Infectious Disease Exam 2 (USC BMEN 342 from slides)

acquired specific immunity

product of B and T cells

they undergo a selective process that specializes them for reacting to only 1 specific antigen or immunogen

immunocompetence

ability of body to react with countless foreign substances

antigens (immunogens)

chemical substance that simulates a response by T and B cells

protein or polysaccharide on or inside cells/viruses

what are the 2 characteristics of the third line of defense?

specificity- highly specific to the antigen that it is directed at

memory- rapid movement of lymphocytes that have been programmed to recall their first engagement with the antigen

What are the principal stages of immunologic development and interaction?

1. lymphocyte development and differentiation

2. Presentation of antigens

3. The challenge of B and T lymphocytes by antigens

How do B cells respond

produce antibodies

How do T cells respond?

cell-mediated immunity (recognize antigen and activated phagocytes and other immune stuff to fight it off)

What are the major functions of immune system markers?

•Attachment to nonself or foreign antigens

•Binding to cell surface receptors that indicates self

•Receiving and transmitting chemical messages to coordinate the response

•Aiding in cellular development

What kind of cell surface receptors indicate self?

MHC molecules

Class I MHC genes

Markers appear on all nucleated cells

Display unique characteristics of self

Allow for recognition of self and the regulation of immune reactions

Each human inherits a particular combination of class I MHC genes

Class II MHC genes

code for immune regulatory receptors found on macrophages, dendritic cells, and B cells

involved in presenting antigens to T cells during cooperative immune reactions

Class III MHC genes

encode proteins involved with the complement system

CD molecules

-cluster differentiation

-markers important in immunity

-found on membranes of variety of different cells involved in immune response

how many CD molecules have been described?

300

What are the 3 kinds of antigen presenting cells?

dendritic cells, macrophages, and B cells

tissue dendritic cells

ingest antigen, migrate to nearest lymphoid organ, and present antigen to T cells

What happens when B cells and T cells are challenged by an antigen?

they proliferate and differentiate (this makes clones.. some are memory cells)

what do helper t cells do?

activate macrophages

assist B cell processes

help activate cytotoxic T cells

marked by CD4

what do regulatory T cells do?

control the T cell response

prevent autoimmunity and destruction of normal biota

What do cytotoxic T cells do?

destroy infected host cells and other foreign cells

killer T cell marked by CD8

How do B cells respond to an antigen?

it divides and gives rise to plasma cells

plasma cells then release antibodies into tissue and blood

antibodies attach to antigen and mark it for destruction

What are the markers found on T cells?

antigen-specific T cell receptor

CD3

CD4

CD8

CD3 markers

surround T cell receptor and assist in binding

CD4 markers

binds to MHC class II molecules

CD8 markers

found on cytotoxic T cells and binds MHC class I molecules

T cell circulation

they constantly circulate between the lymphatic system and circulatory system

migrate to specific T cell areas of the lymph nodes and spleen

What are the surface receptors of B cells?

IgM and IgD, CD molecules

Why do distinct B cells develop?

as a result of gene modification and selection

Antigen of new lymphocytes

each new lymphocyte has an antigen receptor that recognizes a unique antigen

What happens when new B and T cells migrate to secondary lymphoid tissue?

some cells die if they aren't used, others become activated and leave

What are antibody variability genes

V= variable (heavy and light)

J= joining (heavy and light)

D = diversity (heavy)

these are genes are arranged differently for every B and T cell type so they can recognize different antibodies

What are antibodies (immunoglobulins) made of?

2 heavy chains

2 light chains

each light chain bound to the Y part of heavy chains via disulfide bonds (antigen-binding fragment)

2 heavy chains bound together at bottom of Y via disulfide bonds (crystallized fragment)

How do B-cell receptors (immunoglobulins) bind antigens?

pockets at the top ends of the Y

highly variable in shape to fit wide range of antigens

variable regions

found in antigen binding sites

amino acid position highly varied from one B cell clone to another (as a result of genetic reassortment)

constant regions

amino acid content does not vary greatly

Can B cell receptors (imunoglobulins) be secreted?

yes!

How are T cell receptors different from B cell receptors?

relatively small

never secreted

Everything else is the same: has variable and constant regions, has same antigen binding site, formed by genetic modification

what is a clone?

a genetically unique line of lymphocytes arising from extensive recombinations of surface proteins

does the proliferative stage of lymphocyte development (making clones) require presence of foreign antigen?

no!

epitope

the part of an antigen molecule that an antibody binds to (this is what gets recognized)

What happens when an epitope enters the immune surveillance system?

it encounters lymphocytes until one of them is the match for it and that lymphocyte (clone) undergoes division and expands to take out the epitope

What is immune tolerance?

Immune system's lack of response to self antigen AKA doesn't kill your own body cells

removes any potentially harmful clones through clonal deletion

What can be an antigen?

whole microbes or their parts

cells/substances from other humans, animals, plants, and other molecules

complex molecules like proteins

What are the chemcial categories of antigens?

proteins and polypeptides

lipoproteins

glycoproteins

nucleoproteins

polysaccharides and lipopolysaccharides

What are the MW ranges to be an antigen?

weak antigen: 1000-10,000

most immunogenic: 100,000

What are alloantigens?

