Immune System Overview Flashcards
Adaptive Immunity
- Aquired
- Specific recognition of small portion of organism or triggering antigen, Specific response to infectious agent
- Generate memory of initiator
- Should eliminate self-reacting cells
- Two types: Humoral and Cell-mediated
Innate Immunity
- Natural
- First line of defense
- No previous exposure to antigen required
- Nonspecific: Physical and chemical mechanical barriers
Natural Killer Cells
- 10-15% of total lymphocytes
- Destroy virus-infected and tumor cells
- Lack antigen specificity
Mast Cells
Inflammatory cells, in tissues
Antigen Presenting Cells (APC)
- Dendritic cells
- Macrophages
- B cells
- Have MHC Class 2
Epitope
- Specific site on the antigen to which antibody or T cell receptors bind
- One antigen can have many epitopes
Antibody Structure
- Each monomer of antibody - “Y” shaped
- 2 heavy chains: give antibody its name
- 2 light chains: both kappa or both lambda
- Each monomer has 2 Fab (antibody- binding) regions Each Fab contains 1 heavy and 1 light chain
- Each monomer has 1 Fc (crystallizable) containing 2 heavy chains
- Complement fixation occurs at Fc region
Secondary Lymphoid Organs
Lymph nodes, spleen, Peyer’s patches
Primary Immune Response
IgM antibody appears first, followed by IgG on first exposure to antigen
Secondary Immune Response
- Follows re-exposure to the same antigen
- Shorter response time
- Larger quantity of IgG
- Persists longer due to memory cells
Active Immunity
- Infection/exposure to antigen (natural)
- Vaccination (artificial)
Passive Immunity
- Igs crossing placenta
- Abs secreted in breast milk
- Injections of gammaglobulins and Abs
Adoptive Immunity
- Anti-cancer treatment
- Introduction of natural killer cells
Forbidden Clone
Self-reactive clone of lymphocytes not destroyed, the immune response to self-antigens could cause disease.
Sequestered Antigen
Antigens (eye lens, sperms) not normally in contact with the immune system get released (trauma, surgery etc.), and hence won’t be recognized as self-antigens.
Immunologic Deficiency
With aging, suppressor T lymphocytes decrease and no longer control T helper/B lymphocyte interactions.
Features of Autoimmune Disease
- Most autoimmune diseases are chronic
- Significant morbidity and mortality result
- Women more frequently affected
- Mostly in adults between 20-40 yrs of age
- Some diseases cause initial tissue damage; others do not
Beneficial Autoantibodies
CD5 cells produce autoantibodies to clear dead cells and remove damaged cellular components.
Central Tolerance
- Initiated during fetal development
- Eliminates cells with potential to react strongly with self-antigens
Peripheral Tolerance
- Occurs in the circulation
- Process involves mature lymphocytes
Factors Causing Loss of Tolerance
- Genetic
- Hormonal
- Environmental
- Failure of a regulatory sequence in the immune response
Mechanisms for Developing Autoimmunity
- Molecular mimicry and cross-reactivity
- Alteration of self-antigens
- Trauma exposing sequestered antigens
- Polyclonal activation of self-reactive lymphocytes
- Altered expression of MHC receptors
Effector Mechanism Classification
(underlying initiator) Initiator of damage: Autoantibody T cells - Cytokines released by lymphocytes can add to the tissue damage
Organ or System Attacked Classification
Organ-specific: damage is to a single organ
Example: Hashimoto’s thyroiditis
Systemic: autoantibodies cause damage in multiple organ systems
Example: systemic lupus erythematosus (SLE)
B cell Maturation
- Undifferentiated stem cell in bone marrow
- Progenitor (Pro-B) cell – CD45R on membrane, DNA rearrangement
- Pre-B cell – IL-7 receptor on cell surface
- Mature B cell (virgin B cell)
IL-4
- Promotes vigorous proliferation of the activated B cell
- Up-regulates B cell production of MHC Class II
IL-5
- Stimulates proliferation of activated B cells
- Stimulates differentiation of B cells into plasma and memory cells
IL-6
Stimulates differentiation of activated B cells into plasma cells
Memory B cell Characteristics
Express high levels of complement receptors and adhesion molecule
Isotype
- Portion of constant region of heavy chain that differs between Ig classes and subclasses
- Portion of constant region of light chains
Allotype
Variation of alternative alleles at a single gene locus
Idiotype
- Part of hyper variable regions of antibody (ab) molecule
- Unique to abs produced by single clone of B cells
IgG
- 80% of total human immunoglobulin
- Monomer (2 heavy and 2 light chains)
- Responsible for long-term immunity
- Only Ig able to cross placenta
- Activates classical complement pathway
- Has 4 subclasses, each with different biological activity
IgA
- 10-15% of total immunoglobulin
- 2 subclasses:
- Serum IgA: usually a monomer
- Secretory IgA: dimer or tetramer with secretory piece, allowing IgA to resist proteolysis
- Secretory IgA is the predominant Ig in secretions: mucous membranes, saliva, tears
IgM
- 5-10% of total serum immunoglobulin
- Pentamer joined by a J chain
- First Ig produced in the immune response
- Can be found in low concentrations in secretions
- Effective activator (due to size) of the classical complement pathway
IgD
- 0.2% of total serum immunoglobulin
