Serology Day 1 - Immune system, immunoglobulins, complement Flashcards
Antigen
Molecule that is capable of eliciting formation of antibodies in an immune competent host
Reacts with antibody or t cell
Not able to evoke IR in first place
Antibody
GlycoPROTEIN binds w/ antigen “lock & key”
Produced by B cells and plasma cells in response to a foreign substance exposure
Aka immunoglobulins
Immunogen
Any substance that is capable of inducing a humoral or cellular IR and combine with it
Immunoglobulin structure
Y shaped - 2 heavy chains & 2 light chains (kappa, lambda)
2 Fab regions
1 Fc region
The larger the hinge region the greater the chances of degredation
Fab
Antibody binding region of monomer.
Contains 1 heavy and 1 light chain
Fc
Crystallizable region. Contains 2 heavy chains. Complement fixation occurs here
Immune system
Defense mechanism
Mammels - rid host of pathogens
Invertebrates - some immune response
Ability to distinguish self
Recognition phase
Self ➡️ normally no I.R.
Non-self ➡️ response phase
Innate (natural) immunity
Most primitive General recognition Antigen independent First line Rapid Non-specific (physical and chemical barriers)
Adaptive (acquired) immunity
- specific recognition of small portion of organism or antigen (antigen dependent)
- memory of initiator
- eliminate self reacting cells
- 2 types: humeral and cell mediated
- lag time between exposure and Max response
Autoimmunity
When self-reacting cells persist and are not destroyed.
Abnormal I.R. to host’s cells or tissue.
Antibody or cell mediated
Innate immune defenses in body
Flushing of urinary tract, pH GI Flora Stomach acid pH Antimicrobial in saliva, tears Physical barriers: cillia, mucus Skin - fatty acids, Flora
Leukocytes
Wbcs
Neutrophils (polymorphonuclear neutrophilic leukocyte) PMN
Removes infectious agent by phagocytosis
Most abundant in circulation 55-75% of wbcs
Granulocyte
Nucleus
- mature PMN - multi-lobed (segmented) - immature PMN - non-segmented bands
Monocytes
2-9% of wbcs
Agranulocytes
Nucleus - convoluted and Lacy
Cytoplasma - large amount of grey/blue w/small purple granules
Quickly removed from bloodstream to tissues where they become macrophages and histiocytes.
Interleukins produced by T Helper 2’s
IL-4, IL-5, IL-6
All help activate B cells so they can become plasma cells and produce antibodies
Plasma cells
Differentiated B cell, no longer has membrane IgM or IgD
Each plasma cell secretes an antibody with a specific variable portion (matches with a specific epitope)
Memory B cell
Long-lived, circulate through blood to lymphoid tissues
Have high levels of complement receptors/adhesion molecules
Repeat activation of a Memory B cell much easier than Mature B cell
Epitope (antigenic determinant)
Structure on antigen that elicits antibody response
Isotype
Changes in constant region of heavy chains which results in different classes of immunoglobulins (IgG, IgM, IgD, etc)
Allotype
Minor changes in constant region of heavy chains that create subclasses (IgG1-4)
Idiotype
Changes in hypervariable region (both heavy and light chains) which changes which epitope is recognized (could be different parts of same antigen)
IgG
80% of all immunoglobulins
Monomer, long-term immunity, only Ig to cross placenta, activates classical pathway, has 4 subclasses
IgA
10-15% total Ig 2 subclasses (serum IgA usually a monomer, secretory IgA usually dimer or tetramer with secretory piece)
IgM
5-10% of all Ig
Pentamer joined by J chain, first Ig produced in immune response, sometimes found in secretions, large size makes it good activator or complement
Effective in microbial killing
IgD
0.2% of all Ig
Monomer, membrane-bound to mature B cells, long hinge region makes it prone to proteolysis
Regulates activation of B cells
IgE
Less than 0.002% of all Ig
Binds mast cells/eosinophils at Fc region, binds allergen and caused degranulation (histamine released to cause allergic response), immune response to parasites
Classical complement pathway
Antibody-dependent, components numbered C1-9
Recognition: C1q, C1r, C1s
Activation: C4, C2, C3
Membrane attack complex: C5-C9
Membrane attack complex (MAC)
C5 cleaved to C5a (potent anaphylatoxin) and C5b (binding molecule for C6-9)
C6-7 deposit on cell membrane, lysis begins when C8 is added and forms channel, C9 completes channel (lysis due to uncontrolled loss of nutrients and influx of water)
Alternate complement pathway
Antibody-independent Factor D = similar to C1qrs Factor B = similar to C2 Properdin = stabilizing molecule Once C3 is cleaved, follows same path and classical
Mannose-Binding Lectin (MBL) pathway
Innate immune system, important in infants who don’t have mom’s antibodies any more but don’t have own immune system, binds to carbohydrates
Total Hemolytic Complement (CH50) assay
Checking patient ability to myself standard amount of antibody coated sheep RBC’s
If low, a factor is deficient
If 0, no complement at all
AH50 Assay
Alternate pathway function, use rabbit blood
If both CH50 and AH50 abnormal, defect is in C3, or C5-9
If only CH50 abnormal, defect in C1, C2, or C4
Macrophages
Large, round nucleus w/ 1-2 nucleoli
Cytoplasm - vacuolated w granules
Specialized in tissue
Specialized macrophages
Dust cell - lung Kupffer cell - liver Mesangial phagocyte - kidney Microglial cell - brain Osteoclast - bone
Natural killer cells
10-15% of lymphocytes
Destroy virus- infected and tumor cells
Lack antigen specificity
Basophils
Inflammatory cells circulating
Mast cells
Inflammatory cells in tissue
Eosinophils
Allergy, parasitic infections
Antigen presenting cells (apc)
Dendritic cells (innate)
Macrophages (innate)
B-cells (adaptive)
Major histocompatibility complex (MHC)
Aka human leukocyte antigen (HLA)
Must be on surface of APC for t-cell activation
Associated with organ and tissue rejection
Class 1 MHC - on most cells
Class 2 MHC - on APC
Epitope
Specific site on the antigen to which antibody or T cell receptors bind. An antigen can have many
Proteolytic enzymes
Pepsin - 2 fragments: 1 Fc & 1 F(ab)2
Papain - 3 fragments: 2 Fab & 1 Fc
Primary lymphoid organs
Bone marrow - produces B cells over lifetime of host
Thymus - produces T lymphocytes until host reaches puberty (CD4:CD8 ratio is 2:1)
Secondary lymphoid organs
Lymph nodes, SPLEEN, Peter’s patches
Lymphocytes - wbcs
Significant role in IR
Small, round, 10-12um diameter
Round nucleus w/ dense nuclear chromatin
Scant, blue cytoplasma
Primary IR
IgM 1st, IgG next after first exposure to antigen
IgM large and captures lots of antigen, but declines faster
Secondary IR
Follows re-exposure to same antigen
Shorter response time
Larger quantities of IgG produced
- persists longer due to memory cells
Active/acquired immunity
Infection/exposure to antigen (natural)
Vaccination (artificial)
Passive immunity
Your own immune system not producing
IgG cross placenta
Abs secreted in breast milk
Injections of gammaglobulins and Abs
Adoptive immunity
Depending on what patient “needs”
Anti-cancer treatment
Introduction of natural killer cells
