unit 4: immune response Flashcards
what is the immune response
protection against infection by recognition of SPECIFIC antigens and responding to them
what are PAMPs and DAMPs
PAMPs: pathogen-associated molecular patterns
- molecules associated with various pathogens, recognized by the innate immune system
DAMPs: damage-associated molecular patterns
- molecules associated with cellular damage or stress, act as signals to alert the immune system for repair
the role of skin and mucosal membranes in innate immunity
- physical barriers of foreign agents
- skin is slightly acidic to prevent the growth of some organisms
- mucus acts as a protective coating
- cilia help move foreign particles out of respiratory tract by “sweeping”
non-specific phagocytosis in innate immunity
- first line of defence after epithelial barriers (skin)
- lacks specificity and memory
- neutrophils and macrophages are phagocytes in innate immunity
- can be enhanced by opsonization
what characterizes the adaptive immune response
- specificity
- memory
- amplification
what are antigens
molecules that evoke and antibody response when introduced to a host
what are immunogens
molecules which elect an immune response
- larger, usually polysaccharides
what are haptens
smaller antigenic molecules, complex with larger carrier molecules
what happens when components of the body become antigenic
may be recognized as foreign, such as what happens in cancer
- helpful do the body can remove them
- binding of hapten allows this to happen
what is self tolerance
the lack of response to our own antigens
- clonal deletion suggests during embryonic development those lymphocytes which potentially react against self are deleted
what are lymphocytes
B cells and T cells - KEY PLAYERS in the immune response
- they proliferate when an antigen is presented to them
cell mediated immunity = function of T cells
- T cells transform into effector T cells which destroy antigen-bearing cells
- helper and “suppressor” T cells enhance and suppress the immune response
humoral immunity = function of B cells
- transformation of B cells into plasma cells (antibody-producing cells)
what are the 4 cells of the immune response
lymphocytes, natural killer cells, antigen present cells, dendritic cells
what are the 2 types of lymphocytes
T cells and B cells
the T denotes “thymus dependent”
the B denotes “bursa equivalent” (bone marrow)
- thymus and bone marrow are sites of priming
overview of B cells
- have cell surface antibody-receptor complex
- when Ab/Ag interaction happens B cells proliferate = clonal expansion
- clonal expansion produces plasma cells and memory cells
B cells: plasma cells
- make antibodies specific to the antigent
- off center nucleus and abundant basophilic cytoplasm
- differentiate into 5 classes of immunoglobins: IgG, IgM, IgA, IgE, IgD
B cells: memory cells
- presist for long periods of time
- react to the antigen rapidly
- responsible for “memory” of immunity
Overview of T cells
- have T cell receptor complexes on the surface
- TCR only recognizes antigens presented on another cell
- naive T cells are activated and begin to proliferate
- end result of activation depends on T cell activated
T cells: CD4+T cells - helper T cells
- usually have more of these
- secrete cytokines which influence most of the other cells in the immune system
- these cytokines cause activation of macrophages, inflammation and proliferation
- further divided into TH1 and TH2 cells
T cells: TH1 helper T cells
- activated by release of IFN-gamma which activates macrophages and B cells
- B cells then secrete antibodies to mediate phagocytosis and activate complement
T cells: TH2 helper T cells
- activated by IL-4 which stimulates B cells to differentiate into IgE secreting plasma cells
- IL-5 and IL-3 are also released which activates mast cells and eosinophils
- produces a type 1 hypersensitivity reaction
T cells: CD8+T cells - cytotoxic T cells
- directly kill virus infected cells and/or tumour cells
- lesser role in secretion of cytokines
what are the roles of activated T cells
- cell mediated immunity: kill any cell who’s surface antigen they recognize
- “Helper” roles: cytokines they produce are “mediators” that influence functions of macrophages and lymphocytes
- delay hypersensitivity
what are natural killer cells
- an innate type of lymphocyte
- nonspecific
3 main features of NK cells
- Non-specific cytotoxic activity: directly kill cells without prior sensation by releasing cytotoxic granules which contain enzymes to induce apoptosis
- immunoregulation: interact with other immune cells by releasing cytokines to influence their function
- lack of antigen specific receptors: rely on a balance of activating and inhibitory signals from cells - lack of inhibitory signals = abnormal cell = NK cell activated
