1. A secondary immune response occurs upon reexposure to an antigen and results in a faster and stronger response than the primary response due to memory cells. 2. The secondary response has a very short or negligible lag phase and the antibody concentration increases much more rapidly than in the primary response, reaching levels 100-1000 times higher. 3. Memory B and T cells generated during a primary response enable a rapid secondary response through faster activation, greater sensitivity, and production of more effective antibodies.

1. Introduction
➢A secondary immune response is a response to an illness that has
occurred for the second time
➢It activates previously generated memory cells
➢Secondary immune response is different from the primary response,
both qualitatively and quantitatively
➢The log phase in secondary response is very short or negligible
➢Lag face is absent in secondary response
➢Raise of antibody concentration is about 100 to 1,000 fold higher than
the primary response resulting a short log phase

3. 1° Immune Response
1. Following the first exposure to a
foreign antigen, a lag phase occurs in
which no antibody is produced, but
activated B cells are differentiating
into plasma cells. The lag phase can
be as short as 2-3 days, but often is
longer, sometimes as long as weeks
or months.
2. The amount of antibody produced is
usually relatively low.
3. Over time, antibody level declines to
the point where it may be
undetectable.
4. The first antibody produced is
manily IgM (although small amounts
of IgG are usually also produced).
2° Immune Response
1. If a second dose of the same antigen
is given days or even years later, an
accelerated 2° or anamnestic immune
response (IR) occurs. This lag phase
is usually very short (e.g. 3 or 4
days) due to the presence of memory
cells.
2. The amount of antibody produced
rises to a high level.
3. Antibody level tends to remain high
for longer.
4. The main type of antibody produced
is IgG (although small amounts of
IgM are sometimes produced).

4. Immunological Memory Is Sustained By Clones
Of Long Lived Memory T Cells And B Cells
➢After the level of pathogen-specific antibody made during a primary immune response
has declined, immune defences relaxed and the potential for that pathogen to re-
establish an infection increases
➢During a primary immune response, the clonal expansion of pathogen-specific T cells
and B cells gives rise both to short lived effector cells that work to stop the infection and
to long-lived memory T cells and memory B cells
➢In the secondary immune response, these memory cells are activated by antigen to
proliferate and differentiate into effector cells
➢Several factors contribute to this difference: memory cells are more sensitive to
infection, more easily activated, and more abundant than naive lymphocytes specific for
the same pathogen
➢Memory B cells have also undergone isotype switching and affinity maturation and so
will produce more effective antibodies than IgM made at the beginning of the primary
infection with the pathogen

5. Vaccination Against A Pathogen Can Generate
Immunological Memory That Persists For Life
➢The goal of vaccination is to immunize people with a benign form of a
pathogen and induce immunological memory
➢Any infection with the real pathogen will meet a secondary immune
response that terminates the infection before it causes disease
➢Smallpox virus was once an effective killer of humankind: from 1850 to
1979
➢About 1 billion people died from smallpox
➢Worldwide vaccination programs progressively reduced the spread of the
virus to the point at which in 1972 mass vaccination was discontinued in the
United States and in 1979 the smallpox virus was eradicated worldwide

6. Pathogen–Specific Memory B Cells Are More Abundant And
Make Better Antibodies Than Do Naive B Cells
➢In primary infection, proliferation and differentiation of antigen-specific
naive B cells produces large numbers of antibody – secreting plasma cells
➢A smaller number of memory B cells to deal with future infections
➢The first antibodies to be made in the primary response are low – affinity
IgM
➢As the response proceeds, somatic hypermutation, affinity maturation, and
isotype switching give rise to high-affinity IgG, IgA, and IgE
➢Memory B cells are derived from the clones of B cells making the highest-
affinity antibodies
➢On a second infection, 10-100 times more pathogen-specific B cells
respond than did naive B cells in the primary response

7. Immunodeficiency
• Cause for Immunodeficiency:
Human Immune system:
❖Very specific
❖Dependent on memory of cells and
lymphocytes that recognise foreign antigen
and infected cells respectively.
• Any alterations in these functions
Immunodeficiency.

