Humoral and cell mediated immunity, Educational Platform

2. Humoral and cell mediated immunity
By
M. Zubair
Lecturer kmu

3. IMMUNITY
• is the balanced state of multicellular
organisms having adequate biological
defenses to fight infection, disease, or
other unwanted biological invasion, while
having adequate tolerance to avoid
allergy, and autoimmune diseases.
• a condition of being able to resist a particular
disease especially through preventing
development of a pathogenic microorganism or
by counteracting the effects of its products

4. Immune Cells

5. Three Lines of Defenses

6. First Line of Defense
It is nonspecific Defense:
• Intact Skin: Forms mechanical barrier that prevents
entry of pathogens and other harmful substances
into body.
• Intact mucous membranes: Form mechanical
barrier that prevents entry of pathogens.
• Mucous: Traps pathogens in respiratory and
digestive tracts.
• Nasal hair: Filter and trap microbes in nasal
passage.

7. First Line cont…
• Gastric juice: Contains HCl that destroys
pathogens in stomach.
• Lysozyme: Found in tears and saliva that
Kills microbes.
• Urine: Flushes out lower urinary tract; and,
its lower PH also inhibits some microbial
growth.

8. Second Line of defense
• Nonspecific cellular and chemical defense
• Inflammatory response: Prevents spread of
harmful agents to adjacent tissues; promotes
tissue repair; release chemical mediators to
attract phagocytes and stimulate third line of
immune response.
• Fever: It is systemic response initiated by
pyrogens (i.e. prostaglandin); elevetaed body
temperature inhibits microbial proliferation.

9. Second Line cont…
• Phagocytes: Engulf pathogens and contribute
immune response.
Antimicrobial proteins:
►Interferon: Proteins released by virus
infected cells that protect uninfected cells from
viral overtake; mobilize immune system.
►Complement: Enhances phagocytosis by
opsonization, Lyses microbes, and intensifies
inflammatory and immune responses.

11. Third Line of defense
• It’s response is antigen specific, means differentiates
pathogens.
• Third line of defense consists of humoral and cell
mediated immune response.
• For each type of pathogen, the immune system
produces cells and antibodies that are specific for that
particular pathogen.
• They fight off pathogens and provide long term
immunity by keeping record of the antigen into its
memory.
• Secondary response is thus relatively rapid and
stronger than the primary response.

12. Nonspecific immune cells
• Phagocytes:
– Neutrophyles – bacteria
– Eosinophyles – enzymes that kills parasites
– Macrophages - "big eaters"
• Non phagocytic leukocytes:
– Basophiles – role in allergic response
– Mastocytes
– Natural killer lymphocytes – antiviral and anti-tumor activity

13. Nonspecific immune cells
• Macrophages have important functions in both innate and antigen-
specific immune responses.
• As phagocytic cells with antigen nonspecific activity, they help to
contain infectious agents until specific immunity can be marshaled.
• In addition, early in the host response, the macrophage functions as
an accessory cell to ensure amplification of the inflammatory
response and initiation of specific immunity.
• Macrophages are activated by the presence of antigen to engulf and
digest foreign particles.
• Activated macrophages act as antigen presenting cells (APCs)
that break down complex antigens into peptide fragments that can
associate with class I or II Major Histocompatibility Complex (MHC)
molecules. Macrophages can then present these complexes to the
helper T cell so that nonself-self recognition and activation of the
immune response can occur.

14. Presentation of antigen to helper T cell by an
antigen-presenting cell (APC)

15. NK cells
• The NK cell is a nonspecific effector cell that can kill tumor cells and
virus-infected cells.
• They are called natural killer cells because, unlike T cytotoxic cells,
they do not need to recognize a specific antigen before being
activated.
• NK cells kill after contact with a target cell. The NK cell is
programmed automatically to kill foreign cells.
• Programmed killing is inhibited if the NK cell membrane molecules
contact MHC self-molecules on normal host cells.
• The mechanism of NK cytotoxicity depends on production of pore-
forming proteins (i.e., NK perforins), enzymes, and toxic cytokines.

