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Microbiology > Immunology Exam 1 > Flashcards

Immunology Exam 1 Flashcards

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1
Q

What plays an important role in transplant rejection? Why?

A

MHCs (Major Histocompatibility Complex), over 1000s of diff alleles for each MHC encoded gene leads to increased polymorphism (most polymorphic gene system in body) and decreases likelihood that two random individuals would have identical sets of MHC

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2
Q

What is the exogenous process? What is the purpose? Which MHC molecule is involved with this process?

A

The process by MHC Class II presents antigens on APCs. Foreign material is phagocytosed by a APC (antigen presenting cell=macrophage, B cell, dendritic cell) and is broken into small peptides in the phagolysosome. MHC Class II polypeptide complexes are made in ER and transported thru Golgi to the phagolysosome with an invariant chain attached at the binding site. Once in the phagolysosome, the invariant chain is excised, and peptide loaded into binding groove and transported to outside of cell for presentation to CD4+ cells

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3
Q

What is the endogenous process? What is the purpose? What MHC is involves in this pathway?

A

Proteins within a cells cytosol are broken down via a proteosome in normal cell turnover, small pieces of peptides are transported to ER (where MHC Class I are being made) and are “tried on” by the MHC Class I. The unfit peptides are returned to cytosol for further breakdown. Once a “fit” is made, the complex is transported to plasma membrane for presentation to CD8+ T cells. The occurs in almost all uncleared cells (not RBCs).MHC Class I does not differentiate between host peptides and foreign peptides

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4
Q

What are the genes that encode MHC in humans called? What are the different names and how many genes/proteins for each type of MHC?

A

Human Leukocyte antigen (HLA)
6 encode for MHC Class one : HLA-A,-B, -C (3=maternal, 3=paternal)
6 encode for MHC Class Two: HLA-DP,-DQ,-DR (3=maternal, 3=paternal)

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5
Q

What is the primary function of the MHC? What binds to the MHC?

A

Present antigens to T cells, are requires for function of T cell arm of adaptive immune system, TCR of CD4+ binds with peptide epitope complexed with MHC Class II complex, TCR of CD8+ binds with peptide epitope complexed with MHC Class I

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6
Q

What is an important characteristic of MHCs that allows a full survey of the contents of the cell to be presented?

A

They have promiscuous binding (able to bond with 1000s of diff antigenic peptides)

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7
Q

What happens when a CD8+ cell binds to its conjugate MHC? What about CD4+?

A

CD8+ T cell is activated when it attaches to MHC Class II + peptide complex causing clonal proliferation of their effector cell (helper T cells) that secrete cytokines (signaling molecules), CD4+ T cell is activated when it attaches to MHC Class I + peptide causing clonal proliferation of its effector cell (Cytotoxic T cells=CTLs that are programmed to kill the infected cell they bind to)

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8
Q

What are the 3 main purposed of the immune system?

A

Prevent infection, control infection and eliminate the pathogen and its products

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9
Q

What happens when the immune system “turns on its host”?

A

Autoimmunity and allergy

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10
Q

What is one of the most important features of the immune system?

A

Distinguishing self from non-self

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11
Q

What are the two main branches of the immune system?

A

Innate and adaptive immunity

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12
Q

What are the main characteristics of innate immunity?

A

Fast acting, always “on” at a basal level and is the first line of defense, non-specific response via binding of evolutionarily conserved pathogenic epitopes (ex. Can tell diff between gram positive and gram negative, but not two different types of gram negative bateria), present at birth, initiates inflammatory response and signals adaptive immune response, does NOT make memory

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13
Q

What are the main characteristics of adaptive immunity?

A

Specialized response, activated ONLY when specific pathogen is encountered, gets quicker/stronger each exposure (HAS MEMORY), slower response time, separated into humoral and cell-mediated responses) not mutually exclusive

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14
Q

What are the three reasons why adaptive immunity is effective and protective?

A

Diversity-diff types of cells and soluble molecules
Specificity- cells/soluble molecules are specific for particular antigen
Memory- able to respond better and faster with each exposure

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15
Q

What are some examples of innate immune responses?

A

Phagocytosis, productions of antimicrobial peptides, toxic reactive species

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16
Q

Why is the innate immune response considered innate?

A

It is not dependent on prior contact with pathogen and it is the only functional immune response we have at birth

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17
Q

What are the three innate response mechanisms?

A

Barrier defense, soluble defense, cellular defense

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18
Q

What is skin’s and nail’s role in innate immunity?

A

Intact skin serves as an almost inpenetrable barrier with a slightly acidic pH that is not ideal for most pathogens, the continuous sloughing of skin also constantly sheds pathogens, the outer layer is keratinize which makes it difficult for microbes to make use of it metabolically. Nails are also keratinized creating a hard impenetrable surface

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19
Q

What are the main physical barriers of the innate immune system?

A

Skin, nails, mucosal surfaces, normal flora, fever and eyes

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20
Q

What are mucosal surfaces role in innate immunity?

A

Not as effective as skin b/c it is so thin, but the mucus is thick (difficultly/binding mov’t for microbes), the mucus contains antimicrobials: lactoferrin and lysozyme

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21
Q

What are the specific functions of the antimicrobials lactoferrin and lysozyme?

A

Lactoferrin sequesters iron which rids the area of nutrients, lysozyme breaks up peptidoglycan (major substance in most bacteria)

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22
Q

What is the function of normal flora in innate immunity?

A

Normal flora are microbes that are naturally found in body whose binding prevents other pathogens from binding, they also use up all available nutrients and can secrete bacteriocins (toxins harmful to other bacteria)

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23
Q

What is the function of fever in innate immunity?

A

Retards/prevents growth of pathogens (prefer normal body T) and speeds process of hematopoiesis

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24
Q

What are eyes function in innate immunity?

