytes
what opsonin promotes phagocytosis of coated cells?
Cell bound C3b is an opsonin that promotes phagocytosis of coated cells
If a patient lacks the C!NH complement factor in the classical pathway what disease will they have?
Hereditary angioedema because of an overproduction of C2b
what is the deficiency of complement proteins for a patient that has a predisposition to have systemic lupus erythematosus?
Deficiency in the C1, C2, C4 proteins
this increases precipitation of immune complexes in tissues and inflammation
having a deficiency in of the MCL in the lectin pathway produces what types of symptoms in patients?
susceptibility to bacterial infections in infants
-have inability to initiate lectin pathway
What pathways are Factor B and/or Factor D found in for complement activation?
Alternative pathway
Having a deficiency in Factor B/D in the alternative complement activation pathway produces what symptoms/signs in patients?
Susceptibility to pus forming bacterial infections
-lack of sufficient opsonization of bacteria
What complement protein are there clinical test for?
C2, C3, C4, C1 INH protein and CH50
an Immunodeficiency that is extremely severe and is usually fatal in early life is caused by what type of complement protein deficiency?
Component of C3
What does a deficiency in Factor H and/or Factor I cause?
Deficiency in Factor H or Factor I causes C3 deficiency and susceptibility to bacterial infections
a deficiency in ________ and _______ on erythrocytes causes paroxysmal nocturnal hemogloinuriea inherited deficiency.
DAF and CD59
RBCs are not protected and get lysed
a deficiency of _______ and ________ formation causes a lack in terminal components C5-C9 and causes repeated Neisseria infection and impaired bactericidal activity.
C9 and MAC
_________ is an important component of innate and adaptive immunity
________ is a mult-step process by which mono-nuclear cells innnately engulf large particles, whole microorganisms, and injured or dead host cells
In phagocytosis the cell surrounds the particle with _______ __ _____ _______ by an energy and cytoskeleton-dependent process.
extension of plasma membrane
where does microbial killing and digestion occur in phagocytosis?
microbial killing and digestion takes place in the vesicle called a phagosome
what cells are the professional phagocytes?
neutrophils, macrophages, dendritic cells
what is the CD marker of neutrophils?
what is the CD marker of macrophages?
what is the most abundant white blood cell in circulation?
what do neutrophils secrete?
IL-8 and C5a
where are mono-nuclear phagocytes developed at?
bone marrow from stem cells
what do mono-nuclear phagocytes circulate as?
circulate in the blood as monocytes
what are the resident mono-nuclear phagocytes called?
what are the three steps involved in phagocytosis?
1. Recognition of Microbes by macrophage cell surface receptors
2. Ingestion
3. Killing of intracellular microbes by respiratory burst
In response to an infection what occurs with respect to phagocytosis?
1. Chemotaxis: facilitated by Bacterial N-formyl-methionyl peptides, vascular permeability, increased adherence molecules on vascular endothelial cells, integrins on phagocytes
2. Attachment occurs via receptors on neutrophils and macrophages to recognize microbes (mannose receptors or receptors for opsonins)
What are some receptors in action to activate phagocytes?
1. Toll-like receptors
2. G-protein coupled receptors
3. cytokine receptors
TNF trigger respiratory burst activation
Phagocytes have high affinity receptors that specially bind to antibody molecules, complement proteins, and lectins that act as opsonins. What is one of the most critical for phagocytosis of microbes?
Opsonization of microbes by IgG
What are the steps involved in the ingestion of a microbe?
1. cytoskeleton dependent process of engulfment
2. forming pseudopodia
3. phagosome formation
4. phagolysosome (fusion of phagosome with preformed lysososmes containing granules) to form phagolysosome
4. microbicidal molecules found in lysosome of activated neutrophils
True of False
Neutrophils do not present antigens.
what are examples of bactericidal agents produced in the phagolysosome of phagocytic cells?
acid, toxic oxygen derivatives, toxic nitrogen oxides, antimicrobial peptides and proteins, lysosomal enzymes
When a cell phagocytosis a microbe how is it killed once it is ingested?
