class notes 11 - flashcards

Flashcards based on lecture notes covering T cell receptors, hypersensitivity reactions, autoimmunity, immunodeficiencies, and amyloidosis.

What percentage of circulating lymphocytes is made up of T cells?

60-70%

What are the two main types of TCRs found on T cells?

α/β TCR and γ/δ TCR

Which subset of T cells with γ/δ TCR moves to epithelial surfaces?

5%

What molecular complex is the TCR non-covalently bound to?

CD3 molecular complex

What are the two distinct subsets of T cells that co-express either CD4 or CD8 molecules?

CD4+ T cells and CD8+ T cells

Which MHC class do CD4+ T cells interact with?

MHC-II

What is the function of TH1 cells?

Promote a CMI response by secreting IL-2 & IFN-γ

What is the function of TH2 cells?

Promote a humoral response by secreting IL-4 & IL-5

Name two additional subsets of CD4 T cells.

Regulatory T cells (Treg) and pro-inflammatory TH17 cells

Which MHC class do CD8+ T cells interact with?

MHC-I

What type of cells are CD8+ T cells?

Cytotoxic Lymphocytes (CTLs)

What other molecule do CD4+ and CD8+ T cells express?

CD28

Can T cells react with soluble antigens?

No, they only recognize processed, membrane-bound antigens.

What is the first signal required for T cell activation?

TCR engages MHC-bound antigen

What happens if the first signal for T cell activation is lacking?

No immune recognition

What is the second signal required for T cell activation?

CD28 molecules interact with B7 co-stimulatory molecules on APCs

What happens if the second signal for T cell activation is lacking?

The T cell will undergo apoptosis.

What is the third signal required for T cell activation?

Cytokine signaling causes activation of T cell to create an effector response

What happens if the third signal for T cell activation is deficient?

Tolerance (i.e., anergy) is induced

Name two cytokines that induce expression of IL-2 and IL-2 receptors.

IL-12 and IL-1

What percentage of circulating lymphocytes is made up of B cells?

10%

What variable molecule is expressed on the surface of B cells?

IgM

What is the antigen-binding component of the B cell receptor complex?

IgM

Name three types of non-variable surface molecules expressed by B cells.

Fc receptors, Complement Receptor 2 (CD21), and CD40

What is the function of CD40 on B cells?

Interacts with CD40 ligand on activated TH cells to induce maturation of B cells to Ab-secreting plasma cells

How can B cells be stimulated to secrete antibodies?

TH dependent or TH independent processes

What happens in TH dependent stimulation of B cells?

IgM bound antigen is internalized, processed, and presented with MHC II to TH cells, leading to plasmablast, plasma cell, and memory B cell formation.

What happens in TH independent stimulation of B cells?

Antigen binding of IgM induces plasmablast formation and may progress to plasma cell formation.

What percentage of circulating lymphocytes is made up of NK cells?

10-15%

What surface markers are found on NK cells?

CD16 and CD56

What type of receptor is CD16 and what is its function in NK cells?

Fc receptor for IgG necessary for Antibody Dependent Cell-Mediated Cytotoxicity (ADCC)

What do NK cells recognize on target cells?

MHC-I

What does MHC stand for?

Major Histocompatibility Complex

Which cells express MHC I?

All nucleated cells

Which cells express MHC II antigens?

Antigen Presenting Cells (APCs)

What contributes to the variation in susceptibility or resistance to pathogens between individuals?

Differences in the ability of particular MHC alleles to effectively present antigens

What are TLRs?

Toll-like Receptors; conserved receptors important for innate immune responses.

What are PAMPs?

Pathogen Associated Molecular Patterns that trigger innate defense molecules

Name three examples of PAMPs.

LPS, CpG, double-stranded RNA

What is the ultimate result of TLR activation?

Transcription of Nuclear Factor-kappa B (NF-κB)

What is required for all hypersensitivity reactions?