A

Wash eyes and blink to free eye of pathogens, tears also contain lysozyme

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25
Q

What are the two cells crucial in the cellular defense arm of innate immunity and what are their functions?

A

Macrophages and Neutrophils = phagocytes
Macrophages: tissue fixed, long lived phagocytes that differentiate from monocyte progenitor cells found in blood, are large irregularly shaped cells with big cytoplasm, also function as APC (antigen presenting cell in adaptive immunity), they “patrol” tissues for antigens and signal neutrophils and other leukocytes to site of infection
Neutrophils: short lived, type of WBC, effective phagocytes that are found in the blood (signaled to tissue), aka PMNs (polymorponuclear cells ) due to segmented nucleus, on top of being phagocytic they are cytotoxic granulocytes that is secrete granules with enzymes and toxins that kill pathogens

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26
Q

What are characteristics of phagocytes?

A

Kill in non-specific way, acidic (pH 4.5, protons translocated), contain ROS/RNS (reactive oxygen/nitrogen species that destroy proteins, nucleus acids and lipids), contain antimicrobial enzymes peptides = lactoferrin (nutrient deprivation), bacteriocides (defensins that create holes in membranes) and hydrolysis vis lysozyme (deconstructs carbs)

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27
Q

How do the cells of the innate immune system “detect” a pathogen and signal a response?

A

Contain cell bound PRRs (pattern recognition receptors) that bind to PAMPs of pathogens, this triggers a receptor activated signaling pathway that causes phenotypic change in cell causing expression of genes that code for cytokines and other chemical messengers to be produced and released from cell to initiate innate/adaptive immune response

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28
Q

What is a cytokine? What is its significance in the innate immune response?

A

Chemical messengers that prompt biological changes to surrounding tissue as well as other areas of the body (brain), they recruit other cellular defenders to the area of infection, it makes up the soluble defense system of the innate immune response

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29
Q

What is an example of a PRR? What are the different functions of its 9 subgroups?

A

TLR (toll like receptor) that binds to PAMPs causing phagocytosis and activations of the cell to release cytokines, not much diversity w/in TLRs and each subtype binds same kind of antigenic epitope TLR 1&2: bac. lipopeptides, 2: bac. peptidoglycan, 4: LPS, 5: bacterial flagellin, 2&6: bac.lipopeptides, 3,7,8,9 all inside endosome: bac. nucleic acids

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30
Q

What cell does innate immune system rely on heavily to clear up initial infection? Why? Why is this an issue? How is it overcome?

A

Neutrophils are able to be recruited to site of infection within 30-60 mins (quickest response) and are experts at phagocytosis therefore are most relied on (macrophage usually first to detect infection however), however, they circulate in the blood therefore must undergo extravasation to get to the tissue

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31
Q

What is extravasation? What is the purpose? What are the steps?

A

process of blood immune cells getting to site of infections, circulating cells must overcome the low rate of diffusion’s at the vasculature and the rapid movement of blood flow. 1. Rolling-released cytokines dilate nearby blood vessels slowing blood flow and allowing for low affinity interactions (via integrin) to occur b/t endothelial cells and leukocytes (like Velcro ball rolling down Velcro ramp) 2. Adhesion-high infinity interactions bring leukocyte to a full stop and cell knows where it will exit 3. Transendothelial migration: cytoskeleton of leukocyte changes allowing it to “spread out”, junctions between endothelial cells loosen and leukocyte is able to migrate to the tissue where it “follows bread crumb trail” to the site of infection

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32
Q

What is the purpose of inflammation?

A

Deliver immune cells/effector molecules to the site of infection, provide physical barrier to prevent spreading of infection, promote tissue repair

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33
Q

How does edema occur? What is its importance?

A

The release cytokines create “leaky” endothelium via loosened junctions allowing plasma fluid to leak into the area of infection, this creates a physical barrier between the site of infection and the surrounding area

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34
Q

What is inflammation defined by and what causes these changes?

A

Rubor (redness), Calor (heat), Dolor (pain), Tumor (swelling) which are all caused by regulated changes via the blood vessels (increased blood flow to area, vasodilation, plasma fluid leakage, cellular influx)

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35
Q

What are the approximate response times of the two phagocytes involved in innate immunity that we discussed?

A

Neutrophils (30-60mins), monocytes (4-6 hrs)

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36
Q

What is the unintended effect of degranulation? Why? What cell participates in degranulation? What is the effect/physical symptoms?

A

The neutrophils release granules that kill the pathogen but they cannot be directed specifically at the pathogen therefore there is a bystander effect and healthy tissue is destroyed, the granules can also stimulate the nerves causing pain, accumulation of the dead cells/fluid cause purulent exudate (pus), more neutrophils=more pus

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37
Q

What is the acute phase response? What is it regulated by? What is the name of a specific cytokine that causes it?

A

It is the systemic arm of the inflammatory response triggered by cytokines (ex. IL-1) that promote body changes to support host defense (ex. Fever), which is regulated by the hypothalamus. IL-1 aka a pyrogen bc it is a substance that produces fever (shows how cytokines are a soluble defense mechanism of the body with long range effects in the body)

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38
Q

What are the two forms of antibodies? What is the difference between the two?

A

BCR (is is membrane tethered to a B cell and has hydrophobic tail) and secreted antibody

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39
Q

What can be expected of a developing, immature, naive B cell?

A

Does not secrete antibodies, begin expressing BCR during development (IgM and IgD)

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40
Q

What is the single effector function of B cells?

A

Produce antibodies

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41
Q

What is the function of antibodies? What can’t they do?

A

Recognition of antigen and binding to epitopes on antigen, they can neutralize the antigen, activate complement, participate in ADCC and act as poisonings to enhance phagocytosis but CANNOT directly kill or remove antigens themselves

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42
Q

What region of an antibody determines the biological activity/function within the body?