8. Classification
•Most are genetically
determined
•Less common
•May arise as complications
of cancers, infestations,
malnutrition, or side effects
of immunosuppression,
Irradiation and
chemotherapy.
•More common
Primary
Immunodeficiency
Secondary
Immunodeficiency

9. Primary Immunodeficiency
• Most important feature:
• High Incidence in Males: Why ?
• 6 X-linked ID’s have been
described:
5 - Affect
Lymphocytes
1- Affect
Phagocyte

11. Severe Combined
Immunodeficiency(SCID)
• Synonyms: Glanzzman-Rinker syndrome,
Bubble Boy Disease, Thymic Alymphoplasia
• Genetic disorder characterised by absence of
T-lymphocytes.
• Impairment of both cellular & humoral
response
• Specific defects in antigen presentation &
functional immune molecules.

12. SCID-Types
• Main Types:
➢Autosomal recessive (-ve T & B cells)
➢X-linked recessive(+ve B cells)
• Other important types:
➢Nezelof Syndrome
➢SCID associated with ADA & PNP deficiency.

13. Features of SCID
• Absent tonsils
• Small or absent lymph nodes
• Absent thymic shadow
• Lymphopenias
• Decreased Number of T cells
• Severe agammaglobulinemia (Swiss type of
agammaglobulinemia)
• No IG’s usually present

14. Bruton’s X-linked Agammaglobuinemia
• Primarily B-cell defect
• Boys-more affected
• Severe reduction in γ-globulins
• IG’s, circulating and marrow B-cells.
• Probable cause: Molecular defect at
Xq22.Mutation of bruton tyrosine kinase.
• Therapy: IV IG’s.

15. DiGeorge’s syndrome
• Also called thymic hypoplasia
• Congenital disorder
• Abnormalities in structure derived from 3rd
and 4th pharyngeal pouches
• Predominantly T cell defect
• Charactersitics: Neonatal tetany(absence of
parathyroid)
• Therapy: Thymic transplants

16. Ataxia-telangiectasia
• Autosomal recessive
• Incidence: 25:10,00,000
• Characteristics: Progressive cerebellar ataxia,
ocular and cutaneous telangiectasias, severe
sino-pulmonary infections, progeric changes,
sclerodermoid changes
• Thymus: fetal-like histological pattern.
• Translocation between 14 and 7

17. Wiskott-Aldrich Syndrome
• X-linked condition
• Incidence: 4:10,00,000
• Severe eczema, recurrent infections, Bloody
diarrhea, chronic otitis
• T cells appear bald :?
• Platelets: Decreased in number, small
• Failure to recognise polysaccharide antigens.
• Defect: Failure in expression of sialophorin.

18. Chronic Granulomatous Disease
• Incidence:1:10,00,000
• Defect: Inability of phagocytes to produce
superoxide ineffective reduction of O2.
• Failure to express respiratory burst associated
with phagocytosis.
• Central necrosis and granulomatoid response
in lung, liver, bone , skin and lymph nodes.
• Presence of numerous pigmented
macrophages.

19. Chediak-Higashi Syndrome
• Rare autosomal disorder
• Abnormal large granules in leucocytes leading to:
– hypopigmentation/partial albinism
– severe immunodeficiency
– neurologic abnormalities
– mild bleeding tendencies
• Defective gene: CHS1

20. Leucocyte-Adhesion defect
• Autosomal recessive disorder
• Inability of phagocytic cells to adhere to
endothelial cells and migrate to infected sites
• Characteristics: delayed cord dehiscence and
scar formation, recurrent diarrhea and
respiratory symptoms, leucocytosis
• Defect in CD18 gene
• Treatment: Bone marrow transplantation

21. Other Primary ID’s
• Selective IgA deficiency
• Common variable Immunodeficiency
• X-linked lymphoproliferative disease
• Job’s syndrome

22. Complement deficiencies
• Involves 19 proteins:
11-classical, 3-alternate, 5-regulatory
• Alteration in the expression of these proteins
Autoimmune & Immunodeficiency diseases
Classical AI affecting vessels & glomeruli
Alternate Pyogenic infections
Regulatory Hereditary Angioneurotic edema

23. Diagnosis of Primary Immunodeficiencies
• Histopathology
• Immunohistochemistry
• Monoclonal Antibodies
• Cell separation by flow cytometry
• Insitu Hybridisation

24. Therapy
• Supportive therapy- antibiotics
• Replacement therapy-IV immunoglobulin
infusion, ADA-rich RBC infusions
• Definitive therapy- Fetal thymic grafts, bone
marrow transplantation
• Stem-cell therapy
• Gene therapy