Specific Autoimmune Diseases Flashcards
What are the two types of out body’s defenses?
Non-Specific (Innate)
Specific (Adaptive)
Give an overview of Specific Defenses (5 things)
- ) takes time to develop after birth (optimum reached later in life)
- ) 3rd line of defense after non-specific
- ) Enhancement (improves after each encounter)
- ) has memory (best immunity)
- ) Specific- given cells and proteins protected only against one or a few different pathogens
What are the 2 types of Specific/Adaptive response?
Antibody mediated (Humoral) Cell-Mediated
What is the end goal of Antibody/Humoral mediated response?
to activate specific B lymphocytes–> activated B lymphocytes –> secrete antibodies
What is an Antibody?
an antimicrobial protein complex
What is the end goal Cell-Mediated response?
- activate specific cytotoxic T Cells (Tc)
- protect against viruses , cancer cells, and other cellular intracellular pathogens
what do Tc cells do?
find cancer cells and infected host cells and kills them
*Intracellular pathogens–> all viruses, some cellular pathogens
What is an antigen?
Where are they found?
any molecule that can stimulate a specific immune response; generally big molecules
includes: proteins, glycoproteins, nucleic acids, polysaccharides
Found= on viruses, prokaryotes, eukaryotes, humans
what is the normal function of an antigen?
attachment, transport, invasions, adhesives, enzymes (others)
What are the antigen classes ?
- Self Antigens
- Non-self antigens (foreign antigens)
- Tumor antigens (altered-self antigens)
what is an epitope?(5)
- antigenic determinant
- smaller part of an antigen that is actually “recognized” as self, non self, or altered self
- recognized by B or T lymphocytes via their unique surface receptors
- what a secreted antibody will specifically bind to
- a specific epitope may be found on more than 1 antigen-thus, a single antigen will posses many different epitopes and many of the same type
what is an epitope composed of?
Composed of 6-10 amino acids, 6-10 monosaccharides
A body’s specific defenses must learn to distinguish self from non-self, and self from altered-self.
What else must it learn?
It must learn to not respond to normal self (immunological tolerance) but respond to non self and altered self
The Immune Recognition/ Discrimination recognition is at the molecular level and involves receptors on unique _________ and ________ and coreceptors.
B and T lymphocytes
T helper and cytotoxic T cells
Primary Lymphoid Tissues = ________ and ________;
describe what happens in these tissues
Where B and T lymphocytes mature
- learn to recognize non-self and respond (alloreactive)
- learn to recognize self and not respond (not autoreactive); *cells that fail to do this are eliminated
Secondary Lymphoid Tissue= _________, ___________, _________;
describe what happens here
- lymph nodes, lymph nodules, MALT
- location where where B and T lymphocytes first meet epitope/antigen brought by antigen presenting cells
- Lymphocytes circulate between the blood and secondary lymphoid tissues
What is similar about T and B Lymphocytes
- each is covered by 1000s of identical surface receptors that can “recognize” 1 or a few closely related epitopes
- non covalent bounds
- 10-100s of millions of different types of B and T cell
- receptors are membrane
B lymphocytes prior to exposure are referred to as_____
naive B-cells
they have a low state of readiness
What is the difference between B and T lymphocytes?
B: cell receptors remembrance bound forms of antibody
T: membrane bound protein receptors, but not antibody
Can B,T, and NK lymphocyte be distinguished from each other?
not morphologically, but they have different surface antigens which can identify them–> referred to as cluster differentiation
what are 3 main aspects of adaptive immune response?
- ) Specficity- immune cells recognize and react w/ individual molecules (antigens) via direct molecular interactions
- ) Memory- immune response to specific antigen is faster and stronger upon subsequent (initial antigen exposure induces growth and division of antigen-reactive cells–> results in multiple copies of antigen reactive cells
- )Tolerance- immune cells not able to react w/ self antigen and self reactive cells are destroyed during development of the immune response
Describe Antibody Mediated Response (6 steps)
- ) APC pathocytizes pathogen and processes epitopes. It puts pathogen’s epitopes in its MHC class II molecules
- ) APC presents epitope via its T cell receptors to Th cells–> specific Th cells that recognize the epitope are activated
- ) B cells bind the antigen specifically using membrane bound antibody receptors.–> next, B cells endocytose the antigen and process it down into epitope–> these epitopes are placed in their MHC class II molecules–> B cell activated into plasma cell via cytokines from Th cells–> plasma cells secrete antibody
- ) Activated Th cells present the epitope in their MHC class II molecule to the membrane bound antibody receptors on B cells that recognize that same epitope
- ) B cells are activated–> undergo clonal expansion into plasma cells and memory cells
- ) plasma cells synthesize and secrete antibody against specific epitopes on specific antigen on specific pathogens
What is a plasma cell (2)
- an activated B cell (also known as an effector B cell)
- secrete antibody against specific epitopes
describe the structure of an antibody
- Y shaped
- composed of 4 polypeptide chains held together by disulfide bonds (2 identical heavy chains and 2 identical light chains)
- each chain is composed of several globular functional domains (constant, variable, hyper variable)
Where is the Constant region? Describe it
- region located between the carboxyl terminus of polypeptides and the variable region that has the same amino acid sequence from antibody to antibody
- includes Fc region (fragment crystallizable)
What are variable regions? what are hyper variable regions?