A

The heavy chain (constant region)

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43
Q

What region of the antibody determines the antigen specificity? Are the two of these regions identical?

A

The variable region (N terminal) determines the antigen specificity. Each arm of the antibody is composed of non identical VH and VC regions, however the VH and VC of the other arm are identical to its namesake on the other, variable region composed of first 110 a.a sequence of chain

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44
Q

How many parts of the constant heavy chain? Is this different for different isotopes?

A

3 parts in IgG, IgA, IgD; 4 parts in IgM, IgE

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45
Q

In what situation would the VH and VL regions of one antibody be the same as an antibody of a different isotype?

A

If they came from the same mother cell

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46
Q

What happens if you treat an antibody with papasin?

A

Enzyme cleaves the antibody at the hinge region forming 2 Fab regions (can bind antigen, each of VH/VL and CH/CL), 1 Fc region which can associate with effector molecule but cannot bind to antigen (binds to Fc receptors on immune cells that phagocytize during opsonization when Fab bound to antigen). This breaking up doesn’t occur naturally in body, just experiment used to identify different portions of antibody

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47
Q

What is the hinge region? Where is it present?

A

Area between CH1-CH2 that allows antibody to bind to epitopes at diff angles (not present on antibodies with 4 CH regions s/a IgM, IgE)

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48
Q

What is the J chain? What is it’s purpose and where is it located?

A

Is is a small protein chain involved in oligomeric forms of IgM (pentameter, 10 binding sites) and IgA (dimer, 4 binding sites), one J chain required for each, important in mucosal immunity

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49
Q

What are the main characteristics of IgM?

A

Present as monomeric (membrane bound BCR form on naive B cells) and pentamer in serum, first isotype produced when B cells are activated by T cells, it is the “default” antibody, found on ALL naive B cells as BCR, only isotype produced by a fetus (begins at about 20 wks after gestation), Jobs= activate complement and act as BCR

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50
Q

What are the main characteristics of IgD?

A

Found mainly on surface of naive, mature B cells, very little levels in serum, least common Ig made

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51
Q

What are the main functions of IgG?

A

It is the most prominent Ig in tissues (due to small size), most predominate Ig in serum, only isotype to pass placenta (in effective titers for up to 6 months), doesn’t begin to be produced until between 4-6 mo, it is a multifaceted Ig: neutralizes to prevent entry, activates complement and acts at opsonins

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52
Q

What are the main functions of IgA?

A

Most abundant of all Ig (as far as sheer quantity made), monomeric or dimeric, Most predominant Ig in secretions (tears, saliva, mucus, breast milk etc) and mucosal surfaces, but mostly found in secretions (not serum, dimeric in mucosal and secretions

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53
Q

What are the main functions of IgE?

A

Very little free IgE in serum/tissues, nearly all are bound to high affinity IgE receptors (Fc receptors) on surface of mast cells, basophils, eosinophils, when antibodies cross linked = degranulation of these cells, for this reason it mainly acts to mediate allergic responses (IgE binds to parasite/allergen and then to Fc receptors on above cells causing degranulation)

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54
Q

Where does B cell development begin?

A

The bone marrow

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55
Q

What are the 7 steps of B cell development up until a naive B cell?

A
  1. Cell commits to lymphoid lineage (becomes lymphoid progenitor cell)
  2. Commits to becoming a B cell (not a T cell)
  3. Enters pro-B cell stage
  4. Enters pre-B cell stage
  5. Enters immature B cell stage
  6. IgD expression (mature B cell)
  7. Naive B cell
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56
Q

Where does the pro-B cell stage occur and what happens during this stage?

A

Occurs in the bone marrow, the HC is produced via gene rearrangement of V,D,J genes (many types of each, only one of each is chosen) to create the variable region (others are permanently removed), if this rearrangement is unsuccessful = apoptosis, constant region of HC is makes IgM first (it is first on the locus, IgD later)

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57
Q

Where does the pre-B cell stage occur? What happens in this stage?

A

It occurs in the bone marrow, LC is rearranged via same method as HC however just V & J are involved. If unsuccessful = apoptosis, constant region of LC is the same for all isotypes

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58
Q

What happens in the immature B cell stage?

A

IgM is now expressed as BCR, developing B cells checked to see if the recognize self (this is called negative selection). If they do recognize self, they get a “do over” and variant region of LC is rearranged, if still recognize self after this then apoptosis

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59
Q

What happens when immature B cells become mature (but naive)?

A

Once negative selection is done, the immature B cell moves to the spleen where is receives signals to begin expressing IgD (not considered isotype switching) the cell is then a mature, naive B cell and leaves the spleen into circulation, if it does not bind an antigen within 2-8 wks -> apoptosis. Variable chain is determined via DNA splicing = permanent , therefore all progeny will have same VH/VL sequence. B cell is now said to be antigen DEPENDENT

60
Q

What are the hallmarks of a mature naive B cell?

A

Expression of both IgM and IgD as their BCRs

61
Q

What four events occur after antibody binds an antigen in secondary lymphoid organs?

A
  1. Clonal expansion
  2. Affinity maturation
  3. Isotype switching
  4. Career decision
62
Q

How many ways can B cell activation occur and what are they called?

A

2 ways:
T-dependent activation (req T cell help)
T-independent activation (no T cells req)

63
Q

How many signals required for T cell dependent B cell activation? What are they? What is the purpose of this?

A

2 signals:
Signal 1: Antigen binds to BCR and signal sent to nucleus = primed B cell
Signal 2: CD40 on primed B cell interacts with CD40L on effector T helper cell -> full activation
This ensures that the antigen is a real threat and isn’t a false alarm

64
Q

What is the “B cell side of the story” for T dependent B cell activation?