what are antigen presenting cells
- include macrophages, interdigiting dendritic cells and follicular dendritic cells
- APCs ingest the antigen and present its fragments on its surface with MHC complex
- leads to T cell activation and lymphokine release
what are dendritic cells
- cell in the immune response
- follicular dendritic cells are responsible for antigen presentation and initiate the adaptive immune response
- interdigitating dendritic cells produce cytokines which care important for the innate immune response
what are antibodies
- molecules secreted from plasma cells after B cell differentiationto combat antigens
- comprise of a family of serum proteins called immunoglobins
structure of antibodies
- have a heavy and light chain
- body is constant in all Ig classes
- variable part = antigen-binding site (tip)
- constant region has receptors for complement
how are antibodies produced around and after birth
- new borns rely on passively acquired antibodies from their mother (mostly IgG)
- IgG crosses the placenta in utero
- at 3-4 months immunoglobins are at their lowest as maternally derived antibodies decrease (passive immunity = temporary)
what is colostrum
thick, yellow milky fluid secreted by the mammary gland
- has lots of immunoglobins which the gut of the neonate can absorb to acquire
how do antigens react with antibodies
- once antigens enter the body the non-specific inflammatory response tries to stop the antigen
- some antigens are carried through lymphatic flow which exposes them to macrophages and lymphocytes
- phagocytosis happens and the antigen is presented on macrophages to T and B cells
- T cells are activated and B cells become plasma cells to secrete antibodies
- end result = antibody enters the blood and binds antigen
why might your lymph node under your jaw become enlarged in the case of a sore throat?
- there is a response to an antigen stimulus
- T and B cells are arranged into follicles, when enlarged are characteristic of a reactive node
what does reactive (or hyperplastic) mean
responding to an antigen stimulus
what are the effects of antigen-antibody interactions
- agglutination
- opsonization
- compliment fixation
antigen-antibody interactions: agglutination
- formation of large clumps of Ag and Ab
- 2 binding sites on antibodies cross-links a number of antibodies to antigens (makes phagocytosis easier)
- if the antigen is a toxin, agglutination may neutralize the toxin
antigen-antibody interactions: opsonization
- coating of the antigen with antibody
- allows increased phagocytosis by leukocytes with the Ab receptor
-known as immune phagocytosis
antigen-antibody interactions: complement fixation
- a system of 9 proteins (C1-C9) form the MAC complex which punches holes in cell membranes
- ## a cell with Ab/Ag complex initiates the complement cascade, results in cell lysis
when would agglutination or opsonization occur rather than complement fixation
when antigen is cellular (e.g. bacteria) = agglutination and opsonization, cause inactivation of the antigen or its lysis
when antigen is macromolecular = complement activation, phagocytosis by scavenger cells
what is the primary immune response
- occurs after the first exposure of an antigen
- “Lag” period between when antigen enters the body and antibody appears in the serum
- in this lag period, B cells undergo clonal expansion so plasma cells can secrete Ab
In the primary immune response, what is the order that antibodies are made in
first = IgM
second = IgG
later = all others
what is the secondary immune response
- following second exposure to the same antigen there is an accelerated response
- No lag period, specific Ab production occurs rapidly due to memory: anamnestic response
- IgG is the main antibody secreted here
what is passive immunity
transfer of pre-formed antibody from one person to another
what is a disadvantage of passive immunity
only temporary - Ab will be metabolized and removed, no memory
3 examples of passive immunity
- Transplacental immunity: natural acquisition of Ab (IgG) across the placenta
- Colostral immunity: natural acquisition of Ab through milk in first few hours of life
- Therapeutic immunity: medical administration of Ab against an agent, toxin or byproduct - examples include snake antivenins and tetanus antitoxin
what is active immunity
development of antibodies in response to an antigen
- occurs naturally with infection
what is vaccination
- altered form of the organism (e.g. inactive form) is used to induce a response
- Reacts with the same lymphocytes that would respond to the pathogenic form if it were the “primary exposure”
- When real exposure occurs there is a rapid increase in specific antibody level