- Variable: amino acid sequence varies from antibody to antibody made by different B cells
- Hyper variable: unique amino acid sequence near amino end of polypeptides
- varies from antibody to antibody made by different B cells
- includes the antigen binding sites region
The _____ form of antibody has 2 identical (but unique to the B cell) antigen binding site
monomeric form
The _____ form of antibody has 4 identical (but unique to B cell) antigen binding sites,___ monomers held together by ____ and ______
- Dimeric Form
- 2
- secretory piece
- J chain
The _____ form of antibody has 10 identical (but unique to the B cell) antigen binding sites. It is composed of ___ monomeric units joined to each other by ____ _______ ____
- Pentameric form
- 5
- J chain polypeptide (valence=10)
True or False: All antibodies made by the same B cell have identical antigen binding sites.
Explain your answer.
True
-because they are all identical, can bind to the same epitope/s
-
- ) A given B cell can potentially make up to ___ different classes of antibody.
- ) Does each class have their own antigen bindings sites or are they all the same?
- ) What does this mean?
- ) 5
- ) they are all the same (each class has the same antigen binding sites)
- ) means they can bind to the same epitope
-(other differences between the 5 classes)
Concerning IgG:
- ) how many antigen binding sites
- ) properties
- ) distribution
- ) 2
- ) major circulating antibody (~80% of antibodies in blood serum); four subtypes; some activate complement; monomer
- ) extracellular fluid, blood, and lymph; can cross blood vessel wall and placenta
- ) opsonin; activate complement, bind to viruses and toxins and block their effects (neutralization)
Concerning IgM:
- ) how many antigen binding sites
- ) properties
- ) distribution
- ) function
- ) 10 (pentamer) or 2 (monomer)
- ) 5-10% antibodies in serum; usually on service of naive (unactivated) B cell; pentamer
- ) Blood and lymph (usually in bv b/c too big to enter tissues); monomer is B cell surface receptor
- ) strong complement activator; opsonin; first antibody to appear after immunization
Concerning IgA:
- ) how many antigen binding sites
- ) properties
- ) distribution
- ) function
**SEE SLIDE 42
- ) 2 or 4
- ) 5-10% antibodies in serum- most common form= in mucus membranes and body secretions (mucus, saliva, tears, and breast milk); most abundant antibody in body; important circulating antibody; major secretory antibody; monomer
- ) Secretions (saliva, colostrum, cellular, and blood fluids); monomer in blood; dimer in secretions
Concerning IgD:
- ) how many antigen binding sites
- ) properties
- ) distribution
- ) function
- ) 2
- ) 0.2% serum antibodies; monomers; minor circulating antibody; mostly membrane bound on naive B cells surfaces
- ) Blood and lymph; B lymphocyte surfaces
- ) as a receptor
Concerning IgE:
- ) how many antigen binding sites
- ) properties
- ) distribution
- ) function
- ) 2
- ) 0.002% serum antibodies; monomer; involved in allergic reactions and parasite immunity; Fc region binds to receptors on mast cells and basophils
- ) Blood and lymph; some bind to mast cells and eosinophils (Ch4)
- ) Type 1 hypersensitivity- release histamine and other inflammatory mediators; Attract IgG, phagocytes, and NK cells in parasitic worm larvae infection
what are the functions 8 functions of an antibody?
- ) neutralization
- ) inhibit transport proteins on cellular pathogen, growth, and replication
- ) Opsonization
- ) Initiate/activate complement pathway (classical pathway)
- ) Antibody dependent cellular cytotoxicity (ADCC)
- ) Initiate Acute inflammation
- ) Bind to epitopes on pathogen and prevent it from adhering to surface (IgA at body surfaces)
- ) Agglutination
Elaborate on what “Neutralization” is (2)
- antibody binds to virus or toxins and prevents virus or toxin from binding to receptors
- viral or toxin neutralization
Elaborate on what “Opsonization” is (2)
- antibody binds specifically to a pathogen and enhances phagocytosis and some complement factors
- Fc receptors on phagocyte bind to Fc constant region of the antibody bound to the pathogen
Elaborate on what “Antibody-dependent cellular cytotoxicity” is (2)
-any antibody bound specifically to an epitope on a large pathogen can have a NK cell, macrophage, or eosinophil bind to the Fc region and release cytotoxic chemicals into the pathogen
Elaborate on “Initial Acute inflammation” as it concerns function of antibody
IgE binds to IgE receptors on mast cell–> causes degranulation and release of inflammatory mediators
What is Agglutination?
antibody binds to several pathogens–> causes them to clump together*promotes phagocytosis
What is a Primary Immunological Response?
