I&i Week 1

Front 1

Innate immunity

Back 1

That state of immunity with which one is born. It exists regardless of exposure to antigen and is not enhanced by repeated exposure to antigen.

Front 2

Adaptive immunity

Back 2

State of immunity that is developed as a result of
exposure to an antigen. It is specific for the particular antigen and is enhanced following repeated exposure to the same antigen.

Front 3

CD

Back 3

Cluster of Differentiation – a nomenclature system that classifies many molecules on
immune and hematopoietic cells. Numbers next to the CD only denote the order in which the
molecule was discovered. CD3, CD4 and CD8 are markers for T cells, CD19 & 20 for B cells.

Front 4

Passive--Generally and Natural immunity

Back 4

Passive Immunity (generally): Normally occurs when specific (pre-formed) antibody or serum) is
transferred from an immunized individual to a non-immunized individual.
Antibodies or sera are usually obtained from humans or animals that have been deliberately
immunized or have naturally recovered from active infection.

Natural - protective antibody (IgG) transferred from mother to infant via
placenta (e.g. against diphtheria, tetanus, mumps, rubella), responsible for immunity in the first few months to 1 year of life

Front 5

Passive - artificial immunity

Back 5

Artificial –necessary in:
i. individuals who cannot make antibodies (SCID patients)
ii. immunocompromised individuals who might develop disease before active
immunization can stimulate a protective immune responses (usually in 7-10
days). Examples include cancer patients undergoing radiation and
chemotherapy and human immunoglobulin against Hepatitis B or cytomegalovirus (CMV)
iii. individuals exposed to deadly toxins (e.g. from snake or black widow spider
bite; tetanus toxin).

Front 6

Passive - adoptive immunity

Back 6

A form of passive immunization that involves the transfer of
cells with the ability to confer immunity. Usually involves transfer to the same (autologous) host (e.g. adoptive transfer of T cells in cancer immunotherapy).

Front 7

Commensal flora

Back 7

one of the essential functions of these commensal microorganisms is to
participate in protecting skin and mucosae from invasion with microbial pathogens.
Commensals compete with pathogenic microorganisms for nutrients and also present a
physical barrier to invasion.

Front 8

Facultative pathogens

Back 8

Sometimes, normal flora on the skin or in the gut can become pathogenic due to special
circumstances, for example when the fungus Tinea cruris/pedis, which normally lives on the
skin becomes pathogenic because the integrity of the epidermis has been mechanically or otherwise compromised (jock itch or athlete’s foot).

Front 9

Obligatory pathogens

Back 9

microorganisms that cause diseases can be classified
into three main homogenous families, bacteria, viruses and fungi, and the fourth,
heterogenous group, parasites, which include pathogens such as intracellular protozoa (e.g.
Plasmodium malarie, Trypanosoma brucei) and large multicellular, chiefly intestinal, worms (e.g. schistosoma, tapeworms).

Front 10

Hematopoietic stem cells

Back 10

bone marrow derived
precursor to all cellular elements

Front 11

Common myeloid progenitor

Back 11

1) common granulocyte precursor
2) Unknown precursor that leads to
a) monocyte -->
dendritic cell, macrophage, mast cell

Front 12

Common lymphoid progenitor

Back 12

1) B cell
2) T/NK cell precursor --> T cell, NK cell

Front 13

Common granulocyte precursor

Back 13

Neutrophils, basophils, eosinophils

Front 14

Common erythroid megakaryocyte progenitor

Back 14

1) megakaryocyte --> platelets
2) erthyroblast --> erythrocyte

Front 15

primary lymphoid organ

Back 15

site of lymphocyte
development, i.e. where lymphoid stem cells proliferate and
differentiate into mature cells (lymphopoiesis). Location where
lymphocytes acquire antigen receptors and learn to distinguish “self” from “non-self”.

