Adaptive immunity

Lecture 7
Wesam Mohammed Emharib
 Introduction
 It is also called acquired immunity and mediated by two arms which work in coordinated
manner. Humoral immunity (antibody mediated immunity) and cellular immunity these
are two main branch of adaptive immunity.
 In general humoral immunity eliminates extracellular pathogen whereas cellular
immunity eliminates intracellular pathogen.
 Adaptive immunity can be transferred to un immunized person this called (passive
acquired immunity ) or induced by infection or vaccination this called (Active acquired
immunity)
 Passive acquired immunity could be natural .e.g. ( immunoglobulin G which pass
through placenta from infected mother to fetus ) or artificial ( by injected prepared
immunoglobulin against particular pathogen to patient )
 Active adaptive immunity it also two types natural ( which acquired after infection ) and
artificially (which induced by vaccination)
 T lymphocyte is a major player in all mechanisms of adaptive immunity ( activate
macrophage , stimulate B cell response and recognize peptide fragment displayed on
MHC of antigen presenting cell)
 Adaptive immunity pass through the following stages (lymphocyte antigen recognition-
lymphocyte activation-lymphocyte proliferation-lymphocyte differentiation into effector
cells -microbial elimination by effector lymphocyte–lymphocyte apoptosis and memory )
 In this lecture we will divide it into five main parts
1- Production of effector cells
2- T cytotoxic mediated immunity
3- Macrophage activated by TH1
4- B cell activation by T helper cell (humoral immunity )
5- Immunological memory

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Production of effector cells
 Naïve lymphocyte to become effector cell must be activated and this occurs by two
signals.
 Firstly naïve lymphocyte must be recognizing antigenic peptide which displayed on MHC
II of antigen presenting cells APC (dendritic cell, macrophage) and B cell. This signal is
insufficient for activation and required co-stimulatory signal.
 Co- stimulatory signals are required for activation and clonal expansion of naïve
lymphocyte and principle of this signal is binding of co stimulatory molecule B7 which
expressed on APC with CD28 protein expressed on T naïve lymphocyte

Figure 1 : Naïve lymphocyte activation

 The most potent activator of naïve lymphocyte in vivo is dendritic cell
 Immature dendritic cell engulf antigen and migrate to local lymphoid tissue where
express co stimulatory molecules and activate naïve lymphocyte
 Recent studies demonstrate that naïve T cells receive survival signals during their
migration to lymphoid tissue through interaction with dendritic cells at the same
moment this interaction ensuring that dendritic cell don’t encounter antigenic peptide
on their MHCII
 The Naïve lymphocytes which don’t encounter antigen will leave lymphatic tissue where
as naïve lymphocyte which encounter antigen activated and proliferate

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 Soluble antigens cannot display by macrophage. In contrast dendritic cell can take up
the soluble antigen by process called macro-pinocytosis then displaying it on MHCII.
Whereas B cell bind to these kind of antigens through their immunoglobulin receptor (B
cell receptor ) and then internalized the antigen to processing it into peptide fragment
displayed on MHCII to T helper cell in order to drive their differentiation or display the
peptide fragment to naïve lymphocyte after expressing co stimulatory signals in order
to activate naïve lymphocyte.

Figure 2: Presentation of soluble (extracellular) antigen by B cell

 After activation naïve T cell will start in synthesis IL2 and its receptor CD25. IL2 when
bind to CD25 receptor of naïve lymphocyte induce their proliferation. Co stimulatory
signal is essential for synthesis and secretion of IL2 thus absence of this signal lead to
inactivation of naïve.

Figure 3: IL2 Signal induce T cell proliferation

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 Proliferating T cell differentiate into effector T cell which do not require co stimulatory
signal

Figure 4: Naïve T helper differentiation

 Naïve cytotoxic T cell can be activated by antigenic peptide which displayed on MHC I
and in presence of co stimulatory signal