- first exposure to specific pathogen
- typically takes 5-10 days to see any antibody–> increases over several weeks until peak reached
- first antibody seen= IgM
- second antibody= IgG
- If memory cells form as result–> immunity will develop
What is a Secondary Immunological Response?
- If memory cells form/survived–> each subsequent exposure to that pathogen will not reach disease threshold b/c stronger, quicker secondary response
- Mostly IgG
What is hypersensitivity? (2)
- over reaction of some part of the body defenses to a foreign, but usually non pathogenic, antigen (i.e.: allergen)
- occurs on second and subsequent exposures
what is an autoimmune disease?
- when immune system loses (or never obtained) self-tolerance and responds to hosts own healthy cells/tissues/organs (body’s defenses against awn healthy self)
- can involve auto antibodies or auto reactive T cells
- some types seem to involve antigen mimicry b/w non-self and self antigens on tissues
- genetic component=-> receptor proteins and genes; maybe mutation
- *example on slide 68
what is an immune deficiency?
when one or more of the body’s defenses is absent or lost
describe Type 1 Hypersensitivity (5)
- known as allergic or anaphylactic
- involves IgE-Mast cell interactions
- occurs after individual first sensitized to antigen (pathogen, venom, allergen) due to specific epitopes–IgE is made in response to allergen–> binds to IgE receptors on mast cells via Fc receptors
- occurs within 30 min (second and subsequent exposures)
- can be localized or systemic depending on which mast cells are sensitized and how the individual was exposed
In Type 1 Hypersensitivity, what happens when the body is exposed to the foreign antigen a second time? (and all subsequent exposure to the pathogen)
antigen crosslinks with 2+ IgE molecules bound to mast cells–> mast cell undergoes degranulation–> releases inflammatory mediators
how does the antigen enter the body during localized hypersensitivity type 1?
inhalation or ingestion
-only mast cells along exposure route are sensitized
how does the antigen enter the body during systemic hypersensitivity type 1?
injection/bite into circulation
-many mast cells around body sensitized
describe Type 2 Hypersensitivity (6)
- known as cytotoxic
- involves IgG (or IgM) binding yo surfaces on host cells and marking them for attack
- attack by complement(MAC), phagocytosis by macrophages, or other cytotoxic cells
- Occurs 5-12 hrs after exposure
- Can involved foreign antigens attaching to cell surface of host cell (i.e.: malaria and erythrocytes, virus infected cells)
- Transfusion rejection (ABO and Rh)
Describe Hemolytic Disease of Newborn (a Type 2 Hypersensitivity)
- Rh + father and Rh- mother
- first Rh+ child: If Rh antigens enter mother’s circulation (i.e., during birthing), mother will likely produce anti Rh+ antibody (IgG) and memory cells
- All subsequent Rh+ babies: anti Rh+ antibody can cross placenta and attack baby’s erythrocytes–> complement and lysis of cells–> baby compensates by making large # immature cells called erythroblasts (also toxic products of erythrocyte destruction)–> after birth baby=jaundice w/ severe anemia –> severe cases often fatal
how do you prevent Hemolytic Disease of Newborn?
prevent with passive immunization
-anti Rh antibody–> combines with baby’s Rh+ that enter maternal circulation
Describe Type 3 Hypersensitivity (5)
- known as immune complex mediated
- involves IgG antibodies against soluble antigens in blood or tissue fluid
- immune complexes form with certain ratio of antibody to antigen–> these can deposit and get trapped in small blood vessels (i.e.: glomerulus of nephron)–> this can induce inflammation and cause damage
- occurs 3-8 hrs after exposure
- examples= glomerulonephritis, serum sickness
Describe Type 4 Hypersensitivity (5)
- known as cell mediated–no antibody involvement
- involves Tc , Th cells (cytokines), and macrophages
- delayed hypersensitivity –> occurs 24-48 hrs after exposure
- sensitization occurs when foreign epitopes (particularly those that bind to tissue cells) are phagocytize by macrophages and presented to T cell receptors–> this causes T cell proliferation/maturation and memory cells –> subsequent exposure to the antigen can result in cell-mediated hypersensitivity
the TB skin test is an example of a Type 4 Hypersensitivity. Explain the process
- ) TB protein antigen injected into skin
2. ) If previous exposure to M. tuberculosis or BCG vaccine, inflammatory reactions appears ~1-2 days later
what causes Allergic Contact Dermatitis?
Haptens from plants (i.e.: catechol in poison ivy), cosmetics, or jewelry get on skin–> in some individuals, this induces a reaction by Tc cells, macrophages
What are the 2 forms of Immune Deficiency? Describe them
- ) Hereditary Form:
- usually due to recessive mutations (1 copy inherited from each parent) in the genes for key proteins in stem cells for leukocytes
i. e.: Severe Combined Immunodeficiency - ) Acquired
- due to disease, cancers, chemicals
i. e.: AIDS
Describe Severe Combined Immunodeficiency (4)
- can be due to several different mutated alleles
- most autosomal on X-linked
- affects lymphoid precursor cells
- severest form lacks any functional B or T lymphocytes