16. Specific Immunity
• Specific or acquired immunity develops during an individual’s lifetime.
• It distinguishes self from nonself, and responds specifically to different
pathogens and foreign molecules.
• Components:
– Lymphocytes are key players in the specific or acquired immune
response:
• Lymphocytes represent 20% to 40% of blood leukocytes;
• T lymphocytes (also called T cells), which participate in cell-
mediated immunity (60-70%);
• B lymphocytes (also called B cells), which participate in humoral
immunity (10-20%);
• Cell-mediated immunity involves the production of cytotoxic T cells, which
have the ability to destroy antigen-bearing cells.
• Humoral immunity is characterized by the transformation of B cells into
plasma cells, which secrete immunoglobulins (antibodies) that have specific
activity against the inciting antigen.

17. T cells
• T cells are maturated in the thymus.
• There, they learn how to distinguish self from nonself. Only the T
cells that ignore self antigen molecules are allowed to mature and
leave the thymus. Without this training process, T cells could attack
the body's cells and tissues.
• Mature T cells are stored in secondary lymphoid organs (lymph
nodes, spleen, tonsils, appendix, and Peyer's patches in the small
intestine).
• These cells circulate in the bloodstream and the lymphatic system.
After they first encounter a foreign or abnormal cell, they are
activated and search for those particular cells.

18. Immune Cells
Pathway for Tcell differentiation

19. Types of T cells
• Helper T (CD4) cells help other immune cells. Some helper T cells help B
cells produce antibodies against foreign antigens. Others help activate killer
T cells to kill foreign or abnormal cells or help activate macrophages
enabling them to ingest foreign or abnormal cells more efficiently.
– The Th1 response is characterized by the production of interferon -
gamma, which activates the bactericidal activities of macrophages, and
induces B-cells to make opsonizing (coating) antibodies, and leads to
cell mediated immunity.
– The Th2 response is characterized by the release of interleukin 4, which
results in the activation of B-cells to make neutralizing (killing)
antibodies, leading to humoral immunity.
– Generally, Th1 responses are more effective against intracellular
pathogens (viruses and bacteria that are inside host cells), while Th2
responses are more effective against extracellular bacteria, parasites
and toxins.

20. Types of T cells
• Th1 cells:
– secrete IL-2, IL-12, IFN gamma, TNF-beta;
– activate macrophages, amplifying their cytokine secretion
capacity and potential for presentation of antigens;
– activate synthesis of IgG but not IgE;
– are involved in delayed hypersensitivity reactions;
– are activated by signals from intracellular bacteria and viruses;
• Th2 cells:
– secrete IL-4, IL-5, IL-6, IL-10;
– activate the synthesis of IgE;
– stimulate proliferation and activation of eosinophils;
– are stimulated by allergens or parasite components.

21. Types of T cells
• Killer (cytotoxic) T cells (CD8) attach to particular foreign or
abnormal (for example infected) cells because they have
encountered them before. Killer T cells may kill these cells by
making holes in their cell membrane and injecting enzymes into the
cells or by binding with certain sites on their surface called death
receptors.
• Suppressor (regulatory) T cells produce substances that help end
the immune response or sometimes prevent certain harmful
responses from occurring.
• Sometimes T cells—for reasons that are not completely understood
- do not distinguish self from nonself. This malfunction can result in
an autoimmune disorder, in which the body attacks its own tissues.

22. Types of T cells
• Γδ T cells (gamma delta T cells) represent a small subset of T cells,
which possess a different receptor on the surface (TCR). Most T
cells receptor consists of two chains α-and β-gp. Unlike T cells, γδ
cells have a TCR composed of gamma and a delta chains. This
group is more poorly represented than beta alpha cells. They are
abundant in the intestinal mucosa.
• Natural killer T cells (NKT) are a heterogeneous group of T cells,
which have properties of both NK cells and T cells and represents
only 0.2% of all circulating T lymphocytes in the blood.