Front 16

Innate immunity vs. adaptive immunity

Back 16

Innate:
- Exists prior to exposure to antigen
- response not enhanced by repeated exposure
- no antigen specific response
- no immunological memory
- several physical components (see other flashcard)
- biochemical components (complement, lysozyme, low pH, interferons)
- neutrophils, monocytes, NK cells, macrophages, DC, NKT cells

Adaptive
- Developed in response to antigenic insult/encounter
- resistance improved by repeated exposure
- immunologic memory
- no physical components
- biochemical components include: antibody and lymphokines (IL2, IL4, IFN-gamma, IL5)
- Cells: B and T lymphocytes, DC

Front 17

Physical components of innate immunity

Back 17

skin, mucus, coughing, sneezing, crying; urination, competition for space and nutrients by host normal
flora; epithelial tissues produce antimicrobial peptides (e.g., defensins)

Front 18

Sequence of inflammatory events (general)

Back 18

1) Vasodilation
2) Increased vascular permeability
3) Influx of immune cells
4) Elimination of pathogen, tissue repair and regeneration

Front 19

Sequence of inflammatory events (in depth)

Back 19

1) The infectious pathogen at the site sends a “danger signal” to tissue macrophages and dendritic cells when it binds to cell Toll-like receptors (TLR)
2) cause recruitment of leukocytes, activation of anti-microbial activity & get the adaptive immune responses going
3) The macrophages are stimulated to secrete inflammatory cytokines (IL-1 and (TNF-α) that increase expression of adhesion molecules on endothelial cell surfaces --> recruit immune cells from blood. Also, chemokines {IL-8,
macrophage chemotactic protein-1 (MCP-1), RANTES}
4) immune cells ingest/degrade the
pathogens.
5) Immature dendritic cells (as well as macrophages) at the infection site also pick up a pathogen and its antigens and are induced to mature by the “danger signal”.
6) Matured DCs (and macrophages) then migrate via the lymphatic system to the lymph node draining the infection.
7) The DC “present” the pathogen’s antigens to T cells and stim division and differentiation into pathogen-specific effector lymphocytes.

Front 20

TLR characteristics

Back 20

TLRs are a bridge
between innate and adaptive immune systems, causing recruitment of leukocytes, activation
of anti-microbial activity & get the adaptive immune responses going. TLR are invariant, hardwired, and often more than 1 per cell is expressed. Some are extracellular where they bind
bacteria and their byproducts, while others are intracellular where they bind to viruses and
their products. Different combinations of TLRs produce a combinatorial recognition repertoire
which recognizes invariant microbial molecules. There are 10 TLRs identified in humans;
TLR4 recognizes Gram-negative bacteria while TLR3 recognizes viral RNA.

Front 21

Immunogen

Back 21

An antigen that is capable of binding to components of the immune response and evoking an immune response such as the production of antibodies or secretion of cytokines.

all immunogens are antigens but not all antigens are immunogens

Front 22

Hapten

Back 22

molecule that is capable of binding to an antibody but unlike an immunogen, is
unable to evoke an immune response such as antibody production.
Can bind only to a single antigen binding site (paratope) on an antibody molecule.(antibody molecule has two
antigen binding sites).
Ex) low molecular weight compounds (dinitrophenol {DNP}, benzene), drugs (aspirin) and antibiotics (penicillin).

Can be immunogenic when conjugated to carriers. Ex) Hib vaccine. influenzae polysaccharide covalently linked to tetanus toxin. Abs ar emade against both parts, even though only the carrier is recognized by T cells.

Front 23

Epitope

Back 23

(antigenic determinant): Portion of antigen that combines with antibody or T cell receptor. An immunogen generally contains numerous epitopes

Front 24

Kinetics of antibody production (phases)

Back 24

Lag phase - time btwn initial exposure and detection of Abs (4-7 days in primary response)

Exponential phase: rapid inc in circulating Abs due to inc # and activity of Ab-secreting plasma cells

Steady state - Ab synth = degradation

Declining phase - antibody synth wanes as immunogen is eliminated

Front 25

Primary vs. Secondary immune response

Back 25

Secondary responses have shorter lag time, extended plateau and slower AB decline. Affinity of Abs is higher in secondary as well.

