PCB 3233 EXAM 6

If you got multiple immunizations with the same antigen, what would you find with regard to Ab levels (IgG) and antibody affinity?

-IgG would increase

-affinity would be high

What is the difference between protective immunity and secondary immune response?

Primary response:

-small number of pathogen-specific cells respond at the start

-delay before pathogen-specific antibodies are produced

-non-isotype-switched antibody having a mixture of affinities for the pathogen is produced at the start

-high threshold of activation

-delay before effector T cells are generated and are able to enter infected tissues

-innate immunity works alone until an adaptive response is generated

Secondary response:

-large numbers of pathogen-specific cells respond immediately

-pathogen-specific antibodies already present

-antibodies are isotope-switched and have high affinity for the pathogen

-lower threshold for activation

-effector T ells are present and can enter infected tissue immediately

-close cooperation between innate and adaptive immunity from the start

What cells/molecules are used in each?

primary- naive cells

secondary- memory cells (not naive)

Do B-cells go through the same types of processes during a secondary immune response as they do during a primary immune response?

yes

Do we typically have more memory B-cells specific for antigen in a secondary IR than we had naïve B-cell (antigen specific) in the primary response?

more memory cells in 2 response

Know what original antigenic sin is and how to use the concept if you are asked a clinical type of question.

a phenomenon whereby the first influenza strain to infect a person constrains the future response to the other strains

Can a naive B cell be activated in a secondary immune response?

No

Can we use this knowledge to help us in things like hemolytic disease of the newborn (how does RhoGAM work)?

-Yes

-RhoGAM tricks mom's immune response into thinking that it is a 2 immune response

-First pregnancy of RhD- mother carrying a RhD+ fetus-->primary immune response, IgM plus low amounts of low-affinity IgG-->minor destruction of fetal erythrocytes by anti-RhD IgG--> healthy newborn baby

-Second and subsequent pregnancies of RhD- mother carrying a RhD+ fetus--> secondary immune response abundant, high-affinity IgG transcytosed to fetal circulation-->massive destruction of fetal erythrocytes triggered by anti-RhD IgG-->Anemic newborn babies

-First and subsequent pregnancies of RhD- mother carrying a RhD+ fetus and infused with anti-Rh IgG-->primary immune response to RhD is inhibited by the presence of RhD-specific IgG--> fetal erythrocytes are not destroyed-->healthy newborn babies

Understand figure 11.12

Highly mutable viruses such as infuenza gradually escape from immunological memory without stimulating a compensatory immune response. A person's history of infection with infuenza is shown here. The first infection is with a strain of influenza virus that elicits a primary antibody response to viral epitopes A, B, C, and D. The next four infections are with viruses that successively lose the epitopes of the first virus and gain in turn the epitopes E, F, G, and H. With each infection the strength of the person's memory response declines but cannot be compensated for by a new primary response until all the epitopes of the original strain are lost at the fifth infection. Then, no memory response is elicited, disease ensues, and a primary immune response against all the new epitopes is made.

Understand figure 11.6

The amount and affinity of antibody increase

after successive immunizations with the same antigen. This figure shows the results of an experiment on mice that mimics the development of specific antibodies when a person is given a course of three immunizations (1º, 2º, and 3º) with the same vaccine. The upper

panel shows how the amounts of IgM (green) and IgG (blue) present in blood serum change over time. The lower panel shows the changes in average antibody affinity that occur. Note that the vertical axis of each graph has a logarithmic scale because the observed changes in antibody concentration and affinity are so large.

How long does it take for a primary IR vs a secondary IR?

-primary: 8 days

-secondary: 4 days

Which T-cells decline in an HIV patient? What is the significant # of those cells for a transition to AIDS?

-CD4 TH-cells

-200 microliter

Know gp 120 and 41 and what they do? What is the precursor polypeptide these are created from?

membrane glycoproteins, insert proteins

-Gp 120 binding

-Gp 41 fusion

What are tat, rev, protease, integrase and reverse transcriptase and what is the function of each? Are all of these brought (premade) by the virus when it infects the cell or are some made after the cell is infected? Which have to be made after infection?

