Week 2- Innate Immune + Antibody Flashcards
Lecture and practice
What are examples for the soluble antimicrobial molecules of the innate Immune system?
Defensins
Lyzozymes
Calprotectin
Defensins
Amphipathic molecules that form holes in microbes membranes. Found in mucusal surfaces first line bounderies.
Lyzozymes
Desteoys bacterial cells wall by breaking glucosidil bonds between peptidoglycin components.
Caloprotectins
Inhibits bacterial growth by chelation of manganese and zinc (which are vital for it).
What are the factors macrophages secret in order to recruit more cells for Inflammation?
TNF alpha
IL1
IL6
IL8
What are the ways Neutrophils kill bacteria?
Phagocytosis
Degranulation
NET
What are the two kinds of activations of Recruited macrophages?
IFN-gamma - classical activation: Bactericidal and cytokine release
IL4,IL13 - alternative activation: Supression and scavenger activity
What are the 3 modes of Intracellular killing in Macrophages?
Lysosomal
Oxidative burst
NO-mediated
What are the 3 kinds biological signals possible ti be collected by macrophages upon meeting apoptotic bodies?
Find me - MCP- Membrane Cofactor Protein (CD46) , IL8
Eat me - Phosphatidylserine
Tolerate me - IL10, TGFbeta , PGE2
What are Innate lymphoid cells?
Cells that have the diversity of Cytokines production comparable to those of T cells but, doesn’t have the same focused specificity.
What is the fate of cells that do not have MHC-I on their membrane (healthy Immune sys)?
Killed by NK cells - Perforins and Granzyme B invasion.
These are normally Virus infected cells or cancer cells.
Give examples for KIR and KAR?
What do they attach to?
(Killing Inhibitory and Killing activator Receptor)
KIR - NKG2A - binds MHC-I
KAR - NKG2D - binds Ubiquitous molecule on surface
Example for an antibody-depedent cellular cytotoxicity?
CD16(Fc-gamma-RIII) surface molecule of Nk cell binding the Fc segment of target antibody.
Fc receptors of IgG and IgE?
Function?
IgG - Fc gamma receptor - opsonin
IgE - Fc epsilon receptor - parasitic defense
What are typical signals that TLRs detect on bacteria?
Lipids, Carbohydrates (LPS), Flagellar proteins
What are the intracellular Cytoplasmic PRRs and what do they recognize?
RIG like helicases - recognize viruses
NOD like receptor- recognize intracellular bacteria
What is the systemic influence of IL-1 and TNF-alpha?
PGE production is increased and reaches the Hypothalamus - Fever
What are DAMP?
Damage associated molecular pattern:
Hsps, uric acid, HMGB1, ds DNA, necrotic factors
Shouldn’t be found outside the cells!
What is an Inflamasome?
Cytoplasmic Enzyme catalyzes to Pro-Cytokines cleavage. Assembled from NLR, ASC and Caspase-1 .
What are the revised concepts of the Innate Immune system?
- specificity is limited
- cells can be long lived
- memmory is limited
IgM - Structure: Conformation and Chains, Percentage in serum. Crosses placenta or Not?
IgM :Pentamer, Heavy chain: μ, Light Chain: ƙ or λPercentage in serum: 6%
Does Not Cross Placenta.
IgM -General Function, Complement Sys.
IgM : Main antibody of primary response. Monomer form serves as BCR. Activates Complement Sys. with highest Efficacy.
IgG - Structure: Conformation and Chains, Percentage in serum. Crosses placenta or Not?
IgG :Monomer, Heavy chain: γ, Light Chain: ƙ or λPercentage in serum: 80%
Does Cross Placenta!
IgG -General Function, Complement Sys.Number of Subtypes (Allotypes)
IgG :Main blood antibody of secondary response.Activates Complement Sys. Has 4 Subtypes.
IgA - Structure: Conformation and Chains, Percentagein serum. Crosses placenta or Not?
IgA:Dimer (with Secretory Component), Heavy chain: α, Light Chain: ƙ or λ. Percentage in serum: 13%
Does Not Cross Placenta.
IgA - General Function, Complement Sys.Number of Subtypes (Allotypes)
IgA: Secreted into mucous, tears,saliva. Does Not activate Complement Sys. Has 2 Subtypes
IgE - Structure: Conformation and Chains, Percentagein serum. Crosses placenta or Not?
IgE:Monomer, Heavy chain: ε, Light Chain: ƙ or λ. Percentage in serum: 0.1%
Does Not Cross Placenta.
IgE - General Function, Complement Sys.
IgE: Antibody of allergy and anti-parasitic activity.Does Not activate Complement Sys.
IgD - Structure: Conformation and Chains, Percentage in serum. Crosses placenta or Not?
IgD:Monomer, Heavy chain: δ, Light Chain: ƙ or λ. Percentage in serum: 1%
Does Not Cross Placenta.
IgD - General Function, Complement Sys.
IgD:B-cell receptor, Not secreted regularly.Does Not Cross Placenta.
What are Idiotypes?
The unique amino acid sequence of the VH and VL domains of a given antibody - differences in epitope specificity.
IgG4 Allotype - Relative Amount and Function
IgG4 Allotype:Lowest Amount. Allergy Immunotherapy.
