Lecture 17: Diseases of Immunity

what is the focus of pathology of the immune system?

diseases that are the result of inadequate or inappropriate immune responses

what are the recognition molecules in innate immunity?

PAMPS, PRRs, DAMPS

what are PAMPs?

pathogen associated molecular patterns on infectious organisms

what are PRRs?

pattern recognition receptors expressed by host cells

what are DAMPs?

danger/damage associated molecular patterns → endogenous molecules released with cell damage or inflammation

what is innate immunity?

a group of non-specific first line defense mechanisms that occur immediately or within a very short time frame following exposure to antigens

which type of immunity does not have memory?

innate

what cells have PRRs?

endothelial cells, phagocytic cells, and ILCs

what will cells do when they have PRRs?

recognize and respond to PAMPs and other cell surface molecules on microbes

what is adaptive immunity?

occurs days to weeks after exposure to microbial antigens during the innate immune response at barrier systems provided by skin or mucosae

how is the adaptive immune response different from innate?

adaptive is highly specific to antigens that induce them, and the response is remembered

adaptive immune responses must be

against molecules that are foreign to the animal and not against structural and/or functional molecules of the animal itself

what can the adaptive immune system do through the MHC system?

distinguish foreign molecules from self-molecules

the defenses and mechanisms of adaptive immunity include

• cell-mediated immunity mediated by T lymphocytes against intracellular pathogens

• humoral immunity mediated by B lymphocytes against extracellular pathogens and toxins

what are the cells of immunity?

T lymphocytes, B lymphocytes, dendritic cells, and natural killer cells

where do T lymphocytes originate and migrate to?

originate in bone marrow and migrate to thymus

when can T lymphocytes recognize antigens?

only after it has been processed into peptide fragments and associated with MHC molecules

where is the antigen associated with the MHC in most instances?

on the surface of an antigen-presenting cell, a virally infected cell, a neoplastic cell, or a cell of a foreign tissue graft

what do TH1 lymphocytes do?

synthesize and secrete IL-2 and IFN-gamma, stimulating CTL and macrophages, and induce a cell-mediated immune response

what do TH2 lymphocytes do?

synthesize and secrete IL-4, IL-5, IL-6, and IL-13 which stimulates B lymphocytes to develop into antibody-secreting plasma cells and inhibit macrophage functions, and induce an antibody response

what type of T lymphocyte responses would occur during a protozoal infection?

• TH1: elimination of organism and survival of host

• TH2: rapid proliferation of the organism and death of the host

what would happen during a TH2 response to an allergen?

elaboration of IgE through IL-4 and stimulation of eosinophils through IL-5, and the development of an allergic reaction

what is a functionally distinct subpopulation of CD4+ T lymphocytes?

regulatory T lymphocyte (Treg)

what is the function of Tregs?

suppress the response of self-reactive CD4 lymphocytes that have escaped the negative selection process in the thymus

what are the 2 phases of B lymphocyte development?

antigen-independent phase in the primary lymphoid tissues followed by an antigen-dependent phase in secondary lymphoid tissues

what is the antigen receptor of the B lymphocyte?

membrane-bound immunoglobulin

what signifies a mature B lymphocyte?

when B lymphocytes express IgM and IgD on their surface

in the antigen-dependent phase, antigen-activated mature B lymphocytes differentiate into

IgM-secreting plasma cells or switch to another antibody isotype

an evaluation of the rearranged genes of a B lymphocyte can be used to

molecularly phenotype B lymphocyte neoplasms

which lymphocytes can recognize soluble antigens?

B lymphocytes

a failure to express CD40 ligand has been associated with

an inability to isotype switch, resulting in a hyper-IgM syndrome

mononuclear phagocytic cells include

circulating monocytes and tissue-based macrophages

what is one primary function of macrophages?

phagocytosis

what are the cell types that normally express MHC class II molecules?

macrophages, dendritic cells, and B lymphocytes

what cells will only express MHC class II on activation?

macrophages

what is the most important antigen-presenting cell for initiating primary immune responses to protein antigens?

antigen-presenting dendritic cells

what cells are non-specific cytotoxic cells that are important in early responses to tumor cells and viral infections?

