IMMUNODEFICIENCIES

1. IMMUNODEFICIENCIES AND
TUMOURS

2. • Def. It’s a state of the bodies failure of its immune system to defend
itself against infections and malignancies effectively.( there is
compromised or absent capacity to mount defence.)
• There are basically two broad categories: (Specific cellular immunity)
• Primary immune deficiency.
• Acquired immune deficiency.
• There are many disease entity in each and their manifestation tend to
cross into each other.

3. • Many primary immunodeficiency disorders are inherited — passed down
from one or both parents.
• The genetic code which is the blueprint for producing the cells of the
body (DNA) cause many immune system defects.
• There are more than 300 types of primary immunodeficiency disorders,
and researchers continue to identify more.
• They can be broadly classified into six groups based on the part of the
immune system is affected:

4. • T cell deficiency.
• B cell deficiency
• Combined B and T cell deficiency
• Compliment deficiency
• Defective phagocytes
• Idiopathic
• These defects manifest in failure of the body to mount appropriate
defence against aggression.

5. General manifestation
• Recurrent infections
• Failure to thrive
• Retarded growth
• Autoimmune disorders
• Increased risk of malignancies
• Damage to CNS, heart ,lungs and GIT.
• Death

6. T cell deficiency
• The immunological cell deficiency is variable . Selective T cell
deficiency results in the following.
• There is impairment or absence of thymic T cell maturations.
• T cell dependant zone may be absent in the spleen and lymph node in
severe forms.
• cases present with Fulminant ;viral ,fungal or pneumocystis infection
in presence of normal immunoglobulin levels.
• Examples :DiGeorge,s syndrome rare congenital abnormality of the
3rd and 4th pharyngeal pouches(Thymic and parathyroid aplasia
together with cardiac and aortic arc abnormality.)

7. • NEZELOF’S SYNDROME, associated with T cell deficiency and
underdevelopment of the thymus in absence of other congenital
malformation in the Digeorge’s syndrome.
• Ataxia telangiectasia ,there is cerebellar abnormality and systemic
blood vessels leading to: ataxia skin and conjunctival haemorrhage
and immunodeficiency.
B cell deficiency
• In this case there is normal cell mediated immunity but the humoral
response is absent or impaired.
• X linked agammaglobulineamia Brunton

8. • This is an impaired B cell differentiation rather than absence of b cell
linage.
• Treatment is life long parental immunoglobulins.
• X-liked hypogammaglobulineamia with hyper IgM.
• IgG and IgA are absent.
• Others :selective agammaglobulineamia due to impaired
differentiation Transient hypogammaglobulineamia,Neutrophil
deficiency disease, agranulocytosis and qualitative deficiency
neutrophil deficiencies.

9. • Combined immunodeficiency's not compatible with life.
• Secondary immunodeficiency.
• These are common in both humoral and cellular.
• This can occur in infections
• Selective immunotherapy in organ transplants.
• It is the undesired consequence of cytotoxic therapy
• Secondary immunodeficiency associated with malignancy: Abnormal
proliferation of blood cell and lymphoid tissue of whatever cause
replacing the normal blood cells results into immunosuppression.

10. • Blood and lymphoid malignancies are notorious for causing
immunosuppression.(examples……)
• Immunodeficiency can also be caused by loss of immune
components: Nephrotic syndromes, Chronic git inflammations.
• Numerous infections are associated with immusupresion Viral
infections Herpes CMV,EBV measles malaria HIV and AIDs.

11. Host defence against Tumours.
• The body is known to mount defence against tumours.
• Most humoral responses cannot prevent tumour growth.
• However, effector cells, such as T cells, macrophages, and natural
killer cells, have relatively effective tumoricidal abilities.
• Effector cell activity is induced by cells that present tumour-specific
antigens (TSAs) or tumour-associated antigens (TAAs) on their surface
(these cells are called antigen-presenting cells) and is supported
by cytokines (eg, interleukins, interferons).
• Despite the activity of effector cells, host immunoreactivity may fail to
control tumour occurrence and growth.

12. Cellular Immunity
• T cell is the primary cell responsible for direct recognition and killing
of tumour cells.
• T cells carry out immunologic surveillance, then proliferate and
destroy newly transformed tumour cells after recognizing TAAs.
• The T-cell response to tumours is modulated by other cells of the
immune system; some cells require the presence of humoral
antibodies directed against the tumour cells (antibody-dependent
cellular cytotoxicity) to initiate the interactions that lead to the death
of tumour cells.
• In contrast, suppressor T cells inhibit the immune response against
tumours.