A

BCR recognizes and binds antigen in the secondary lymphoid organ forming a primed B cell
The antigen undergoes BCR mediated phagocytosis. Since B cells are APCs, the antigen undergoes the exogenous pathway and is presented on a MHC Class II

65
Q

What is the “CD4+ T cell side of the story” in T dependent B cell activation?

A

APC in tissue phagocytizes the same pathogen, processes it an presents it on a MHC Class II, the APC then travels (probably dendritic cell b/c they can travel) to the secondary lymphoid organs where T cells accumulate, CD4+ naive T cell’s TCR binds to the MHC Class II and peptide on the APC and T cell is activated. Activated T cell proliferates and differentiates creating effector T helper cells (these are the cells that will be involved in the CD40-CD40L binding)

66
Q

What happens when the effector T helper cell interacts with the primed B cell?

A

The CD4+ binds with the MHC Class II on the B cell and the CD40L of the T helper cell binds with CD40 of the primed B cell (this is the second signal), it is sent to the nucleus forming a fully activated B cell (T cell also secretes cytokines which help in the steps taken after activation)

67
Q

What is clonal expansion?

A

The activated B cell makes more of itself (rapid proliferation) all variable regions of the progeny will be the same as the mother cell, affinity maturation (somatic hypermutation) and isotype switching occur during this time

68
Q

What is affinity maturation?

A

B cells undergo high rate of mutation at certain DNA sites w/in variable region of BCR (if successful this allows antibody to bind antigen with high affinity), these are only small point mutations

69
Q

What is isotype switching?

A

Upon B cell activation, IgD is immediately dropped leaving only IgM to be expressed, to allow for other Ig to be expressed, there must be recombination at a DNA level to express either IgG, IgA or IgE (depending on immune response needed), this is mediated by interactions with CD4+ T cells

70
Q

What are the two career decision paths that an activated B cell’s progeny can take?

A

They can become plasma cells which are effector B cells that are terminally differentiated (no other changes, no dividing, affinity maturation or isotype switching) that secreted Ig until apoptosis (usually a few days)
OR
Become memory B cells which at not terminally differentiated, however, they are non prolific ad long lived, they re enter circulation in the body, and wait for antigen re encounter causing reactivating without the help of T cells this time, the reactivated cells undergo the same stages the mother cell underwent after activation

71
Q

What is an antigen?

A

Any material/molecule that can be specifically bouncy by antibodies/lymphocytes. The more visible a substance, the more likely to elicit a response

72
Q

What is an immunogen/immunogenicity?

A

An antigen that elicits an immune response (not all antigens are immunogens)
Immunogenicity is the ability of an antigen to induce and immune response

73
Q

What is an epitope?

A

Specific region/site of the antigen that is recognized by antibody/BCR or TCR, they are usually present in multiple copies (antigens only bind small portion of whole antigen)

74
Q

What are haptens?

A

Molecules (usually small) that can be bound by antibodies but do not elicit an immune response unless they are conjugated to a carrier protein (typically host protein)

75
Q

What are some characteristics of proteins as antigens?

A

Virtually all proteins elicit an immune response due to size 3D shape and complexity, the more complex, the more vigorous the response, each of the 4 levels of protein structure contributes to immunogenicity
Primary structure: a.a seq can be sequential epitope (req for T cells)
Secondary Structure: alpha helix and beta sheet backbones help form 3D structure
Tertiary Structure: How protein folds determines conformational/discontinuous epitopes
Quaternary Structures: the juxtaposition of diff polypeptides in a protein composed of multiple polypeptides subunits (ex. AB toxins)

76
Q

What are polysaccharide’ s role as antigens?

A

Because of repeating subunits, epitope density = high (repetitive structures tend to elicit good immune responses
However, usually only elicit response when bound/associated w proteins
Are NOT processed (broken down like proteins) and presented on MHC b/c TCR only reacts/bind peptides
Known as T-independent antigens

77
Q

What are nuclei acids role as antigens?What is a clinical example?

A

Poorly immunogenic alone, but more so when they are complexed with protein. Example= Systemic Lupus Erythematosus-autoimmune disease where patients produce antibodies against native dsDNA

78
Q

What are lipids role as antigens? What is an example of one?

A

Rarely immunogenic, unless complexed to protein (lipoproteins) or polysaccharides (glycolipids) which makes them larger/more complex
Ex. LPS is on of the most potent stimulators of immune system

79
Q

What three sets of antibodies are generated when the host is injected with a hapten-carrier complex?

A

Hapten-specific antibodies
Carrier-specific antibodies
Antibodies specific to hapten-carrier complex

80
Q

What is an example of a hapten-carrier complex eliciting an immune response? What is the effect? How does it happen?

A

Drug induced immune hemolytic anemia (Rare)

  • Drugs are administered at high does for extended periods and form covalent bonds with RBCs (Methyldopa/IV Penicillin)
  • This causes the RBC to be viewed as foreign by the body and undergoes attack
  • Lysis of RBCs with MAC (C5b6789) via classical complement pathway via IgM/IgG can occur
  • OR opsonization of the complex to be “tagged” to be eaten
  • This causes anemia (RBCs destroyed)
81
Q

What are characteristics of BCR/antibody epitopes?

A

BCRs/Antibodies bind to native antigen (it is not processed), the epitope. Must be accessible (surface/external face)
Can be:
-sequential
-Conformational/discontinuous: not next to each other in sequence, but the are when protein takes on another higher structure (ex. Loop)
-Protein, polysaccharide, lipid, DNA

82
Q

What are characteristics of TCR epitopes?