Activated macrophages and neutrophils convert molecular oxygen into reactive oxygen species, which are highly reactive oxidizing agents that destroy microbes
How is the Phagocyte Oxidase System induced to a ROI?
induced by IFN-gamma and or TLR stimulation
-it increases glucose and oxygen consumption and trigers assembly of enzymatic complex NADPH oxidase
what reactive oxygen species do phagocytes convert molecular oxygen into?
reactive oxygen intermediates that are formed are superoxide radical, hydrogen peroxide, and hydroxy radical singlet O2 with membrane associated reduced from of nicotinamide adenine dinucleotide phosphate (NADPH) as a co-factor
what disease is a result of a genetic deficiency of NADPH oxidase?
results in immunodeficiency disease called chronic granulomatous disease
-induced granulomas which are due to recurrent bacteria and fungi infections
how does the inducible Nitric Oxide Synthase Enzyme function?
1. induced by IFN-gamma or TLR stimulation
2. Phagocytes produce Reactive Nitrogen Intermediates: iNOS converts arinine to citruline and releases nitiric oxide gas
3. NO gas combines with H2O2 or superoxide to produce reactive peroxynitrite radicals that kill microbes
which is more toxic hydrogen peroxide or superoxide?
H2O2 is more toxic than superoxide except in catalase positive staphlococci
Mycobacteria and Leishmania species are resistant to ROI
what activated cell increases their expression of receptors for TNF and secretes TNF-alpha., IFN-gamma secreted by Th-1 cells increase micro antimicrobial action- NO and O2 by this cell. CD40 expression on this cell also increases interaction with CD40 ligand on T-cells which increases B7 and MHC class II on this cell
Activated macrophages
what are the effector functions of activated macrophages?
1. migration into tissues
2. killing of microbes
3. inflammation enhanced adaptive immunity
4. tissue repair
what is the physiological function of MHC genes?
encode peptide binding molecules for recognition by antigen specific T-lymphocytes
_______ _______ _______ are called human leukocyte antigens
Human MHC molecules
where are human MHC molecule genes located?
chromosome 6
what loci encode for Class I MHC?
three loci encode for class I MHC
-A, B, and C
mainly A and B
what loci encode for class II MHC?
encoded by DP, DQ, DR
(mainly DR)
which class MHC has a highly polymorphic loci that is encoded for by complement proteins and cytokine proteins?
Class I MHC are expressed on virtually ______ nucleated cells
Class II MHC are expressed mainly on __________ ______
professional APCs
Examples of APCs that Class II MHC could be found on are:
dendritic cells, macrophages, B lymphocytes
-also on non-professional APCs that need IFN-gamma activation for induction of MHC such as endothelial cells and thymic epithelial cells
true or false
macrophages are activated by IL-12, which enables them to activate T-cells
MHC molecules are ________ ______ on antigen presenting cells that display _________ for immune recognition by antigen specific T-lymphocytes
membrane proteins
what are processed into peptides and loaded onto MHC molecules?
protein antigens derived from the extracellular space or the cytosol are processed into peptides and loaded onto MHC molecules
what is the physiological function of MHC?
Peptide presentation to T-lymphocytes
True or False
Class I and Class II MHC genes are not polymorphic
Class I and Class II MHC genes are highly polymorphic: more than 250 alleles for some of these genes in the population
how do T-cells recognize peptide?
T-cells recognize peptide presented in the form of a MHC
describe the structure of a class I MHC molecule
a polymorphic alpha chain non-covalently attached to a non-polymorphic beta2 microglobulin
-peptide binding occurs between the 2 alpha chains
where does peptide binding occur on a Class I MHC?
in-between the alpha chains
describe the structure of a class II MHC
a polymorphic alpha chain non-covalently attached to a polymorphic Beta chain
*both chains are polymorphic
*binding of peptide occurs between the alpha-1 and beta-1 chains
what three components are required for stable expression of a fully assembled class I MHC molecule on the cell surface
-alpha chain
-B2 microglobulin
-bound antigenic peptide
what induces HLA expression on cells?
induced by IFN-alpha and beta
IFN-gamma, and TNF-alpha
describe the class I MHC pathway.