13. • Cytotoxic T lymphocytes (CTLs) recognize antigens on target cells and lyse these
cells.
• These antigens may be cell surface proteins or may be intracellular proteins (eg,
TAAs) that are expressed on the surface in combination with class I major
histocompatibility complex (MHC) molecules.
• Tumor-specific CTLs have been found in a number of malignant tumours:
• Melanoma,Neuroblstoma,sarcoma,breast carcinoma, lung carcinoma, cervical
and endometrial carcinoma colonic and renal carcinoma, Ovarian and testicular
carcinoma and Nasopharyngeal carcinoma.
•

14. • Natural killer (NK) cells are another population of effector cells with
tumoricidal activity.
• In contrast to CTLs, NK cells lack the receptor for antigen detection
but can still recognize normal cells infected with viruses or tumour
cells.
• Their tumoricidal activity is termed natural because it is not induced
by a specific antigen.
• Natural killer T (NKT) cells are specialized CD1d-restricted T cells that
recognize lipid antigens.

15. • Following stimulation, NKT cells lead to activation of both innate and
adaptive immune cells in the tumor microenvironment.
• NKT cells are innate-like T cells that quickly respond to antigenic
stimulation and rapidly produce large amounts of cytokines and
chemokines.
• Macrophages can kill specific tumour cells when activated by a
combination of factors, including lymphokines (soluble factors
produced by T cells) and interferon

16. • They are less effective than T-cell–mediated cytotoxic mechanisms.
Under certain circumstances, macrophages may present TAAs to T
cells and stimulate tumour-specific immune response.
• There are 2 polarized states of tumour-associated macrophages
(TAM):
• TAM-1 (M1) cells facilitate T cell killing of tumours
• TAM-2 (M2) cells promote tumour tolerance.
• M1 and M2 are considered to exist on a continuum until they
maximally differentiate (polarize) into M1 and M2

17. • Dendritic cells are dedicated antigen-presenting cells present in
barrier tissues (eg, skin, lymph nodes).
• They play a central role in initiation of the tumour-specific immune
response.
• Lymphokines produced by immune cells stimulate growth or induce
activities of other immune cells.
• Such lymphokines include interleukin-2 (IL-2), also known as T-cell
growth factor, and the interferons

18. • . IL-12 is produced by dendritic cells and specifically induces CTLs,
thereby enhancing antitumor immune responses.
• Regulatory T cells are normally present in the body and help prevent
autoimmune reactions.
• They are produced during the active phase of immune responses to
pathogens and limit strong immune responses that could damage the
host.
• Accumulation of these cells in cancers inhibits antitumor immune
responses.

19. • Myeloid-derived suppressor cells consist of immature myeloid cells
and their precursors.
• These cells increase in number in cancer as well as in inflammation
and infection.
• The cells have potent immune suppressive activity.
• Two populations of these cells are recognized:
• Granulocytic
• Monocytic

20. • Myeloid-derived suppressor cells accumulate in large numbers in
cancers and predict poor clinical outcomes in various types of cancer.
•
Failure of Host Defenses
• Although many tumours are eliminated by the immune system (and
thus are never detected), others continue to grow despite the
presence of TAAs.
• Several mechanisms have been proposed to explain this deficient host
response to the TAA, including the following.

21. • Suppression of immune response by chemical, physical, or viral agents (eg, helper
T-cell destruction by human immunodeficiency virus [HIV]).
• Suppression of the immune response by the tumour itself through various
complex and largely uncharacterized mechanisms that cause various problems:
• including decreased T, B, and antigen-presenting cell function, decreased IL-2
production, generation of exhausted T cells, and increased circulating soluble IL-2
receptors (which bind and hence inactivate IL-2)
• Suppression of the immune response by cytotoxic drugs or radiation

22. • Presence and activity of TAM-2 (M2) polarized cells, myeloid-derived
suppressor cells, and regulatory T cells promoting tumour tolerance.
• Specific immunologic tolerance to TAAs in a process that involves
antigen-presenting cells and suppressor T cells, possibly secondary to
prenatal exposure to the antigen.