Immunology II Flashcards
(65 cards)
Primary Lymphoid Organs
Bone marrow- where B cells develop
Thymus (bilobed)- where T cells develop:
Progenitor cells from the bone marrow migrate to the thymus where the cortex contains immature thymocytes, which mature and migrate to the medulla
In the medulla they learn to discriminate between self and non-self during fetal development and short time after birth, then leave the medulla and enter the peripheral blood circulation where they are tranported to the secondary lymphoid organs
Reaches its maximum size and activity at birth
Atrophies with age –almost disappears at puberty
DiGeorge syndrome:
Congenital absence of thymus results in an immediate and drastic reduction in T cells that produces a potentially lethal wasting disease
Secondary Lymphoid Organs
The secondary lymphoid organs have two major functions:
- Trap and concentrating foreign substances
- Main sites of production of Abs and T cells
The major secondary lymphoid organs include:
Spleen- responsive to blood-borne antigens
Lymph nodes- protect the body from antigens that enter from the skin & internal surfaces via the lymphatic system
Mucosa-associated lymphoid tissue (MALT):
Scattered along mucosal linings
Protect against Ags entering the body directly through mucosal surfaces
Spleen: Anatomy
White pulp: has many WBCs and this includes T and B cells, and when the B cells mature they leave and go to the red pulp and are associated with RBCs and other cells
The spleen is important for phagocytosis facilitated by Ab and other opsonization methods, therefore you find phagocytosis of encapsulated cells is important to happen in the spleen because without the spleen it is difficult for phagocytes to capture these encapsulated cells
People without spleen, frequent infections with encapsulated bacteria
Lymph Nodes
Lymph nodes are clustered in strategic points in the body: neck, axillae, groin, mediastinum, abdominal cavity
Filter Ags from interstitial tissue fluid and lymph during its passage from the periphery to the thoracic duct
Two types:
Somatic nodes: Lymph nodes that protect the skin
Visceral nodes: Deep lymph nodes protecting the respiratory, digestive, and genitourinary tracts
MALT
More than 50% is lymphoid tissue
Mucosa-associated lymphoid tissue is composed of
GALT- line the intestinal tract (Gut)
BALT line the respiratory tract (Bronchus)
Genitourinary tract lining lymphoid tissue
Secretory IgA (sIgA) Major effector mechanism; only Ab that can be secreted out of the body/tissue Secreted directly onto the mucosal epithelial surfaces
Examples of MALT
Peyer patches that line the small intestine and mainly secrete IgA; always the cells that makes IgA regardless is the B cell
Appendix
Tonsils
M cells that are associated with the intestine and the purpose of their existence is the increase the surface area that is exposed to the nutrients within the intestines; they have microfolds on only one side of the intestine to increase the absorption of the nutrients
Absorb, transport, process, present antigens to subepithelial lymphocytes
Polyclonal Ab
Polyclonal Abs are a heterogeneous mix of Abs that recognize multiple epitopes but Ab specificity against the same Ag (many Ab, one Ag); recognizes many epitopes on only one type of antigen
Produced by variety of Ab-producing cells
They are many clones of cells
Polyclonal Abs recognize & react against different epitopes on the Ag
Avidity- sum of the affinities to the different epitopes or the sum of the members of the polyclonal group
Isolate them by growing them in a mouse
Monoclonal Ab
Monoclonal Abs are produced by a single clone of cells (only one B cell)
Resultant Abs are identical in all aspects with the same affinity and same binding specificity
Recognize the same epitope
They are produced in hybridoma between activated B cells and malignant plasma cells (fusion) so lengthen the live of the B cells and give the myeloma cells Ab producing abilities
IgG
Antigen binding sites in the variable region
Constant part of light chain doesn’t really have a function associated with it, but the heavy chain part is the Fc fragment where we treat the molecule with papain that is an enzyme that can break the proteins on the certain site and get two identical fragments of Fab, which maintains the function of the Ab because they contain the Ag binding site needed to bind Ag
The Fc fragment (H/heavy chain) crystallizes in the cold and can bind to Fc receptors on other cells and so if you have a complete Ab by binding to the antigen specifically, then the Ab can bind to the cell (phagocyte, macrophage, NK, etc) and this will bring the antigen closer to the cell so it can be phagocytosed and then destroyed
Heavy Chain Designation: gamma
Subclasses: 4
Biologic Activity: opsonin, fixes complement, crosses placenta
IgM
IgM heavy chain has an extra domain compared with IgG
J chain- small cysteine-rich protein that initiates cross linking of C3 and C4 of 5 IgM monomers producing the pentameric form of IgM found in circulation
Cysteine rich regions to form disulfide bridges to combine the chains together and bind the whole complex together
When the B cells mature, they produce IgM first; if the B cells matures further in a process called Class Switching, it changes to other Ig’s; the change must keep the specificity the same or it doesn’t serve the purpose; the variable part does not change and the constant region will change