Primary - IgM. Secondary - IgG

Front 26

BCR/Antibody structure

Back 26

Bound antibody (with transmembrane anchor domain) is called B cell receptor (BCR)

- 2 heavy chains (one variable VH and 3 constant domains - CH1, CH2, CH3)
- 2 light chains (one variable VL and one constant domain CL)
- CH1 and CH2 on heavy chain are linked via a flexible linker - hinge region that allows pivoting and optimal Ag binding

Front 27

TCR structure

Back 27

Always membrane bound and can only recognize its antigen when bound to the self MHC molecule

- 1 variable domain and one constant domain
- W/n Variable domain there is a framework region (FR) and loops of complementarity-determining region (CDR). The CDRs contact pMHC complex and recognize antigen.

- CDR1 and CDR@ are less variable and interact mostly with MHC
- CDR3 dominantly interacts with peptide Ag in MHC groove

TCR interactions with peptide:MHC complex are always weak, which helps T-cell discriminate between self and foreign peptides bound to MHC

Front 28

Antigen binding - Affinity vs. Avidity

Back 28

Affinity - strength of bond between a single epitope and a single antigen binding site on the receptor. depends on H bonds, electrostatic fores, hydrophobic forces, and van Der Waals.

Avidity - strength of the multiple interactions btwn a multivalent antigen and a bivalent/multivalent receptor. ex) sum of all interactions between all available TCR molecules and all MHC molecules bearing the antigenic peptide. Avidity predominates bc most natural antigens have multiple epitopes; high avidity can supercede low affinity (IgM vs. IgG)

Affinity and avidity determine whether a given lymphocyte will be activated (threshold for activation)

Front 29

Cross-reactivity (examples)

Back 29

Ability of a receptor to react with antigen other than the one which originally activated it.
Examples:
1) Abs against cowpox cross react with epitopes of variola virus (smallpox)
2) Antibodies against S. pyogenes M protein cross-react with heart tissue --> rheumatic fever
3) Abs against inactivated tetatnus toxin are protective against the tetanus toxin

Front 30

7 Factors of immunogenicity

Back 30

1) Foreignness, phylogenetic distance (except highly conserved molecules)
2) replicability (live vacs are more immunogenic than live attenuated/dead). inc copy number
3) HIgh molecular weight >6000 daltons
4) chemical complexity
5) degradability (must be degraded and processed by APCS to be immunogenic)
6) Responding organism's genetics - absence of MHC molecules/TCR/BCR = lack of response
7) dose of immunogen/route of admin. SubQ is better than IP or IV (diffuse more slowly more likelihood of interact with dendritic cells and langerhans cells. Too low or too high a dose can lead to failure to induce immune response or to tolerance.

Front 31

CD4 T cells

Back 31

Also known as Th cells. express CD4, secrete numerous cytokines, help activate dendritic cells?, help B lymphocytes to produce antibodies, help CD8 T cells to mature and produce cytokines

- can also directly eliminate microbial pathogens
- or induce macrophages to kill pathogens

CD4 T cells can also be further divided into Th1, Th2, and Th17 depending on what tyupe of cytokines they make

Front 32

CD8 T cells

Back 32

also called cytotoxic cells.
destroy microbe-infected cells and tumor cells by direct killing
- stop microbial invasion by secreting cytokines

Front 33

T reg cells

Back 33

express CD4
regulate immune responses by controlling the activities of other immune cells (including other T cells)

Front 34

Cytokines of
Th1
Th2
Th17
T-reg

Back 34

Th1 - IFN-1, IL-12, IFN-gamma
Th2 - IL-10, IL-4, IL-5, IL-13, IL9
Th17 - IL-6 + TGFb + IL-22
Treg - IL-6 + TGFb

