Immunology: Chapter 11 Flashcards

Question

TH1

Answer 1

Produce: IFN-gamma | Inhibits TH2 differentiation

Answer 2

Produce: IL-10 Suppresses: IL-12 and TH1 differentiation

Answer 3

Activated by: gycolipid antigens presented on CD1 proteins (MHC-like molecules) When activated, produce very large amounts of IL-4 and IFN-gamma Polarize a CD4 T cell response to the TH2 variety IL-4 is dominant

Answer 4

Not normally present in lymph nodes, are recruited there under conditions of infection Activated --> produce abundant IFN-gamma, but little IL-4 Polarize a CD4 T cell response to TH1 variety

Answer 5

Once response is established, it is hard to shift to the other response Differentiation is irreversible and can not be changed once it has occurred In many infections, there is a mixed TH1 and TH2 response

Answer 6

Protozoan parasite Leishmania C57BL/6: produce TH1 Activate macrophage to kill parasite BALB/c: produce TH2 Macrophages are NOT activated and there is sensitivity to the disease Injection of anti-IL4 antibody, within the 1st few weeks of infection, induces BALB/c to make TH1, preferentially (survival)

Answer 7

Cytokine therapy 2 types: Dominated by TH1 response: IL-2 and IFN-gamma stimulated; benign Tuberculoid Leprosy Make TC1 --> activates macrophages to get rid of leprosy bacilli Dominated by TH2 response: provides useless antibodies against an intracellular pathogen; can be fatal Lepromatus Leprosy Make TC2 cells, which suppress TH1

Answer 8

Low density (and/or interacts weakly): TH2 High density: (and/or interacts strongly): TH1 Ex: allergy requires production of IgE, which requires high levels of IL-4, but doesn't occur in the presence of IFN-gamma Antigens that DO elicit IgE-mediated allergy Delivered in minute does TH2 cells --> IL-4, NO IFN-gamma Allergens do NOT elicit response ** Innate immune response biases CD4 differentiation to TH1 cells Allergens are delivered in minute doses across thin mucosa Sensitization: agents that normally induce TH1 reposes, can induce TH2 responses instead

Answer 9

ALL effector cytotoxic CD8 T cells must leave lymph node & travel to sites of infection to destroy infected cells Effector helper CD4 TH1 cells leave lymph node to activate macrophages at site of infection Effector T cells are rapidly recruited (initially only a few will be antigen specific) At peak of adaptive response, most effector T cells will be antigen-specific Activated T cells have an inherent ability to enter all tissues in very small #'s

Answer 10

Recruit more effector T cells Recruit monocytes and polymorphonuclear leukocytes Change the shape of the endothelial cells Increased blood flow Increased vascular permeability Increased emigration of leukocytes, fluid, and protein into a site of infection