Heavy Chain Designation: mu
Subclasses: 1
Biologic Activity: fixes complement, agglutination, antigen receptor, indicative of acute infections
IgA
IgA2: secretory IgA is dimeric and held together by J chain and secretory component
IgA1: serum IgA is monomeric
Heavy chain has three constant regions
Only Ig that is secreted outside of the body/tissue to fight infections in the mucosa in the body; eye (conjunctivitis), intestine, respiratory system
Heavy Chain Designation: alpha
Subclasses: 2
Biologic Activity: secretory Ab and agglutination
IgE
IgE is similar to IgG
Has 4 constant region domains on the H-chain like IgM
Allergy
Defense against parsitic infestation
Heavy Chain Designation: epsilon
Subclasses: 1
Biologic Activity: anti-parasitic and allergy Ab
IgD
Similar to IgG in structure, but NEVER secreted
Functions as a receptor on the B cell always
Variable parts have specificity and bind certain antigens; determines which Ig that is released from the B cell
Part of the receptor/signaling complex of B cells
Heavy Chain Designation: delta
Subclasses: 2
Biologic Activity: antigen receptor
Primary Ag-Ab Reaction
The first interaction between Ag & Ab
Key-lock principle like enzymes, but doesn’t need an enzyme
Ag-Ab interaction is precise = specific
Characteristics of Ag-Ab reaction:
i. Rapid, in seconds
ii. Independent of electrolytes, salt, buffer
iii. Not visible
Chemical Interactions for Ab-Ag Reactions
Four noncovalent interactions hold antigenic determinants w/in Ab-binding site:
- Coulombic (electrostatic, ionic) interactions
- Van der Waals forces- weak attractive force between atoms or nonpolar molecules caused by a temporary change in dipole moment arising from a brief shift of orbital electrons to one side of one atom or molecule, creating a similar shift in adjacent atoms or molecules
- Hydrogen bonds
- Hydrophobic interactions
Affinity and Avidity
Affinity is the strength of Ag-Ab bonds between a single epitope and an individual Ab’s binding site
Avidity: The binding strength between a multivalent Ab (polyclonal Ab) and a multivalent Ag
K = [Ag..Ab]/[Ag][Ab] = Ab affinity/association constant
K = Associated complex/dissociated Ag & Ab
Dissociation constant: 1/K, meaning that you put the [Ag] [Ab]/ [Ag….Ab]; the smaller the amount of D, the higher the affinity; reverse of other equation
The higher K, the higher the association between Ab-Ag
Secondary Ag-Ab Reaction/Response
Secondary Ag-Ab reaction: the conversion of the invisible primary reactions macroscopically visible ones as in the case of precipitation and agglutination
Secondary response: the immune response which follows a second encounter with a particular Ag
Lattice Formation
Occurs when Ag-Ab complexes aggregate in form of precipitation in liquid medium - or -
Agglutination, including particulate components, other than Ag and Ab, such as cells
A regular arrangement of units into an array such that a plane passing through two units of a particular type or in a particular interrelationship will pass through an indefinite number of such units; e.g., the atom arrangement in a crystal.
Reference to a complex between several Ab and Ag at the same time instead of one Ab to one Ag
Cytotoxic T cells
Cytotoxic T cells kill infected cells to prevent pathogen production
Cytotoxic T cell receptors detect viral protein fragments on the surface of infected cell
Large numbers of virus specific cytotoxic T cells are produced
EBV infection in B cells cause Tc cells to make up the vast majority of WBCs
Resting vs. Active B cells
No Gall bodies
No LGL morphology
Monoribosomes scattered in the cytoplasm
Activated B cells have rough ER whereas inactive ribosomes aren’t attached to the ER
T cell Independent Defense Mechanisms
Phagocytosis
Chemotaxis
Complement Cascade: Classical Pathway
Classical: requires IgG in a complex with Ag, or IgM; these are the activators; this pathway is associated with acquired or adaptive immunity
Activated after the Alternative pathway via Antigen-IgG (1-3) complex, pentameric IgM
Non-Activators: IgG4, IgA, IgE because they lack C1q receptors and cannot bind C1q
C3b is produced and that point on is the same for both pathways and goes on until it produces the membrane attack complex and destroys the cell
Complement Cascade: Alternative Pathway
Alternative: does not require Ab to be activated
activated by components of the infectious agents like cell wall of bacteria, yeast, fungi, LPS, aggregated IgA, cobra venom; NO need for Ab-Ag complex or IgM for activation
This pathway is the first pathway to be activated because only the presence of the bacterium itself is sufficient enough to activate it, whereas the classical needs Ab in order to be activated
C3b is produced and that point on is the same for both pathways and goes on until it produces the membrane attack complex and destroys the cell
Complement
Non-immunoglobulin serum proteins
Involved in:
i. Control of inflammation
ii. Stimulation of phagocytosis
iii. Activation of cell lysis
Cascade of different proteins that act upon each other as enzymes, and this system is designed to cause lysis of certain cells like bacteria, or own body cells sometimes as well
Defense: opsonization and stimulation of phagocytosis and inflammation process