BRS Immunology Flashcards
Function of immune system?
Removal of foreign material/microorganisms
Is innate immunity specific or non specific?
Nonspecific
Innate immunity is developed when?
By birth
The protective factors in innate immunity are independent of what?
Antigenic stimulus.
Is innate immunity fast or slow?
Fast
Is innate immunity first or second?
First
Is adaptive immunity specific or nonspecific?
Specific
How is adaptive immunity actively acquired? (2
Infection or vaccination
How is adaptive immunity passively acquired? 2
Placental transfer
Injection of specific antibody
4 main types of physical and chemical barriers to microbial invasion in innate immunity?
- Skin and mucus membranes block and secrete
- Defensins in phagocytic vacuoles are secreted and damage bacteria
- Cathelicidins are released in granules to cause pores to form in bacteria
- Lysozyme is released in lacrimal and saliva secretions
What cells are involved in early detection of pathogens? (3)
- Macrophages
- Neutrophils
- Dendritic cells
Macrophages, neutrophils, and dendritic cells all possess what type of special receptor?
Pattern Recognition receptors
Pattern recognition receptors recognize what?
Which are found where?
Pathogen-Associated Molecular patterns (PAMP’s)
Found on many microorganisms
One of the most important types of PRR’s is what?
Toll-like receptors
Toll like receptors recognize what?
PAMP’s on selective microorganisms
Upon binding a toll-like receptor to a PAMP, what does the cell do?
Releases Interleukin
Function of interleukin? 3
- Incite inflammation
- Incite phagocytosis
- Removal of organism
Natural killer cells detect host cells with what main feature?
Depressed levels of major histocompatability class I molecules which is caused by viruses
NK cells binding to an infected cell’s MHC class I is through what receptor?
Killer-activated receptor
How can a cell with adequate MHC class I levels prevent destruction by NK cells?
NK cells have a Killer Inhibition Receptor which determines if a cell has adequate MHC I levels
What initiates inflammation?
Microbial induced release of pro-inflammatory cytokines
Pro-inflammatory cytokines include? (2)
TNF-Alpha
IL-1
Pro-inflammatory cytokines induce what? 2
Adhesion molecules on leukocytes (Integrins)
Adhesion molecules on endothelial cells (selectins)
How do neutrophils slow their flow in order to undergo diapedesis into injury site?
By neutrophils’ integrins binding to endothelial selectins and intracellular adhesion molecules (ICAM)
Phagocytic cells are recruited by what chemokines? 3
IL-8
Macrophage inflammatory protein (MIP)
Interferon-gamma (IFN-gamma)
First cells to arrive at seen of infection?
Neutrophils
What follows neutrophils to infection site? (3)
- Macrophages
- Monocytes
- Lymphocytes
Phagocytized membrane-enclosed organisms are destroyed in phagocytic vacuoles by what? 4
- Lysosomal enzymes
- hydrogen peroxide
- Nitric oxide
- O2-anion
Repair of the damage caused by excessive inflammation is done by what two ways?
- Down-regulate cytokines
2. Produce extracellular matrix
How are cytokines down-regulated in post-infection?
IL-4, IL-10, and TGF-Beta down regulate the cyotkines
How is extracellular matrix produced in post-infection?
PDGF and TGF-Beta induce it following increased proliferation and activation of fibroblasts
Chemokines are induced to release by what event?
Injury
How do chemokines function?
Transmit signals through seven transmembrane receptors that activate and recruit leukocytes to tissue damage sites
Two categories of chemokines based on sequence pair of amino acid cysteine?
- C-X-C Chemokines (Alpha)
2. C-C Chemokines (Beta)
Alpha chemokines attract what mostly?
Neutrophils
Examples of alpha chemokines include what? 5
IL-8, platelet factor 4, IFN-gamma, inducible protein 10, macrophage activation factors
What do beta chemokines attract mainly?
Monocytes and T lymphocytes
Examples of beta chemokines include what?
MCP’s
MIP
RANTES
What are cyotkines?
Intracellular signaling proteins acting locally by binding to high affinity receptors
Two main characteristics of chemokines as a whole?
- Redundant: Many cytokines induce same response
2. Pleiotrophic: A single cytokine can induce many different responses
Steps of Neutrophils undergoing diapedesis? 6
- Injury occurs and induces release of IL-1 and TNF-alpha
- IL-1 and TNF-alpha cause selectins to be expressed
- Endothelial selectins bind to PMN’s selectin receptor to cause “rolling”
- IL-8, MIP, and MCP release cause activation of PMN’s integrins
- Integrins bind to endothelial ICAM’s
- Diapedesis occurs and is facilitated by PECAM-1
What are lymphokines?
Cytokines made by lymphocytes
What are examples of endogenous pyrogens? (3)
IL-1
IL-6
TNF-alpha
What induces MCP, IL-8, and the acute phase resposne?
Endogenous pyrogens (IL-1, IL-6, TNF-alpha)
Functions of TGF-Beta 5
- Wound healing
- Immunosupressive
- Inhibits IL-2
- Inhibits proliferation of many cells
- promotes switching of B cell synthesis to IgA
Humoral immunity is mediated by what?
