Chapter 1: Elements of the Immune System Flashcards
Define Innate Immunity
Non-Antigen-Specific immune response.
*Phagocytic Cells that engulf and destroy invaders
Toll-Like Receptors: Define
Antigen-presenting cells (like phagocytes). Interact w/invader molecules
Define: Adaptive Immune Response
Antigen specific. Destroys invaders that were not destroyed by the Innate Immune Response
What does the Adaptive Immune Response consist of?
B and T Cells.
Macrophages
1. What marker distinguishes them from Granulocytes and Lymphocytes?
- Name 3 roles Macrophages play w/in the Immune System?
- What IL’s do macrophages produce?
- Although not completely understood yet, what do we think chronic activation will do to the RPE?
- Esterase
- a. Direct destruction of foreign pathogens
b. Activating the Immune System
c. Strong Secretory Cell (release proteases. IL-1 (affects T cell Growth. Direct effect on CNS, w/a by-product being the start of a FEVER) - IL-12, 10, and 18. Also TGF-B
- Thought that it starts the initial changes that LEAD to AGE-RELATED MACULAR DEGENERATION!
What are the 2 major WBCs that create cytokines?
- What is the most important Lymphocyte?
Macrophages and Lymphocytes
- IL-2
T Helper Cells
- Th1: What cytokine profile do they have?
- Th2: same as above? (5)
- IFN-y
2. IL-4,5,13 maybe 10 and maybe TGF-B
T Helper
- Th1 is usually associated with what?
- Th2: Associated with what?
- Start of disease
2. related to Disease Downregulation, Allergy initiation, or Parasitic Diseases
What is the purpose of Chemokines?
Direct Cell adhesion, homing, and Angiogenesis. They start directional migration of WBCs
*Plays a major role in Ocular Inflammatory disease and maybe other conditions as well.
- What is the basis of a large part of the ocular inflammatory process?
- T-cell Responses to an Antigen.
Studies of inbred mice showed something interesting in regards to uveitis. What was shown in regards to Thymic expression of T-cell receptors?
- 4 strains were resistant to Uveitis when ARRESTIN was used as the IMMUNIZING Antigen and all 4 expressed arrestin in their thymus.
However, B10.A and B10.RIII were susceptible to uveitis induction when IRBP was used as the immunizing antigen.
Where do B cells come from?
- From the Same PLURIPOTENTIAL STEM CELL in the Bone Marrow as the T CELL comes from.
What will the B cell develop into?
a Plasma cell that can secrete Immunoglobulin
What is the role of the B Cell?
It’s the EFFECTOR Cell in HUMORAL IMMUNITY
B Cells: At first, they express what to things on their surface?
IgM and IgD
What are the five major classes of immunoglobulins expressed?
GAMED
The Structure of immunoglobulin has a symmetry w/2 heavy and 2 light chains that are UNIFORMLY SEEN in ALL CLASSES EXCEPT…?
IgM and IgA
For a PRIMARY RESPONSE, B cells will produce what?
- IF they encounter these antigens again, what will they switch to?
- IgM
2. They will switch production to IgG.
What is the MAJOR circulating Immunoglobulin in Humans?
IgG (about 75%)
*Crosses BBB and enters eye.
IgM: Where is it normally seen?
Pentamer. Linked by Disulfide Bonds and J Chains. Stays w/in Systemic Circulation and WONT cross the BBB or the Placenta!!
Initial Antibody Responses to Exogenous Pathogens are from what class?
IgM
What’s the major role of both IgG and IgM?
- They help effector cells thru what process?
They Interact w/Both EFFECTOR CELLS and the COMPLEMENT SYSTEM. They do this to LIMIT Invasion of the Exogenous Organism.
- OPSONIZATION (Antibody coating on an invading organism)
IgA: It’s what kind of Immunoglobulin?
- Major Extravascular Immunoglobulin (Gut, Respiratory Tract, Tonsils, Salivary and LACRIMAL Glands)
IgE: It’s slightly heavier than what chain?
- What 2 cells have Fc Receptors for IgE?
- Important Defense Mechanism against what?
- Important role in what?
- IgG. Due to heavy chain having an extra Constant Domain
- Mast Cells and Basophils (reason why they thing it mediates Allergic or Anaphylactoid Reaction)
- Parasites
- Ocular surface disease, but not ocular inflammation
Mast Cells: Store what?
- Involved in what?
- Histamine (Type I hypersensitivity RxN involved)
2. External Ocular Conditions
Where does Eosinophils come from?