-tat binds to transcription activation region of viral mRNA and prevents transcription from shutting off

-rev control supply of viral RNA to cytoplasm:

-delivers RNA needed to create viral proteins

-protease cleaves polyprotein to create virion proteins and enzymes

-Gp160->41 and 120

-integrase integrates cDNA into host genome

-all are in virus to begin with

How many RNA molecules make up HIV genome? How many make up influenza's genome?

-HIV: one long strand of RNA

-influenza: 8

What is lymphocyte topic vs. macrophage trope (HIV)? Which co-receptors are associated with each? Which is associated with early infection and which is associated with late infection? Which is associate with a worse prognosis?

-Macrophage tropic: CCR5 receptor, Req modest levels of cell surface CD4 (macrophages, dendritic cells and T cells), early infection

-Lymphocyte tropic: CXCR-4 receptor, requires high levels of cell surface CD4 (T-cells go quick) , late infection, more severe (AIDS)

What is the reverse transcriptase inhibitor you learned about in class? What mechanism does it use to inhibit HIV?

-Nucleoside analog reverse transcriptase inhibitor (NRTI)

-Interrupts early stage of virus replication; cross BBB better than other drugs and has serious side effects and possible long term toxicity

What two things are routinely tested after a person has been diagnosed with HIV?

-CD4 T- cell count

-Viral Load

What does HAART stand for and what is used in it? What do anti-viral drugs do/don't do for the patient?

-Highly active antiretroviral therapy

-reduced change of any one mutation allowing uncontrolled growth

-decrease viral load

-delays unspread of opportunistic infections

-slows HIV spread

-Doesn't prevent transmission

What is a super-antigen typically (bacterial toxin)? What does it do? What leukocytes (s)/ cytokine (s) are involved?

-molecules that, by binding nonspecifically to MHC II molecules and TCR, stimulate the polyclonal activation of T cells

-Stimulate a massive but ineffective T-cell response

-Die by apoptosis

-T-cells and MHC molecules

-causes tpcix chock syndrome; massive amounts of IL-1, IL-2 and TNF released

What are antigenic shift and drift? Which one is worse? What disease state are theses associated with?

- antigenic shift: pathogen goes into another animal and gets new hemaglutin proteins on surface: pandemic

-antigenic drift: arise through (point) mutations: epidemic

What confers protective immunity against influenza?

-mutation and recombination allow escape

-antibodies bind to viral envelope during primary IR

-protective immunity is determined by the strain you are exposed to

Strep.pneumoniae

-zero type specific

-different strains

influenza

-zero type specific

-different strains

trypanosomes

-Use gene rearrangement to change their surface antigen

-more than 1000 types

-life cycles involves both mammalian and insects: transfer to humans via insects

-replicate in extracellular spaces

-glycoproteins (VSGs)

Herpes

-infect epithelial cells and spreads to sensory neurons serving the infected area

-latent

Varicella Zoster

-type of herpes

-chicken pox

-dormant in dorsal root ganglia

Treponema pallidum

-syphilis

-coats itself with human protein

toxic shock syndrome (TSS)

a severe illness characterized by high fever, rash, vomiting, diarrhea, and myalgia, followed by hypotension and, in severe cases, shock and death; usually affects menstruating women using tampons; caused by Staphylococcus aureus and Streptococcus pyogenes

____is the major____ molecules stored in mast cell granules

-histamine

-vasoactive

Which synthesized molecules act most like histamine in the late phase reaction but are much more potent than histamine?

leukotrienes

Define allergic reaction.

Exaggerated immune system response that are inappropriate and damaging to tissues

Allergens

common environmental antigens that cause hypersensitivity reactions

allergies are group into 4 types according to the

effector mechanisms that produce the reaction

what are the 4 types of hypersensitivity reactions?

Type I

Type II

Type III

Type IV

Type I hypersensitivity

-inhalation

Type II hypersensitivity

-injection

Type III hypersensitivity

-ingestion

Type IV hypersensitivity

-skin contact

What is Type I mediated by?

IgE

Type I is considered

immediate

examples of type I

pollen; hay fever/ rhinitis

What is Type II initiated by?

initiated by IgG and IgM antibodies

type II has ____ components

modified

type II includes ___ activation and. ____

complement activation ; phagocytosis

type II results in

cell lysis

examples of type II

penicillin

what is Type III initiated by?