Front 35

MHC class I structure
function

Back 35

all nucleated mammalian cells express class I

- heterodimer of an alpha chain non-covalently boun to B2-microglobulin (B2m)
- alpha chain has three domain, 1, 2, 3.
- a1 and a2 form the peptide-binding cleft

Class I survey the intracellular environment and thus are key in defending against viruses, ic bacteria, parasites, and tumors

Front 36

MHC class II structure
function

Back 36

only APCs and thymic epithelial cells normally express class II

- 2 non-covalently bound chains, alpha and beta
- alpha chain has a1 and a2 domains
- beta chain has b1 and b2 domains
- peptide binding cleft is made from a1 and b1

class II molecules dominantly survey ec compartment, response against extracellular microbes

Front 37

Generation of MHC class I binding peptides

Back 37

- Pathogen proteins are degraded into peptides in the cytosol by proteasomes
- peptides are transported to the ER by transporter associated with antigen processing-1 and -2 (TAP1 and TAP2)
- peptides are trimmed and loaded onto MHC1 in the ER, trans via golgi to the cell membrane

CD8 cells

Front 38

Generation of MHC class II binding peptides

Back 38

Th1 and Th2 cells

-extracellular pathogens in the ecf taken up by phagocytosis
- degraded in phagolysosome
- newly synth MHCII molecules in the ER are prevented from binding peptides in the ER bc they are associated with invariant chain (IC). IC is degraded in the endocytic vesicle

Front 39

Type I hypersensitivity
Pathogenesis
Examples
Clinical diagnosis

Back 39

Basics: IgE antibodies binding to mast cells, immediate. anaphylactic shock

Atopic ppl are genetically predisposed to make IgE in response to certain antigens (instead of IgG). and to have higher levels of eosinophils.

Primary exposure - sensitization via Th2 stimulating B cells to make antigen-specific IgE. IgE )made after class switching) binds to mast cells (or basophils) via FCe receptors.

Secondary: effector phase. Antigen binds to IgE on mast cells. cross-linking of IgE causes granule and cytokine release. (See other flashcards)

Ex) allergic rhinitis, allergic asthma, hives, eczema, anaphylaxis

Clinical - do an intradermal injection of allergen and see wheal and flare reaction (edema and erythema). takes 10-15 mins. see late reaction in 5-8 hrs.

Do RAST test (see other card)
Treatment see other card

Front 40

Treatment of Type I hypersensitivity

Back 40

1) Avoid allergan
2) Allergen-specific immunotherapy - give very low dose allergen over months, grad. inc. to induce blocking IgG antibodies. (IgG Abs would suck up all the allergen before it gets to IgE on mast cells). 20-30 shots.
3) Desensitization - low doses every 15 mins to slowly trigger all mast cells - penicillin in ICU.
4) Mast cell stabilization - drugs that block degranulation - sodium comoglycate
5) mediatior antagonists - antihistamines, epi
6) Steroids (block PGs)
7) Anti-IgE monoclonal Abs. Omalizumab (IgG1 subclass) binds Fc portion of IgE to block IgE from binding to FCe receptor on mast/basophil. Works great, but pricey.

Front 41

RAST test

Back 41

radioallergosorbent test

1) Bind antigen to cellulose disc
2) Put pts. serum IgE on it.
3) Wash away excess
4) Put a radiolabeled anti-IgE antibody in it.
5) Wash away excess.

The amt of radiolabeled Ab = amt of IgE in pts. serum

Front 42

Mediators of Type I hypersensitivity

Back 42

1) Histamine - smooth muscle contraction. inc vasc permeability (edema)
2) ECF-A (eo chemotactic factor) - attracts eos
3) Leukotrienes C4 and D4 - prolonged smooth muscle contraction and inc. vasc. permeability
4) PAF (platelet activating factor) - causes platelets to release histamine --> bronchoconstriction, vasodilation, local THROMBOSIS
5) Thromboxanes/PGs - vasoactive, bronchoconstriction, LEUKO chemotactics
6) IL-3, 4, 5 (most important), GM-CSF, TNF-alpha: IL- 5 stimulates bone marrow to make more eos! ILs increase adhesion molecules on endothelium.