Prior sensitization of the individual, from past exposure to the offending antigen

What is the sequence of events in Type I hypersensitivity reactions?

Allergen presentation -> TH2 cells -> IL-4 -> IgE -> IgE binds mast cells -> re-exposure -> degranulation and synthesis of mediators

What is anaphylaxis?

Severe type I hypersensitivity reactions with systemic involvement, including laryngeal oedema, bronchospasm, and systemic hypotension

What is the shock organ in dogs during anaphylaxis?

The liver

What is atopy?

Type I hypersensitivity causing pruritic dermatitis, especially in dogs

What is allergic rhinitis?

Type I hypersensitivity reaction also know as hayfever

What is asthma?

Type I hypersensitivity reaction targets airways and respiratory mucosa

What is heaves in horses?

Allergic bronchitis with bronchial constriction (asthma-like condition)

What type of hypersensitivity is flea allergic dermatitis?

Type I

Which antibodies are involved in Type II hypersensitivity?

IgG or IgM

What are the three outcomes for Type II hypersensitivity?

Cell lysis, ADCC, or opsonization followed by phagocytosis

What is neonatal isoerythrolysis in horses?

Erythrolysis caused by maternal IgG against erythrocyte antigens of the foal

What is pemphigus vulgaris?

Type II hypersensitivity resulting from Ab against epithelial desmosomes

What is myasthenia gravis?

Type II hypersensitivity caused by Ab disruption of cell function; Ab against acetylcholine receptors interferes with neural stimulation of the motor end plate, causing weakness

What is involved in Type III hypersensitivity?

Formation of insoluble antigen-antibody immune complexes

What is an Arthus reaction?

Local necrosis from type III vasculitis, usually in the skin

What is purpura haemorrhagica?

Type III hypersensitivity that may occur in horses after Strangles

What is serum sickness?

Type III hypersensitivity that may occur if a patient receives multiple treatments with antiserum

What is the hallmark Type IV hypersensitivity?

Dense infiltrates of sensitized T- cells

What is the tuberculin reaction?

Example of Type IV, swelling at the site tuberculin injection

What causes recurrent bouts of inflammation in Equine Recurrent Uveitis?

Autoimmunity to self antigen

What is granulomatous inflammatory lesion?

Essentially a type IV hypersensitivity reaction

What immune reaction is likely involved in organ transplant rejection?

Type IV hypersensitivity

What is a direct pathway?

MHC-II cells (i.e. Antigen Presenting Cells) of the donor present allogeneic MHC antigens to T cells of the recipient

What occurs in Graft vs Host Disease?

The grafted lymphocytes recognise the recipient's MHC as foreign

What are proposed mechanisms for the development of autoimmunity?

Breakdown in t-cell anergy, molecular mimicry, polyclonal lymphocyte activation, exposure of sequestered antigens, failure of suppressor T cells, or failure of apoptotic mechanisms

What is anergic for a t-cell development?

Antigen Presenting Cells may express co-stimulatory molecules or secrete TH1 stimulatory cytokines that induce anergic T-cells to proliferate

What is molecular mimicry?

An immune response against a microbe induces cross-reacting immune effectors against a self antigen

What is polyclonal lymphocyte activation?

General stimulation of multiple lines of T-cells, including anergic cells, incited by bacterial superantigens

What are examples of bacterial superantigens?

Enterotoxin A (staphylococcal food poisoning), toxic Shock Syndrome Toxin 1 (TSST-1)

What results from limited, specific autoimmunity?

Appear to be against a single self-antigen

What is systemic lupus erythematosus?

Prototpye example of a disease relating results from polycloncal assaults

How may autoimmunity diseases related to genetics in humans?

Associated with specific MHC haplotypes

Who is more susceptible to autoimmunity?

Females are predisposed to many types of autoimmune diseases compared to males

How may autoimmunity diseases related to environmental factors?

Identical twins of SLE patients have about a 1/4 chance of developing SLE themselves