A

Must be sequential, TCR only recognizes epitopes that have been processed and presented on MHC, however, for this reason, the epitopes don’t have to be on the antigen surface (like BCR), (ex. Can be nuclear or cytoplasmic protein of the antigen), must be protein (only reacts to peptide sequences)

83
Q

What is the complement system? What are the two functions? What are characteristics? Innate or Adaptive?

A
  • 20-30 proteins that work together in signaling cascade-type manner (outside of cells)
  • Fx: opsonization, lysis, enhance inflammation
  • Very rapid system
  • It is regulated
  • Composed of serum and cells surface proteins
  • Has 3 activation pathways that all lead to same end results
84
Q

What is a zymogen? What is an example of one?

A

A protein that exists in an inactive state and must be cleaved to activate, ex. Complement proteins

85
Q

What are the two products formed when a complement protein is formed? What are characteristics of each? Are there any exceptions?

A

The large moiety binds to activation complex or target cell’s membrane = b, and the smaller piece is released and usually soluble = a

EXCEPTION: C2= C2b is the soluble portion, while C2a is larger/binding peptide

86
Q

What is opsonization? How does it occur (in terms of complement function)? Why is it important? Which complement molecules and antibodies act as opsonins?

A
  • The “tagging”/coasting of pathogens to increase phagocytosis
  • Macrophages and neutrophils have complement receptors on their cell surfaces, when bound to opsonins = “eat me” signal
  • C3b and C4b act as opsonins and IgG (adaptive immune response)
  • Important because enveloped pathogens(Gram neg bacteria, enveloped viruses) have slippery outside, hard for macrophage to “latch on”, opsonins help this process (think of pricking a buttered potato)
87
Q

What is the function of lysis in the complement pathways?

A
  • The final product = MAC = membrane attack complex which forms holes/pores in a pathogens membranes
  • MAC = C5b6789(n)
  • Works for any enveloped pathogen with a membrane (gram negative bacteria, enveloped virus/parasites)
  • All different pathways of the complement system lead to same end result
88
Q

What is the function of the complement system in inflammation?

A
  • The “a” fragments of the complement proteins that are released after cleavage function as anaphylatoxins (C3a, C4a, C5a)
  • They recruit additional immune cells to infection site/enhance inflammation
  • Increase vascular permeability/adhesion molecule expression on endothelial cells
  • Increase expression of adhesion molecules on neutrophils/are chemoattractants for these cells (important in extravasation)
89
Q

What is the classical pathway of the complement system? What immune response is it a part of?

A

It is a part of the adaptive immune response and only triggered by IgM and IgG

  • Initiation: C1 complex binds to Fc regions of 2/or more different antibodies attached to an antigen-> activated C1 enzymatic activity
  • C1 cleaves C4 (C4b binds to target)
  • C1 cleaves C2 (C2a bind to C4b->C4b2a)
  • C4b2a then cleaves C3 (it is known as C3 convertase)->C4b2a3b
  • C4b2a3b = C5 convertase which cleaves C5, C5a then binds to target in new position
  • C6 then binds to C5a
  • C7 binds to C5a6
  • C8 binds to C5a67
  • Multiple C9’s bind to C5a678 forming the MAC complex -> C5a6789(n)
  • C3a, C4a, C5a = anaphylatoxins formed
  • C3b and C4b= opsonins formed
90
Q

What is the alternative pathway? What kind of immune response is it a part of? How does it differ from the classical pathway?

A
  • Part of the innate immune response, can be activated via multiple mechanisms
  • C3 spontaneous cleaves when in environment around pathogens and small amount of C3b is in circulation
  • After spontaneous cleavage, C3b binds to the microbial surface
  • The rest of the pathway is just like the classical pathway leading to C5b6789(n) (MAC) formation
  • anaphylatoxins C3a, C5a formed
  • opsonin: C3b formed
  • No products from cleavage of C4 formed
  • Doesn’t involve C1 binding to antibody (hence innate immune response)
91
Q

Why is complement regulation important? How does it occur? What are three structures that act as complement inhibitors?

A
  • Complement system could potentially damage healthy tissue if not regulated
  • Soluble/serum proteins disrupt the enzymes formed at particular stages of the complement cascade
  • C1 inhibitor (C1INH)-irreversible binds to C1=cannot cleave C4 or C2
  • Degradation of C3b-occurs via Factors H & I
  • Protectin-binds to C5b678 complex preventing recruitment of C9 (completion of MAC)
92
Q

What is the proposed link between the complement system and Age-Related Macular Degeneration? What is ARMD?

A
  • Leading cause of irreversible vision loss in elderly
  • Causes deterioration/breakdown of macula (loss of VA/Central Vision)
  • Complement factor mutations have been found in many patients such as:
  • Factor H mutations (loss of complement inhibitor acting on C3b
  • C3 mutations: inhibit breakdown of C3 (increased levels of C3 available)
  • C9 Mutations: increases levels of C9 available (MAC)
  • Drusen contains complement proteins
  • Non regulated complement=destruction of healthy tissue
93
Q

What would occur if there was an issue in B cell development? Would there be no B cells?

A

There would be B cells, but there would be little or no antibodies

94
Q

What would happen if T cell development was disrupted? Is there a clinical name?

A

The immune response to intracellular and extracellular (B cells would be affected) pathogens would be disrupted because T cells play a large role in B cell activation. The ability to acquire T cell and B cell memory to a pathogen would be diminished. Patients often have Severe Combined Immunodeficiency (SCID) which is one of the most devastating immunodeficiencies.

95
Q

Where do T cells derive from? What is the first step in T cell development?

A

Derive from lymphoid progenitor cells in the bone marrow. First step = commit to becoming a T cell (not a B cell) and travel to the thymus. Then known as a thymocyte.

96
Q

What is the second step in T cell development of the thymocyte? Describe in detail.