NK cells

how are NK cells different from cytotoxic lymphocytes?

they are not MHC restricted, are constitutively cytolytic, and do not develop memory cells

true or false: NK cells are the cytotoxic cell of innate immunity.

true

what does the MHC distinguish?

self from non-self

what requirement is the basis for MHC restriction?

that most T lymphocytes only recognize fragments of antigen when they are bound to MHC molecules

where are MHC class 1 molecules present?

on all nucleated cells

what is the major function of MHC class 1 molecules?

the presentation of peptide fragments of antigens to CTL (CD8+)

where are MHC class II molecules present?

on antigen-presenting cells (B lymphocytes, dendritic cells, and macrophages)

what is the main function of MHC class II molecules?

the induction of TH lymphocytes

what are MHC molecules important in?

regulating T lymphocyte development in the thymus in the peripheral lymphoid tissues

what does the MHC influence?

• transplant acceptance or rejection

• immune responsiveness

• the pathogenesis of many diseases

what are hypersensitivity reactions?

inappropriate or misdirected responses to a specific antigen that results in harmful reactions upon exposure of a sensitized host to that specific antigen

what do animals require for hypersensitivity reactions?

a sensitization phase

where do harmful effects of hypersensitivity reactions occur?

in the effector phase

type 1 hypersensitivities are also known as

immediate-type hypersensitivity

type 1 hypersensitivities are most often the result of what?

an IgE response directed against environmental or exogenous antigens causing the release of vasoactive mediators

type 1 hypersensitivity reactions are most commonly the result of

an IgE-mediated immune response directed against environmental and parasite antigens

what is a type 1 hypersensitivity?

an allergic reaction that occurs within minutes of exposure to an antigen to which the host has been previously sensitized

sensitization phase of of type 1 hypersensitivities

occurs during the initial exposure to an antigen when the host develops an antigen-specific IgE response

the effector phase of type 1 hypersensitivities can be

• limited to an acute inflammatory reaction, resulting from the release of mast cell mediators

• can progress to a late-phase reaction

• or a chronic reaction

where do mast cells reside?

in vascularized tissue

mast cells can be activated by

• cytokines (IL-8)

• complement products (C3a and C5a)

• drugs (nonsteroidal antiinflammatory drugs, codeine, and morphine)

• physical stimuli

non-IgE mediated activation of mast cells is referred to as

anaphylactoid reaction

IgE-mediated activation is referred to as

type 1 hypersensitivity

the immediate response of type 1 hypersensitivities is characterized by

• increased blood flow

• increased vascular permeability (edema)

• smooth muscle spasm

what is recruited to the sites of type 1 hypersensitivity reactions?

eosinophils are recruited by chemokines

what are the 3 types of responses that can result from type 1 hypersensivities?

• an acute inflammatory response

• a late-phase response

• a chronic inflammatory response

what is the genetic predisposition to develop localized type 1 hypersensitivity reactions to innocuous antigens?

atopy

what happens in atopic dermatitis?

the lesion may progress to a late-phase response or chronic inflammation characterized by more intense inflammatory infiltrates or to a type IV hypersensitivity reaction

what does anaphylaxis refer to?

an acute systemic hypersensitivity to an antigen that is mediated by IgE and involves mast cell activation resulting in a shocklike state

systemic anaphylactic reactions often correlate to what?

the primary shock organ

what is the primary target tissues of anaphylactic reactions?

blood vessels and smooth muscle

there are no pathognomonic lesions of anaphylaxis other than

in cases with upper airway edema or pulmonary hyperinflation

what is the major shock organ in dogs?

the liver

what are the most common types of antigens that can elicit a systemic anaphylactic reaction?

drugs, vaccines, venom of stinging insects, and heterologous sera

localized type 1 hypersensitivity reactions are restricted to

a specific tissue or organ

what is a cutaneous manifestation of a type 1 hypersensitivity reaction that results in inflammation of the skin?

allergic dermatitis

dietary type 1 hypersensitivity reactions in the dog and cat more commonly present as

cutaneous disease