Cell Mediated Immunity And Humoral Immunity Compare Contrast Essay

Abstract

Background. Given the high infant measles mortality rate, there is interest in whether a measles immunization regimen beginning at <12 months of age provides lasting immunity.

Methods. Measles-specific immune responses were evaluated in 70 children aged 5–10 years after primary measles vaccine administered at 6, 9, or 12 months.

Results. At 5–10 years of age, the stimulation index for measles T-cell proliferation was 11.4 (SE, 1.3), 10.9 (SE, 1.5), and 14.4 (SE 2.1) when the first measles dose was given at 6, 9, or 12 months, respectively. Neutralizing antibody concentration (geometric mean titer [GMT]) in those immunized at 6 months of age was 125 mIU/mL (95% confidence interval [CI], 42–377) in the presence of passive antibodies (PAs) and 335 mIU/mL (95% CI, 211–531) in those without PAs; in those immunized at 9 months, GMTs were 186 mIU/mL (95% CI, 103–335) and 1080 mIU/mL (95% CI, 642–1827) in the presence and absence of PAs, respectively. The GMT was 707 mIU/mL (95% CI, 456–1095) when vaccine was administered at 12 months (P ≤ .04).

Conclusions. Measles-specific T-cell responses were sustained at 5–10 years of age regardless of age at time of primary measles immunization. Neutralizing antibody concentrations were lower in cohorts given the first vaccine dose at 6 months of age and in the presence of PAs; however, responses could be boosted by subsequent doses. Starting measles vaccination at <12 months of age may be beneficial during measles outbreaks or in endemic areas.

Measles remains the leading cause of vaccine-preventable childhood mortality globally despite substantial declines through immunization programs [1]. In 2008, 164 000 measles-related deaths occurred [2], with the highest fatality rates seen during the first year of life [3]. Although disease burden is greatest in developing nations, the changing epidemiology of measles in developed countries is a concern [2–12]. The United States was declared free from endemic measles transmission in 2000; nevertheless, cases continue to be imported [5, 6, 11, 12]. The year 2008 saw the highest measles incidence since 1998 (131 cases), and 21% of cases were in children younger than the recommended age for primary vaccination, with these children representing 26% of measles hospitalizations [4]. Of the 222 cases of measles in the United States in 2011, 90% of the cases were imported, and 14% of the cases occurred in infants aged <12 months [5]. Control of measles in the United States is complicated by a shift to an earlier loss of transplacentally acquired measles antibodies in infants [8–10]. In the United States, approximately 40% of infants aged 6 months lack passive antibodies (PAs) against measles [7, 8, 12] and remain vulnerable to infection until they are immunized.

Previously, high immunization coverage and persistent PAs in the United States afforded herd immunity to infants younger than the recommended age for vaccination [13], but measles caused by imported cases show that the current level of herd immunity in the United States is now insufficient for the protection of exposed infants. Recent outbreaks show a shift to increased measles incidence in children aged <12 months who lack protection by PAs [4, 5, 14]. Thus, giving the first measles vaccine dose to younger infants might benefit those aged 6–12 months in the United States, where measles has been reintroduced, and those aged <12 months in the developing world, where mortality is high in infants [15].

Measles immunization of infants aged as young as 3 months has shown partial success [16–18], with failures in younger infants attributed to interference from passively acquired antibodies and to limitations of the developing immune system [7, 17, 19]. An early primary measles immunization strategy was effective in a measles outbreak in the United States as well as in countries where measles is endemic [20, 21]. Yet, information about how well measles-specific immunity persists after early primary immunization is limited. To evaluate the longevity of both humoral and cellular immunity to measles after early immunization, we studied children aged 5–10 years, comparing those who had received their primary measles immunization at 6 or 9 months of age with those vaccinated at 12 months of age.

METHODS

Study Populations

Subjects included 70 healthy children who had received their primary measles vaccine dose at 6 (n = 26), 9 (n = 23), or 12 (n = 21) months of age in an earlier study [7, 19]. Those immunized at 6 or 9 months of age received a second measles dose at 12 months of age [22], and all participants received a measles vaccine dose at 5 years of age (Figure 1). Children with chronic illness were excluded.

Figure 1.

Study design representing the timing of initial and subsequent measles vaccine doses and immune evaluations for each cohort. *Blood samples were collected on all infants, as previously reported [13], and used to determine passive antibody concentrations prior to primary measles immunization. †Blood samples were collected on all infants, as previously reported [13]. ‡Measles, mumps, and rubella virus vaccine live (MMRII) given at 5 years. §Blood samples were collected at random time points from children initially immunized at 9 (n = 23) or 12 (n = 21) months of age and who were now aged 5–10 years. ¶Blood samples were collected at random time points from children initially immunized at 6 months of age (n = 26) and who were now aged 5–10 years. Abbreviation: MMRII, measles, mumps, and rubella virus vaccine live.

Figure 1.

