Immunology Flashcards
What are the types of hypersensitivity and how can they be grouped?
Hyper sensitivity I, II, III, IV
Hypersensitivity I, II, III are all antibody mediated
Hypersensitivity IV is T cell mediated
Describe hypersensitivity I
IgE mediated. Occurs when person has been sensitized to the antigen due to prior exposure. Exposure to antigen -> class swithing and memory
Ex: Person who has anaphylaxis due to beesting
On first exposure, Th2 cells bind to bee sting antigen presented on Bcells and cause the B cells to class switch to producting IgE. On subsequent exposure to bee sting antigen, the Bcells release IgE which binds the antigen. Mast cells recognize IgE FC portion using FCeRI. Crossinglinking of IgE on mast cells leads to mast cells releasing mediators such as histamine, chemokines, cytokines, and arachidonic acid metabolites.
Describe hypersensitivity II
Cytotoxic + antibody mediated
Occurs via preformed IgG and IgM
IgG or IgM bind to cell surface/ extracellular matrix which leads to complement activation and antibody mediated cell mediated cytotoxicity (ADCc)
Ex: some drug allergies, goodpasture syndrome
Describe hypersensitivity III?
Takes days to manifest
Involve immune complex formation (with IgG binding the antigen) which activates complement and neutrophils (leading to inflammation)
IgG binds antigen -> immune complex form -> neutrophils recognize FC poriton of IgG -> inflammation cytokines -> widespread tissue damage
Ex: lupus erythematosus, serum sickness
Describe hypersensitivity IV?
Takes days to weeks to months to form
T cell mediated response
APC (macrophages) prime Th1 Tcells to the antigens on MHC II. ON subsequent expsorue to antigne, Th1 T cells rapidly proliferate, causing large macrophage reponse and cytokine release.
Ex: granuloma formation, PPD positive skin test due ot TB infection, Graft versus host disease
Describe the TNF gamma, IL 12 cycle
Macrophages (APC) ingest antigen and release IL-12. IL-12 promotes Th1 T cell activation. Th1 T cell release INF gamma which activates more macrophages. Macrophages release more IL 12 etc. etc.
What do M cells do in the GI tract?
M cells are responsible for sampling antigens in the GI tract and transporting them to GALT (to activate B cell response)
Pathway: M cells sample antigens in gut -> transport them to Peyer’s patches/GALT -> Dendritic cells and B cells recongnize these antigens -> B cells present antigen to T cells activated by dendritic cells -> B cells activated by Th2 cells via CD40L/CD40 + IL 4 class switching to IgA -> B cells release IgA which is transporte to GI tract
What does CTLA 4 do?
CTLA 4 is released by T regulatory cells and binds to B7, thus blocking the co-stimulatory signal (B7 + CD28). This blocks the activation of T cells, leading to T cell cycle arrest.
How can antibodies be used in tumor therapy?
Antibodies can be given which specifically bind to tumor associated antigens (TAA), thus leading to ADCC (antibody dependent cytotoxicity). One example of this is with B cell lymphoma. Antibodies can be given which are specific for CD20 expressed on B cells. When the antibodies bind, it will promote cytotoxicity.
Antibodies can also be given to prevent inhibition of T cells by cancer cells. Some tumor cells upregulate expression of CTLA 4 or PD1 which lead to T cell suppression. Thus, treatment using anti-CTLA4 or anti-PD1 antibodies can upregulate T cell activation -> leading to tumor supression.
Describe the complement cascade. What are the three pathways?
Complement proteins are plasma proteins that augment the immune inflammatory response
There are three known pathways of activation:
1) Classical Pathway -> IgG/IgM binds to antigen on surface of bacteria -> antibody exposes complement binding site -> complement cascade activates via C1 protein
2) Alternative pathway: Complement cascade activates by just the antigen alone -> factor B and D function to active complement cascade
3) Lechtin pathway: Lectin -> serum protein -> mannose on surface of bacteria -> activates complement cascade
What are the functions of each complement protein?