Figure 5: Naïve T cytotoxic activation and differentiation

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  T cytotoxic mediated immunity
 All viruses and some bacteria are obligate intracellular parasite because these pathogen
lack metabolic apparatus they replicate only inside host mammalian cells
 Although these pathogens are susceptible to antibodies but once them inside host cells
become unreachable by humoral immunity.
 Intracellular pathogen eliminated only by destruction or modification the cells which
harboring the infection. This is function of T cytotoxic cell.
 It is noted that defect in T cytotoxic function or losing MHC I which display antigen to
CD8 increases vulnerability to intracellular pathogen infections.
 T cytotoxic induce apoptosis of infected cells by effector proteins stored in granules of
CD8
 These effector molecules are (the granzyme and perforin). The granzyme able to induce
apoptosis in any target cell whereas perforin is a pore forming protein which able to
form hole in cell membrane of target cell through which granzyme enter to induce
apoptosis.
 Another effector protein produced by CD8 is INF Gama which activate macrophage,
inhibit viral replication and induce MHC I expression.
 The CD8 function is limited only to infected cells, and this precision allow adjacent cells
to be undamaged, thus reduce level of tissue injury.

Figure 6: T cytotoxic activation and function

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 Figure7: Precise function of CD8

Figure 8: Effector molecules of CD8 cell

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 Macrophage activation by T helper 1 cells
 The interaction between TH1 and macrophage occur through MHC II displayed antigenic
peptide. The activated specific T cell (TH1) will induce the macrophage to become more
efficient cell in order to kill microbe which engulfed by process of phagocytosis.
 The TH1 induce macrophage by production of two effector molecules ( macrophage
activating factor also called INF Gama and CD40 ligand)
 These two molecules induce macrophage by augmenting it to produce nitric oxide
(NO)and superoxide ions (O2) also increase expression of MHC II

Figure 9: Macrophage activation by TH1

 Macrophage can lead to tissue damage there for it is function is regulated by antigen
specific T cells
 TH1 Enhance macrophage to kill microbe which engulfed and resist the intracellular
killing
 Cytokine which produced by TH1 induce macrophage to kill chronic intracellular
microorganism, stimulate production of new macrophage in bone marrow and recruit
new macrophage to site of infection.
 The loss functions of TH1 against intracellular microorganism explaining predominance
of HIV infection in AIDS patient.

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  B cell activation by T helper cell
 B cell activation essential step in humoral immunity
 Humoral immunity mediated by antibody secreted form active of B cell which called
plasma cell
 Antigen bind to BCR (B cell receptor ) signals will activate B cell or antigen internalized
and processed into peptide fragments which displayed to T helper cell to activate T
helper which induce B cell to proliferate and differentiate into plasma cell (secreting
antibody specific to antigen )
 Antibodies protect host from infection by one of these functions:
1- Neutralization microbial product e.g. toxin
2- Opsonization of microbe then FC part of antibody bind to effector cell which kill the
pathogen
3- Complement activation by antibody antigen complex which enhance microbial cell
opsonization or directly kill microbial cell
 Two signals required for activation B cell, the first delivered through its antigen receptor
(BCR). Whereas the second depend on whether the antigen is thymus dependent or
thymus independent.
1- Thymus dependent antigen.
Second signal will delivered through MHC II display antigen peptide to T helper cell. Also
interaction between CD40 ligand on T helper and CD40 receptor on B cell contribute to
second signal.
2- Thymus independent antigen
it is polymeric antigen, so the second signal delivered through extensive cross linking of
antigenic peptide with BCR

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Figure 10: Humoral immunity

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Figure 11: B cell activation

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figure 12: B cell activation by thymus dependent antigen

figure 13 : Phases of B cell activation

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 Immunological memory
 Its ability of immune response to respond more rapid and potent to antigen which that
have been faced previously
 Its indicate preexistence of antigen specific colony
 Memory immune response called secondary, tertiary depending on number of exposure
to specific antigen
 Memory immune response differ on primary immune response in quantity and quality
 For example; immunoglobulin type differ in secondary immune response than in
primary immune response
 Memory B cell already switched to mature type of immunoglobulin after few days. Thus
in first days of the memory immune response, memory B cell will produce small amount
of IgM then large amount of mature IgG
 In some cases of infection or vaccination memory immunity is long life immunity

Figure 14: Quantity difference between primary and secondary immune response

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Figure 15: Course of adaptive immunity

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 References

Abbas AK, Lichtman. AH, eds.2005. Cellular and molecular immunology .Elsevier
Saunders
Janeway et al 6ed.2005. Immunobilogy . Garland science

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