23. The central role of Thelper cells (CD4)

24. B cells
• B cells are formed in the bone marrow. B cells have particular sites
(receptors) on their surface where antigens can attach.
• B cells are the major cells involved in the creation of antibodies that
circulate in blood plasma and lymph, known as humoral immunity.
• In mammals there are five types of antibody IgA, IgD, IgE, IgG, and
IgM, differing in biological properties.
• Each has evolved to handle different kinds of antigens.
• Upon activation, B cells produce antibodies, each of which
recognizes a unique antigen, and neutralize specific pathogens.

25. B cells
• The B-cell response to antigens has two stages:
– Primary immune response:
• When B cells first encounter an antigen, the antigen attaches to a
receptor, stimulating the B cells.
• Some B cells change into memory cells, which remember that
specific antigen, and others change into plasma cells. Helper T cells
help B cells in this process.
• Plasma cells produce antibodies that are specific to the antigen that
stimulated their production. After the first encounter with an antigen,
production of enough of the specific antibody takes several days.
Thus, the primary immune response is slow.
– Secondary immune response
• Whenever B cells encounter the antigen again, memory B cells very
rapidly recognize the antigen, multiply, change into plasma cells,
and produce antibodies. This response is quick and very effective.

26. B cells

27. Primary and secondary phases of the humoral
immune response to the same antigen.

28. Immunity
Non specific
Physical
barrier
(skin, mucous
membrane)
Inflammation
Phagocytes
(neutrophils,
macrophages),
Chemical
barrier
(lysozyme,
HCl,
interferon)
Specific
Humoral
Immunity
Cell-mediate
Immunity

29. • Nonspecific Defense/immunity
– body’s primary defense.
– intact skin & healthy mucous membranes
– lysozyme (in saliva and tears) destroys bacteria
– stomach acid destroys ingested bacteria
– phagocytes engulf bacteria entering the body
– inflammatory response including fever
– Complement proteins in plasma
• Specific Defense/immunity
– directed against antigens, or molecules recognized
as foreign bodies.
– produces antibodies to destroy invader.
– memory cells develop and remain in circulation.
– Two main types of cells: B cells and T cells

30. Nonspecific cellular components
• Natural killer cells (NK cells):
Lymphocytes that can destroy other cells,
especially tumor cells and other infected
cells.
• Macrophages (phagocytes) often act as
antigen presenting cells (APCs).
• This is then identified by T cells.

32. Cell mediated Immunity
• Cell mediated immunity Involves T-lymphocytes that
act against infected cell or foreign cell or tissue.
• T cells are produced in bone marrow but mature in
the thymus gland.
• Also regulate the activation and proliferation of other
immune system cells
• Cell mediated immune response is directed against
bacteria and viruses inside phagocytic cells or
infected host cells.
• This also causes rejection of implanted tissue.
• T lymphocytes proliferate into different types of cells

33. Types of T cells
• Helper T-Cells: which activate macrophages and
help B cells.
Helper T cell also produce chemicals called
cytokines such as interlukin and interferon.
• Cytotoxic T-Cells: destroy target cells on contact by
producing toxin (perforin) that lyses infected cells.
• Suppressor T-Cells: (also called regulatory T cells)
are involved in stopping the reaction once the
danger is finished.
• Memory T-Cells: are long-lived cells which give
long term immunity against that pathogen.

34. Humoral immunity
• B cells or B lymphocytes are responsible
for antibodies production.
• This provides resistance to bacteria and
viruses and bacterial toxins
• Antibodies or immunoglobulins that
recognize different types of antigens.

35. B cells cont…
• B cells are produced and matured in stem
cells of bone marrow.
• Mature B cells are found in lymphoid tissues
like spleen and lymph nodes.
• B cells Recognize antigen by antigen
receptors on cell surface.
• We make 100 million lymphocytes a day, so
equal number must die. This death of cells is
known as ‘Apoptosis’ or ‘programmed cell
death’

36. Activation of B cells
• Each B cell produces an antibody against a
particular antigen.
• When antigen comes in contact with B cells they
form plasma cells and B memory cells.
• Plasma cells start the production of antibodies
while Memory cells give long term immunity
against that pathogen by keeping its record.
• Antibodies start binding to antigen and thus
inactivate the antigens.
• Secondary response of immune system is quicker
and stronger than the primary one.