IgG1 Allotype - Relative Amount and Function
IgG1 Allotype:Highest Amount. Best Opsonin
What are the factors Influencing the Isotype Switch?
- Cytokine Amount and Kind
- Kind of Inflammatory response
- Position in the Body
Elevated Serum IgE could mean:
Hypersensitivity type 1 - Allergy
Elevated Serum IgM in Pregnancy could mean:
Intrauterine Infection
Elevated IC (Antigen+Antibody) of Self antibodies in serum:
Hypersensitivity type 2 :-ABO or Rh Incompatibility -Hemolytic Anemia (could be Penicillin linked)Hypersensitivity type 3 : Systemic Lupus Erythematosus
Elevated IC (Antigen+Antibody) of Foreign antibodies in serum:
Hypersensitivity type 3 :Serum Disease, Passive Immunisation - Hepten could come from Chemotherapy.
Antibody with High Sensitivity - Meaning
High amount of the Epitopes bound by the Antibody are ones that actually should be bounded.
Antibody with High Specificity- Meaning
High amount of the Epitopes not bound by the Antibody are ones that actually should not be bounded.
What is Cross-Reactivity?
The ability of the antibody to bind multiple antigen counterparts (for different antigens with shared epitopes)
What is Avidity?
The overall strength of binding between Antigen and Antibody.
Type 1 Hypersensitivity
Anaphylactic IgE mediated degranulation of mast cells - Inflammation.
Response to earlier exposed antigen - food or drug allergies.
Type 2 Hypersensitivity
Antibodies bind to cell-surface antigens leads to inflammation and cellular destruction (Cytotoxic).
Examples -
Hyperacute transplantation rejection.
M protein causes Rheumatic fever - Polyarthritis
Type 3 Hypersensitivity
Type 3 - 3 things, Ag,Ab and Complement .
Elevated amount of IC *IgG with Antigen causes activation of complement and in turn neutrophil lysosomal enzymes.
Examples are Post-streptococcal Glomerulonephritis or SLE
Where are Alpha-Defensins Secreted? (HNP1-4)
Neutrophils, Gingival sulcus, Inflammatory Sites, Salivary Ducts cells.
Where are Beta-Defensins Secreted? (hBD1-3)
Epithelial Linings and Salivary Ducts
What cytokines Induce the formation of M1 cells from a normal macrophage? What will this cell do?
IFNγ - Classical Activation will cause the formed M1 to have Bactericidal activity and release Inflammatory cytokines.
What cytokines Induce the formation of M2 cells from a normal macrophage? What will this cell do?
IL4/IL13 - Alternative Activation will cause the formed M2 to be Scavenging and promote Suppression host defence.
Find me sign molecules-
Membrane Cofactor Protein (MCP or CD46) , IL8
Eat me sign molecules-
Phosphatidylserine
Tolerate me molecules-
IL10, TGFβ , PGE2
Missing sialic acid on human cells will cause:
phagocytes activation and alternative complement activation
Give an example for KIR:
KIR - NKG2A - binds MHC-I
Give an example for KAR:
KAR - NKG2D - binds Ubiquitous molecule on surface
Two kinds of Opsonic receptors:
Fc Receptors and Complement Receptors
What are Fcε receptors?
Bind IgE, High affinity receptor is expressed on mast cells and basophils – have role in immunity against parasites and allergy (low affinity receptor has regulatory function)
Scavenger receptors - Part of Which receptor family?
Example
PRR Family
Example: CD14- LPS Receptor
Lectin receptors - Part of Which receptor family?
Example
PRR Family
Example: Macrophage Mannose receptor
Intravesicular receptors (TLR) - Nucleic acids are recognized by TLRs in the _______
Intravesicular receptors (TLR) - Nucleic acids are recognized by TLRs in the endosome
What mediator leads to the inflammatory response production intracellularly, after TLR Recognition of PAMP?
NF-kB
CD80/CD86 - Function? When are they Formed?
Costimulatory membrane proteins on DC for T cell interactions. Formed after PAMP/DAMP detection, Signal for Maturation of DC.
DAMP - What process invokes its reaction with Immune cells?
Necrosis
What is the immediate enzyme formed by the Inflammasome?
CASPASE-1 (from PRO-CASPASE-1)
What is the purpose of CASPASE-1?
Conversion of pro-interleukin 1β and pro-interleukin 18 to IL-1β and IL-18, setting the course for Inflammation.
What are the molecules complexed with Pro-caspase-1 for activation?
NLR and ASC
What is the common features of many Autoinflammatory disorders (inflammasomopathies) ?
Common feature: elevated IL-1 beta secretion (due to the defective regulation of the pro- IL-1 beta conversion to active IL-1 beta transition.
IgM is said to have low affinity but high ______ because it has 10 weak binding sites for antigen as opposed to the 2 stronger binding sites of IgG, IgE and IgD with higher single binding affinities.
IgM is said to have low affinity but high avidity because it has 10 weak binding sites for antigen as opposed to the 2 stronger binding sites of IgG, IgE and IgD with higher single binding affinities.
BCR Light Chains 2 possibilities?
λ and κ