Antigens that differ between members of the same species, such as MHC molecules and ABO red blood cell antigens

this is why its hard for organ transplant

what are superantigens?

bacterial toxins that activate T cells at a rate 100 times greater than regular antigens

results in an overwhelming release of cytokines and cell death

ex)toxic shock syndrome and some autoimmune diseases

Steps for B cell activation and antibody synthesis

1. specific antigen binds to B cell

2. antigen taken in by B cell and degraded into small peptides then bound to MHC II receptors on surface of B cell

3. MHC II receptor attached to antigen links with corresponding T cell antigen receptor, CD3, and CD4

4. These bindings cause signal in B cell nucleus to activate it

5. Activated B cell differentiates into plasma cells, memory cells, and regulatory cells

6. all 3 cells divide and carry out their duties

plasma cells

short-lived factories for antibodies of same specificity as original B cell

memory cells

a long-lived lymphocyte that is ready to encounter the same antigen whenever it comes back

regulatory cells

secrete IL-10 to regulate T cell response

What do T cells need before they are activated?

MHC recognition

What are cell-mediated immunities of T cells?

very complex due to specificity of T cell with antigen

involve several subsets of T cells whose actions are dictated by the antigen

produce cytokines with a spectrum of effects based on antigen

What are 2 ways that helper T cells activate macrophages?

directly by receptor contact

indirectly by releasing cytokines like interferon gamma

How to B cells regulate T cell response?

already activated regulatory B cells can secrete their own cytokines to dampen T cell response

How are B cells activated to become plasma cells?

by cytokines from activated T cells

What are 2 types of killer T cells?

perforins and granzymes

perforin

protein that punch holes in membrane of target cells

cause ions to leak out

creates a passageway for granzymes to enter

granzymes

enzymes that attack proteins of target cells

What type of cells can cytotoxic T cells destroy?

virally infected cells

cancer cells

cells from other animals/humans

What are natural killer cells?

lymphocyte related to T cells

lack specificity for antigens

FIRST to attack cancer cells and virus infected cells

Why aren't natural killer cells considered part of specific cell-mediated immunity?

they don't have antigen receptors

What are natural killer T cells?

hybrid of T cells and NK cells

have T cell receptors and NK markers

What are natural killer T cells stimulated by and what do they produce?

stimulated by glycolipids on foreign cells

rapidly produce cytokines, granzymes, perforins (trigger cell death in target cells)

What is special about the attachment between the antigen-binding fragment and the crystallized fragment of antibodies?

the attachment allows swiveling of the antigen-binding fragments

what are functions of the crystallized fragment (bottom part of the Y)?

serves as an anchor

bind to various cells and molecules of the immune system and complement

sometime causes release of cytokines

What is the function of antigen-binding fragment?

binds antigens

amino terminal end consisting of the variable regions

hypervariable region

site on the antibody where epitope binds

frequently mutated to allow a diverse range of antigens to bind

a minimal complementary fit is necessary for antigen to be held effectively (?)

Functions of antibodies

1. coat surface of bacteria and prevent its normal function and reproduction

2. opsonization- bind to microbes and encourage phagocytes to eat them

3. neutralization- fill surface receptors on a virus to prevent from acting normal

4. agglutinate - bind to microbes and aggregate to immobilize them

5. interacts with complement to rupture cells and some viruses

6. neutralizes bacterial exotoxins (antitoxin)

J chain

The joining chains of the IgM and IgA antibodies

secretory component of immunoglobulins

helps IgA move across mucous membranes

IgG

2 antigen binding sites

binds to phagocytes

function: memory antibodies, neutralizes toxins, fixes toxins, opsonizes

IgA

has either 2 (monomer) or 4 (dimer) antigen binding sites

secretory antibody on mucous membranes

IgM

10 antigen binding sites

produced at first response to antigen

serves as B cell receptor

IgD

2 antigen biding sites

receptor on B cells

IgE

2 antigen binding sites

binds to mast cells and basophils

antibody of allergy

worm infections

Which immunoglobulin has the most antigen binding sites?

IgM

Which immunoglobulin crosses the placenta?

IgG

Which immunoglobulin can be a dimer? a pentamer?

IgA, IgM

Which immunoglobulin(s) fix complement?

IgG and IgM

How to monitor antibody production overtime?

Titer

shows conc of antibodies in the serum

primary immune response

first exposure to antigen

what happens during latent period of primary response?

there is a lack of antibody production and antigen is concentrated in the lymphoid tissues

secondary (amnesiatic) response

immune system is exposed again to same antigen weeks, months or years later

rate of antibody production and response is much quicker

natural immunity

acquired as part of normal life experiences

active natural immunity

natural exposure to an antigen that results in immunity of that antigen

passive natural immunity

babies have maternal antibodies that they are born with via IgG antibodies in the placenta or mothers milk

artificial immunity

produced purposefully through medical procedures

active artificial immunity

vaccination triggers immune system to produce antibodies of specific disease

passive artificial immunity

injection of antibodies via immunotherapy or donor blood

immune serum globulin (gamma globulin)

artificial passive

extracted from pooled blood of human donors

concentrated to increase effectiveness

injected intramuscularly and protects for 2-3 months

specific immune globulin

artificial passive

derived from more specific group of blood donors who have high conc of certain antibodies

limited in availability

basic principles of vaccinations

exposes person to antigenic material NOT pathogenic

stimulates primary immune response that primes system for future exposure

if pathogen ever enteres, immune system will be ready to rock

What can be injected in a vaccine

live, attenuated (reduced in force) cells or viruses

killed cells or inactivated viruses

antigenic molecules derived from bacteria or viruses

Requirements for Effective Vaccine

no serious harm/side effects

protects against exposure to pathogen

stimulate B and T cell response

produce memory cells

inexpensive and shouldn't require numerous doses

whole cell vaccines

killed viruses/ bacterial cells or inactivated viruses

Advantages of live attenuated vaccines

strongest immune response, long-lasting protection, require fewer doses, induce cell-mediated immunity

disadvantages of live attenuated vaccines

special storage, can be transmitted to others, can become virulent again

subunit vaccines

vaccines that only contain a selected component of a microorganism

toxoid

inactive bacterial extoxin used in a subunit vaccine