- Monomer
- Most IgD is membrane-bound to mature B cells
IgE
- Less than 0.002% of total serum Ig
- Binds to mast cells and basophils at Fc
- Fab binds allergen and causes degranulation of these cells: Histamine release initiates allergic response
- Provides immune response to parasites
Complement System
- Works with antibody to defend against bacterial infection
- Aids in antigen presentation
- Causes organism lysis
General features Of Complement System
- Most abundant component is C3
- Helps in getting rid of immune complexes and inflammatory products
- Complement fragments are opsonins, chemotactic agents, and anaphylatoxins
- Complement system is linked to the coagulation, fibrinolytic, and kinin cascades
Complement Factor Creation
- Most components manufactured in liver
- C1 comes from intestinal epithelial cells or activated macrophages
- Factor D made in adipose tissue
Classical Pathway
An antigen/antibody reaction is required to activate the pathway (1 molecule of IgM or 2 closely associated molecules of IgG)
- Recognition: C1q, C1r, C1s
- Activation: C4, C2, C3
- Membrane attack complex (MAC): C5-C9
MAC
- Involves C5-C9
- Activated C4b2a3b cleaves C5 – begins final stage of the complement cascade
- C5 cleaved to C5a (a potent anaphylatoxin) and C5b (binding molecule for C6-C9)
- C6 and C7 deposited on cell membrane; lysis begins with the addition of C8 (a channel is formed in the cell membrane– Potassium leaks out of cell)
- C8 binds multiple C9 molecules, completing the channel – Sodium, calcium, and water enter the cell, causing lysis
Alternate Pathway
- Not activated by antibody but by cell walls of bacteria, fungi, viruses, and some parasites
- Factor D: similar function to C1qrs
- Factor B: similar to C2
- Properdin: stabilizing molecule
- Once C3 is cleaved, process for forming MAC is identical to classical pathway
MBL
- Part of innate immune system
- Functions early in bacterial infection
- May be important in children aged 6-18 months; the time between decrease in maternal antibody and full development of child’s adaptive immune system
- Carbohydrates that bind to MBL:
- Mannose
- n-acetylglucosamine
- fucose
- glucose
Total Hemolytic Complement (CH50) Assay
- Screening test for function of classical pathway:
- Based on ability of patient’s complement to lyse a standardized amount of antibody-coated sheep RBCs
- CH50 low if any factor is deficient
- Value is “zero” in total lack of complement
- CH50 value: dilution that lyses 50% RBCs
AH50 Assay
- Screening test for alternate pathway function:
- Rabbit blood cells (can activate alternate pathway) used instead of sheep RBCs
- Sequence of factors D, B, P, and C5-C9 are evaluated
- If both CH50 and AH50 are abnormal, defectisin C3 or C5 through C9
- If only CH50 is abnormal, defect is in C1, C4, or C2
Sensitivity
The proportion of individuals with the disease who test positively with the test
High sensitivity = few false negatives
Specificity
The proportion of individuals without the disease who test negatively for the disease
High specificity = few false positives
Titer
Determination of antibody levels that change during acute and convalescence phases. Best approach to diagnosis an acute infection is the presence of specific IgM tests vs. detection of IgG during convalescence.
Prozone Readings
If titer reads initially negative in preliminary tubes, then becomes positive, the antibody has been sufficiently diluted to allow the Ag/Ab complex to form. –These dilutions are @ zone of equivalence.
Antigen/Antibody Detection Tests
- Precipitation tests: followed by electrophoresis Agglutination tests:
- Latex agglutination
- Hemagglutination
- Inhibition reactions Complement fixation tests
- Immunoassays and labeling techniques
- Molecular diagnostics assays
Common Dysproteinemias
Multiple myeloma: Neoplastic proleferation of single clone of plasma cells. These produce a specific type of gamma globulin
Waldenstrom’s Macroglobulinemia: Plasma cell proliferation disorder malignant lymphocytes produced
Primary versus Secondary Response (Ig)
Anamnestic Response
Secondary response with high levels of IgG, after a second exposure to an antigen that created memory cells
Factors the influence Ab-Ag reactions (4)
- pH
- Concentration of Reactants
- Length of incubation
- Temperature
Hapten
A low molecular weight molecule that is too small to generate an immune response alone; needs and adjuvant
Classical Pathway
Triggered by Ab
- C1
- C4/C2/C3
- C5-C9
Alternative Pathway
Triggered by lipoproteins found in bacterial walls
- C3b
- Bb
- P
- Form C3bBb3bP/C5-C9
Heterophile Ag
Heteroantigens that exist in unrelated plants and animals that are nearly identical and can cause cross-reactivity
Heterophile Ab
Stimulated by one Ag but can react with an unrelated surface Ag present on other cells
Forssman Ag
An Ag found in certain animals and pneumococci that are not Paul-Bunnell Ag
Forssman Ab
A heterophile Ab not related to IM that causes hemagglutination
Interpreting Paul-Bunnell Test Results
If agglutination occurs, the IM was caused by EBV
MonoSpot test Principle
Agglutination of horse RBCs with Paul-Bunnell Ag that will only agglutinate in the presence of anti-Paul-Bunnell IgG
