unit 4: immune response Flashcards
(91 cards)
1
Q
what is the immune response
A
protection against infection by recognition of SPECIFIC antigens and responding to them
2
Q
what are PAMPs and DAMPs
A
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
3
Q
the role of skin and mucosal membranes in innate immunity
A
- 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”
4
Q
non-specific phagocytosis in innate immunity
A
- 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
5
Q
what characterizes the adaptive immune response
A
- specificity
- memory
- amplification
6
Q
what are antigens
A
molecules that evoke and antibody response when introduced to a host
7
Q
what are immunogens
A
molecules which elect an immune response
- larger, usually polysaccharides
8
Q
what are haptens
A
smaller antigenic molecules, complex with larger carrier molecules
9
Q
what happens when components of the body become antigenic
A
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
10
Q
what is self tolerance
A
the lack of response to our own antigens
- clonal deletion suggests during embryonic development those lymphocytes which potentially react against self are deleted
11
Q
what are lymphocytes
A
B cells and T cells - KEY PLAYERS in the immune response
- they proliferate when an antigen is presented to them
12
Q
cell mediated immunity = function of T cells
A
- T cells transform into effector T cells which destroy antigen-bearing cells
- helper and “suppressor” T cells enhance and suppress the immune response
13
Q
humoral immunity = function of B cells
A
- transformation of B cells into plasma cells (antibody-producing cells)
14
Q
what are the 4 cells of the immune response
A
lymphocytes, natural killer cells, antigen present cells, dendritic cells
15
Q
what are the 2 types of lymphocytes
A
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
16
Q
overview of B cells
A
- have cell surface antibody-receptor complex
- when Ab/Ag interaction happens B cells proliferate = clonal expansion
- clonal expansion produces plasma cells and memory cells
17
Q
B cells: plasma cells
A
- make antibodies specific to the antigent
- off center nucleus and abundant basophilic cytoplasm
- differentiate into 5 classes of immunoglobins: IgG, IgM, IgA, IgE, IgD
18
Q
B cells: memory cells
A
- presist for long periods of time
- react to the antigen rapidly
- responsible for “memory” of immunity
19
Q
Overview of T cells
A
- 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
20
Q
T cells: CD4+T cells - helper T cells
A
- 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
21
Q
T cells: TH1 helper T cells
A
- activated by release of IFN-gamma which activates macrophages and B cells
- B cells then secrete antibodies to mediate phagocytosis and activate complement
22
Q
T cells: TH2 helper T cells
A
- 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
23
Q
T cells: CD8+T cells - cytotoxic T cells
A
- directly kill virus infected cells and/or tumour cells
- lesser role in secretion of cytokines
24
Q
what are the roles of activated T cells
A
- 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
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what are natural killer cells
- an innate type of lymphocyte
- nonspecific
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3 main features of NK cells
1. Non-specific cytotoxic activity: directly kill cells without prior sensation by releasing cytotoxic granules which contain enzymes to induce apoptosis
2. immunoregulation: interact with other immune cells by releasing cytokines to influence their function
3. 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
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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
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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
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what are antibodies
- molecules secreted from plasma cells after B cell differentiationto combat antigens
- comprise of a family of serum proteins called immunoglobins
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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
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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)
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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
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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
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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
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what does reactive (or hyperplastic) mean
responding to an antigen stimulus
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what are the effects of antigen-antibody interactions
1. agglutination
2. opsonization
3. compliment fixation
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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
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antigen-antibody interactions: opsonization
- coating of the antigen with antibody
- allows increased phagocytosis by leukocytes with the Ab receptor
-known as immune phagocytosis
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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
-
40
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
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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
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In the primary immune response, what is the order that antibodies are made in
first = IgM
second = IgG
later = all others
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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
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what is passive immunity
transfer of pre-formed antibody from one person to another
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what is a disadvantage of passive immunity
only temporary - Ab will be metabolized and removed, no memory
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3 examples of passive immunity
1. Transplacental immunity: natural acquisition of Ab (IgG) across the placenta
2. Colostral immunity: natural acquisition of Ab through milk in first few hours of life
3. Therapeutic immunity: medical administration of Ab against an agent, toxin or byproduct - examples include snake antivenins and tetanus antitoxin
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what is active immunity
development of antibodies in response to an antigen
- occurs naturally with infection
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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
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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
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what is serology
study of antigen-antibody reactions in the lab
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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
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what does the presence of serum antibodies indicate in a serological test
ONLY indicates previous exposure organism, not necessarily active disease
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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
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what are the 4 types of hypersensitivity reactions
1. Type I: immediate hypersensitivity
2. Type II: Antibody mediated hypersensitivity
3. Type III: Immune-complex mediated hypersensitivity
4. Type IV: Cell mediated hypersensitivity
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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
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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
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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
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types of mediators in Type I hypersensitivity
1. primary performed vasoactive mediators
2. secondary generated lipid mediators
3. cytokine synthesis mediators
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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
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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
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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
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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
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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
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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
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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
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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
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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
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what is central in pathogenesis of tissue injury
complement activation by Ab/Ag
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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
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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
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Type IV hypersensitivity: cytotoxic T cells mechanism
CD8+ cytotoxic T cells directly kill tissue cells expressing intracellular antigens (APC)
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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
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what is an allograft
graft of tissue between 2 individuals of the same species, but different genotype
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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
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what are histocompatibility agents
HLA antigens on surfaces of nucleated cells
- coded for by MHC
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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
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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
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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
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what is an autoimmune disease
immune-mediated response is directed against “self” (failure of self-tolerance)
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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
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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
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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
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secondary immunodeficiency disease
- can arise from malnutrition, cancers, chemotherapy, and infection
- occur more frequently
- most important = AIDS
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what is AIDS
- acquired immunodeficiency syndrome
- immunosuppression which leads to opportunistic infections, cancers and neurological signs
- caused by infection with a retrovirus - HIV
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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)
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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
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what type of immunity does AIDS primarily affect
cell-mediated immunity
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what is the defining characteristic of HIV
Loss of CD4+ T cells
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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
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what are major sites of infection by HIV
CD4+ T cells, dendritic cells, lymph nodes and macrophages
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course of HIV infection
1. early acute phase: culminates in virus specific immune response, detection of virus-specific antibodies
2. middle chronic phase: HIV test is positive but few signs of disease, viral replication continues in lymphoid tissue
3. Final “crisis” phase: disease progresses to a severe opportunistic infection and very low CD4+ cell count, death results around 2 years after