Answer 11

``` Rapidly lost Eter afferent lymph and return to bloodstream Most are memory or effector Protect host from re-infection OR, die by apoptosis ```

Answer 12

Macrophages sit in tissues | Memory and effector T cells MIGRATE through tissues

Answer 13

Differentiation triggered by IFN-gamma | Requires continuous stimulation by IL-12

Answer 14

Differentiation triggered by TGF-B and IL-6 | Requires continuous stimulation by IL-23

Answer 15

Heterodimers 1 peptide is the same for both sytokines Other is unique for either IL-12 or IL-23 Receptors are heterodimers 1 receptor chain is the same for both receptors Other is unique for either IL-2 or IL-23

Answer 16

CD8 T cells making antigen-specific contact with antigen-presenting cells is helped by CD4 T cell on the SAME antigen-presenting cell Signals include: Greater synthesis of B7 co-stimulatory molecules (bind to CD28 and CD8) Activating cytokines released by CD4 T cell that bind to receptors on CD8 T cell **Help from CD4 T cells is generally required when the pathogen does not induce much in the way of an inflammatory response

Answer 17

Significant inflammatory response Ample production of B7 and CD40 co-stimulatory molecules on antigen presenting cells Pathogens: lysteria monocytogenes (food poisoning) and Berkholderia pseudomallei They carry ligands for TLRs that cause ample activation of antigen-presenting cells

Answer 18

CD8 response that does NOT require CD4 T-cell help Dendritic cells have been strongly activated; secrete cytokines: IL-12 IL-18 Causes naive antigen-nonspecific CD8 T cells to secrete large amounts of IFN-gamma CD8 T cells help contain the infection, even though they do not recognize pathogen antigens NK cells can also be induced to secrete IFN-gamma under the same conditions IFN-gamma is secreted in the 1st few hours and is essential for survival

Answer 19

Naive B cells enter follicle Encounter antigen Migrate to boundary of B and T cell zones Meet recently activated B cells After 5 days, frimary foci of proliferating B cells appears in the T-cell areas Antibodies secreted by B cells differentiating early in response provide early protection Trap antigen in the form of antigen-antibody complexes on the surface of local follicular dendritic cells

Answer 20

Two populations of proliferating antibodies

Answer 21

B cells activated in primary foci migrate to adjacent follicles or to local extra follicular sites of proliferation Grow exponentially for 2-3 days and divide 6-7 times Progeny at end of cycle are antibody-producing plasma cells W/o somatic hypermutation

Answer 22

Migrate to primary follicles to form germinal centers that undergo isotype switching and affinity maturation before becoming: Memory cells, or Leaving the germinal center --> long-lived antibody-producing cells Leave germinal centers as plasmablasts Originating in follicles of Peyer's patches Lymph to blood and enter lamina propria of gut and other endothelial surfaces Originating in peripheral lymph node or spleenic folicles Migrate to bone marrow Produced in mucosal tissues, stay in mucosal tissue Source of antibody that can last in the blood for years Small numbers of B cells continue to proliferate in the follicles for months and replenish plasma cells in bone marrow

Answer 23

Viral infections: cytotoxic CD8 T cells or antibody responses (clear viruses from body or prevent virus from taking hold) Pathogens that from intracellularly: (Rickettsia; typhus) cytotoxic CD8 T cell response Pathogens that grown in macrophage vesicles: CD4 TH1 response Extracellullar bacteria: (Staph or Strept) IgM and IgG antibodies opsonize the bacteria and make them sensitive to phagocytosis

Answer 24

Causes hemorrhagic fever One of the most lethal viruses known Some people become infected but remain asymptomatic Strong IgG response early in infection is essential to survival Response clears virus from the bloodstream and allows time for the activation of CD8 T cells People died when antibody response did not occur

Answer 25

Goal of vaccine development Consists of: Immune reactants (antibody or effector T cells) In initial infection, or By vaccination Long-lived immunological memory Mild or inappropriate exaction upon reinfection years later **Most established vaccines against acute childhood viral infections work by inducing protective antibodies that prevent establishment of disease

Answer 26

Requires preexisting antibody Polio virus rapidly infects motor neurons and destroys them unless they are neutralized Specific IgA on epithelial surfaces can neutralize the virus before it enters the body

Answer 27

``` Persist for the life of the host Ex: Herpes zoster Causes chickenpox on primary infection Lies latent in the body for years Can be reactivated by stress to cause shingles ```

Answer 28

Most effector cells are no longer useful--> removed Most die by apoptosis and are rapidly cleared by macrophages Some effector cells are retained Provide raw material for memory T-cell and B-cell responses

Answer 29

Long-lived after inception or vaccination Specialized memory cells that persist for years in the absence of antigen Ex: natural infections People on remote islands suffer epidemics from measles Virus disappears for years Re-introduction: people born before original epidemic do not get the disease, and people born after, do. Ex: vaccines Smallpox eradicated Before, children were routinely vaccinated against it People retain strong vaccine-specific CD4 and CD8 T cell responses as long as 75 years after immunization Titers of antivirus antibody do not show measurable decline

Answer 30

Doesn't depend on repeated exposure to antigen Small % is dividing at any time, most are in resting state T-cell memory cells reach a maximum after ~5 days Memory B cells require somatic hypermutation and achieve a maximum in ~1 month Precursors to memory cells appear much earlier