Study design representing the timing of initial and subsequent measles vaccine doses and immune evaluations for each cohort. *Blood samples were collected on all infants, as previously reported [13], and used to determine passive antibody concentrations prior to primary measles immunization. †Blood samples were collected on all infants, as previously reported [13]. ‡Measles, mumps, and rubella virus vaccine live (MMRII) given at 5 years. §Blood samples were collected at random time points from children initially immunized at 9 (n = 23) or 12 (n = 21) months of age and who were now aged 5–10 years. ¶Blood samples were collected at random time points from children initially immunized at 6 months of age (n = 26) and who were now aged 5–10 years. Abbreviation: MMRII, measles, mumps, and rubella virus vaccine live.

A single blood sample was collected from each child when he/she was aged 5–10 years (Figure 1). Data were analyzed for the whole group and for subgroups of subjects who were aged 5–6 years (1–2 years from last measles immunization) and 7–10 years (3–5 years from last measles immunization) to differentiate peak responses to vaccine from steady state immunity, respectively.

Participants were recruited through the Palo Alto Medical Foundation, Palo Alto, California. Written consent was obtained. The Stanford University Committee for the Protection of Human Subjects and the Institutional Review Board of Palo Alto Medical Foundation approved the study. No cases of measles were identified in our area during the 10-year follow-up period.

Vaccines

Infants aged 6 and 9 months received measles virus vaccine live (Attenuvax) followed by measles, mumps, and rubella virus vaccine live at 12 months and 5 years. Infants aged 12 months received measles, mumps, and rubella virus vaccine live with a second dose at 5 years (all vaccines, Merck & Co).

Plaque Reduction Neutralization

Sera were stored at −80°C and tested for measles neutralizing antibody using a modified plaque reduction neutralization (PRN) assay [23]. In brief, serum samples were tested in parallel with the World Health Organization Measles Reference Serum II (66/202, obtained from the National Institute for Biological Standards and Control). In this assay, a titer of 1:8 corresponded to 8 mIU/mL of measles neutralizing antibody; <1:4 mIU/mL was considered negative. Measles antibody concentrations of ≥120 mIU/mL indicated measles seroprotection [24].

Immunoglobulin G Antibody Avidity

Measles virus–specific immunoglobulin G (IgG) antibody avidity was determined by enzyme immunoassay, as previously described [25]. In brief, sera samples were stored at −80°C. Flat-bottom, 96-well Maxisorp plates (Nalge Nunc Intl) coated with 1 μg/well of Edmonston measles virus–infected Vero cell lysate (Advanced Biotechnologies, Inc) were incubated with sera diluted 1:100. Avidity was determined by the dissociation of measles virus–specific IgG bond with the addition of the chaotropic agent ammonium thiocynate, NH4SCN (Sigma) and detected by alkaline phosphatase–conjugated rabbit antihuman IgG (H&L; Accurate Chemical & Scientific Corp). Substrate p-nitrophenyl phosphate (Sigma) was added to plates and read at absorbance 405 nm endpoint on microplate reader (Spectramax 190; Softmax Pro 4.0, Molecular Devices). The avidity index (AI) was determined as the concentration of NH4SCN that caused 50% reduction of measles virus–specific IgG binding. Optical density readings <0.3 in absence of NH4SCN and <30% dissociation were considered negative.

T-Cell Proliferation Assay

Peripheral blood mononuclear cells were separated from whole blood by Ficoll-Hypaque gradient and added to 96-well microtiter plates at 3.0 × 105 cells/well in Roswell Park Memorial Institute 1640 medium (Mediatech), as described previously [7, 19]. Measles antigen was prepared from lysates of Vero cells inoculated with Attenuvax measles vaccine (Merck & Co). Vero cell lysates made in parallel served as control antigen.

T-cell proliferation was measured by 3[H]-thymidine uptake after incubation of peripheral blood mononuclear cells with dilutions of 1:16 and 1:32 antigen and Vero cell control (optimal dilutions determined previously [19]) in duplicate wells for 5 days. The stimulation index (SI) is the ratio of mean counts per minute in antigen wells divided by the mean counts per minute in corresponding Vero cell control wells; the highest SI was used for statistical analysis. An SI ≥3.0 was considered positive [7, 19]. Phytohemagglutinin (0.1 mg/mL; Difco) served as the positive control and phosphate-buffered solution served as the negative control for each assay and were processed under the same conditions as the antigen and Vero cell control.

Statistics

Antibody titers are reported as geometric mean concentrations (GMCs) with 95% confidence intervals (CIs), and avidity is reported as AI. T-cell proliferation is reported as SI ± standard error (SE). Responses were compared by Student paired or unpaired t test and Fisher exact test. P < .05 was considered statistically significant.

RESULTS

Cellular Immunity

The mean SI (±SE) in 5–10 year old children was 11.4 (1.3) and 10.9 (1.5) in children given primary vaccination at 6 or 9 months of age, respectively (Table 1). These responses were comparable to the mean response of 14.4 (2.1) in children vaccinated at 12 months and 5 years of age.

Table 1.