Front 43

Type II hypersensitivity
Pathogenesis
Examples

Back 43

Basics - Antibody dependent cellular cytotoxicity. Antigen on cell surface.

1) Foreign antigen on cells induces Ab formation.
2) Ab binds to cells --> act. complement ("fixes") and induces lysis and phagocytosis.
3) Ab can also bind to Fc receptor to any cell that has an FcR and induce ADCC. like NK.

Ex)
1) Transfusion reactions.
2) Erthyroblastosis fetalis - anti-Rh antibodies in mom (made from previous kid exposure) cross placenta and destroy fetus RBCs.
3) Autoimmune hemolytic anemia
4) Goodpasture's. Ab binding on basement membrane (see smooth deposits). Pulm hemorrhage/glomerulonephritis
5) Rheumatic fever. Ab to Step M protein damages heart/kidney via cross-reactivity
6) Drug-induced rxn
7) Anti-receptor disease: myasthenia, grave's
8) Graft rejection - preformed Abs to HLA antigen causes severe nonreversible damage to graft.

Clinical: check presence of Abs against antigen via ELIZA or Western. OR biopsy.

Decreased renal function, pulm infilitrates, hemoptysis, low platelets

Treat: prevention by blood cross-matching. Rhogam for Rh- mother with Rh+ babies, supportive plasmapheresis/dialysis, immune suppressants.

Front 44

Type III hypersensitivity

Back 44

1) Abs combine with free Ag to make insoluble complexes, which deposit on blood vessel walls.
2) Complexes act. complement. chemoattractant (C5a > C3a) and anaphylatoxin (C3< C4< C5)
3) PMNS (neutros) release lysosomal enzymes and damage the vessel/tissue

3 Types
1) Persistent infection, usually IC --> kidney/infected organ
2) AI - kidney, joint, arteries, skin
3) extrinsic/env antigen --> lung

Biopsy - humpy-bumpy immune complex deposits in SLE patients (renal sections)

Front 45

Examples of Type III hypersensitivity

Back 45

1) serum sickness - AB response to passive immunization w/ foreign antiserum
2) RA - rheumatoid factor is IgM against Fc part of IgG that deposits in joints.
3) Infectious disease - malaria, viral, fungal, leprosy
4) Farmer's lung (moldy hay spores)
5) Arthus -
6) Glomerulonephritis (post-strep. has to be humpy bumpy biopsy)
7) SLE - AB against DNA.

Treat - supportive care.
Immunosuppressants

Front 46

Three types of IV hypersensitivity
overview of mechanism

Back 46

1) Contact
2) Tuberculin
3) Granulomatous

Sensitization then activation. 1-2 weeks after Ag exposure to generate Th1 cells?
1) Th1 cells (sometimes Th17) enter tissue where an APC presents an antigen on MHC II.
2)Th1 cells secrete cytokines (IL2, IFN-gamma, TNFalpha, IL17), chemokines, cytotoxins that make MACROS come/be activated
3) Activated macrophages kill things and destroy tissue

Front 47

Contact hypersensitivity

Back 47

Max response 2-3 days
- eczema at site of Ag (as opposed to type I hypersensitivity)
- EPIDERMAL

Most common causes: heavy metals (nickel, chromate), rubber, poison ivy/oak. Latex.

Test by patch test.

Heavy metals haptenate cell surface proteins and induce DTH via binding to TLR4, mast cells involved

Front 48

Tuberculin hypersensitivity

Back 48

- 2-3 days max rxn
- DERMAL
- mostly macros involved

Front 49

Granulomatous hypersensitivity

Back 49

Takes at least 2 weeks but up to months to develop.