- What do these cells contain?
Bone marrow from a Myeloid Progenitor…separate stem cell from neutrophils.
- Anti-inflammatory agents (like Histaminase). also, H2O2….cause death of invading organisms.
Neutrophils are the most abundant what?
- What is their role?
WBC
- Acute Inflammation. Attracted to inflammatory sites by IL-8 and Interferon-y and C5a.
* Phagocytosis
Complement System: Purpose of proteins in this system?
- Act as a Substrate for enzymes that precede it in the cascade and then they act as part of a proteolytic complex for the next protein in the cascade.
Complement System: Classic Component pathway?
C1q, C1r, and C1s…Form an enzyme that CLEAVES C4 to C4a and C4b.
C4b binds to cell membrane, then C2 binds, then it’s split by C1s to C3a and C3b. They join next, to make C4b,2a,3b.
This new complex cleaves C5 into C5a and C5b. C5b binds to cell membrane, and C6,7, and 8 bind to it. This new complex then leads to C9 polymerization into the membrane
Alternate pathway: What does it need?
Does not need Antibody but can be activated directly by BACTERIAL CELL WALLS…so it’s NONSPECIFIC.
Why has Complement been an area of special focus?
Due to possible role in PATHOGENESIS of AMD. (Complement has been found in DRUSEN of AMD eyes.
Type 1 RxN: Mediated by what?
- What do they bind to?
- What happens to these cells
- Example?
- IgE
- Mast Cells or Basophils
- Degranulaiton of these cells occur
- Ex: Hay Fever: Lg amt of Edema w/o Structural damage
Type 2: RxN: Mediated by what?
- Cytotoxic Antibodies. Mediate Hemolytic Disorders
Type 3: AKA?
- What is it exactly?
- Believed to be a major contributor to what disease?
- Immune Complex-Mediated Inflammatory Response.
- Binding of Antibody to an Antigen then it deposits as a Complex…and can START the COMPLEMENT CASCADE
- Intraocular Inflammatory Disease like Behcet’s Disease
Type 4: Mediated by what?
T CELSS…so Cell-mediated immune response, NOT Humoral Response.
**Sarcoidosis
*Probably really IMPORTANT in Intraocular Inflammatory disease (t-cell dysregulation/ T-cell controlled inflammatory responses)
Type 5?
Antibody can be a stimulant to a target cell or organ…like Graves’ Disease (LATS Antibody)
- The Eye is considered to be a PRIVILEGED what?
2. What is missing from the eye?
- Immune Site.
2. Lymphatic Drainage.
What 4 ways are believed to help the eye protect itself?
- Blood-Ocular Barrier
- Soluble or Membrane Bound Inhibitors that block the function of an organism.
- Kill invaders or cells that could cause unwanted inflammation
- There may be a way to induce tolerance.
It appears that the Eye expresses FasL like the testes and brain do. What do we think this does?
- Allows for APOPTOTIC Cell death in cells that express Fas, thus is looks to be 1 Method of IMMUNE PRIVILEGE in the EYE.
There are many cells in the eye that can communicate with the immune system. What are they?
- Langerhans’ Cells (cornea) and CB (that express Ia)
- Muller Cells (major effect on T Cells)
- RPE (similar characteristics to Macrophages)
- Vascular Endothelium
What does corneal endothelial cells do?
Block T-cell proliferation.
Why do most fungal lesions tend to begin as Choroiditis?
Due to HIGH BF to the Choroid and its anatomy that can act as sort of a TRAP for MANY BLOODBORNE PATHOGENS!
- The retina is an extension of what?
2. It has Many Tight Junctions. Why could inflammation be an issue here?
- of the CNS
- It can Alter PERMEABILITY which can ALTER Retinal Function. We can see Autotoxicity due to high degree of Oxidative Metabolism in the Retina that could create Oxygen Radicals.
Class I Antigens:
- All Controlled by what 3 Loci in Humans?
- Are they Homogenous?
- They can serve as Recognition Antigens for what?
- A,B,C.
- No. Heterogeneous.
- For CD8 (Cytotoxic) T Cells when they attack Virally infected Cells
Class II Antigens
- Produced by what?
- Class III Antigens: Made w/in what region? Control what?
- HLA-D/DR Locus
2. MHC Region and control LEvels of C1,2, and 4.
Variants of the CFH Gene have been associated with what disease of the eye?
AMD and Multifocal Choroiditis
What can be seen in the Aqueous Humor of pt’s with Uveitis?
Immune Complexes