A

Prior to this step, cell known as “double negative”, CD4-/CD8- (neither is expressed. Undergo random gene arrangements of V,D,J to create diversity while making the TCR (T cell receptors), successful rearrangement = checkpoint in development, each TCR made of alpha and beta protein (other kinds but this one binds the most diverse array of peptide) and each has a variable and a constant region. The beta chain is made first, if successful a signal is sent to the nucleus and the thymocyte begins expressing both CD4+/CD8+ (Double positive)

97
Q

What is an delta-gamma BCR? Where is it found?

A

Less common BCR found in specific tissues (skin/mucosal)

98
Q

Does TCR undergo isotype switching and/or affinity maturation like BCR?

A

No, there are no further modifications once TCR is made, all progeny will have same antigen specificity (like BCRs) there just won’t be the ability to make small point mutations in DNA to create higher affinity connections with the antigen

99
Q

What is thymic selection? What are the two steps?

A

It is the process of thymocyte “education” ensuring only thymocytes with specific characteristics can develop further
Step 1: Positive selection for self-MHC
Step 2: Negative selection against T cells that have receptors that recognize self antigens (avoid autoimmunity)

100
Q

What happens in positive selection (step 1 of thymic selection)? What are the 2 main goals?

A

Goal 1: self recognition
Goal 2: Lineage choice
Thymocyte is considered double positive at this point and can bind to MHC I or II. But it MUST have affinity for MHC molecules to proceed, thymocyte interacts in the thymus with specialized epithelial cells that express both MHC I and MHC II. If it doesn’t bind to either -> apoptosis.
Goal 2: Depending on what MHC it does bind to dictates the lineage choice (MHC I->becomes CD8+ cell and CD4+ are lost; MHCII->CD4+ cell and CD8+ are lost)
If thymocyte survives (only very small percent survive) it becomes “single positive”

101
Q

What is the negative selection process of thymic selection (T cell development)? What is the purpose?

A

Some T cells that have TCR that recognize self antigens will survive positive selection since it is only dependent on the ability to bind to MHC I or II, these must be eliminated to avoid autoimmunity.
Thymocytes interact with thymic dendritic cells presenting both MHC I and II complexed with a “self” peptide
If thymocyte binds self peptide ->apoptosis
Goal: make sure T cells bind to self MHC molecules that only present foreign peptide/antigen

102
Q

Where does naive T cell activation take place?

A

In the secondary lymphoid organs

103
Q

What factors determine the type of response that occurs when antigen is recognized by naive T cells? What happens? What are the two kinds of responses?

A

This set the adaptive response in motion and dictates if it will be a humoral or cell mediated response
Dependent on:
-Type of antigen presented (exogenous, endogenous)
-MHC molecule that’s presenting (Class I or II)
-Cytokines present

104
Q

Where do APCs and naive T cells meet? What takes place here?

A

In the secondary lymphoid organs, antigen presentation takes place

105
Q

Where do naive T cells circulate?

A

Throughout the body

106
Q

What are the steps of antigen recognition by a naive T cell?

A

APCs present MHC ClassI (on all nucleated cells) and Class II, they phagocytose the antigen in the tissue (or in the secondary lymphoid organ which is less likely) and travel to the secondary lymphoid organ where they present the peptide on the MHC
The naive T cell binds to the MHC+peptide and this step dictates the response
-Humoral: MHC Class II and CD4+ —> T cells that help B cells
-Cell Mediated: MHC Class I and CD8+ —> cytotoxic T cells

107
Q

What happens during T cell activation?

A
  • TCR recognizes and binds the MHC + peptide complex
  • Signaling cascades within T cell which alter gene expression leading to clonal proliferation and differentiation of daughter cells
  • Once naive T cell recognizes appropriate MHC + peptide complex it is activated and differentiates into either a T helper cell (TH1, TH2, TH17) for CD4+ or CTL (cytotoxic T lymphocyte for CD8+ which is programmed to kill), they then proliferate and acquire their effector function (said to be experienced now, no longer naive
108
Q

What percent of children/adults in the US have allergies?

A

40%

109
Q

What is another term for allergy? What causes it?

A

A hypersensitivity reaction. Immune response goes beyond usual scanning for foreign pathogens to recognizing/reacting to what should be innocuous foreign antigens. The humoral or cell mediated response is the same for normal pathogens, however, it occurs at a much to high intensity against innocuous antigens or at an inappropriate location in the body

110
Q

How many different hypersensitivity reactions are there and are the within the humoral or cell mediated branch of the immune system? Which are quicker?

A

4 total: I-IV
I-III: Humoral branch, Antibody mediated, quickest symptom presence
IV: Cell mediated, T-cell mediated, slower symptom presence

111
Q

What type is “Immediate Hypersensitivity”? What causes it? How quickly does a response occur and when does it clear up?

A

It is Type I, reactions occur within 2 minutes of re-exposure to the allergen, resolving within 2 hrs of removal of stimulus
IgE mediated rxns stimulated by release of inflammatory mediator by mast cells (main cellular component of Type I rxns)

112
Q

What happens during initial exposure in type I hypersensitivity? What about future exposures?

A

-Initial: IgE produced by plasma cells, bind to Fc receptors of mast cell surface
Future exposures: Mast cell bound IgE crosslinked via antigen (allergen) binding causing degranulation of mast cells (release of vasoactive/pro-inflammatory molecules=histamine, prostaglandin, lekotrienes)

113
Q

What are examples of Type I hypersensitivity rxns?

A

“Plain ol’ allergies”= hay fever, allergic conjunctivitis

114
Q

What are the mechanisms of the allergic response in Type I Hypersensitivity?