why are vaccinations given to babies in a series after birth
- the ability to mount an active immune response is slowly developing in babies
- Vaccinate early enough to be protective without being too early
- if passively acquired maternal antibody levels have not declined, they block the vaccine - no immune response induced
what is serology
study of antigen-antibody reactions in the lab
what is the purpose of serological tests
- look for antibodies in the patients serum, level present measured by its titer
- titer indicates the dilution of reactivity between Ab/Ag
- Higher Ab in serum = greater dilution of that serum = high titer
what does the presence of serum antibodies indicate in a serological test
ONLY indicates previous exposure organism, not necessarily active disease
what is a hypersensitivity reaction
normal protective immune responses “gone wrong”
- may be inadequately controlled, inappropriately targeted or directed at harmless antibodies
- leads to tissue damage and disordered function
what are the 4 types of hypersensitivity reactions
- Type I: immediate hypersensitivity
- Type II: Antibody mediated hypersensitivity
- Type III: Immune-complex mediated hypersensitivity
- Type IV: Cell mediated hypersensitivity
types of localized type I hypersensitivity reactions
Hay fever: reaction site is mucosal membranes of nasal sinuses (lead to sneezing)
Skin allergies (urticara, hives)
Allergic gastroenteritis
Asthma
what defines Immediate (type I) hypersensitivity
- often referred to as anaphylactic
- Infiltration of eosinophils in the affected tissue - these cells release mediators responsible for the tissue injury
- can be localized or systemic
Systemic type I hypersensitivity reactions
- more serious than localized
- includes anaphylaxis: exposure to a small dose of antigen leads to a body-wide response
- e.g. allergy to peanuts
types of mediators in Type I hypersensitivity
- primary performed vasoactive mediators
- secondary generated lipid mediators
- cytokine synthesis mediators
type I hypersensitivity: primary performed vasoactive mediators
- released from mast cell granules, responsible for type I hypersensitivity
- Most important = HISTAMINE - increases vascular permeability, vasodilation, bronchoconstriction and increased mucus secretion
type I hypersensitivity: secondary generated lipid mediators
- activated by phospholipase A - produces arachidonic acid and its metabolites from mast cell membrane phospholipids
- also leads to platelet-activating factor production
- causes same effects as primary mediators, except vasodilation
type I hypersensitivity: cytokine synthesis mediators
- secreted cytokines (TNF) and chemokines released from mast cells recruit and activate other inflammatory cells - amplify response
- results in release of additional mediators, local tissue damage
what defines antibody mediated (type II) hypersensitivity
- antibody is directed against specific antigens on cell surfaces
- when the Ab/Ag complexes cell injury can occur
- Results from one of three different antibody dependent mechanisms… 1) Opsonization & Phagocytosis, 2) inflammation, 3) Antibody mediated Cellular Dysfunction
examples of type II hypersensitivity diseases
myasthenia graves: antibodies are formed to acetylcholine receptors
graves disease: hyperthyroidism caused by antibodies binding to the TSH receptor has a stimulating effect on the release of thyroid hormone
what is immune Hydros Fetalis
- produced by Rh incompatibility
- Complement is activated and fixation of the C56789 complex destroys cells the body needs
- RBCs or platelets are destroyed because the antigen was attached to its surface
what defines immune-complex mediated (type III) hypersensitivity
- an antigen elicits the formation of a specific antibody, interaction between the antibody and antigen result in intravascular immune complexes
- Immune complexes are deposited in the walls of small vessels and lead to complement activation, acute inflammation and tissue injury
- End result = fibrinoid necrosis of small vessels
Type III hypersensitivity: Local Immune complex diseases
e.g. the arthus reaction
- tissue necrosis occurs at site of antigen entry
- repeated exposure to antigen = high levels of antibody in serum
- Ab/Ag complexes are formed and deposit locally in small blood vessels
- leads to acute vasculitis and local tissue necrosis
Type III hypersensitivity: systemic Immune complex diseases
- prototype = serum sickness
- results from exposure to large dose of antigen - when more Ag is present than Ab immune complexes are formed of a critical size
- deposit in walls of vessels and activate complement, leading to necrosis
what is central in pathogenesis of tissue injury
complement activation by Ab/Ag