C1 -> activates c3 convertase
C3 -> cleaved into C3A and C3B
C3A -> activates mast cells
C3B -> helps to cleave C5 into C5A and C5B. Also functions to opsonoize pathogens
C5A -> activates mast cells and neutrophils
C5B -> combines with C6,7,8,9 -> creates MAC (membrane attack complex)
C1 esterase inhibitor -> inhibits formation of c3
Decay accelerating factor (CD55) -> inhibits formation c3
What do defensins do?
Defensins are proteins part of the innate immune system that create pores in the bacetrial plasma membrane
What are PAMPS? TLRs, mannose receptors, NOD receptors, and RIG-1 helicase?
Cells of innate immunity express pattern-recognition receptors that recognize molecular patterns not present on eukaryotic cells (pathogen-associated molecular patterns – PAMPs).
TLRs are found on macrophages, dendritic cells, and mast cells that recognize these PAMPs. Ex: TLR4 recognizes LPS on gram negative bacteria.
Mannose receptor -> regoznies mannose as part of the polysaccharaide capsule
NOD receptors -> help recognize peptidoglycan inside the cell
RIG helicase -> helps recognize viral nucleic acids inside the cell.
What is the role of CD14
CD 14 is expressed on macrophages and monocytes and acts as a coreceptor for TLR4 recognition of LPS on gram negative bacteria.
What is the significance of DiGeorge Syndrome w.r.t. immune system?
Developmental defect in the 3rd and 4th pharyngeal pouches resulting in impaired formation of the thymus, parathyroid glands and the heart
Affected patients have a spectrum of T cell deficiency from mild or moderate in partial DiGeorge syndrome to severe T cell deficiency in complete DiGeorge syndrome, which is a condition similar to SCID.
What happens if there is CD40L deficiency?
Hyper IgM syndrome since B cells are not told to class switch
B cell activation and immunoglobulin isotype switching and affinity maturation requires interaction of CD40 ligand, which is expressed on activated CD4 T cells and CD40, which is present on B cells, monocytes and other antigen presenting cells
What is selective IgA deficiency?
Low levels of IgA
Selective IgA deficiency is the most common PID; however, most patients are asymptomatic but a small number may manifest recurrent sinopulmonary infections, autoimmunity and allergy.
What happens if there is a defect in RAG1, RAG2, and Artemis?
Defect in RAG1, RAG2, and Artemis -> low Bcells and Tcells (SCID)
What is NADPH oxidase deficiency called?
CGD (chronic granulomatous disease)
Neutrophils unable to kill bacteria due to low levels of hydroge peroxide production
What is X-linked agammaglobulinemia?
Lack of Bruton’s tyrosine kinase
Immature B cells can’t mature -> low IgG, IgM, IgA, IgE, IgD
What is Job’s Syndrome?
Hyper IgE syndrome
Mutation in STAT3 = Defect in maturation of Th17 T cells
No Th17 - > low neutrophil activation
What bacterial infection is associated with complement deficiency?
Neisseria Meningitidis
What is the role of TLR4?
TLR4 binds to CD14+LPS
Allows innate immune cells to react in the prescence of bacteria -> release IL-1 and cause fever
“In the blood, LPS binds to a plasma protein (LPS-binding protein; LBP) and this complex interacts with CD14 receptors on monocytes and macrophages. The LBP-CD14 complex activates a membrane protein called Toll-like receptor-4 (TLR-4), resulting in the production of cytokines. These are primarily the proinflammatory cytokines IL-1 and TNF, which act synergistically to induce fever, alter endothelial cells leading to increased adherence of leukocytes to endothelial surfaces, stimulate the production of leukotrienes and prostaglandins and produce a secondary wave of cytokine production with concomitant effects on a number of physiologic targets resulting in the septic shock syndrome. “
