Week 1: Innate Immunity Flashcards
What are major functions of innate immunity?
Complement activation, Inflammation, cell activation, priming of the adaptive immune response
What does the innate immune system recognize?
Foreign molecular structures called pathogen-associated molecular patterns (PAMPs), stress or damage indicators expressed by body cells (DAMPs), The absence of certain “self” marker molecules
What PAMPS does TLR1 recognize?
Triacyllipopeptides
What PAMPS does TLR2 recognize?
Peptidoglycans, GPI-linked proteins, lipoproteins, zymosan, phosphatidylserine
What PAMPS does TLR3 recognize?
dsRNA
What PAMPS does TLR4 recognize?
LPS, F-protein, mannans
What PAMPS does TLR5 recognize?
Flagellin
What PAMPS does TLR6 recognize?
diacyllipopolypeptides, zymosan
What PAMPS does TLR7 recognize?
ssRNA
What PAMPS does TLR8 recognize?
ssRNA
What PAMPS does TLR9 recognize?
CpG unmethylated dinucleotides, dinucleosides, HSV components, Hemozoin
What happens when a TLR recognizes a PAMP?
It triggers cell signaling leading to gene transcription events to combat the foreign material
What PAMPs do C-type lectin receptors recognize?
mannose receptor, Dectin 1, DC-SIGN
What PAMPS does scavenger receptors recognize?
SR-A, SR-B
What occurs when either a C-type lectin receptor or a scavenger receptor recognize a PAMP?
They initiate phagocytosis
What kinds of chemicals are involved when a cell phagocytizes a bactera?
Reactive oxygen/nitrogen species
What is the overall goal of the complement system?
control inflammation
What is involved in the alternative pathway of the complement system?
opsonization and facilitated uptake of coated microorganism by phagocytes
What is involved in the classical pathway of the complement system?
Opsonization, chemotaxis of phagocytes, increased blood flow, increased permeability and damage to plasma membranes on cells of invader, release of inflamm. mediator from mast cells
Is the classical pathway a part of the adaptive or innate immune system?
adaptive
Is the lectin and alternative pathways a part of the innate or adaptive immune system?
Innate
What proteins are involved in the classical pathway of complement?
C1q (cleaves and initiates downstream complement compounds) and C5b (binds to membrane and forms the membrane attack complex)
What proteins are involved in the lectin pathway?
Mannose binding protein (binds to bacterial carbohydrates and initiates downstream complement compounds), C5b (membrane attack complex)
What proteins are involved in the alternative pathway?
C3 (spontaneously cleaved by serum proteases activated by bacteria), C3b (leads to downstream activation of complement components)
T/F: antigen-antibody complexes activate the classical pathway?
True
T/F: microorganisms activate the lectin pathway
True
T/F: Microorganisms activate the alternative pathway
True
What is the function of C3a, C4a and C5a?
chemotactic factors that increase directional migration of PMNs and macrophages, activate PMNs, macrophages, mast cells and basophil degranulation, ca
In terms of potency, describe which is more powerful: C3a, C4a and C5a
C5a»_space;> C3a»_space;> C4a
What is the function of C3b and C4b?
deposited on any surface with an exposed amine or hydroxyl, acting as opsonins, cleave more C3
What prevents opsonization of host cells?
decay-accelerating factor (DAF) for C3b and C4b, protectin (CD59) and homologous restriction factor (HRF) for C5b
What is the function of C5b?
binds to microorganisms or host body cells, acts as a focal point for the deposition of the membrane attack complex
What opsonin receptors lead to phagocytosis?
Collagen-domain receptor (CD91/calreticulin), Complement receptors (CR1, CR3, CR4, CRIg, C1qRp), Ig Fc receptors (Fc(alpha)R, Fc(gamma)R)
What are the four hallmarks of inflammation?
Influx of fluid (edema), Increased temp (hyperthermia), Decreased oxygenation (local hypoxia), Influx of WBCs (extravasation)
What complement protein stimulates basophils and mast cells to degranulate?
C5a
What is the result of histamine release?
increased vascular permeability
What is the result of Prostaglandin E2 release?
vasodilation, increased vascular permeability
What is the result of Leukotriene D2 release?
neutrophil chemotaxis, increased vascular permeability
What is the result of leukotriene D4 released?
increased vascular permeability
What is released as a result of mast cell and basophil degranulation?
Histamine, prostaglandin E2, leukotriene D2, leukotriene D4
What is released from macrophages after they are activated?
TNF, IL-1, IL-8
What is the result of TNF alpha release?
fever, stimulates expression of E-selectin
What is the result of IL-1 release?
local inflammation, activates endothelium to express adhesion molecules. Induces production of chemokines to recruit leukocytes, system effects: fever, acute phase response, neutrophil production
What is the result of IL-8 release?
chemotaxis for neutrophils
What do NK cells released when activated?