1. antigen uptake: protein antigens from intracellular bacteria/viruses in the cytosol are processed by proteasomes
2. antigen processing: after processing by the proteasomes they are transported into the ER
3. MHC biosynthesis: class I MHC is found in the ER
4. Peptide-MHC association: peptide and class I MHC bind and exit out and are finally displayed for recognition by CD8+ T-cells
How does the Epstein Barr virus cause mononucleosis latent infection of B-cells?
inhibits proteasome activity and hydrolyzing of viral proteins
-cannot process virus and form peptide to bind with MHC-I molecule in the ER
What are the three loci found in the class II MHC molecule?
What are the 3 components necessary for the heterotrimer for stable expression of fully assembled class II MHC molecules on cell surface/
alpha chain
beta chain
bound antigenic peptide
what induces the expression of class II MHC molecules
expresson is induced on cells by IFN-gamma
are extracellular or intracellular protein antigens displayed by class II MHC?
extracellular protein antigens or microbes are endocytosed by vesicles where the antigens are processed to be displayed by class II MHC
where do the extracellular processed peptides bind to the class II MHC molecules?
the peptides bind to Class II MHC molecules in the vesicle that endocytosed them
Class II MHC molecules present to what type of T-cell?
CD4+ T-cells
Where are class II MHC molecules synthesized at?
in the ER and transported by endosomes with an associated protein called the invariant chain which occupies the peptide binding cleft of the newly synthesized class II molecule
how is the invarient chain displaced on the class II MHC molecule?
when fusion of the MHC-II and the extracellular protein occurs the invariant chain leaves
how do mycobacteria evade the cell-mediated immunity?
Mycobacteria inhibit phagolysosome fusion
how does herpes simplex virus evade cell mediated immunity?
inhibition of antigen presentation: HSV peptide interferes with TAP transporter
what microbe inhibits proteosomal activity?
cytomegalovirus (CMV)
Epsteini-Barr Virus (EBV)
how does EBV affect B-cells?
production of IL-10 inhibits macrophages and dendritic cells
which virus secretes soluble IL-1 and IFN-gamma to evade cell-mediated immunity?
Pox virus
-inhibition of effector cell activation
what type of APCs are part of the class II MHC pathway?
dendritic cells, mono-nuclear phagocytes, B-lymphocytes, endothelial cells, thymic epithelium
what type of APCs are part of the class I MHC pathway?
all nucleated cells
what are the responsive T-cells in class II MHC pathway?
CD4+ T cells
what are the responsive T-cells in class I MHC pathway?
CD8+ T-cells
what is the source of the antigen in the class II MHC pathway?
endosomal/lysosomal proteins mainly internalized from extracellular environment
what is the source of antigen in the class I MHC pathway?
cytosolic proteins mostly synthesized in the cell, may enter cytosol from phagosomes
where is the site of peptide loading of MHC in class II MHC pathway?
specialized vesicular compartment
What type of vesicular compartment are protein antigens found in that are presented to class II MHC associated peptides?
acidic vesicular compartments of APCs
what type of protein antigen generates a class I MHC associated peptide?
Protein antigens present in the cytosol generate Class I MHC associated peptides
True or False
Each MHC molecule displays one peptide at a time but can present more than one peptide
True or False
MHC molecules bind only peptides
True or False
Peptides are acquired during intracellular assembly of MHC molecules
How long will an MHC molecule display the bound peptide?
MHC molecules displays bound peptides for long enough to be located by T-cells
what are the most polymorphic genes in the MHC gene?
most polymorphic genes are A and B from class I and DR from class II
what six class II MHC alleles are inherited?
three from each parent
one set of DP, DQ, and DR
MHC molecules and genes are co-dominant. Which are the most polymorphic?
A,B and DR are most polymorphic
A and B for class I
DR for class II
It has been found that if an individual inherits these particular HLA alleles they have a relative higher risk of developing ankylosing spondylitis and Rheumatoid arthritis, Type 1 diabetes mellitus, and Pemphigus vulgaris.
Ankylosing spondylitis: HLA-B27
Rheumatoid arthritis: HLA-DR4
Type 1 diabetes melitus: HLA-DR3/DR4
Pemphigus vulgaris: HLA-DR4