A
  • IgE mediated allergies/allergic asthma = result of CD4+Tcell/humoral response
  • First exposure=no symptoms, naive B cell binds allergen and presents to T Cell transduction signals 1 and 2 = activated B cell which proliferates/isotype switches creating plasma and memory cells expressing IgE antibodies specific for the allergen
  • These IgE antibodies bind to Fc receptors on mast cells (non-antigen bound IgE antibodies will remain bound to these mast cells)
  • Secondary exposure: allergen binds to the IgE’s bound to mast cells causing mast cells to degranulate releasing pro inflammatory mediators (histamine, prostaglandins, Leukotrienes)
115
Q

What occurs due to the release of histamine (type I hypersensitivity)? Prostaglandins? Leukotrienes?

A

-Histamine binds to receptors on endothelial cells causing separation at cell-cell junctions = increased vascular permeability (swelling & edema - like bug bites); histamine binds to receptors on smooth muscle cells causing constriction (asthma)
-Prostaglandins: Increase vasodialation
Leukotrienes: Increase smooth muscle contraction

116
Q

What are the treatments for asthma/allergies that we talked about?

A
  • Saline/Artificial Tears (flush allergen)
  • Mast cell stabilizers (prevents mast cells from degranulating)
  • Antihistamine (Zrytek, Claritin): binds to receptors on endothelial/smooth muscle cells blocking histamine binding
  • Steroids: Anti-inflammatories (exact MOA unknown), used in severe cases of inflammation (Vernal Keratoconjunctivitis VKC, Atopic Keratoconjunctivitis AKC)
117
Q

What are the downfalls of using corticosteroids for inflammation due to allergic reaction?

A

Can cause apoptosis of immune cells and continued use can lead to cataract formation (due to degradation product)

118
Q

What is type II Hypersensitivity known as? What is the cause? How long does is take for symptoms to arise and how long does it take for them to go away?

A
  • Cytotoxic Hypersensitivity, it is the result of a humoral response, develops within hours of re-exposure and normally resolves w/in 24 hrs after removal of stimulus
  • Occurs when Ig directed against cell surface/tissue fixed antigens (antigens seen as foreign so Ig bind to host cell causing attack on own cells, Ig bound here so host’s cells are marked for destruction via ADCC or classical complement activation)
  • Antibody-Antigen complex stays put, doesn’t move like other Hypersensitivity rxn
  • Can be self-antigen (autoimmune) or antigens that have become attaches to host cell
  • Antigen can be intrinsic to cell membrane or extracellular matrix (Rh factor) of exogenous antigens that have become bound (penicillin)
119
Q

What are two specific examples of Type II hypersensitivity that we discussed?

A
  • Autoimmune hemolytic anemia: penicillin attaches to haptenates surface of RBCs, 1st exposure = Ig made (sensitization) -> no symptoms, subsequent exposures cause Ig to attach to drug on host cells = destructions, humoral immune response (complement, phagocytosis or ADCC lysis of RBCs -> anemia)
  • Rhesus-incompatibility rxns (Rh factor): Rh = antigen on surface of RBCs, Rh- mom develope antibodies to Rh antigens (if 1st preg=Rh+ baby and RBCs from baby enter her circulation during birth -> separation of placenta from uterine wall), if sensitized mother’s anti-Rh are IgG they can cross placenta during future preg w another Rh+ baby (must have Rh+ dad), can cause harm to fetus (possible hemolytic disease bc fetus’ RBCs seen as antigen), can be avoided if Rhogram (anti-Rh antibodies) give to mother writhin 48-72 hrs of delivery to block sentization
120
Q

What is the type II Hypersensitivity rxn? What causes it?

A

Immune Complex-mediated hypersensitivity
-Immune complexes occur when soluble antigens bind to antibodies (normally, these are removed via phagocytosis via Fc receptors) however, in this reaction these complexes are deposited in small vessels (kidneys, joints) causing acute inflammatory rxns

121
Q

What are the steps of the immune-complex mediated hypersensitivity?

A

Type III

  • The classical complement cascade is activated releasing C3a, C4a, C5a (recruit neutrophils)
  • Neutrophils/macrophages activated and release effector molecules (reactive oxygen intermediates, lytic enzymes) causing bystander damage to local tissues
122
Q

What is serum sickness? What is it an example of?

A

Develops when a person receives antibodies (systemically) s/a antitoxin/anti venom from a diff species, the recipient recognizes proteins in the serum as foreign generating antibodies against them, forming soluble/circulating immune complexes. Example of Type III hypersensitivity

123
Q

What are the distinctions between Type II and Type III hypersensitivity?

A
  • In type II, Ig bings directly to cells/tissues and the Ag epitope is on the cells/tissue -> tissue is damaged when Ag binds it directly and initiates damage mech (ADCC/complement lysis)
  • In type III, antibodies and antigens form complexes that can be deposited in tissue, Ig-Ag complexes CIRCULATE around then can be deposited in certain tissues (glomeruli, capillaries), tissue is damaged due to bystander effect when Ig-Ag complexes become deposited in these tissues and activate the complement (too large to undergo phagocytosis)
124
Q

What is Type IV hypersensitivity? How does it occur? What is an example?

A

Delayed-Type Hypersensitity (DTH)

  • Rxns utilize same mechs as cell mediated immunity
  • Ig do not play a role in effector phase
  • Considered hypersensitivity bc nature of the antigen (it is one that a person should NOT respond to)
  • Peaks at 24-72 hrs
  • Ex. Poison ivy dermatitis: pentadecacatechol is hapten that easily penetrates the skin and haptenates to cytosolic proteins
  • When presented on class I/II it is seen as foreign
  • CD4+ AND CD8+ activate
  • CD4+ recruit macrophages/neutrophils-> inflammatory rxn
  • CD8+ initiates cell death
125
Q

What kind of hypersensitivity is involved in graft rejection? What happens?