IFN gamma
What is the result of IFN gamma?
activation of phagocytic cells and NK cells
What are the three principle tissue changes during acute inflammation?
increased blood supply to affected area, increase capillary permeability, increase in leukocyte migration into affected tissue
What can often occur during chronic inflammation during infection?
granuloma formation to wall off the invader
What do sites of acute inflammation have higher numbers of?
neutrophils and activated helper T cells
What do sites of chronic inflammation have higher numbers of?
macrophages, cytotoxic T cells, B cells
What cell is the first to present the antigen? What cell is the first to respond to infection?
Macrophages phagocytose the invader first, neutrophils are first to respond
Describe the response of immune system to invasion?
Macrophages phagocytose (1) neutrophils show up, (2) helper T cells, (3) cytotoxic T cells, (4) B cells
What is secreted by macrophages to recruit PMNs and CD4+ T cells
IL-8
What are the three most important cytokines for inflammation?
TNF-alpha, IL-1, IFN gamma
Describe the steps for leukocyte adhesion
- Tethering (E-selectin binds to CD15), 2. Triggering (chemokines activate a tethered cell, 3. Adhesion (activation of integrins CR3/LFA-1 from cell with ICAM-1 on epithelium)
What two responses can tissue cells do to prevent infection?
Send interferons/cytokines to signal IS, make defensins and cathelicidins for antimicrobials
What is the signaling of differentiation for Neutrophils?
(IL3 + GM-CSF) –> (IL3+GM-CSF + G-CSF)
What are the effector cells of acute inflammation or infection?
PMNs
How do PMNs kill foreign bodies?
Fc receptor bind to antibodies; antibody-dependent cellular cytotoxicity
What do granules of eosinophils contain?
Major basic protein
What is major basic protein?
potent toxin for helminth worms, induces histamine release from mast cells, activates neutrophils and platelets, can provoke bronchospasm
What complement components activate Eosinophils?
C5a and C3a
What is the signaling for differentiation of eosinophils?
(IL3 + GM-CSF) –> (IL3 + GM-CSF + IL-5)
What receptors are found of basophils?
Fc(epsilon)R1, contains IgE on its cell surface
How is histamine released from basophils?
IgE on surface is cross-linked by antigen
What complement components activate basophils?
C5a and C3a
What is the signaling for differentiation of basophils?
(IL3 + GM-CSF) –> (IL3 + GM-CSF + IL4)
What are monocytes called in peripheral tissue, liver, brain and lungs respectively?
Macrophages, Kupfer cells, Microglial cells, Bronchial alveolar macrophages
What is the signaling for differentiation of monocytes?
(IL3 + GM-CSF) –> (IL3 + GM-CSF + M-CSF)
What cytokines and lymphokines are produced by macrophages?
IFN alpha, IL-1beta, IL-6, TNF alpha, IL-8, IL-12
What is the signaling for differentiation of macrophages?
IL3 + GM-CSF –> IL3 +GM-CSF + M-CSF –> GM-CSF + M-CSF (REMOVAL OF IL3)
Describe classical dendritic cells?
process and present foreign protein antigens to T cells
Describe follicular dendritic cells
passively present foreign antigen in the form of immune complexes to B cells in lymphoid follicles
What is the difference between follicular and classical dendritic cells?
Classic: present Ag to T-cells; FDCs present to B-cells in lymphoid tissue
T/F: NK cells are not from lymphoid progenitors?
False; they are from lymphoid progenitors
What are important markers of NK cells?
CD16 and CD56
What do NK cells recognize?
damaged cells by a deficiency of MHCI antigen
What cytokines activate NK cell killing?
Interferons
What cytokines activate NK cells to secrete IFN gamma?a
IL-12, TNF-alpha
What is the signaling for differentiation of NK cells?
IL-7 –> IL-2
What are severe congenital neutropenias?
Lack of ability to produce or maintain a normal level of neutrophils; leads to frequent bacterial infections
What is chronic granulomatomas disease?
Inability to produce hydrogen peroxide and hypochlorous acid; inability to kill phagocytosed bacteria
What is Chediak-Higashi Syndrome?
Defect in gene LYST (CHS1), lysosomal trafficking gene that affects lysosomes and melanosomes; problems with pigmentation and also phagocytosis; increased susceptibility to bacterial infections
What is Luekcyte adhesion deficiency?
Lack of integrin subunit, the common beta chain, inability to recruit innate immune cells to site of inflammation; increased susceptibility to bacterial, fungal and viral infections