All the other stuff happens. Also, plasma cells and Cytotoxic T cells come to site may cause tissue damage as well.

but then Macrophages can't kill agent/intracellular organism. So, forms epitheloid cell. then fibrosis to wall off the thing.

Prominent in parasitic infections (eggs), Fungus, sarcoidosis, and Crohns. filamentous bacteria.

Front 50

Anaphylaxis respiratory components

Back 50

1) Bronchial constriction
2) Increased mucus production
3) Larygeal edema causing obstruction(!!)
4) Air trapping (blebs) bc expiration is a passive process

also have urticaria
Shock and death w/n minutes

Front 51

Tissue changes in local Type I hypersensitivity

Back 51

Localized swelling and redness

anaphylaxis is systemic

Front 52

mast cell mediators

Back 52

1) Histamine
2) Neutrophil chemotactic factor
3) Enzymes
4) Proteoglycans
5) leukotrienes
6) Pgs
7) Cytokines (TNF, IL-1)

HELPP-PCT

Front 53

Late phase reaction

Back 53

more destructive
Major role in eosinophils
Release of proteolytic enzymes, major basic protein, and eosinophilic cationic protein

Cause epithelial damage/lysis, stimulate further mast cell granule release
recruitment of additional leukocytes

Front 54

Mechanism of allergen-specific immunotherapy

Back 54

Periodic injections of allergen with increasing dose

Shifts response from IgE to IgG blocking antibodies which do not react with mast cell receptors

Front 55

Three mechanisms of hypersensivity

Back 55

1) Antibody mediated cell destruction via complement (major)
2) Cell/tissue destruction by NK lymphocutes
3) Antibody binding altering function (myasthenia, graves)

Front 56

Transfusion reaction mechanism

Back 56

Result of ABO or Rh incompatability btn donor and recipient.

Circulating Abs against the donor's blood initiate lysis of RBCs. hbg released in plasma --> cardiovascular collapse --> shock/death

Front 57

Hemolytic disease of the newborn

Back 57

Rh+ father, Rh- mother

1) In the first pregnancy the fetus's Rh+ blood evokes an immune response from mom of the IgM type which cannot cross the placenta.
2) In the second pregnancy, the mom produces IgG which can cross the placental barrier.
3) The fetus's RBCs are destroyed in utero.

Use Rhogam

Front 58

Pemphigus vulgaris vs. Bullous pephigoid

Back 58

PV vs. BP = desmosomes vs. hemidesomosomes

PV
- Ab against desmoglein 1 and 3 which destroyes intercellular attachments in epidermis.
- causes separation of upper levels of epidermis from the basal layer

BP
- Antibody against BPAG1 (a plakin) and BPAG 2 (collagen type 18) destroys hemidesmosomes
- Complete epidermal separation from dermis
- 10-15% also have mucosal involvement.

Can test by direct Immunofluoresence of lesional skin. Or indirectly.

Front 59

Type III hypersensitivity facts

Back 59

- small and medium sized complexes (large get phaocytosed by macrophages)
- injury occurs in those places that filter blood (glomerulus, synovium, choroid plexus in brain, dermal capillaries of skin)

- Don't forget that platelet aggregation may lead to microthrombi and ischemic tissue damage
- levels of complement will fall when complexes activate it --> measure to diagnose

- Immune complexes containing IgG and IgM antibodies (which fix complement) and Abs which bind to white blood cell Fc receptors are most pathogenic
- Endothelial cells play a role through production of IL 1,6,8, and CAM, proteolytic enzymes

Front 60

Post-infectious Glomerulonephritis (Streptococcus)

Symptoms, tests

"humpy bumpy pig"

Back 60

Can be caused after both pharyngitis AND skin infections by Group A beta-hemolytic Strep

Takes at least 7-10 days after infection (up to 2-4 weeks)

Symptoms - actue salt and water retention --> edema and HTN
May need dialysis and other supportive care.
Kids do great. Adults may have chronic issues like hemat/proteinuria