Answer 31

``` Produce high affinity, isotype-switched (IgA, IgG, or IgE) antibodies b/c that are products of somatic hypermutation Produce higher levels of MHC class II molecules Activated by much lower doses of antigen than are required by naive B cells ```

Answer 32

Leads to increasing affinity of antibody due to somatic hypermutation and selection of antigen in germinal centers Naive B cell can NOT compete with a memory B cell in a germinal center b/c memory B cell has a higher affinity for antigen

Answer 33

Pre-existing antibodies will recognize infectious particles If titer of preexisting molecules is high enough, ALL infectious particles will be neutralized and NO secondary infection will occur If not all infectious particles are cleared, secondary immune response is activated Memory B cells have higher likelihood of eliciting a response

Answer 34

Memory B cells circulate between the blood and lymph nodes Just as do naive B cells Memory T cells circulate throughout the tissues and drain into the lymphatic system, then to the blood and back to tissues

Answer 35

Increases in frequency compared to naive T cells After immunization, number of T cells are present at levels of ~100-1000 fold higher than the initial frequency of antigen-specific naïve T cells Persist throughout life. Express high levels of Bcl-2, which promotes survival. Naïve T cells express moderate levels, and effector T cells express little Bcl-2. Cells that are destined to become memory T cells express IL-7 receptor (IL-7R) early on. This isn't expressed by naïve, or most effector T cells. T cells are programmed early on to become either effector or memory T cells Are more like effector T cells than naïve T cells in their profile of cell-surface molecules

Answer 36

Have same general characteristic as CD8 memory cells | Upon reactivation, become either TH2 (secrete IL-4 and IL-5) or TH1 cells (secrete IFN-gamma and TNF-beta)

Answer 37

Memory T cells divide more frequently than naive T cells Survival of naive T cells and memory CD8 T cells requires stimulation by cytokines IL-7 and IL-15 Both express IL-7R-alpha Interaction with self-peptide:self-MHC complexes is required for survival of naive T cells Not required for survival of memory T cells

Answer 38

Effector and Central memory T cells

Answer 39

Rapidly mature into effector T cells Secrete large amounts of IFN-gamma, IL-4 and IL-5 early after restimulation Specialized to enter inflamed tissue Rapid response

Answer 40

Recirculate to T zones of secondary lymphoid tissues, as do naive T cells Very sensitive to receptor cross-linking Take longer to differentiate into effector cells, and do not secrete as much cytokines as effector memory cells after restimulation Sustained response

Answer 41

Central restimulation: not fully committed to either TH1 or TH2, but have pre-programmed disposition to become either from the onset of stimulation Effector restiumlation: are not committed to either TH1 or TH2

Answer 42

Formation requires initial and continued CD4 help and involves CD40 and iL-2 signaling Cannot differentiate in the initial response to pathogen

Answer 43

Provides IL-2 to the T cell. By binding to the antigen-presenting dendritic cell, increases expression of CD40 on the dendritic cell, which binds to CD40L on the T cell. Are not required for Lysteria infections, but still give rise to more robust CD8 T cell response.

Answer 44

Rh- mother carries a Rh+ fetus. At delivery of child, a small amount of fetal Rh+ blood enters mother’s blood stream and elicits production of anti-Rh antibodies Antibodies subside in time but leave memory B cells behind. In a subsequent pregnancy, small amount of Rh+ fetal blood may enter mother’s elicit a strong immune response in fetus. Small amount of antigen delivered tomother during pregnancy is too small to elicit primary response, but mother’s memory B cells require only a tiny amount of antigen for activation. To prevent disease: Give anti-Rh antibody to the mother at the time of sac north, before she can develop her own antibody Fetal EBCs are destroyed before that can elicit response in mother

Answer 45

Individual infected w/ influenza virus at 2 years (makes antibody against all epitopes present on virus) Same individual at 5 years infected with variant influenza virus makes antibody only against epitopes shared with original virus **New epitopes cannot stimulate production of antibody (disease is eliminated so rapidly by secondary response that naive B & T cells responsive to new epitopes can't develop) Antibody responses to new epitopes can be produced only when individual is exposed to variant influenza that shares NO epitopes in common with original strain.

Immunology: Chapter 11 Flashcards

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