A

DTH (hypersensitivity IV-an example of non contact)
CD8+ T cels play a role, recognition of foreign MHC (if not matched)
Death of transplanted tissue via CTLs

126
Q

What is immunization?

A

Process of eliciting a long-lives state of protective immunity against a pathogen. Vaccinations are NOT the only mechanism to achieve immune protection, and vaccinations do not always ensure immunity

127
Q

What is a vaccination?

A

Intentional exposure to a form of pathogen that does not usually cause disease (does not always ensure immunity)

128
Q

What is the relationship between vaccination and immunization?

A

Vaccination is an event, immunization is the (possible) outcome of that event

129
Q

What are the two types of immunizations?

A
  • Passive immunizations

- Active immunizations

130
Q

What are passive immunizations?

A

Provide transient protection against infection, administration of Igs/lymphocytes which then provide TEMPORARY protection to recipient

131
Q

What is active immunization?

A

Use to provide long lasting immunologic protection (referring to administration of a vaccine that can elicit a protective immune response)

132
Q

How is passive immunity achieved? What are characteristics of passive immunity?

A
  • Results from the transfer of pre-formed Igs/immune cells from one person to another
  • Rapid, but temporary (due to half life)
  • Does NOT result in memory
  • Does NOT rely on recipient’s immune system to initiate response
133
Q

What is an example of natural passive immunity?

A

Passing of a mother’s Ig to a child across placenta (IgG) and/or colostrum (IgA, T cells, other immune factors s/a lysozyme, lactoferrin)

134
Q

What is an example of artificial passive immunity?

A
  • Abs are administered to a patient

- Hyperimmune sera/convalescent sera = antibodies pooled from human donors w high titers of specific Abs

135
Q

What is immune serum globulin (ISG)?

A

antibodies pooled from at least 1000 human donors

136
Q

What are antitoxins/antivenoms? What are specific examples we talked about?

A

Abs against specific toxins

Ex. Varicella-zoster globulin (VariZIG), rabies immune globulin (RIG), tetanus antitoxin (hyperTET)

137
Q

What is active immunity?

A
  • Introduction of antigen to the individual
  • Involves T/B lymphocyte activation, proliferation, differentiation
  • Offers long term protection (an active immune response is induced and memory cells created)
138
Q

What’s an example of natural active immunity?

A

Infection- exposure to antigen under natural circumstances leading to an immune response

139
Q

What is an example of artificial active immunity?

A

Vaccination- intentional intro of antigen prior to natural exposure, leading to immune response

140
Q

What are the principles of vaccination?

A
  • Generation of active immune response thru stimulation of Abs prod and memory lymphocytes
  • Response/immunity to pathogen should mimic a natural infection as closely/safely as possible
141
Q

What are the two classifications of vaccines?

A

Live attenuated and inactivated

142
Q

What is a live attenuated vaccination? What are the pros and cons?

A
  • Pathogen is alive, however it is modified to be a nonpathogenic form (can be grown in a different animal)
  • Organism can multiply/emulate an actual infection to result in a stronger immunological response
  • Virtually identical to natural infection
  • Can induce humoral and cell-mediated response
  • Usually effective w one dose (except oral administered) (fewer doses needed bc it persists->its alive)
  • No adjuvant needed
  • Not given until 12 mos of age
  • Fragile-can be killed by heat and light / must be handled with care
  • Since its alive, can’t be given to immunocompromised
143
Q

What are inactivated vaccines? What are the pros and cons?

A
  • Can be composed of whole organisms or fractions
  • Can be given to immunocompromised individuals
  • It is not alive, therefore more Ag req = multiple doses (boosters)
  • Not as effective against intracellular pathogens bc produces humoral response
144
Q

What are the steps of Polio contraction?

A
  1. Fecal-oral transmission of virus
  2. Targets pharyngeal/intestinal cells
  3. Enters blood stream (viremia)
  4. Can infect meninges/CNS
  5. Paralysis/Meningitis
145
Q

What is OPV and IPV? What are the main differences between the two? What are the pros and cons of each?

A

They are Polio vaccines
Both: are 3 strains, have high systemic immunity and prevents secondary disease

  • OPV=oral and live attenuated (grown in monkey kidney cells), since it is oral IgA will be the chosen Ab which is well suited for mucosal tissue, therefore it will stop the virus in the pharynx and intestines before it becomes systemic thereby preventing reinfection…since it is alive though, it cannot be given to immunocompromised
  • IPV= injected and inactivated, since it is injected, IgG will be the chosen Ab which isn’t suited for mucosal, therefore it will not prevent initial reinfection (it wont be stopped in pharynx/intestine), it is dead so it can be given to immunocompromised
146
Q

What are the 3 kinds of inactive vaccines we talked about? What are examples of each?

A
  • Killed Whole Bacteria: dead bacteria or virus (ex. Viral - IPV (Polio), hepatitis A, Influenza (shot))
  • Toxoid: Whole/part of a toxin is heat/chemically inactivated, only humoral response develops (ex. Bacterial- tetanus, diphtheria)
  • Subunit: Single/multiple antigens (generally surface protein), does not contain whole organism (ex. Influenza vaccine)
147
Q

What are the 3 types of flu vaccines we talked about? What are characteristics of each? Who are they administered to? Can a person get sick by any of these?

A
  • Live attenuated (FluMist): live attenuated influenza virus (LAIV), temperature mutant (cold adapted), given to 2-49 years, since it is alive a person could get sick
  • Inactivated/subunit intramuscular: split and inactivated virus, chicken egg inactivation then virons split with formaldehyde, given to 3+ years, can’t get sick
  • Subunit intramuscular: subunits of purified HA and NA given to 18+ years, cant get sick
  • If person gets sick, its usually the immune response they are referring to (bodies reaction) not the virus itself

Microbiology (1 decks)

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