what characterizes cell mediated (type IV) hypersensitivity
- mediated by SENSITIZED T cells which are either cytotoxic or helpers
2 mechanisms - CD4+ TH1 helper T cells or CD8+ cytotoxic T cells
Type IV hypersensitivity: helper T cell mechanism
- CD4+ TH1 cells respond to tissue antigens by secreting cytokines that stimulate inflammation and activate phagocytosis
- CD4+ TH17 cells recruit neutrophils
Type IV hypersensitivity: cytotoxic T cells mechanism
CD8+ cytotoxic T cells directly kill tissue cells expressing intracellular antigens (APC)
type IV hypersensitivity diagnostically: tuberculin test
Tuberculin: inactivated antigen that causes tuberculosis
- delayed reaction occurs to provide evidence of previous exposure
- Direct T cell mediated cytotoxicity is the cause of necrosis in cancer cells and other foreign cells
what is an allograft
graft of tissue between 2 individuals of the same species, but different genotype
what are histocompatibility molecules
- have role in the induction and regulation of normal immune function
- histocompatibility determines if a transplant will be successful
- molecules bind to peptide fragments of a foreign protein for presentation to antigen-specific T-cells
- reactivity to transplanted cells can be directed against cell surface antigens
what are histocompatibility agents
HLA antigens on surfaces of nucleated cells
- coded for by MHC
what do major histocompatibility complexes encode for
Class I MHC molecules: found in all tissues (e.g. HLA)
Class II MHC molecules: more restricted tissue distribution, expressed on APCs and B cells
T cell mediated organ transplant rejection (type IV hypersensitivity)
- type IV hypersensitivity reactions can lead to classic acute rejection of an organ transplant
- Recognition of organ as foreign triggers an immune response that damages the organ
Antibody mediated rejection of
- anti-HLA antibodies are developed along with T cell mediated rejection
- Targets vascular endothelium, platelet aggregation and coagulation - leads to ischemia
what is an autoimmune disease
immune-mediated response is directed against “self” (failure of self-tolerance)
theory for how autoimmune diseases can arise
- clonal deletion phase in embryonic development being faulty
- Individual born with clones of lymphocytes can react against normal tissue
- failure of self tolerance can also develop if individuals have lymphocytes with receptors for self-antigens which fail to be suppressed by T suppressor cells
what is anergy
inactivation of lymphocytes induced by exposure to antigens under certain conditions
- genetic and gender factors have role in predisposition to the development of AI diseases
primary immunodeficiency disease
- affects specific humoral or cellular immunity, or nonspecific innate host mechanisms
- rare, genetically determined
- Severe combined immunodeficiency (SCID): shows defects in humoral and cell-mediated immunity
secondary immunodeficiency disease
- can arise from malnutrition, cancers, chemotherapy, and infection
- occur more frequently
- most important = AIDS
what is AIDS
- acquired immunodeficiency syndrome
- immunosuppression which leads to opportunistic infections, cancers and neurological signs
- caused by infection with a retrovirus - HIV
how does HIV cause AIDS
- the human immunodeficiency virus transcribes its RNA into DNA and then integrates it into cellular DNA
- DNA transcription is initiated due to exposure to antigens or cytokines
- Anything that promotes T cell activation and growth will promote death of HIV infected cells (helper T cells)
structure of HIV
- outer lipid envelope of the HIV retrovirus is studded by gp120 and gp41
- Inner core protein p24 is the most readily detected viral antigen of HIV
- Antibodies used to detect it are against p24 agent
what type of immunity does AIDS primarily affect
cell-mediated immunity
what is the defining characteristic of HIV
Loss of CD4+ T cells
what are some other Cell Affected HIV infections other than AIDS: infection of monocytes and macrophages
- HIV can infect and multiply in non-dividing macrophages
- Macrophages can transport HIV to other body sites, mostly nervous system
- Dendritic cells at mucosal surfaces have important roles in viral capture and transport to lymph nodes - infect CD4+T cells
what are major sites of infection by HIV
CD4+ T cells, dendritic cells, lymph nodes and macrophages
course of HIV infection
- early acute phase: culminates in virus specific immune response, detection of virus-specific antibodies
- middle chronic phase: HIV test is positive but few signs of disease, viral replication continues in lymphoid tissue
- Final “crisis” phase: disease progresses to a severe opportunistic infection and very low CD4+ cell count, death results around 2 years after