IgG and IgM immune complexes

type III includes

immune complex reactions

examples of type III

non-human therapeutic proteins

type IV includes

cell mediated immunity

type IV is considered

delayed type hypersensitivity

type IV is caused by

T cells

examples of type IV

poison ivy; TH2- asthma and all others are TH1

simple explanation of type I

free antibodies bind to cell surface antigens

with type I ____ and ___release ___

-basophils

-eosinophils

-inflammation mediators

simple explanation of type II

free antibodies bind to cell surface antigens

type II includes

altered self antigens or heteroantigens

type II phagocytosis and

complement activation (MAC) cellular damage

type II result in

cellular destruction

simple explanation of type III

free antibodies bind to soluble antigens to create immune complexes

type III=phagocytosis and

complement activation

type III results in

tissue destruction

simple explanation of type IV

sensitized T-cells are responsible for symptoms not antibodies

type IV results in

inflammation

wheel and flair

immediate and inflammatory reaction=degranulation IgE mast cell

what is needed for a mast cell to degranulate?

the mast cells degranulate, which leads to eosinophils coming out to the site,

then eosinophils degranulate and lead to more mast cells degranulization

which will lead to more eosinophils infiltrating the site, which is going to lead to more mast cell

what are the symptoms of allergic rhinitis

runny nose, sneezing

what is another name for allergic rhinitis

hay fever

with allergic rhinitis we are shedding

eosinophils, they leave though our mucus

activated mast cells release

histamine (other mediators)

increased permeability of

capillaries activate nasal epithelium to produce mucus

eosinophils attracted from

blood

activated eosinophils release

inflammatory mediators

activated eosinophils are

shed into the nasal passage

what are the symptoms of urticaria

raised bumps (the wheel and flair)

what is another name for urticaria

hives

acute asthma is a

type I response

acute asthma can lead to

chronic asthma

what type is chronic asthma and what cell mediates?

when it becomes chronic you become sensitized to all kinds of things not just the allergin:

-chronic asthma is type 4

-TH2 response

-you still have mast cells and eosinophils present

Depending on the tissue affected the symptoms will differ but if the allergen goes systemic what can happen?

systemic is from ingesting things but can also end up with a swollen face, hives etc

why does a systemic allergy response lead to other side effects?

because when you ingested it the allergen is small enough and soluble enough that it makes its way into the blood stream and its distributed throughout the entire body

if allergen goes systemic how is this treated?

epinephrin =(epic pen)

poison ivy is what type of hypersensitivity reaction?

Type 4: hypersensitivity

what molecules are released in response to a type IV hypersensitivity reaction? Which type of T cell most often directs this release?

-T cell mediated

-delayed type

-T cell mediated can be so dangerous because you have T upper 1 mediated, T upper 2 mediated , CD8 T cell mediated

-typically with these you will see a TH1 response , TH1's activate macrophages

example of type IV response?

poison ivy

how does epinephrine help during an allergic reaction?

-stimulates reform of tight junctions of endothelial cells

-relaxes bronchial smooth muscle

-stimulate the heart

what blood type can type A receive

type A or type O

what blood type can type AB receive

any type of blood

what blood type can type B receive

type B or type O

what blood type can type O receive

type O only

if you have type A what antibodies are in your serum?

you have anti-B in your serum

if you have type AB what antibodies are in your serum?

no antibodies in your serum

if you have type B what antibodies are in your serum?

you have anti A in your serum

if you have type O what antibodies are in your serum?

Anti A and anti B in your serum

Cross match example: Mike gets in an accident and needs a transfusion. So we need to make sure the donor is a match. So we are going to mix Mikes serum and donors blood. Because we want to make sure he doesn't have antibodies that can tag her incoming transfusion red cells for destruction.

Who's serum or plasma is used and who's RBC's are used?

serum=recipient

RBC's= donor

Langsteiner's law

-He said for every ABO antigen you lack on the surface of your red cell, you have the corresponding antibody.

-If you have type A, you have antibody B

-If you have AB, you have no antibodies

-If you have type I, you have all the antibodies

which molecules are prepackaged?

histamines TNF alpha

which have to be synthesized?

leukotrienes

histamines can act on

smooth muscle, endothelial cells, epithelial cells