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Phagocytic immuno

defficiencies

Phagocytosis

Multiprocess.

Major mechanism of removing microbes.

Defense against extra cellular microbes.

Major system of providing immunity.

Deficiency / malfunctioning of this system is known as


phagocytic dysfunctions.

Phagocytic system

Composed primarily of

Neutrophils

Eosinophil's

Monocytes

Dendritic cells

Macrophages

Phagocytes

Macrophages are the chief phagocytic cells

Free macrophages wander throughout a region in search


of cellular debris

Kupffer cells and microglia are fixed macrophages

Neutrophils become phagocytic when encountering the


infectious materials

Eosinophils are weakly phagocytic against parasitic


worms

Mast cells bind and ingest a wide range of bacteria

Stages in phagocytosis

Migrate to the site of infection.

Adhere to the tissues.

Engulf invading materials.

Digest & kill it

Oxygen dependent and independent mechanism.

Immunodeficency diseases
caused by defects in
phagocytes

Phagocytic defects are 18%of immunodeficency


disorders

May be intrinsic or extrinsic

Intrinsic are functional defects in phagocytes itself

Extrinsic affects phagocytes functions indirectly i.e.


absence of activating cytokines

Patients with these disorders have bacterial and fungal


infections

Phagocytic dysfuntions:

Affect the innate and acquired response to pathogens

Dysfunction in:

Action required to phagocytize

Migration and adhesion of phagocytic cells

Phagocyte defect

A defect in the phagocytic system results in a decreased number of


phagocytic cells.

Age of onset of infection:


.Early onset at birth
specific pathogens:
.staphylococcus
.psedomonas
.klebsiella
Primary site:
deep tissue infections with high grade bacterial pathogens
lungs,skin,regionallymph nodes
Special features:
poor wound healing etc.
Clinical diseases:
CGD,Jobs syndrome,Cyclic neutopenia etc.

Diagnosis work up:

Jobs syndrome/hyper IgE


syndrome

Conditions:

Patient has coldstaphylococcal abscesses

Eczema(rashes)

skeletal defects

high levels of IgE

Fail to produce gamma interferone by helper T cells

Th-2 cells are increased which increases the IgE

As a result histamine is released

Inflammatory response is blocked so coldabscesses of


lymph nodes and skin.

Treatment:

No known cure for job syndrome

Antibiotics are used to control bacterial


infections

Chediak-Higashi Syndrome

Rare Autosomal recessive

Abnormal giant granules and organelles in the cell

Diminished killing of intracellular organisms (lysosomes


and degranulation), leading to massive infiltration of
lymphocytes and macrophages in liver, spleen, lymph
nodes

Failure of fusion of lysosome with phagosome

Strep and Staph main problem recurrent infections

Soon after birth or in children younger than 5 years

Treatment:

Involves antimicrobial drugs

There is no useful therapy for the phagocyte defect

Myeloperoxidase deficency

Either reduce in number or function

Surprisingly patients of this have less infectious diseases

Myloperoxidase catalyze production of


hypochlorite:micrbicidal agent

More infectious diseases are expected

Intracelluler killing mechanisms are intact to kill these


microbes

Clinical features

Fungal infections(candidiasis)in deep tissuesespecially


in patients of diabetes

LAD
Leukocyte

adhesion deficiency
Autosomal recessive
Group of disorders in which the
leukocyte interaction with
vascular endothelium is
disrupted

subunit of integrins
Selectin ligands

Consequences:
Recurrent

soft tissue bacterial infection


Increased blood WBC counts
No pus formation or effective wound
healing

Cyclic neutropenia:

Autosomal dominant disease

Low neutrophil count less than 200 per microliter for


6days of 21days cycle

During neutropenic patient is susceptible life threaning


bacterial infection

As neutrophils are normal patients are not susceptible

Causes:

Mutationin gene encoding neutrophil elastase

Irreguler production of granulocytes colony stimulating


factor play role in this disease

Interferon Gamma receptor


deficency

Atypicale mycobacteria or bacillus calmette


guerin(BCG)

Mutation on the gene encoding either ligand binding


portion or signal transduction portion of receptor for
interferon_Gamma

As a result macrophages are inactivated and severe


mycobacterial infections occur

Neutropenia:

Stap.aureus and str.pnemoniae enteric gram negative


rods

Neutrophils count below 500 microliter leads to these


infections

Cytotoxic drugs cancer chemotherapy leukemia and


autoimmune destruction of neutrophils

Treatment:

Ciprofloxacin is used to prevent the infections in


neutropenic patients

Complement defects
regarding immunodeficency

Complement:

A group of heat labile serum proteins present in


inactivated form

Activated by certain factors that may be antigens

Helps to clear pathogens

Promotes chemotaxis,opsonization,phagocytosis of
pathogens and bacteriolysis etc

Complement
system:

Consist of appro 20 proteins present in serum

Important component of immune system

Complement defects:

Form of primary immunodeficency disorder

deficency in any component of complement


system can lead immunocompromised and
overwhelming infections

Deficency may be inherited or acquired

Acquired caused by infections,uncontrolled


complement activity

Defeciencies in classical
pathway
components(C1q,c1r,C4,C2
,C1-inh)

C1,C4,C2 deficiency prone to immune complex


diseases coomonly SLE,glomarolonephritusand
vasculitis

C2 deficency also assosiated with recurrent


pyogenic bacterial infections e.g.
streptococci,staphylococci

Alternative pathway
deficiencies(properdin
factor B&D):

Increased risk of Nisseria infection

No involvement of immunocomplex diseases

MBL deficiency:

Results in serious pyogenic infections in children

Increased respiratory tract infections

This deficiency found to be 2-3 times in SLE patients

C3 deficency & MAC


deficiency:

Required for opsonization

Defect in pathway result in deficency of C3 leads


to problems with opsonization

C5-C9 deficiencies results in Niesseria infections


e.g. Niesseria meningitus

Hereditary angioedema:

Autosomal dominant

Deficency of C1 inhibiter

Increased cappillary permeability

Edema in several organs

Treatment:

Steroid,oxymetholone and danazole

Systemic lupus
erythmatosus:

Deficency leads to inability to clear circulating


immune complexes

Deposition of complexes in tissues

Result in assosiate inflammatory response

Reduce clearance of apoptotic bodies

Results in deveolpment of autoantigens

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