Measles Immunity in Children Aged 5–10 Years After an Early Vaccine Regimen

Age at Time of Primary Measles ImmunizationaNo. of Measles Vaccine Doses Interval Between Last Vaccine Dose and Blood Draw, Mean in Years (range) GMC, mIU/mL (95% CI)bAvidity Index, MeancStimulation Index (±SE)d
6 mo (n = 26) 2.3 (1–5) 199 (110–361) 1.4 11.4 (1.3) 
9 mo (n = 23) 2.8 (1–6) 419 (254–690) 1.7 10.9 (1.5) 
12 mo (n = 21) 2.8 (1–6) 823 (544–1244) 2.2 14.4 (2.1) 
Age at Time of Primary Measles ImmunizationaNo. of Measles Vaccine Doses Interval Between Last Vaccine Dose and Blood Draw, Mean in Years (range) GMC, mIU/mL (95% CI)bAvidity Index, MeancStimulation Index (±SE)d
6 mo (n = 26) 2.3 (1–5) 199 (110–361) 1.4 11.4 (1.3) 
9 mo (n = 23) 2.8 (1–6) 419 (254–690) 1.7 10.9 (1.5) 
12 mo (n = 21) 2.8 (1–6) 823 (544–1244) 2.2 14.4 (2.1) 

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The presence of PAs at the time of primary measles immunization had no effect on the mean SI (Tables 2 and 3). No differences in T-cell responses were found in a subgroup analysis of children aged 5–6 years compared with children aged 7–10 years (boost responses vs steady state; Table 3).

Table 2.

Effects of Passive Antibodies and Age of Primary Measles Immunization on Persistence of Measles Immunity in Children Aged 5–10 Years

Age at Time of Primary Measles ImmunizationaGMC, mIU/mL (95% CI)bAvidity Index, Meanc

Cell-mediated vs Humoral Immunity
(Similarities and Differences between Cell-Mediated and Humoral Immunity)

The immunity induced in an organism by the exposure of a foreign antigen is called Active Immunity. The active immunity is mediated through two distinct mechanisms, and they are named as (1) Cell-mediated immunity and (2) Humoral immunity. These two immune pathways show considerable differences in their components, their targets, and the method of killing of pathogens.

Cell-mediated immunity: The cell-mediated immunity is facilitated by the activated TH cells (T-Helper cells) and Cytotoxic T Lymphocytes (CTLs). Cytokines secreted by the TH cells activate the phagocytic cells. These activated phagocytic cells then phagocytosis and kill the microbes. The cell-mediated immunity is particularly important against the bacterial and protozoan pathogens.

Humoral Immunity (antibody-mediated immunity): The Humoral immunity is mediated through antibodies. Antibodies are produced by the B cells. These antibodies bound to specific microbial antigens. Binding of antibodies to antigens neutralize the microbes and target them for elimination by various effector mechanisms. The humoral immunity is the major defense mechanism against the extracellular microbes trying to invade the host systems.

The present post discusses the Similarities and Differences between Cell-mediated and Humoral Immune Systems with a Comparison Table.

Similarities between Cell-mediated and Humoral Immunity

Ø  Both the cell-mediated and humoral immune systems are active immunities.

Ø  Both the systems are effective against a wide variety of microbial pathogens.

Ø  In both cases, there will be a lag period.

Ø  Immunological memory is present in both the systems.

Ø  Both the systems are ineffective in immune deficient individuals.

Difference between Cell-mediated and Humoral Immunity

Sl. No.Cell-mediated ImmunityHumoral-Immunity
1The cell-mediated immune response is mediated by T-cells.The humoral immune response is mediated by antibodies (produced by B-cells).
2Antibodies are not formed in cell-mediated immune response.Antibodies are formed in humoral immune response.
3Receptors are used in cell-mediated immunity to detect antigens.Antibodies are used in humoral immunity to detect antigens.
4T-cell receptors binds to the T-cells and then the T-cell themselves binds to the antigen.Here the B-cells produce antibodies and the antibodies bind to the antigen.
5It protect against fungi, virus and intracellular bacterial pathogens.It protect against extracellular bacterial and viral pathogens.
6Cells involved in cell-mediated immunity: Macrophage, Helper T cells, Natural killer T cells and Cytotoxic T cells.Cells involved in humoral immunity: T-Lymphocytes, B-Lymphocytes and Macrophages.
7Cell-mediated immunity mediates delayed hypersensitivity (type IV).Humoral immunity mediates immediate hypersensitivity (type I, II and III)
8Cell-mediated immune response provides the immunological surveillance.Humoral immunity does not provide immunological surveillance.
9It can eliminate tumor cells and thus can provide immunity against cancerIt cannot eliminate tumor cells.
10Cell-mediated immune response also participates in the rejection of organ transplants.Humoral immunity may be involved in the early graft rejection due to pre-formed antibodies.
11Only the T cell dependent antigens led to cell mediated immunity.In humoral immunity response, the B cells directly bind to soluble antigen and results in the antibody production.
12Both CD4+ and CD8+ T cells are involved in cell mediated immune response.Only TH cells are involved in humoral immune response.

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