Antibodies
Humoral immunity is responsible for what?
Neutralizing microorganisms and toxins and removes antigens in the body fluids by amplifying phagocytosis or lysis by complement
Cell-mediated immunity is mediated by what types of cells? (3)
Cytotoxic T
NK Cells
Activated macrophages
Cell-mediated immunity is responsible for what?
Eradicating microorganisms inside body cells
Two central lymphoid organs?
Bone marrow
Thymus
What happens at the central lymphoid organs?
Immunocompetent cells are developed
Peripheral lymphoid organs include what? (4)
- spleen
- lymph nodes
- Tonsils
- peyer’s patches
What happens at peripheral lymphoid organs?
Immunocompetency is expressed
Multipotential stem cells oiginate where? (2)
- fetal liver
2. bone marrow
When stem cells migrate to fetal thymus, they acquire what?
Phenotypic characteristics of T cells
T cells are characterized by what special protein markers?
Clusters of Differentiation (CD)
What are the major CD’s on all peripheral T cells?
CD2 and CD3
CD4 defines what subset of T Cells?
Helper T cells
Helper T cells do what?
Aid responsiveness of B cells and other immunocompetent cells
Helper T cells differentiate into what 3 types?
Based on what?
Th0, Th1, Th2
Cytokines expressed
CD8 defines what subset of T cells?
Cytotoxic T cells
Regulatory T cells (Tregs) are composed of what two types?
- Naturally occurring with (CD4, CD25, and FoxP3 markers)
2. Adapative
Naturally occurring Tregs can do what?
Supress other T cells
Adaptive Tregs are functional when?
End of immune response
Antigenic receptors are specific for what?
Each antigen epitope
What are the two types of antigenic receptors on T cell membranes?
Alpha:Beta TcR
Gamma:Delta TcR
The homing area exists where?
Periarteriolarly in spleen
Paracortical and deep cortical regions in lymph
GI
Bronchus
What percentage of T cells leave thymus?
What happens to rest?
1-2%
Apoptosis
What are the stages of development of Th1 cell? 8
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 90% obtain alpha:Beta TCR
- 70% become ThO with CD4+ and CD8-
- Become Th1 and secrete IL-2, IFN-gamma, and TNF-alpha
What are the stages of development of Th2 cell? 8
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 90% obtain alpha:Beta TCR
- 70% become ThO with CD4+ and CD8-
- Become Th2 and secrete IL-4, IL-5, IL-6, IL-10, IL-13
What are the stages of development of cytotoxic and supressor T cells? 8
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 90% obtain alpha:Beta TCR
- 25% become CD8+ and CD4-
- Differentiate into either cytotoxic or suppressor T cell
What are stages of development of gamma:delta TCR T cells?
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 4% obtain gamma:delta TCR with CD3+, CD8-, and CD4-
What do T cells with alpha:beta TcR’s respond to?
Peptide antigens bound to MHC
What do T cells with gamma:delta TcR’s respond to?
Nonpeptide antigens but lack MHC restrictions
Function of T cells with gamma-delta receptors? 2
- antibacterial
2. Increased Cell mediated immunity against viruses
Th1 cells are involved in what? 3
- Activation of B cells, Tc cells, Th cells, and APC’s
- Downregulation of Th2 cell functions
- Increased CMI
Th2 cells are involved in what? (5)
- B cell differentiation
- Activation of eosinophils
- Downregulation of Th1 cell functions
- Class switching
- increased antibody
If stem cells remain in bone marrow, they acquire what?
Phenotypic CD markers of B cells
What distinguishes the B-cell antigenic receptor from the T cell?
Membrane bound, epitope-specific, monomeric IgM antibody
Upon antigenic and cytokine stimulus, what will B cells do?
Synthesize and secrete its antibody
B cell homing areas exist primarily where? (4)
Splenic follicles
Red pulp
Lymph nodes
MALT
T and B cells gain immunocompetency when?
Antigenic stimulus
What is the clonal selection theory
The total population of T and B cells is made up of millions of individual clones of cells, each dfined by specific receptor for a particular antigen epitope.
Antigen is modified by by what?
APC’s
Antigen selects what cells upon presentation?
Those T or B cells with membrane-bound receptor specific for its epitope
What are the stages of B cell development?
- Stem cells
- Gains CD19, CD22, and mu chain D-J gene arrangements to become pro-B Cell
- Addition of CD9, CD10, and V-DJ-C gene arrangements with mu chains appearing to become Pre-B cell
- Add CD20, CD21, CD37 and lose CD9 and CD10 while IgM and IgD receptors appear to become immature B cell
- Become mature B cell
- Activation by antigen and T cell cytokines IL-2, IL-4, IL-5, and IL-6 cause B cell to activate
- Activated B cell becomes either plasma cells or memory cells
Plasma cells secrete what antibody?
IgM
Plasma cells have an Ig switch to what?
IgG, IgA, IgE
What is an epitope?
Short sequence of amino acids or sugars in an antigen molecule that binds to the hypervariable region on an antibody
What is the number of repeats of an epitope called?
Valence
Does a microorganism have more than one epitope?
yes