Histo - will see endothelial and mesangial proliferation. Lots of neutrophils and monocytes --> nothing is getting filtered in the kidney

Fluoresence will show lumpy bumpy fluoresence in glomerulus

Front 61

Causes of Type III hypersensitivity

Back 61

1) Infectious - strep, hepatitis, syphilis, malaria

2) Neoplastic - breast ca, melanoma, lung ca

3) Serum sickness - IgG from animal is the antigen for the body

Front 62

Components of granulomas

Back 62

Tb and cocci among others (add!)

Monocytes differentiate into macrophages AND epithelioid cells

Outer edge - fibroblasts, "guarding" memory T cells, macros
Center - epithelioid cells, giant cells.

NO neutrophils - actually inhibited by a factor. Macrophages are inhibited from leaving.

Front 63

Hyperacute rejection of transplanted organs

Back 63

hallmark is pre-formed antibodies
within minutes

ex) kidney turns black on the operating table when blood flow is re-established

Front 64

Acute cellular/acute humoral rejection

Back 64

variable time course, first months after transplant.

Target is usually tubules and blood vessels.

Cellular rejection more common (CD4+ and CD*+ T cells)

Humoral targets the endothelium more.

Front 65

Chronic transplant organ rejection

Back 65

Progressive vascular narrowing and tissue ischemia due to multiple episodes of rejection
usually over years

Front 66

Cell markers for Hematopoietic stem cells

Back 66

CD34 and/or CD133+

no CD3, CD19, etc.

HSCs are self-renewing cells located in bone marrow but a few also circulate in blood

Front 67

Cell markers for B2 cells vs. B1 cells

Back 67

B2 - CD19

B1 - CD 5 (i think check!)

Front 68

B cell development

Back 68

- Occurs in bone marrow
- dependent on exp of ADHESION molecules
- dependent on STROMAL secretion of CYTOKINES and GROWTH FACTORS
- develop in islands of hemtapoietic development - niches

1) A stem cell/lymphoid progenitor docks onto a BM stromal cell with VLA-4 binding to VCAM-1 FINISH THIS

Front 69

Clinical consequences of lack of/removal of lymphoid organs

- Bone marrow
- spleen
- thymus
- lymph node

Back 69

1. Bone marrow – damage - aplastic anemia; SCID defect, etc
2. Thymus – congenital – T cell deficiency; removal - early attrition and
aging of T cells
3. Spleen – polycythemia; defective Ab responses, susceptibility to
encapsulated bacteria
4. LN – rarely indispensible, lymphoedema

Front 70

Innate immunity activation (steps)

Back 70

1) TLR and NLRs on DC and macrophages get a "danger signal" when they bind to infectious pathogens
2) Macros are stimulated to secrete inflam cytokines like IL-1 and TNFalpha that inc expression of adhesion molecules on endothelial cell surfaces. Also secrete chemokines (IL8 and macro chemotactic protein, rantes)
3) The inc expression of adhesion molecules causes more immune cells from blood to go to inflammatory site.
4) Complement components (C3a, C5a) with chemotactic activity are also produced at te site.
5) Now that neutros and monocytes are at site they ingest and degrade the pathogens.
6) immature DCs at the site pick up pathogen and are induced to mature by the danger signal. They migrate via lumphatic system to lymph node to present the pathogen's antigens to T cells.

Front 71

Leukocyte Adhesion Deficiency

Back 71

A deficiency in expression of LFA-1 and Mac-1, leading to impaired recuitment of blood cells to the site of inflammation.

Mutation in the gene encoding the Beta2 subunit (CD18) of the integrin proteins LFA-1 and Mac-1. They are heterodimeric.

LFA-1 is CD11a:CD18 (binds to ICAM-1,2)
Mac-1 is CD11b:CD18 (binds to the same)

Prone to recurrent bacterial infections and impaired wound healing.